MicroRNA expression profiling and potential biomarker exploration in BMSCs of osteoporosis patients based on high-throughput sequencing technology

MicroRNA expression profiling and potential biomarker exploration in BMSCs of osteoporosis patients based on high-throughput sequencing technology | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article MicroRNA expression profiling and potential biomarker exploration in BMSCs of osteoporosis patients based on high-throughput sequencing technology Shunli Zhang, Yongxiong He, Rong Chen, Yuntao Gu, Chunzhao Xu, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5258994/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Bone marrow mesenchymal stem cells (BMSCs) are core stem cells and their differentiation orientation directly manipulates the ongoing of osteoporosis (OP). MicroRNAs (miRNAs) are momentously characterized molecular in BMSCs. However, the leading pattern and trait of miRNAs in OP remain vague and mysterious. Full-scale research of BMSCs-existed miRNA expression between normal conditions and patients experiencing OP is the only way for us to pinpoint the effect of miRNA, making us rationally and effectively utilize miRNA. Objective This review chiefly lies in exploring, selecting, verifying, and confirming the biomarker of miRNAs by dissecting miRNA patterns, which offer diagnosis reference, monitor value, customized feature therapy by developing related preparation, and emerging prognosis indicators. Methods We gathered miRNA-seq datasets from human BMSCs to detect the expression pattern of miRNA. Herein, we searched and distinguished microRNA expression levels of BMSCs, sifted the distinctively existing microRNAs, sought the preferentially expressed microRNAs, had knowledge of the target points of related microRNA biomarkers, and boosted our awareness of the role of miRNAs and the development of pharmaceutical preparation aimed at it. Results These miRNAs manifested aberrant expression variation between matched control and OP cases, they mainly draw upon the Wnt/β-catenin, MAPK, and Notch pathways to perform signal delivery, mediating the osteogenesis, adipogenesis, the balance of these two kinds of differentiated conversion, the proliferation, migration, apoptosis, stemness, and senescence of BMSCs, and biological ongoing of chondrocytes and osteoclasts. In addition, the treatment based on miRNAs of in vitro trials in combination with animal models defined the application of miRNA-linked therapy. Conclusion This paper accorded proof of miRNAs as screening tools, confirmation guidance, treatment means, and prediction indicators of OP, paved the emerging road for clinical practice, and pushed the development of personalized remedies that break through regular remedies. MiRNAs BMSCs Osteoporosis Expression Roles Introduction Osteoporosis (OP) is an abnormal skeleton metabolism disorder associated with the differentiation condition, formation, adsorption, and remodeling of bone [ 1 – 3 ]. This type of disease is embodied in low-level density and inferior quality of bone [ 4 ]. Its occurrence principally depends on natural aging, hormonal changes, bad life habits, nutrient intake, etc [ 5 , 6 ]. OP chiefly appeared in climacteric women, the aged, and teens [ 7 , 8 ]. Currently, the attack rate of OP is manifestly uplifted worldwide [ 9 , 10 ]. Its prevention needs enough calcium ingestion and adequate workouts [ 11 ]. Bone marrow mesenchymal stem cells (BMSCs) were earliest exposed in bone marrow in 1968. Their osteogenesis-oriented differentiation can influence bone formation and loss, and then adjust OP [ 5 , 12 – 14 ]. Thus, it is generally adopted to discern, confirm, and evaluate the ongoing of OP. MiRNAs are defined as shorter (about 22 nt), single-stranded, and noncoding ribonucleic acids initially uncovered in C. elegans in 1993 [ 15 – 17 ]. They are insensitive to RNase addition and stable in many trial situations [ 18 ]. They usually obstruct the expression content and translation course of their target mRNA genes [ 19 ]. They are implicated in many regulatory courses, for instance, the growth, renewal, and senescence of organisms [ 20 ]. MiRNA is linked to the differentiation process of BMSCs and body motion-caused remodeling of the skeleton [ 21 ]. Xu et al have proven that the high enrichment of miR-577 avoided the osteoblasts augmentation by oppositely modulating TSHR on the basis of hyperthyroid-mediated OP [ 22 ]. The ability of miRNAs to act as biomarkers is gradually testified in diverse diseases [ 23 , 24 ]. The majority of papers have uncovered the ability of miRNAs to adjust bone quantity [ 25 – 29 ]. Thus, a widespread probe for the expression trait of miRNAs from BMSCs could contribute to seek available biomarkers and incur the consideration of their function in BMSCs [ 30 , 31 ]. The high-throughput RNA-seq technology offers a wonderful means and way to amply quantify miRNAs in BMSCs. Although some RNA-seq databases deeply dug into the enrichment of miRNAs by means of sequencing technology, the great majority of analyses have locations on account of minor sample collection and discordant expression norms. Currently, few databases share differentially expressed miRNAs in BMSCs, which is not enough to attract us to focus on miRNA functions for the regulation of BMSCs. The concrete mechanisms that miRNAs affect OP are presently intricate and fuzzy, herein we examined and studied the expression and difference of miRNA landscape in terms of miRNA-seq datasets of BMSCs, administered functional explanation and signaling transduction of BMSCs-encompassed miRNAs in OP formation, and unveiled the likelihood and feasibility of manifestly expressed miRNAs as underlying candidates for biomarkers, indicated the value of miRNAs as detection tools applied to clinical studies. Its adoption will be a tremendous progress compared to traditional therapy measures. Materials and methods Data screening and summary We utilized keywords ‘((BMSC) AND (miRNA)) AND (osteoporosis)’ to search miRNA-seq data of BMSCs among patients subjected to OP. Finally, we gained a miRNA-seq dataset termed GSE74209. The expression patterns of miRNA among patients undergoing OP We have perceived the variation of miRNA in two different systems of normal individuals and participants subjected to OP. Herein, we conducted an all-around data query and sift in the PubMed and Medline databases to specify the profiles of miRNAs. We finally determined the number of upregulated and downregulated miRNAs from GSE74209. As Li et al summarized, we noticed the anomalous existence of 80 miRNAs (logFC > 1, p < 0.05). Six samples that were from postmenopausal female cases showed that the miR-4739, miR-3202, and miR-320c were manifestly upregulated in OP, which has been substantiated by RT-PCR [ 32 ], furthermore, Zhou et al stressed the slippage of miR-483-3p level (Table 1 ), which has been deeply testified by H&E and Masson staining[ 33 ]. Table 1 Data origin of miRNAs lineage, and variation trend of miRNAs level. Datasets Upregulated miRNAs downregulated miRNAs Reference GSE74209 MiR-4739 MiR-3202 MiR-320c MiR-483-3p [ 32 ] [ 33 ] The functional elaboration of miRNAs in OP MiRNAs have displayed the ties to the uplift and drop of osteoblasts counts. A report about the age-mediated bone disorder from Li et al deemed that BMSCs-contained miR-188 upregulation turned on the switch that diminished osteoblast orientation and intensified fat gathering of BMSCs, and either histone deacetylase 9 (HDAC9) or RPTOR-independent companion of MTOR complex 2 (RICTOR) is the directly miR-188-targeted downstream gene, their protein content can be restricted by miR-188 combination [ 34 ]. Based on the rats model mimicking menopausal OP, Li et al held that miR-96-5p increment explicitly accelerated cell growth, migration, osteogenic development, and curbed apoptotic occurrence via LNC_000052–miR-96-5p–PIK3R1 transduction pathway [ 35 ]. CoQ10 attenuated the hyperlipidemia-generated OP in vivo model through beefing up the assignment towards osteoblasts and damaging the adipocytes production relying on the miR-130b-3p/PGC-1α axes-mediated activation of mitochondrial activity [ 36 ]. In the OVX-mediated rat model, Kaempferol manifested osteogenesis bias through acting on the miR-10a-3p/CXCL12 cascade [ 37 ]. In vitro induction and sequencing results of human BMSCs from Wang et al demonstrated that melatonin originally curbed the circ_0003865 level, next elevated the miR-3653-3p content, and finally checked the GAS1 expression, thus improving the OP through strengthening the osteogenic advantage [ 38 ]. The exceeded miR-4739 gathering in OP BMSCs disturbed the osteogenic power by encumbering DLX3 content [ 32 ]. Chen et al accorded a piece of accurate evidence that miR-26b aimed at SIRT2 sites triggered the growth and dwindled apoptotic state of chondrocytes [ 39 ]. In the mice model mimicking menopausal OP, we sighted the niggling content of miR-18a-5p, and this phenomenon aggravated osteogenic deficiency through the miR-18a-5p/Notch2 delivery [ 40 ]. Another cellular and animal trial simulating disuse OP exposed that the enhanced miR-132-3p content could aggravate bone lack by hindering skeleton generation [ 41 ]. In BMSCs of the OVX-treated mice, the remarkable drop of GAS5 content checked the osteogenic role via sponging the miR-135a-5p, subsequently impairing the FOXO1 content [ 42 ]. Teng et al testified that Icariin lessened the PTEN content via adding miR-335-5p content, subsequently soothing the OP signs [ 43 ]. The MALAT1 secretion from BMSCs generated the osteogenic impulse by targeting the miR-34c/SATB2 signal [ 44 ]. Jiang et al thought that the miR-183 distinctly declined the regeneration property of BMSCs via restricting β-catenin content [ 45 ]. An in vitro BMSCs stimulation study from Li et al clarified that miR-149-3p militated the fat formation in the FTO-dependent way and irritated bone accumulation [ 46 ]. Huang et al illustrated that the existence of miR-204 or miR-211 in BMSCs restrained the Runx2 content, then constraining osteogenic transformation and contributing to adipogenic motion [ 47 ]. Wang et al notified us of the uplift of miR-100-5p content in OP cases, and this crystal variation forbade the TMEM135 appearance, making OP worsen by prohibiting the osteogenic efficiency [ 48 ]. In human BMSCs, Eisa et al determined that Kynurenine-irritated demonstrable elevation of miR-29b-1-5p level in older participants, which triggered the descent of SDF-1, eventually deterring the bone development [ 49 ]. Wu et al opined that the SERPINB9P1 strengthened the osteogenic force via varying the SIRT6 concentration mediated by the miR-545-3p downregulation [ 50 ]. Lin et al implicated that miR-130a was evidently elevated in the young multitude, which expanded osteoblasts emergence via conversely controlling Smurf2 protein content and militated fat generation through binding to the PPARγ mRNA in the mice-based BMSCs [ 51 ]. In the cleidocranial dysplasia (CCD)-caused bone malfunction, Runx2 deficiency fortified miR-31 content, presenting the disability of growth, osteogenic role, and regeneration property, as well as the aggressive momentum of aging of BMSCs [ 52 ]. In the psoralen‑stimulated in vitro trial, Huang et al obtained the negative variation of miR‑488 in response to psoralen, which provoked osteoblasts-orientation regulation via tightly linking to the Runx2 [ 53 ]. Several microarray datasets verified that miR-483-3p was stupendously expressed in skeleton tissue among healthy participants, moreover, in vitro osteoblast cellular treatment deeply testified the facilitation of osteoblast activity and the obstacle of apoptosis through the miR-483-3p-DKK2-Wnt/β-catenin cascade [ 33 ]. Zhang et al unsealed that the CeRNA PART1 positively sharpened the Runx3 content by sponging miR-185-5p, which developed a regulatory circle, redounding the osteogenic efficiency and impeding the apoptosis of human BMSCs [ 54 ]. Liu et al discovered that the reduction of BMSCs-encompassed miR-142-3P content increased the level of 14-3-3η and MAPK3, eventually leading to osteogenic deficit [ 55 ]. The signal delivery of circEIF4B/miR-186-5p/FOXO1 exerted a dominant role in profoundly modulating bone growth in phytic acid-treated skeleton development [ 56 ]. A chain of negative transduction of circ_0001145/miR-194-5p/Fzd6 pathways accelerated osteogenic tendency by energetically stimulating the Wnt/β-catenin delivery [ 57 ]. Xiang et al informed us of the relative raise of SNHG1 in low-grade osteogenesis orientation, it exerted an unfavorable role for OP by acting on the miR-101/DKK1-Wnt/β-catenin regulatory ways [ 58 ]. Myoblast-secreted Prrx2 constrained the BMSC-existed miR-128 content by activating MIR22HG, further motivating the YAP1 content and translocation into the nucleus, finally redounding the osteogenesis [ 59 ]. In a study based on in vivo diabetic OP (DO) and in vitro models, the BMSC-released EVs with MEG3 load could emphatically stir up NR4A3 enhancement by sponging the miR-3064-5p combination site, and then caused the amplification of PINK1/Parkin cascade, arising the osteoblasts augmentation and osteogenic superiority [ 60 ]. The upregulated content of BMSCs-encompassed miRNA-19b-3p weakened the osteoblasts-dominant orientation through oppositely modulating the EBF2 level [ 61 ]. In this several regulatory axes, like miR-210-3p/KRAS/MAPK [ 62 ], HAGLR/miR-182-5p/Hoxa10 [ 63 ], FGD5 antisense RNA 1/miR-506-3p/BMP7 [ 64 ], SP1/miR-133a-3p/MAPK3 [ 65 ], lncTIMP3/miR-214/Smad4 [ 66 ], miR-133a-FGFR1-MAPK/ERK [ 67 ], TNF-α/miR-23b/Runx2 [ 68 ], miR-483-5p-MAPK1/Smad5 [ 69 ], circRNA_0001052-miR-124-3p-Wnt4/β-catenin [ 70 ], miR-25–3p/ITGB3 [ 71 ], MEG3/miR-217-5p/Notch [ 72 ], wherein the abundant miRNAs were involved in the osteogenic deprivation. Whereas, other transduction delivery, such as miR-26b-GSK3β-Wnt/β-catenin [ 73 ], miR-877-5p/EIF4G2 [ 74 ], miR-218-5p/SOCS3 [ 75 ], miR-34a-5p/HDAC1/ER-α [ 76 ], circCOX6A1/miR-512-3p/DYRK2 [ 77 ], TNF-α/miR-27a-3p/Sfrp1/Wnt3a–β-catenin [ 78 ], miR-486–3p/CTNNBIP1/Wnt/β-catenin [ 79 ], miR-124-3p/GSK-3β/β-catenin [ 80 ], wherein the insufficient miRNAs were reckoned to weaken the osteogenic induction. Apart from the above-mentioned miRNA, we knew that the expression data of a few miRNAs in BMSCs is unknown. MiR-15b-5p/GFAP, miR-150-5P/MMP14/Wnt/β-catenin, miR-935/STAT1 miR-16-5p/Axin2/Wnt/β-catenin axes, miR-29a all eased OP by the delivery of EVs with miRNA into an animal body. Mechanically, they exerted benefited effectiveness separately by lessening the differentiated power of osteoclasts, magnifying the growth and matured state of osteoblasts, underpinning the osteoblasts growth and osteogenic trend, evoking the osteogenic strength, exciting the bone production in DO-, DO-, OVX-, OVX-induced, healthy models [ 81 – 85 ]. The therapy directly aiming at miRNA and the speculation of prospective biomarkers Given the regulatory roles of miRNA in the ongoing of OP that is ascribed to the inducement of older age, menopausal female, diabetes, etc. In bountiful animal models, we have spotted the application of miRNA-based therapy. These therapeutic ways usher us to deeply recognize the function and value of miRNAs. Infusion of aptamer-antagomiR-188 into the bone marrow of animals infinitely delayed the OP acceleration [ 34 ]. Administration of miR-96-5p-based BMSCs by the caudal vein proffered a benign impetus for treating OP [ 35 ]. Subcutaneous injection of OP BMSCs with agomiR-4739 or antagomiR-4739 in combination with HA formed the sharp contrast in vivo experiments, which is a cue for the exploitation of clinical function [ 35 ]. Adenovirus infusion with excessive miR-18a-5p into the femur interior slowed down the pace of menopausal OP, which implicated the emerging function for clinically groundbreaking study [ 40 ]. Pulsed generalized delivery of bone-orientated antagomiR-132 brought out the deceleration of the mechanical unloading-leaded OP [ 41 ]. Animal models of rats from Teng et al told us that either explicit upregulation of miR-335-5p or Icariin therapy moderated the OP ongoing [ 43 ]. The two types of injection treatment of agomiR-34c or antagomiR-34c produced extremely clear divergence, connoting the practical significance of antagomiR-34c treatment [ 44 ]. Intravenous administration of agomiR-130a manifestly combated the OP advancement [ 51 ]. The going down of miRNA-19b-3p in rats developed a crystal deterrent for spinal cord trauma-induced OP [ 61 ]. Zhou et al stated that the utility of ample miR-218-5p forcefully stripped off the OP advancement in the OVX-applied animals [ 75 ]. The utilization of substantial miR-34a-5p in mice born over 18 months ago mitigated the OP exacerbation [ 76 ]. Wang et al described that the infusion of the antagomiR-133a specifically targeted towards BMSC into the femur medulla greatly alleviated skeleton malfunction in OVX-applied mice [ 67 ]. Deng et al held that the administration of agomiR-23b into the tail vein aggravated serious signs of OP, while the adenovirus Runx2 application counteracted the miR-23b-engendered skeleton disability [ 68 ]. Zhou et al elaborated that the employment of FAM-BMSC-aptamer-nanoparticles-enriched antagomir-483-5p aggressively resisted the metabolism defect of the skeleton [ 69 ]. Based on the roles and the beneficial effectiveness of miRNAs from BMSCs, we inferred they could be employed to predict, discern, confirm, assess, and treat OP, shoring up the monitoring, intervention, and prognosis of OP, which hinted at the prospect of miRNAs as promising and efficient biomarkers. Table 2 The predisposing factor of OP, the relative content (ascend↑ or descend↓ ) of miRNA from BMSCs in OP illnesses or the symptom of OP, the miRNA-mediated signaling delivery, the miRNA-bound downstream gene, the miRNA-dependent treatment in OP-based animal model. MiRNAs member Predisposing factor Relative content Signaling delivery Downstream gene Therapeutic means of animal model Reference MiR-188 Older age ↑ - HDAC9 or RICTOR Infusion of aptamer-antagomiR-188 into bone marrow [ 34 ] MiR-96-5p OVX ↓ LNC_000052/miR-96-5p/PIK3R1 PIK3R1 Administration of miR-96-5p-based BMSCs by the caudal vein [ 35 ] MiR-130b-3p Hyperlipidemia ↑ CoQ10/miR-130b-3p/PGC-1α PGC-1α - [ 36 ] MiR-10a-3p OVX ↑ Kaempferol/miR-10a-3p/CXCL12 CXCL12 - [ 37 ] MiR-3653-3p - ↓ Circ_0003865/miR-3653-3p/GAS1 GAS1 - [ 38 ] MiR-4739 Menopause ↑ MiR-4739/DLX3 DLX3 Subcutaneous injection of OP BMSCs with agomiR-4739 or antagomiR-4739 in combination with HA [ 32 ] MiR-26b OVX ↑ MiR-26b/SIRT2 SIRT2 - [ 39 ] MiR-18a-5p Menopausal ↓ MiR-18a-5p/Notch2 Notch2 Adenovirus infusion with exceeded miR-18a-5p [ 40 ] MiR-132-3p Unloading ↑ - - Pulsed generalized delivery of bone-specific antagomiR-132 [ 41 ] MiR-135a-5p OVX ↑ GAS5/miR-135a-5p/FOXO1 FOXO1 - [ 42 ] MiR-335-5p - ↓ Icariin/miR-335-5p/PTEN PTEN Uplift of miR-335-5p [ 43 ] MiR-34c - ↑ MALAT1/miR-34c/SATB2 SATB2 The injection of agomiR-34c or antagomiR-34c [ 44 ] MiR-183 - ↑ MiR-183/CTNNB1 CTNNB1 - [ 45 ] MiR-149-3p - ↓ - FTO - [ 46 ] MiR-204 or miR-211 - ↑ MiR-204/211-Runx2 Runx2 - [ 47 ] MiR-100-5p - ↑ MiR-100-5p/TMEM135 TMEM135 - [ 48 ] MiR-29b-1-5p Older age ↑ Kynurenine/miR-29b-1-5p/SDF-1 SDF-1 - [ 49 ] MiR-545-3p - ↑ SERPINB9P1/miR-545-3p/SIRT6 SIRT6 - [ 50 ] MiR-130a Older age ↓ - Smurf2 or PPARγ Intravenous administration of agomiR-130a [ 51 ] MiR-31 CCD ↑ Runx2/miR-31 - - [ 52 ] MiR‑488 - ↑ Psoralen/miR‑488/Runx2 Runx2 - [ 53 ] MiR-483-3p - ↓ MiR-483-3p-DKK2-Wnt/β-catenin DKK2 - [ 33 ] MiR-185-5p - ↑ PART1/miR-185-5p/Runx3 Runx3 - [ 54 ] MiR-142-3P - ↓ MiR-142-3P/14-3-3η/MAPK3 14-3-3η - [ 55 ] MiR-186-5p Hyperglycemia ↑ CircEIF4B/miR-186-5p/FOXO1 FOXO1 - [ 56 ] MiR-503-5p - ↑ LOC100126784/POM121L9P-miR-503-5p-SORBS1 SORBS1 - [ 86 ] MiR-577 Hyperthyroid ↑ - TSHR - [ 22 ] MiR-194-5p - ↑ Circ_0001145/miR-194-5p/Fzd6/Wnt/β-catenin Fzd6 - [ 57 ] MiR-101 - ↓ SNHG1-miR-101-DKK1-Wnt/β-catenin DKK1 - [ 58 ] MiR-128 - ↑ Prrx2/MIR22HG/miR-128/YAP1 YAP1 - [ 59 ] MiR-3064-5p - ↑ MEG3-miR-3064-5p-NR4A3-PINK1/Parkin NR4A3 - [ 60 ] MiR-19b-3p - ↑ MiR-19b-3p/EBF2 EBF2 The knocking down of miR-19b-3p [ 61 ] MiR-210-3p - ↑ MiR-210-3p/KRAS/MAPK KRAS - [ 62 ] MiR-182-5p - ↑ HAGLR/miR-182-5p/Hoxa10 Hoxa10 - [ 63 ] MiR-506-3p - ↑ FGD5 antisense RNA 1/ miR-506-3p/BMP7 BMP7 - [ 64 ] MiR-133a-3p - ↑ SP1/miR-133a-3p/MAPK3 MAPK3 - [ 65 ] MiR-214 - ↑ lncTIMP3/miR-214/Smad4 Smad4 - [ 66 ] MiR-133a - ↑ miR-133a-FGFR1-MAPK/ERK FGFR1 Infusion of the antagomiR-133a specifically targeted towards BMSC into the femur medulla MiR-23b - ↑ TNF-α/miR-23b/Runx2 Runx2 - [ 68 ] MiR-483-5p - ↑ MiR-483-5p-MAPK1/Smad5 MAPK1/Smad5 The employment of FAM-BMSC-aptamer-nanoparticles-enriched antagomiR-483-5p [ 69 ] MiR-124-3p - ↑ CircRNA_0001052-miR-124-3p-Wnt4/β-catenin - - [ 70 ] MiR-25–3p - ↑ MiR-25–3p/ITGB3 - - [ 71 ] MiR-217-5p - ↑ MEG3/miR-217-5p/Notch - - [ 72 ] MiR-26b - ↓ MiR-26b-GSK3β-Wnt/β-catenin GSK3β - [ 73 ] MiR-877-5p - ↓ MiR-877-5p/EIF4G2 EIF4G2 - [ 74 ] MiR-218-5p OVX ↓ MiR-218-5p/SOCS3 SOCS3 The elevation of miR-218-5p [ 75 ] MiR-34a-5p - ↓ MiR-34a-5p/HDAC1/ER-α HDAC1 The utilization of plentiful agomiR-34a-5p in elderly mice [ 76 ] MiR-512-3p - ↓ CircCOX6A1/miR-512-3p/DYRK2 DYRK2 - [ 77 ] MiR-27a-3p - ↓ TNF-α/miR-27a-3p/Sfrp1/Wnt3a–β-catenin Sfrp1 - [ 78 ] MiR-486–3p - ↓ MiR-486–3p-CTNNBIP1-Wnt/β-catenin CTNNBIP1 - [ 79 ] MiR-124-3p - ↓ MiR-124-3p/GSK-3β/β-catenin GSK-3β - [ 80 ] Discussion OP is a generalized bone-involved disease, and presents as the multitudinous impairment of microstructure and amplified osteopsathyrosis symptom [ 87 , 88 ]. We have realized that miRNAs can effectively act on the differentiation process of BMSCs that finally regulate the OP appearance. We clearly recognized the expression levels of miRNAs from BMSCs and their change characteristics between normal subjects and OP cases, which suggested that miRNAs exerted prominent roles in OP. They mainly draw upon the Wnt/β-catenin, MAPK, and Notch pathways to perform signal delivery, mediating the osteogenesis, adipogenesis, the balance of these two kinds of differentiated conversion, the proliferation, migration, apoptosis, stemness, and senescence of BMSCs, and biological ongoing of chondrocytes and osteoclasts. The existence of β-catenin occupies the most core status that acts as a twofold regulator in sustaining the regeneration property of BMSCs and tempting cellular conversion [ 45 ]. The MAPK- and Notch-mediated pathways are tightly tied to the osteogenic power. Considering that the function and efficacy of numerous miRNAs have not still been described, the survey and study of likely and available miRNA targets aiming at OP disorders will dramatically increase in the following years. The review evidently facilitates the research progress of miRNAs in the adjustment and control of OP and deepens the role exploration of miRNAs in OP. Besides, we noticed that previous reports mostly lacked the segment of miRNA checking. So, functional research of miRNA, more precise miRNA expression patterns, and essential verification steps are eagerly needed to become the following key study points. Meanwhile, to strengthen the applicability and availability of investigation outcomes, substantial clinical and animal studies need to be conducted to offer new threads for the practical usage of miRNAs as examination indicators [ 89 ]. However, clinical researches are usually subjected to low sample quantity, unique individuals, incongruent BMSC isolation approaches, diversified case parameter variables, and discrepancies in the methodology of miRNA analysis in trials [ 90 ]. Thus, if we would like to seek more effective and perfect biomarkers, we need to overcome the above difficulties, which can make a breakthrough in finding novel therapy ways and contribute to biomarker-featured personalized guidance treatment [ 91 ]. All in all, biomarker prediction offers us diagnosis parameters, monitor significance, specific treatment that is better than standardized therapy by employing related agents, and emerging prognosis value [ 92 ]. The growth of chemical engineering in probing the progression of genic molecules allows us to exert the research of molecules with high-throughput RNA-seq technology [ 94 ]. This technology provides multi-miRNA expression patterns and profiles, which advances the discerning, tracing, and analysis of the function of BMSCs and biomarker exploration [ 18 ]. This compensates for unknown mechanisms of OP occurrence [ 95 ]. Current locations are attributed to little cases and datasets, and the lack of unified analysis norms. BMSCs can be used as regenerative therapy in injury-based diseases on account of self-renewal activity, multiaspect-oriented differentiation, ignorable immunogenicity, homing effectiveness, as well as exact divergence tendency and appearance in traumatic sections [ 96 – 99 ]. We underlined the outlook of employing adenovirus-loaded miRNA, and miRNA stimulators and antagonists for the treatment of OP. Additionally, having knowledge of the origin of miRNA emergence also provides direction and guidance to oppose OP. For example, the shRNA treatment of SP1 as the upstream combining aim of miR-133a-3p energetically ameliorated the age-based OP deterioration [ 65 ]. Surprisingly, miRNA-based treatment can be adopted to cure other diseases, such as TNF-α-induced let-7a in OP incommoded the Fas/FasL delivery, subsequently hobbling apoptotic emergence of T-cell, which manifested the downgraded immunologic suppression ability, in turn, the supply of the OP-based BMSCs with the let-7a downregulation made experimental colitis and GVHD get improved [ 93 ]. The distinctively existing target genes that miRNA aims at likely will yield novel and valuable insight for treating OP disease [ 100 ]. Simultaneously, we observed that the concurrent impulse and mutual feedback of a cluster of miRNAs may set off the explosive efficiency compared with a single miRNA, which is attributed to the intensive regulation of a specific gene that is targeted by several miRNAs [ 90 ], which guides our subsequent study direction. Conclusion This paper pointed out the different patterns of miRNAs and the effect of miRNAs on the biological course of BMSCs, insinuated the probability of miRNAs as the screening tools, confirmation guidance, treatment means, and prediction indicator of OP, paved the emerging road for clinical practice, and pushed the development of personalized remedy that breaks through regular remedies. Declarations Ethics approval and consent to participate Not applicable Consent for publication Not applicable Data availability All data generated or analyzed data in the study are included in this article. Competing interests The authors declare that they have no competing interests. Funding This work was supported by Key funded project for scientific research in higher education institutions in Hainan Province: The role and mechanism of chondrocyte exosomes regulating the Gremlin-1/MAPK pathway to induce phenotypic changes in subchondral bone progenitor cells. (NO. Hnky2024ZD-9) and Hainan Provincial Natural Science Foundation High level Talent Project:Mechanism study of TAF15 regulating chondrocyte apoptosis in anterior cruciate ligament injury induced PTOA through NF - κ B signaling pathway(NO. 824RC547). Authors' contributions Shunli Zhang and Yongxiong He Completed the study concept, manuscript drafting and study design, Rong Chen and Yuntao Gu completed the literature study and clinical studies, Chunzhao Xu completed the data acquisition Xiuqiong Du completed the data analysis, Guangji Wang completed the statistical analysis and Xiufan Du completed the manuscript review.All authors reviewed the manuscript. Acknowledgements Not applicable References Wu J, Niu L, Yang K, Xu J, Zhang D, Ling J, et al. The role and mechanism of rna-binding proteins in bone metabolism and osteoporosis. Ageing Res Rev. 2024;96:102234. Zhang B, Zhou Z, Zhang Y, Miu Y, Jin C, Ding W, et al. A sugary solution: harnessing polysaccharide-based materials for osteoporosis treatment. Carbohydr Polym. 2024;345:122549. Luo Y, Liu H, Chen M, Zhang Y, Zheng W, Wu L, et al. Immunomodulatory nanomedicine for osteoporosis: current practices and emerging prospects. Acta Biomater. 2024;179:13–35. Hu X, Wang Z, Wang W, Cui P, Kong C, Chen X, et al. Irisin as an agent for protecting against osteoporosis: a review of the current mechanisms and pathways. J Adv Res. 2024;62:175–86. Ma S, Xing X, Huang H, Gao X, Xu X, Yang J, et al. Skeletal muscle-derived extracellular vesicles transport glycolytic enzymes to mediate muscle-to-bone crosstalk. Cell Metab. 2023;35(11):2028–43. Yao Y, Cai X, Chen Y, Zhang M, Zheng C. Estrogen deficiency-mediated osteoimmunity in postmenopausal osteoporosis. Med Res Rev. 2024. Huo S, Tang X, Chen W, Gan D, Guo H, Yao Q, et al. Epigenetic regulations of cellular senescence in osteoporosis. Ageing Res Rev. 2024;99:102235. Wanionok NE, Morel GR, Fernandez JM. Osteoporosis and alzheimer s disease (or alzheimer s disease and osteoporosis). Ageing Res Rev. 2024;99:102408. Ali M, Kim YS. A comprehensive review and advanced biomolecule-based therapies for osteoporosis. J Adv Res. 2024. Chen Y, Huang Y, Li J, Jiao T, Yang L. Enhancing osteoporosis treatment with engineered mesenchymal stem cell-derived extracellular vesicles: mechanisms and advances. Cell Death Dis. 2024;15(2):119. Osteoporosis prevention. diagnosis, and therapy. JAMA. 2001;285(6):785–95. Wang ZX, Luo ZW, Li FX, Cao J, Rao SS, Liu YW, et al. Aged bone matrix-derived extracellular vesicles as a messenger for calcification paradox. Nat Commun. 2022;13(1):1453. Liu X, Chen C, Jiang Y, Wan M, Jiao B, Liao X, et al. Brain-derived extracellular vesicles promote bone-fat imbalance in alzheimer's disease. Int J Biol Sci. 2023;19(8):2409–27. Fleischhacker V, Milosic F, Bricelj M, Kuhrer K, Wahl-Figlash K, Heimel P, et al. Aged-vascular niche hinders osteogenesis of mesenchymal stem cells through paracrine repression of wnt-axis. Aging Cell. 2024;23(6):e14139. Yates LA, Norbury CJ, Gilbert RJ. The long and short of microrna. Cell. 2013;153(3):516–9. Pritchard CC, Cheng HH, Tewari M. Microrna profiling: approaches and considerations. Nat Rev Genet. 2012;13(5):358–69. Sun K, Lai EC. Adult-specific functions of animal micrornas. Nat Rev Genet. 2013;14(8):535–48. Luo XJ, Zhao Q, Liu J, Zheng JB, Qiu MZ, Ju HQ, et al. Novel genetic and epigenetic biomarkers of prognostic and predictive significance in stage ii/iii colorectal cancer. Mol Ther. 2021;29(2):587–96. Bartel DP. Micrornas: target recognition and regulatory functions. Cell. 2009;136(2):215–33. Gebert L, Macrae IJ. Regulation of microrna function in animals. Nat Rev Mol Cell Biol. 2019;20(1):21–37. Valenti MT, Deiana M, Cheri S, Dotta M, Zamboni F, Gabbiani D et al. Physical exercise modulates mir-21-5p, mir-129-5p, mir-378-5p, and mir-188-5p expression in progenitor cells promoting osteogenesis. Cells. 2019;8(7). Xu T, Zhou P, Li H, Ding Q, Hua F. Microrna-577 aggravates bone loss and bone remodeling by targeting thyroid stimulating hormone receptor in hyperthyroid-associated osteoporosis. Environ Toxicol. 2022;37(3):539–48. Meder B, Backes C, Haas J, Leidinger P, Stahler C, Grossmann T, et al. Influence of the confounding factors age and sex on microrna profiles from peripheral blood. Clin Chem. 2014;60(9):1200–8. Ajit SK. Circulating micrornas as biomarkers, therapeutic targets, and signaling molecules. Sens (Basel). 2012;12(3):3359–69. An JH, Ohn JH, Song JA, Yang JY, Park H, Choi HJ, et al. Changes of microrna profile and microrna-mrna regulatory network in bones of ovariectomized mice. J Bone Min Res. 2014;29(3):644–56. Inose H, Ochi H, Kimura A, Fujita K, Xu R, Sato S, et al. A microrna regulatory mechanism of osteoblast differentiation. Proc Natl Acad Sci U S A. 2009;106(49):20794–9. Huang J, Zhao L, Xing L, Chen D. Microrna-204 regulates runx2 protein expression and mesenchymal progenitor cell differentiation. Stem Cells. 2010;28(2):357–64. Li H, Xie H, Liu W, Hu R, Huang B, Tan YF, et al. A novel microrna targeting hdac5 regulates osteoblast differentiation in mice and contributes to primary osteoporosis in humans. J Clin Invest. 2009;119(12):3666–77. Kim KM, Park SJ, Jung SH, Kim EJ, Jogeswar G, Ajita J, et al. Mir-182 is a negative regulator of osteoblast proliferation, differentiation, and skeletogenesis through targeting foxo1. J Bone Min Res. 2012;27(8):1669–79. Chen T, Wang C, Yu H, Ding M, Zhang C, Lu X, et al. Increased urinary exosomal micrornas in children with idiopathic nephrotic syndrome. EBioMedicine. 2019;39:552–61. Liu CJ, Xie GY, Miao YR, Xia M, Wang Y, Lei Q, et al. Evatlas: a comprehensive database for ncrna expression in human extracellular vesicles. Nucleic Acids Res. 2022;50(D1):D111–7. Li D, Yuan Q, Xiong L, Li A, Xia Y. The mir-4739/dlx3 axis modulates bone marrow-derived mesenchymal stem cell (bmsc) osteogenesis affecting osteoporosis progression. Front Endocrinol (Lausanne). 2021;12:703167. Zhou B, Peng K, Wang G, Chen W, Liu P, Chen F, et al. Mir–483–3p promotes the osteogenesis of human osteoblasts by targeting dikkopf 2 (dkk2) and the wnt signaling pathway. Int J Mol Med. 2020;46(4):1571–81. Li CJ, Cheng P, Liang MK, Chen YS, Lu Q, Wang JY, et al. Microrna-188 regulates age-related switch between osteoblast and adipocyte differentiation. J Clin Invest. 2015;125(4):1509–22. Li M, Cong R, Yang L, Yang L, Zhang Y, Fu Q. A novel lncrna lnc_000052 leads to the dysfunction of osteoporotic bmscs via the mir-96-5p-pik3r1 axis. Cell Death Dis. 2020;11(9):795. Meng M, Wang J, Wang C, Zhao J, Wang H, Zhang Y, et al. Coenzyme q10 protects against hyperlipidemia-induced osteoporosis by improving mitochondrial function via modulating mir-130b-3p/pgc-1alpha pathway. Calcif Tissue Int. 2024;114(2):182–99. Liu H, Yi X, Tu S, Cheng C, Luo J. Kaempferol promotes bmsc osteogenic differentiation and improves osteoporosis by downregulating mir-10a-3p and upregulating cxcl12. Mol Cell Endocrinol. 2021;520:111074. Wang X, Chen T, Deng Z, Gao W, Liang T, Qiu X, et al. Melatonin promotes bone marrow mesenchymal stem cell osteogenic differentiation and prevents osteoporosis development through modulating circ_0003865 that sponges mir-3653-3p. Stem Cell Res Ther. 2021;12(1):150. Chen H, Shi Y, Zhu Y, Zheng Z, Xuzhou H, Wang Q. Effect of bone marrow stromal cells derived mir-26b on chondrocytes of osteoporosis rats. Ann Clin Lab Sci. 2024;54(4):466–73. He P, Yang Z, Li H, Zhou E, Hou Z, Sang H. Mir-18a-5p promotes osteogenic differentiation of bmsc by inhibiting notch2. Bone. 2024;188:117224. Hu Z, Zhang L, Wang H, Wang Y, Tan Y, Dang L, et al. Targeted silencing of mirna-132-3p expression rescues disuse osteopenia by promoting mesenchymal stem cell osteogenic differentiation and osteogenesis in mice. Stem Cell Res Ther. 2020;11(1):58. Wang X, Zhao D, Zhu Y, Dong Y, Liu Y. Long non-coding rna gas5 promotes osteogenic differentiation of bone marrow mesenchymal stem cells by regulating the mir-135a-5p/foxo1 pathway. Mol Cell Endocrinol. 2019;496:110534. Teng JW, Bian SS, Kong P, Chen YG. Icariin triggers osteogenic differentiation of bone marrow stem cells by up-regulating mir-335-5p. Exp Cell Res. 2022;414(2):113085. Yang X, Yang J, Lei P, Wen T. Lncrna malat1 shuttled by bone marrow-derived mesenchymal stem cells-secreted exosomes alleviates osteoporosis through mediating microrna-34c/satb2 axis. Aging. 2019;11(20):8777–91. Jiang N, Jiang J, Wang Q, Hao J, Yang R, Tian X, et al. Strategic targeting of mir-183 and beta-catenin to enhance bmsc stemness in age-related osteoporosis therapy. Sci Rep. 2024;14(1):21489. Li Y, Yang F, Gao M, Gong R, Jin M, Liu T, et al. Mir-149-3p regulates the switch between adipogenic and osteogenic differentiation of bmscs by targeting fto. Mol Ther Nucleic Acids. 2019;17:590–600. Huang J, Zhao L, Xing L, Chen D. Microrna-204 regulates runx2 protein expression and mesenchymal progenitor cell differentiation. Stem Cells. 2010;28(2):357–64. Wang R, Zhang M, Hu Y, He J, Lin Q, Peng N. Mir-100-5p inhibits osteogenic differentiation of human bone mesenchymal stromal cells by targeting tmem135. Hum Cell. 2022;35(6):1671–83. Eisa NH, Sudharsan PT, Herrero SM, Herberg SA, Volkman BF, Aguilar-Perez A, et al. Age-associated changes in micrornas affect the differentiation potential of human mesenchymal stem cells: novel role of mir-29b-1-5p expression. Bone. 2021;153:116154. Wu M, Dai M, Liu X, Zeng Q, Lu Y. Lncrna serpinb9p1 regulates sirt6 mediated osteogenic differentiation of bmscs via mir-545-3p. Calcif Tissue Int. 2023;112(1):92–102. Lin Z, He H, Wang M, Liang J. Microrna-130a controls bone marrow mesenchymal stem cell differentiation towards the osteoblastic and adipogenic fate. Cell Prolif. 2019;52(6):e12688. Xu L, Fu Y, Zhu W, Xu R, Zhang J, Zhang P, et al. Microrna-31 inhibition partially ameliorates the deficiency of bone marrow stromal cells from cleidocranial dysplasia. J Cell Biochem. 2019;120(6):9472–86. Huang Y, Hou Q, Su H, Chen D, Luo Y, Jiang T. Mir–488 negatively regulates osteogenic differentiation of bone marrow mesenchymal stem cells induced by psoralen by targeting runx2. Mol Med Rep. 2019;20(4):3746–54. Zhang J, Xu N, Yu C, Miao K, Wang Q. Lncrna part1/mir-185-5p/runx3 feedback loop modulates osteogenic differentiation of bone marrow mesenchymal stem cells. Autoimmunity. 2021;54(7):422–9. Liu YQ, Xu YC, Shuai ZW. Mir-142-3p regulates mapk protein family by inhibiting 14-3-3eta to enhance bone marrow mesenchymal stem cells osteogenesis. Sci Rep. 2023;13(1):22862. Wu J, Li X, Nie H, Shen Y, Guo Z, Huihan CC, et al. Phytic acid promotes high glucose-mediated bone marrow mesenchymal stem cells osteogenesis via modulating circeif4b that sponges mir-186-5p and complexes with igf2bp3. Biochem Pharmacol. 2024;222:116118. Lu Y, Liu YK, Wan FY, Shi S, Tao R. Circsmg5 stimulates the osteogenic differentiation of bone marrow mesenchymal stem cells by targeting the mir-194-5p/fzd6 axis and beta-catenin signaling. Environ Toxicol. 2022;37(3):593–602. Xiang J, Fu HQ, Xu Z, Fan WJ, Liu F, Chen B. Lncrna snhg1 attenuates osteogenic differentiation via the mir–101/dkk1 axis in bone marrow mesenchymal stem cells. Mol Med Rep. 2020;22(5):3715–22. Li Y, Wang X, Pan C, Yuan H, Li X, Chen Z, et al. Myoblast-derived exosomal prrx2 attenuates osteoporosis via transcriptional regulation of lncrna-mir22hg to activate hippo pathway. Mol Med. 2023;29(1):54. Xu C, Wang Z, Liu YJ, Duan K, Guan J. Harnessing gmnp-loaded bmsc-derived evs to target mir-3064-5p via meg3 overexpression: implications for diabetic osteoporosis therapy in rats. Cell Signal. 2024;118:111055. Liu D, Lin Z, Huang Y, Qiu M. Role of microrna-19b-3p on osteoporosis after experimental spinal cord injury in rats. Arch Biochem Biophys. 2022;719:109134. Hu M, Zhu X, Yuan H, Li H, Liao H, Chen S. The function and mechanism of the mir-210-3p/kras axis in bone marrow-derived mesenchymal stem cell from patients with osteoporosis. J Tissue Eng Regen Med. 2021;15(8):699–711. Huang Y, Tao M, Yan S, He X. Long non-coding rna homeobox d gene cluster antisense growth-associated long noncoding rna/microrna-182-5p/homeobox protein a10 alleviates postmenopausal osteoporosis via accelerating osteoblast differentiation of bone marrow mesenchymal stem cells. J Orthop Surg Res. 2023;18(1):726. Li J, Wu X, Shi Y, Zhao H. Fgd5-as1 facilitates the osteogenic differentiation of human bone marrow-derived mesenchymal stem cells via targeting the mir-506-3p/bmp7 axis. J Orthop Surg Res. 2021;16(1):665. Zhong L, Sun Y, Wang C, Liu R, Ru W, Dai W, et al. Sp1 regulates bmsc osteogenic differentiation through the mir-133a-3p/mapk3 axis: sp1 regulates osteogenic differentiation of bmscs. J Orthop Surg Res. 2024;19(1):396. Wumiti T, Wang L, Xu B, Ma Y, Zhu Y, Zuo X, et al. Lnctimp3 promotes osteogenic differentiation of bone marrow mesenchymal stem cells via mir-214/smad4 axis to relieve postmenopausal osteoporosis. Mol Biol Rep. 2024;51(1):719. Wang G, Wan L, Zhang L, Yan C, Zhang Y. Microrna-133a regulates the viability and differentiation fate of bone marrow mesenchymal stem cells via mapk/erk signaling pathway by targeting fgfr1. DNA Cell Biol. 2021;40(8):1112–23. Deng L, Hu G, Jin L, Wang C, Niu H. Involvement of microrna-23b in tnf-alpha-reduced bmsc osteogenic differentiation via targeting runx2. J Bone Min Metab. 2018;36(6):648–60. Zhou Y, Jia H, Hu A, Liu R, Zeng X, Wang H. Nanoparticles targeting delivery antagomir-483-5p to bone marrow mesenchymal stem cells treat osteoporosis by increasing bone formation. Curr Stem Cell Res Ther. 2023;18(1):115–26. Liu N, Lu W, Qu X, Zhu C. Llli promotes bmsc proliferation through circrna_0001052/mir-124-3p. Lasers Med Sci. 2022;37(2):849–56. Yu D, Li Z, Cao J, Shen F, Wei G. Microrna-25-3p suppresses osteogenic differentiation of bmscs in patients with osteoporosis by targeting itgb3. Acta Histochem. 2022;124(6):151926. Liu N, Cao L, Peng L, Lu W, Dai X, Wang S, et al. Photobiomodulation (800 nm light-emitting diode) treatment promotes bone mesenchymal stem cell proliferation via long noncoding rna meg3-microrna-217-5p pathway. Photobiomodul Photomed Laser Surg. 2023;41(1):10–6. Hu H, Zhao C, Zhang P, Liu Y, Jiang Y, Wu E, et al. Mir-26b modulates oa induced bmsc osteogenesis through regulating gsk3beta/beta-catenin pathway. Exp Mol Pathol. 2019;107:158–64. Shen Y, Zhang Y, Wang Q, Jiang B, Jiang X, Luo B. Microrna-877-5p promotes osteoblast differentiation by targeting eif4g2 expression. J Orthop Surg Res. 2024;19(1):134. Zhou Q, Zhou L, Li J. Mir-218-5p-dependent socs3 downregulation increases osteoblast differentiation inpostmenopausal osteoporosis. J Orthop Surg Res. 2023;18(1):109. Sun D, Chen Y, Liu X, Huang G, Cheng G, Yu C, et al. Mir-34a-5p facilitates osteogenic differentiation of bone marrow mesenchymal stem cells and modulates bone metabolism by targeting hdac1 and promoting er-alpha transcription. Connect Tissue Res. 2023;64(2):126–38. He D, Zheng S, Cao J, Deng J, Ding R, Xu Y, et al. Circcox6a1 suppresses osteogenic differentiation and aggravates osteoporosis via mir-512-3p/dyrk2 axis. Mol Biol Rep. 2024;51(1):636. Zhang DF, Jin XN, Ma X, Qiu YS, Ma W, Dai X, et al. Tumour necrosis factor alpha regulates the mir-27a-3p-sfrp1 axis in a mouse model of osteoporosis. Exp Physiol. 2024;109(7):1109–23. Zhang Z, Jiang W, Hu M, Gao R, Zhou X. Mir-486-3p promotes osteogenic differentiation of bmsc by targeting ctnnbip1 and activating the wnt/beta-catenin pathway. Biochem Biophys Res Commun. 2021;566:59–66. Li Z, Zhao H, Chu S, Liu X, Qu X, Li J, et al. Mir-124-3p promotes bmsc osteogenesis via suppressing the gsk-3beta/beta-catenin signaling pathway in diabetic osteoporosis rats. Vitro Cell Dev Biol Anim. 2020;56(9):723–34. Zhang Y, Cao X, Li P, Fan Y, Zhang L, Ma X, et al. Microrna-935-modified bone marrow mesenchymal stem cells-derived exosomes enhance osteoblast proliferation and differentiation in osteoporotic rats. Life Sci. 2021;272:119204. Xu C, Wang Z, Liu Y, Wei B, Liu X, Duan K, et al. Extracellular vesicles derived from bone marrow mesenchymal stem cells loaded on magnetic nanoparticles delay the progression of diabetic osteoporosis via delivery of mir-150-5p. Cell Biol Toxicol. 2023;39(4):1257–74. Xu C, Wang Z, Liu Y, Duan K, Guan J. Delivery of mir-15b-5p via magnetic nanoparticle-enhanced bone marrow mesenchymal stem cell-derived extracellular vesicles mitigates diabetic osteoporosis by targeting gfap. Cell Biol Toxicol. 2024;40(1):52. Duan J, Li H, Wang C, Yao J, Jin Y, Zhao J, et al. Bmsc-derived extracellular vesicles promoted osteogenesis via axin2 inhibition by delivering mir-16-5p. Int Immunopharmacol. 2023;120:110319. Lu GD, Cheng P, Liu T, Wang Z. Bmsc-derived exosomal mir-29a promotes angiogenesis and osteogenesis. Front Cell Dev Biol. 2020;8:608521. Xu Y, Xin R, Sun H, Long D, Li Z, Liao H, et al. Long non-coding rnas loc100126784 and pom121l9p derived from bone marrow mesenchymal stem cells enhance osteogenic differentiation via the mir-503-5p/sorbs1 axis. Front Cell Dev Biol. 2021;9:723759. Ensrud KE, Crandall CJ, Osteoporosis. Ann Intern Med. 2024;177(1):C1–16. Zhang YW, Song PR, Wang SC, Liu H, Shi ZM, Su JC. Diets intervene osteoporosis via gut-bone axis. Gut Microbes. 2024;16(1):2295432. Wang H, Jin J, Wu J, Qu H, Wu S, Bao W. Transcriptome and chromatin accessibility in porcine intestinal epithelial cells upon zearalenone exposure. Sci Data. 2019;6(1):298. Bang JH, Kim EH, Kim HJ, Chung JW, Seo WK, Kim GM et al. Machine learning-based etiologic subtyping of ischemic stroke using circulating exosomal micrornas. Int J Mol Sci. 2024;25(12). Kalia M. Biomarkers for personalized oncology: recent advances and future challenges. Metabolism. 2015;64(3 Suppl 1):S16–21. Li W, Liu JB, Hou LK, Yu F, Zhang J, Wu W, et al. Liquid biopsy in lung cancer: significance in diagnostics, prediction, and treatment monitoring. Mol Cancer. 2022;21(1):25. Liao L, Yu Y, Shao B, Su X, Wang H, Kuang H, et al. Redundant let-7a suppresses the immunomodulatory properties of bmscs by inhibiting the fas/fasl system in osteoporosis. FASEB J. 2018;32(4):1982–92. Naesens M, Sarwal MM. Molecular diagnostics in transplantation. Nat Rev Nephrol. 2010;6(10):614–28. Kato M, Natarajan R. Diabetic nephropathy–emerging epigenetic mechanisms. Nat Rev Nephrol. 2014;10(9):517–30. Mao Q, Liang XL, Wu YF, Pang YH, Zhao XJ, Lu YX. Ilk promotes survival and self-renewal of hypoxic mscs via the activation of lnctcf7-wnt pathway induced by il-6/stat3 signaling. Gene Ther. 2019;26(5):165–76. Liu D, Kou X, Chen C, Liu S, Liu Y, Yu W, et al. Circulating apoptotic bodies maintain mesenchymal stem cell homeostasis and ameliorate osteopenia via transferring multiple cellular factors. Cell Res. 2018;28(9):918–33. Zhang L, Li Q, Liu Z, Wang Y, Zhao M. The protective effects of bone mesenchymal stem cells on paraquat-induced acute lung injury via the muc5b and erk/mapk signaling pathways. Am J Transl Res. 2019;11(6):3707–21. Chen Q, Zhang Y, Zhu H, Yuan X, Luo X, Wu X, et al. Bone marrow mesenchymal stem cells alleviate the daunorubicin-induced subacute myocardial injury in rats through inhibiting infiltration of t lymphocytes and antigen-presenting cells. Biomed Pharmacother. 2020;121:109157. Tsai MJ, Chang WA, Liao SH, Chang KF, Sheu CC, Kuo PL. The effects of epigallocatechin gallate (egcg) on pulmonary fibroblasts of idiopathic pulmonary fibrosis (ipf)-a next-generation sequencing and bioinformatic approach. Int J Mol Sci. 2019;20(8). Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5258994","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":370426037,"identity":"bf4856cc-d207-4f75-85cc-6a060794d394","order_by":0,"name":"Shunli Zhang","email":"","orcid":"","institution":"The Second Affiliated Hospital of Hainan Medical University","correspondingAuthor":false,"prefix":"","firstName":"Shunli","middleName":"","lastName":"Zhang","suffix":""},{"id":370426038,"identity":"62a4a268-01ce-4d38-81ab-1b2182730d57","order_by":1,"name":"Yongxiong He","email":"","orcid":"","institution":"The Second Affiliated Hospital of Hainan Medical University","correspondingAuthor":false,"prefix":"","firstName":"Yongxiong","middleName":"","lastName":"He","suffix":""},{"id":370426039,"identity":"33ce67da-34eb-42d9-9bcf-79fca58c4139","order_by":2,"name":"Rong Chen","email":"","orcid":"","institution":"The Second Affiliated Hospital of Hainan Medical University","correspondingAuthor":false,"prefix":"","firstName":"Rong","middleName":"","lastName":"Chen","suffix":""},{"id":370426040,"identity":"f10d8ff4-447a-42ad-bcd0-6b2faf0070f9","order_by":3,"name":"Yuntao Gu","email":"","orcid":"","institution":"The Second Affiliated Hospital of Hainan Medical University","correspondingAuthor":false,"prefix":"","firstName":"Yuntao","middleName":"","lastName":"Gu","suffix":""},{"id":370426041,"identity":"5abdf19d-0a5d-4bba-a66b-3709a606086f","order_by":4,"name":"Chunzhao Xu","email":"","orcid":"","institution":"The Second Affiliated Hospital of Hainan Medical University","correspondingAuthor":false,"prefix":"","firstName":"Chunzhao","middleName":"","lastName":"Xu","suffix":""},{"id":370426042,"identity":"03470c86-b259-44f2-a714-fd8bfa77a6ea","order_by":5,"name":"Xiuqiong Du","email":"","orcid":"","institution":"Danzhou People's Hospital","correspondingAuthor":false,"prefix":"","firstName":"Xiuqiong","middleName":"","lastName":"Du","suffix":""},{"id":370426043,"identity":"3f4777ba-1f96-4d14-8c3d-000f7e526054","order_by":6,"name":"Guangji Wang","email":"","orcid":"","institution":"Hainan General Hospital (Hainan Affiliated Hospital of Hainan Medical University)","correspondingAuthor":false,"prefix":"","firstName":"Guangji","middleName":"","lastName":"Wang","suffix":""},{"id":370426044,"identity":"46f5177f-3e6c-4be2-9fa2-edfb224be2e7","order_by":7,"name":"Xiufan Du","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA7UlEQVRIie3PMUvDQBjG8TccJMtJ1nO5byC84YXiEOhXuRchk0jFxfGkcFkKrv0YgX6BK4d1CXTN4ODkHHApWKruShI3h/vNz394AKLoX0osHe9POhfCY4+lnpAIu5Ctp/Pamdv1oqIJSWb7M+e5aVt8l33g0eDicfvQqPSFoDPFpkRhIAtPzVAy63iJKN90sjZXdI3pDciq6oaTxKFRgoQyu+9E3oGSs+Fkv60PHgU7xfXHJSq2o4lnW1gTeCUDECBOSDq2BL4ilTkoVmgoHf2yf36l5FTqech7PBw/dZ6F3WDyU/q3eRRFUfSbLxkbUMH6OxJoAAAAAElFTkSuQmCC","orcid":"","institution":"Hainan General Hospital (Hainan Affiliated Hospital of Hainan Medical University)","correspondingAuthor":true,"prefix":"","firstName":"Xiufan","middleName":"","lastName":"Du","suffix":""}],"badges":[],"createdAt":"2024-10-14 07:38:24","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5258994/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5258994/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":69816603,"identity":"ad88bf3c-9c12-4651-b71f-05ce0085976a","added_by":"auto","created_at":"2024-11-25 13:32:15","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":807416,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5258994/v1/0b7d2271-bd6c-4ca4-ab4b-33932ad17a16.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"MicroRNA expression profiling and potential biomarker exploration in BMSCs of osteoporosis patients based on high-throughput sequencing technology","fulltext":[{"header":"Introduction","content":"\u003cp\u003eOsteoporosis (OP) is an abnormal skeleton metabolism disorder associated with the differentiation condition, formation, adsorption, and remodeling of bone [\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. This type of disease is embodied in low-level density and inferior quality of bone [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Its occurrence principally depends on natural aging, hormonal changes, bad life habits, nutrient intake, etc [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. OP chiefly appeared in climacteric women, the aged, and teens [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Currently, the attack rate of OP is manifestly uplifted worldwide [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Its prevention needs enough calcium ingestion and adequate workouts [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eBone marrow mesenchymal stem cells (BMSCs) were earliest exposed in bone marrow in 1968. Their osteogenesis-oriented differentiation can influence bone formation and loss, and then adjust OP [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan additionalcitationids=\"CR13\" citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Thus, it is generally adopted to discern, confirm, and evaluate the ongoing of OP.\u003c/p\u003e \u003cp\u003eMiRNAs are defined as shorter (about 22 nt), single-stranded, and noncoding ribonucleic acids initially uncovered in \u003cem\u003eC. elegans\u003c/em\u003e in 1993 [\u003cspan additionalcitationids=\"CR16\" citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. They are insensitive to RNase addition and stable in many trial situations [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. They usually obstruct the expression content and translation course of their target mRNA genes [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. They are implicated in many regulatory courses, for instance, the growth, renewal, and senescence of organisms [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. MiRNA is linked to the differentiation process of BMSCs and body motion-caused remodeling of the skeleton [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Xu \u003cem\u003eet al\u003c/em\u003e have proven that the high enrichment of miR-577 avoided the osteoblasts augmentation by oppositely modulating TSHR on the basis of hyperthyroid-mediated OP [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. The ability of miRNAs to act as biomarkers is gradually testified in diverse diseases [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe majority of papers have uncovered the ability of miRNAs to adjust bone quantity [\u003cspan additionalcitationids=\"CR26 CR27 CR28\" citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThus, a widespread probe for the expression trait of miRNAs from BMSCs could contribute to seek available biomarkers and incur the consideration of their function in BMSCs [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe high-throughput RNA-seq technology offers a wonderful means and way to amply quantify miRNAs in BMSCs. Although some RNA-seq databases deeply dug into the enrichment of miRNAs by means of sequencing technology, the great majority of analyses have locations on account of minor sample collection and discordant expression norms. Currently, few databases share differentially expressed miRNAs in BMSCs, which is not enough to attract us to focus on miRNA functions for the regulation of BMSCs.\u003c/p\u003e \u003cp\u003eThe concrete mechanisms that miRNAs affect OP are presently intricate and fuzzy, herein we examined and studied the expression and difference of miRNA landscape in terms of miRNA-seq datasets of BMSCs, administered functional explanation and signaling transduction of BMSCs-encompassed miRNAs in OP formation, and unveiled the likelihood and feasibility of manifestly expressed miRNAs as underlying candidates for biomarkers, indicated the value of miRNAs as detection tools applied to clinical studies. Its adoption will be a tremendous progress compared to traditional therapy measures.\u003c/p\u003e"},{"header":"Materials and methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eData screening and summary\u003c/h2\u003e \u003cp\u003eWe utilized keywords \u0026lsquo;((BMSC) AND (miRNA)) AND (osteoporosis)\u0026rsquo; to search miRNA-seq data of BMSCs among patients subjected to OP. Finally, we gained a miRNA-seq dataset termed GSE74209.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eThe expression patterns of miRNA among patients undergoing OP\u003c/h3\u003e\n\u003cp\u003eWe have perceived the variation of miRNA in two different systems of normal individuals and participants subjected to OP. Herein, we conducted an all-around data query and sift in the PubMed and Medline databases to specify the profiles of miRNAs.\u003c/p\u003e \u003cp\u003eWe finally determined the number of upregulated and downregulated miRNAs from GSE74209. As Li \u003cem\u003eet al\u003c/em\u003e summarized, we noticed the anomalous existence of 80 miRNAs (logFC\u0026thinsp;\u0026gt;\u0026thinsp;1, p\u0026thinsp;\u0026lt;\u0026thinsp;0.05). Six samples that were from postmenopausal female cases showed that the miR-4739, miR-3202, and miR-320c were manifestly upregulated in OP, which has been substantiated by RT-PCR [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e], furthermore, Zhou \u003cem\u003eet al\u003c/em\u003e stressed the slippage of miR-483-3p level (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e), which has been deeply testified by H\u0026amp;E and Masson staining[\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e].\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eData origin of miRNAs lineage, and variation trend of miRNAs level.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDatasets\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eUpregulated miRNAs\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003edownregulated miRNAs\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGSE74209\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMiR-4739\u003c/p\u003e \u003cp\u003eMiR-3202\u003c/p\u003e \u003cp\u003eMiR-320c\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMiR-483-3p\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]\u003c/p\u003e \u003cp\u003e[\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e\n\u003ch3\u003eThe functional elaboration of miRNAs in OP\u003c/h3\u003e\n\u003cp\u003eMiRNAs have displayed the ties to the uplift and drop of osteoblasts counts. A report about the age-mediated bone disorder from Li \u003cem\u003eet al\u003c/em\u003e deemed that BMSCs-contained miR-188 upregulation turned on the switch that diminished osteoblast orientation and intensified fat gathering of BMSCs, and either histone deacetylase 9 (HDAC9) or RPTOR-independent companion of MTOR complex 2 (RICTOR) is the directly miR-188-targeted downstream gene, their protein content can be restricted by miR-188 combination [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]. Based on the rats model mimicking menopausal OP, Li \u003cem\u003eet al\u003c/em\u003e held that miR-96-5p increment explicitly accelerated cell growth, migration, osteogenic development, and curbed apoptotic occurrence via LNC_000052\u0026ndash;miR-96-5p\u0026ndash;PIK3R1 transduction pathway [\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]. CoQ10 attenuated the hyperlipidemia-generated OP \u003cem\u003ein vivo\u003c/em\u003e model through beefing up the assignment towards osteoblasts and damaging the adipocytes production relying on the miR-130b-3p/PGC-1α axes-mediated activation of mitochondrial activity [\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]. In the OVX-mediated rat model, Kaempferol manifested osteogenesis bias through acting on the miR-10a-3p/CXCL12 cascade [\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e]. \u003cem\u003eIn vitro\u003c/em\u003e induction and sequencing results of human BMSCs from Wang \u003cem\u003eet al\u003c/em\u003e demonstrated that melatonin originally curbed the circ_0003865 level, next elevated the miR-3653-3p content, and finally checked the GAS1 expression, thus improving the OP through strengthening the osteogenic advantage [\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e]. The exceeded miR-4739 gathering in OP BMSCs disturbed the osteogenic power by encumbering DLX3 content [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. Chen \u003cem\u003eet al\u003c/em\u003e accorded a piece of accurate evidence that miR-26b aimed at SIRT2 sites triggered the growth and dwindled apoptotic state of chondrocytes [\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e]. In the mice model mimicking menopausal OP, we sighted the niggling content of miR-18a-5p, and this phenomenon aggravated osteogenic deficiency through the miR-18a-5p/Notch2 delivery [\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e]. Another cellular and animal trial simulating disuse OP exposed that the enhanced miR-132-3p content could aggravate bone lack by hindering skeleton generation [\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e]. In BMSCs of the OVX-treated mice, the remarkable drop of GAS5 content checked the osteogenic role via sponging the miR-135a-5p, subsequently impairing the FOXO1 content [\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e]. Teng \u003cem\u003eet al\u003c/em\u003e testified that Icariin lessened the PTEN content via adding miR-335-5p content, subsequently soothing the OP signs [\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e]. The MALAT1 secretion from BMSCs generated the osteogenic impulse by targeting the miR-34c/SATB2 signal [\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e]. Jiang \u003cem\u003eet al\u003c/em\u003e thought that the miR-183 distinctly declined the regeneration property of BMSCs via restricting β-catenin content [\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e]. An \u003cem\u003ein vitro\u003c/em\u003e BMSCs stimulation study from Li \u003cem\u003eet al\u003c/em\u003e clarified that miR-149-3p militated the fat formation in the FTO-dependent way and irritated bone accumulation [\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e]. Huang \u003cem\u003eet al\u003c/em\u003e illustrated that the existence of miR-204 or miR-211 in BMSCs restrained the Runx2 content, then constraining osteogenic transformation and contributing to adipogenic motion [\u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e]. Wang \u003cem\u003eet al\u003c/em\u003e notified us of the uplift of miR-100-5p content in OP cases, and this crystal variation forbade the TMEM135 appearance, making OP worsen by prohibiting the osteogenic efficiency [\u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e]. In human BMSCs, Eisa \u003cem\u003eet al\u003c/em\u003e determined that Kynurenine-irritated demonstrable elevation of miR-29b-1-5p level in older participants, which triggered the descent of SDF-1, eventually deterring the bone development [\u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e49\u003c/span\u003e]. Wu \u003cem\u003eet al\u003c/em\u003e opined that the SERPINB9P1 strengthened the osteogenic force via varying the SIRT6 concentration mediated by the miR-545-3p downregulation [\u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e50\u003c/span\u003e]. Lin \u003cem\u003eet al\u003c/em\u003e implicated that miR-130a was evidently elevated in the young multitude, which expanded osteoblasts emergence via conversely controlling Smurf2 protein content and militated fat generation through binding to the PPARγ mRNA in the mice-based BMSCs [\u003cspan citationid=\"CR51\" class=\"CitationRef\"\u003e51\u003c/span\u003e]. In the cleidocranial dysplasia (CCD)-caused bone malfunction, Runx2 deficiency fortified miR-31 content, presenting the disability of growth, osteogenic role, and regeneration property, as well as the aggressive momentum of aging of BMSCs [\u003cspan citationid=\"CR52\" class=\"CitationRef\"\u003e52\u003c/span\u003e]. In the psoralen‑stimulated \u003cem\u003ein vitro\u003c/em\u003e trial, Huang \u003cem\u003eet al\u003c/em\u003e obtained the negative variation of miR‑488 in response to psoralen, which provoked osteoblasts-orientation regulation via tightly linking to the Runx2 [\u003cspan citationid=\"CR53\" class=\"CitationRef\"\u003e53\u003c/span\u003e]. Several microarray datasets verified that miR-483-3p was stupendously expressed in skeleton tissue among healthy participants, moreover, \u003cem\u003ein vitro\u003c/em\u003e osteoblast cellular treatment deeply testified the facilitation of osteoblast activity and the obstacle of apoptosis through the miR-483-3p-DKK2-Wnt/β-catenin cascade [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]. Zhang \u003cem\u003eet al\u003c/em\u003e unsealed that the CeRNA PART1 positively sharpened the Runx3 content by sponging miR-185-5p, which developed a regulatory circle, redounding the osteogenic efficiency and impeding the apoptosis of human BMSCs [\u003cspan citationid=\"CR54\" class=\"CitationRef\"\u003e54\u003c/span\u003e]. Liu \u003cem\u003eet al\u003c/em\u003e discovered that the reduction of BMSCs-encompassed miR-142-3P content increased the level of 14-3-3η and MAPK3, eventually leading to osteogenic deficit [\u003cspan citationid=\"CR55\" class=\"CitationRef\"\u003e55\u003c/span\u003e]. The signal delivery of circEIF4B/miR-186-5p/FOXO1 exerted a dominant role in profoundly modulating bone growth in phytic acid-treated skeleton development [\u003cspan citationid=\"CR56\" class=\"CitationRef\"\u003e56\u003c/span\u003e]. A chain of negative transduction of circ_0001145/miR-194-5p/Fzd6 pathways accelerated osteogenic tendency by energetically stimulating the Wnt/β-catenin delivery [\u003cspan citationid=\"CR57\" class=\"CitationRef\"\u003e57\u003c/span\u003e]. Xiang \u003cem\u003eet al\u003c/em\u003e informed us of the relative raise of SNHG1 in low-grade osteogenesis orientation, it exerted an unfavorable role for OP by acting on the miR-101/DKK1-Wnt/β-catenin regulatory ways [\u003cspan citationid=\"CR58\" class=\"CitationRef\"\u003e58\u003c/span\u003e]. Myoblast-secreted Prrx2 constrained the BMSC-existed miR-128 content by activating MIR22HG, further motivating the YAP1 content and translocation into the nucleus, finally redounding the osteogenesis [\u003cspan citationid=\"CR59\" class=\"CitationRef\"\u003e59\u003c/span\u003e]. In a study based on \u003cem\u003ein vivo\u003c/em\u003e diabetic OP (DO) and \u003cem\u003ein vitro\u003c/em\u003e models, the BMSC-released EVs with MEG3 load could emphatically stir up NR4A3 enhancement by sponging the miR-3064-5p combination site, and then caused the amplification of PINK1/Parkin cascade, arising the osteoblasts augmentation and osteogenic superiority [\u003cspan citationid=\"CR60\" class=\"CitationRef\"\u003e60\u003c/span\u003e]. The upregulated content of BMSCs-encompassed miRNA-19b-3p weakened the osteoblasts-dominant orientation through oppositely modulating the EBF2 level [\u003cspan citationid=\"CR61\" class=\"CitationRef\"\u003e61\u003c/span\u003e]. In this several regulatory axes, like miR-210-3p/KRAS/MAPK [\u003cspan citationid=\"CR62\" class=\"CitationRef\"\u003e62\u003c/span\u003e], HAGLR/miR-182-5p/Hoxa10 [\u003cspan citationid=\"CR63\" class=\"CitationRef\"\u003e63\u003c/span\u003e], FGD5 antisense RNA 1/miR-506-3p/BMP7 [\u003cspan citationid=\"CR64\" class=\"CitationRef\"\u003e64\u003c/span\u003e], SP1/miR-133a-3p/MAPK3 [\u003cspan citationid=\"CR65\" class=\"CitationRef\"\u003e65\u003c/span\u003e], lncTIMP3/miR-214/Smad4 [\u003cspan citationid=\"CR66\" class=\"CitationRef\"\u003e66\u003c/span\u003e], miR-133a-FGFR1-MAPK/ERK [\u003cspan citationid=\"CR67\" class=\"CitationRef\"\u003e67\u003c/span\u003e], TNF-α/miR-23b/Runx2 [\u003cspan citationid=\"CR68\" class=\"CitationRef\"\u003e68\u003c/span\u003e], miR-483-5p-MAPK1/Smad5 [\u003cspan citationid=\"CR69\" class=\"CitationRef\"\u003e69\u003c/span\u003e], circRNA_0001052-miR-124-3p-Wnt4/β-catenin [\u003cspan citationid=\"CR70\" class=\"CitationRef\"\u003e70\u003c/span\u003e], miR-25\u0026ndash;3p/ITGB3 [\u003cspan citationid=\"CR71\" class=\"CitationRef\"\u003e71\u003c/span\u003e], MEG3/miR-217-5p/Notch [\u003cspan citationid=\"CR72\" class=\"CitationRef\"\u003e72\u003c/span\u003e], wherein the abundant miRNAs were involved in the osteogenic deprivation. Whereas, other transduction delivery, such as miR-26b-GSK3β-Wnt/β-catenin [\u003cspan citationid=\"CR73\" class=\"CitationRef\"\u003e73\u003c/span\u003e], miR-877-5p/EIF4G2 [\u003cspan citationid=\"CR74\" class=\"CitationRef\"\u003e74\u003c/span\u003e], miR-218-5p/SOCS3 [\u003cspan citationid=\"CR75\" class=\"CitationRef\"\u003e75\u003c/span\u003e], miR-34a-5p/HDAC1/ER-α [\u003cspan citationid=\"CR76\" class=\"CitationRef\"\u003e76\u003c/span\u003e], circCOX6A1/miR-512-3p/DYRK2 [\u003cspan citationid=\"CR77\" class=\"CitationRef\"\u003e77\u003c/span\u003e], TNF-α/miR-27a-3p/Sfrp1/Wnt3a\u0026ndash;β-catenin [\u003cspan citationid=\"CR78\" class=\"CitationRef\"\u003e78\u003c/span\u003e], miR-486\u0026ndash;3p/CTNNBIP1/Wnt/β-catenin [\u003cspan citationid=\"CR79\" class=\"CitationRef\"\u003e79\u003c/span\u003e], miR-124-3p/GSK-3β/β-catenin [\u003cspan citationid=\"CR80\" class=\"CitationRef\"\u003e80\u003c/span\u003e], wherein the insufficient miRNAs were reckoned to weaken the osteogenic induction.\u003c/p\u003e \u003cp\u003eApart from the above-mentioned miRNA, we knew that the expression data of a few miRNAs in BMSCs is unknown. MiR-15b-5p/GFAP, miR-150-5P/MMP14/Wnt/β-catenin, miR-935/STAT1 miR-16-5p/Axin2/Wnt/β-catenin axes, miR-29a all eased OP by the delivery of EVs with miRNA into an animal body. Mechanically, they exerted benefited effectiveness separately by lessening the differentiated power of osteoclasts, magnifying the growth and matured state of osteoblasts, underpinning the osteoblasts growth and osteogenic trend, evoking the osteogenic strength, exciting the bone production in DO-, DO-, OVX-, OVX-induced, healthy models [\u003cspan additionalcitationids=\"CR82 CR83 CR84\" citationid=\"CR81\" class=\"CitationRef\"\u003e81\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR85\" class=\"CitationRef\"\u003e85\u003c/span\u003e].\u003c/p\u003e\n\u003ch3\u003eThe therapy directly aiming at miRNA and the speculation of prospective biomarkers\u003c/h3\u003e\n\u003cp\u003eGiven the regulatory roles of miRNA in the ongoing of OP that is ascribed to the inducement of older age, menopausal female, diabetes, etc. In bountiful animal models, we have spotted the application of miRNA-based therapy. These therapeutic ways usher us to deeply recognize the function and value of miRNAs.\u003c/p\u003e \u003cp\u003eInfusion of aptamer-antagomiR-188 into the bone marrow of animals infinitely delayed the OP acceleration [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]. Administration of miR-96-5p-based BMSCs by the caudal vein proffered a benign impetus for treating OP [\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]. Subcutaneous injection of OP BMSCs with agomiR-4739 or antagomiR-4739 in combination with HA formed the sharp contrast \u003cem\u003ein vivo\u003c/em\u003e experiments, which is a cue for the exploitation of clinical function [\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]. Adenovirus infusion with excessive miR-18a-5p into the femur interior slowed down the pace of menopausal OP, which implicated the emerging function for clinically groundbreaking study [\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e]. Pulsed generalized delivery of bone-orientated antagomiR-132 brought out the deceleration of the mechanical unloading-leaded OP [\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e]. Animal models of rats from Teng \u003cem\u003eet al\u003c/em\u003e told us that either explicit upregulation of miR-335-5p or Icariin therapy moderated the OP ongoing [\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e]. The two types of injection treatment of agomiR-34c or antagomiR-34c produced extremely clear divergence, connoting the practical significance of antagomiR-34c treatment [\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e]. Intravenous administration of agomiR-130a manifestly combated the OP advancement [\u003cspan citationid=\"CR51\" class=\"CitationRef\"\u003e51\u003c/span\u003e]. The going down of miRNA-19b-3p in rats developed a crystal deterrent for spinal cord trauma-induced OP [\u003cspan citationid=\"CR61\" class=\"CitationRef\"\u003e61\u003c/span\u003e]. Zhou \u003cem\u003eet al\u003c/em\u003e stated that the utility of ample miR-218-5p forcefully stripped off the OP advancement in the OVX-applied animals [\u003cspan citationid=\"CR75\" class=\"CitationRef\"\u003e75\u003c/span\u003e]. The utilization of substantial miR-34a-5p in mice born over 18 months ago mitigated the OP exacerbation [\u003cspan citationid=\"CR76\" class=\"CitationRef\"\u003e76\u003c/span\u003e]. Wang \u003cem\u003eet al\u003c/em\u003e described that the infusion of the antagomiR-133a specifically targeted towards BMSC into the femur medulla greatly alleviated skeleton malfunction in OVX-applied mice [\u003cspan citationid=\"CR67\" class=\"CitationRef\"\u003e67\u003c/span\u003e]. Deng \u003cem\u003eet al\u003c/em\u003e held that the administration of agomiR-23b into the tail vein aggravated serious signs of OP, while the adenovirus Runx2 application counteracted the miR-23b-engendered skeleton disability [\u003cspan citationid=\"CR68\" class=\"CitationRef\"\u003e68\u003c/span\u003e]. Zhou \u003cem\u003eet al\u003c/em\u003e elaborated that the employment of FAM-BMSC-aptamer-nanoparticles-enriched antagomir-483-5p aggressively resisted the metabolism defect of the skeleton [\u003cspan citationid=\"CR69\" class=\"CitationRef\"\u003e69\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eBased on the roles and the beneficial effectiveness of miRNAs from BMSCs, we inferred they could be employed to predict, discern, confirm, assess, and treat OP, shoring up the monitoring, intervention, and prognosis of OP, which hinted at the prospect of miRNAs as promising and efficient biomarkers.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eThe predisposing factor of OP, the relative content (ascend\u0026uarr; or descend\u0026darr; ) of miRNA from BMSCs in OP illnesses or the symptom of OP, the miRNA-mediated signaling delivery, the miRNA-bound downstream gene, the miRNA-dependent treatment in OP-based animal model.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMiRNAs member\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePredisposing factor\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eRelative\u003c/p\u003e \u003cp\u003econtent\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eSignaling delivery\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eDownstream gene\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eTherapeutic means of animal model\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMiR-188\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOlder age\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026uarr;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eHDAC9 or RICTOR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eInfusion of aptamer-antagomiR-188 into bone marrow\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMiR-96-5p\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOVX\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026darr;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eLNC_000052/miR-96-5p/PIK3R1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003ePIK3R1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eAdministration of miR-96-5p-based BMSCs by the caudal vein\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMiR-130b-3p\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHyperlipidemia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026uarr;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCoQ10/miR-130b-3p/PGC-1α\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003ePGC-1α\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMiR-10a-3p\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOVX\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026uarr;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eKaempferol/miR-10a-3p/CXCL12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eCXCL12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMiR-3653-3p\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026darr;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCirc_0003865/miR-3653-3p/GAS1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eGAS1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMiR-4739\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMenopause\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026uarr;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMiR-4739/DLX3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eDLX3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eSubcutaneous injection of OP BMSCs with agomiR-4739 or antagomiR-4739 in combination with HA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMiR-26b\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOVX\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026uarr;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMiR-26b/SIRT2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eSIRT2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMiR-18a-5p\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMenopausal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026darr;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMiR-18a-5p/Notch2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNotch2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eAdenovirus infusion with exceeded miR-18a-5p\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMiR-132-3p\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eUnloading\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026uarr;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003ePulsed generalized delivery of bone-specific antagomiR-132\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMiR-135a-5p\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOVX\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026uarr;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eGAS5/miR-135a-5p/FOXO1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eFOXO1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMiR-335-5p\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026darr;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eIcariin/miR-335-5p/PTEN\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003ePTEN\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eUplift of miR-335-5p\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMiR-34c\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026uarr;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMALAT1/miR-34c/SATB2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eSATB2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eThe injection of agomiR-34c or antagomiR-34c\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMiR-183\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026uarr;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMiR-183/CTNNB1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eCTNNB1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMiR-149-3p\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026darr;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eFTO\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMiR-204 or miR-211\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026uarr;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMiR-204/211-Runx2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eRunx2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMiR-100-5p\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026uarr;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMiR-100-5p/TMEM135\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eTMEM135\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMiR-29b-1-5p\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOlder age\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026uarr;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eKynurenine/miR-29b-1-5p/SDF-1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eSDF-1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e49\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMiR-545-3p\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026uarr;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eSERPINB9P1/miR-545-3p/SIRT6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eSIRT6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e50\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMiR-130a\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOlder age\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026darr;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eSmurf2 or PPARγ\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eIntravenous administration of agomiR-130a\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR51\" class=\"CitationRef\"\u003e51\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMiR-31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCCD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026uarr;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRunx2/miR-31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR52\" class=\"CitationRef\"\u003e52\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMiR‑488\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026uarr;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePsoralen/miR‑488/Runx2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eRunx2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR53\" class=\"CitationRef\"\u003e53\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMiR-483-3p\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026darr;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMiR-483-3p-DKK2-Wnt/β-catenin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eDKK2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMiR-185-5p\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026uarr;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePART1/miR-185-5p/Runx3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eRunx3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR54\" class=\"CitationRef\"\u003e54\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMiR-142-3P\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026darr;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMiR-142-3P/14-3-3η/MAPK3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e14-3-3η\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR55\" class=\"CitationRef\"\u003e55\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMiR-186-5p\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHyperglycemia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026uarr;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCircEIF4B/miR-186-5p/FOXO1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eFOXO1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR56\" class=\"CitationRef\"\u003e56\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMiR-503-5p\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026uarr;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eLOC100126784/POM121L9P-miR-503-5p-SORBS1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eSORBS1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR86\" class=\"CitationRef\"\u003e86\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMiR-577\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHyperthyroid\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026uarr;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eTSHR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMiR-194-5p\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026uarr;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCirc_0001145/miR-194-5p/Fzd6/Wnt/β-catenin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eFzd6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR57\" class=\"CitationRef\"\u003e57\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMiR-101\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026darr;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eSNHG1-miR-101-DKK1-Wnt/β-catenin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eDKK1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR58\" class=\"CitationRef\"\u003e58\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMiR-128\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026uarr;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePrrx2/MIR22HG/miR-128/YAP1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eYAP1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR59\" class=\"CitationRef\"\u003e59\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMiR-3064-5p\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026uarr;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMEG3-miR-3064-5p-NR4A3-PINK1/Parkin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNR4A3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR60\" class=\"CitationRef\"\u003e60\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMiR-19b-3p\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026uarr;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMiR-19b-3p/EBF2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eEBF2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eThe knocking down of miR-19b-3p\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR61\" class=\"CitationRef\"\u003e61\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMiR-210-3p\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026uarr;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMiR-210-3p/KRAS/MAPK\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eKRAS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR62\" class=\"CitationRef\"\u003e62\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMiR-182-5p\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026uarr;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eHAGLR/miR-182-5p/Hoxa10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eHoxa10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR63\" class=\"CitationRef\"\u003e63\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMiR-506-3p\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026uarr;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eFGD5 antisense RNA 1/ miR-506-3p/BMP7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eBMP7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR64\" class=\"CitationRef\"\u003e64\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMiR-133a-3p\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026uarr;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eSP1/miR-133a-3p/MAPK3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eMAPK3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR65\" class=\"CitationRef\"\u003e65\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMiR-214\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026uarr;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003elncTIMP3/miR-214/Smad4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eSmad4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR66\" class=\"CitationRef\"\u003e66\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMiR-133a\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026uarr;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003emiR-133a-FGFR1-MAPK/ERK\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eFGFR1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eInfusion of the antagomiR-133a specifically targeted towards BMSC into the femur medulla\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMiR-23b\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026uarr;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eTNF-α/miR-23b/Runx2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eRunx2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR68\" class=\"CitationRef\"\u003e68\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMiR-483-5p\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026uarr;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMiR-483-5p-MAPK1/Smad5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eMAPK1/Smad5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eThe employment of FAM-BMSC-aptamer-nanoparticles-enriched antagomiR-483-5p\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR69\" class=\"CitationRef\"\u003e69\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMiR-124-3p\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026uarr;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCircRNA_0001052-miR-124-3p-Wnt4/β-catenin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR70\" class=\"CitationRef\"\u003e70\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMiR-25\u0026ndash;3p\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026uarr;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMiR-25\u0026ndash;3p/ITGB3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR71\" class=\"CitationRef\"\u003e71\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMiR-217-5p\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026uarr;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMEG3/miR-217-5p/Notch\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR72\" class=\"CitationRef\"\u003e72\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMiR-26b\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026darr;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMiR-26b-GSK3β-Wnt/β-catenin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eGSK3β\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR73\" class=\"CitationRef\"\u003e73\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMiR-877-5p\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026darr;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMiR-877-5p/EIF4G2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eEIF4G2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR74\" class=\"CitationRef\"\u003e74\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMiR-218-5p\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOVX\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026darr;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMiR-218-5p/SOCS3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eSOCS3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eThe elevation of miR-218-5p\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR75\" class=\"CitationRef\"\u003e75\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMiR-34a-5p\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026darr;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMiR-34a-5p/HDAC1/ER-α\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eHDAC1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eThe utilization of plentiful agomiR-34a-5p in elderly mice\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR76\" class=\"CitationRef\"\u003e76\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMiR-512-3p\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026darr;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCircCOX6A1/miR-512-3p/DYRK2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eDYRK2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR77\" class=\"CitationRef\"\u003e77\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMiR-27a-3p\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026darr;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eTNF-α/miR-27a-3p/Sfrp1/Wnt3a\u0026ndash;β-catenin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eSfrp1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR78\" class=\"CitationRef\"\u003e78\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMiR-486\u0026ndash;3p\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026darr;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMiR-486\u0026ndash;3p-CTNNBIP1-Wnt/β-catenin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eCTNNBIP1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR79\" class=\"CitationRef\"\u003e79\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMiR-124-3p\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026darr;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMiR-124-3p/GSK-3β/β-catenin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eGSK-3β\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR80\" class=\"CitationRef\"\u003e80\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eOP is a generalized bone-involved disease, and presents as the multitudinous impairment of microstructure and amplified osteopsathyrosis symptom [\u003cspan citationid=\"CR87\" class=\"CitationRef\"\u003e87\u003c/span\u003e, \u003cspan citationid=\"CR88\" class=\"CitationRef\"\u003e88\u003c/span\u003e]. We have realized that miRNAs can effectively act on the differentiation process of BMSCs that finally regulate the OP appearance.\u003c/p\u003e \u003cp\u003eWe clearly recognized the expression levels of miRNAs from BMSCs and their change characteristics between normal subjects and OP cases, which suggested that miRNAs exerted prominent roles in OP.\u003c/p\u003e \u003cp\u003eThey mainly draw upon the Wnt/β-catenin, MAPK, and Notch pathways to perform signal delivery, mediating the osteogenesis, adipogenesis, the balance of these two kinds of differentiated conversion, the proliferation, migration, apoptosis, stemness, and senescence of BMSCs, and biological ongoing of chondrocytes and osteoclasts.\u003c/p\u003e \u003cp\u003eThe existence of β-catenin occupies the most core status that acts as a twofold regulator in sustaining the regeneration property of BMSCs and tempting cellular conversion [\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e]. The MAPK- and Notch-mediated pathways are tightly tied to the osteogenic power. Considering that the function and efficacy of numerous miRNAs have not still been described, the survey and study of likely and available miRNA targets aiming at OP disorders will dramatically increase in the following years.\u003c/p\u003e \u003cp\u003eThe review evidently facilitates the research progress of miRNAs in the adjustment and control of OP and deepens the role exploration of miRNAs in OP. Besides, we noticed that previous reports mostly lacked the segment of miRNA checking. So, functional research of miRNA, more precise miRNA expression patterns, and essential verification steps are eagerly needed to become the following key study points. Meanwhile, to strengthen the applicability and availability of investigation outcomes, substantial clinical and animal studies need to be conducted to offer new threads for the practical usage of miRNAs as examination indicators [\u003cspan citationid=\"CR89\" class=\"CitationRef\"\u003e89\u003c/span\u003e]. However, clinical researches are usually subjected to low sample quantity, unique individuals, incongruent BMSC isolation approaches, diversified case parameter variables, and discrepancies in the methodology of miRNA analysis in trials [\u003cspan citationid=\"CR90\" class=\"CitationRef\"\u003e90\u003c/span\u003e]. Thus, if we would like to seek more effective and perfect biomarkers, we need to overcome the above difficulties, which can make a breakthrough in finding novel therapy ways and contribute to biomarker-featured personalized guidance treatment [\u003cspan citationid=\"CR91\" class=\"CitationRef\"\u003e91\u003c/span\u003e]. All in all, biomarker prediction offers us diagnosis parameters, monitor significance, specific treatment that is better than standardized therapy by employing related agents, and emerging prognosis value [\u003cspan citationid=\"CR92\" class=\"CitationRef\"\u003e92\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe growth of chemical engineering in probing the progression of genic molecules allows us to exert the research of molecules with high-throughput RNA-seq technology [\u003cspan citationid=\"CR94\" class=\"CitationRef\"\u003e94\u003c/span\u003e]. This technology provides multi-miRNA expression patterns and profiles, which advances the discerning, tracing, and analysis of the function of BMSCs and biomarker exploration [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. This compensates for unknown mechanisms of OP occurrence [\u003cspan citationid=\"CR95\" class=\"CitationRef\"\u003e95\u003c/span\u003e]. Current locations are attributed to little cases and datasets, and the lack of unified analysis norms.\u003c/p\u003e \u003cp\u003eBMSCs can be used as regenerative therapy in injury-based diseases on account of self-renewal activity, multiaspect-oriented differentiation, ignorable immunogenicity, homing effectiveness, as well as exact divergence tendency and appearance in traumatic sections [\u003cspan additionalcitationids=\"CR97 CR98\" citationid=\"CR96\" class=\"CitationRef\"\u003e96\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR99\" class=\"CitationRef\"\u003e99\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eWe underlined the outlook of employing adenovirus-loaded miRNA, and miRNA stimulators and antagonists for the treatment of OP. Additionally, having knowledge of the origin of miRNA emergence also provides direction and guidance to oppose OP. For example, the shRNA treatment of SP1 as the upstream combining aim of miR-133a-3p energetically ameliorated the age-based OP deterioration [\u003cspan citationid=\"CR65\" class=\"CitationRef\"\u003e65\u003c/span\u003e]. Surprisingly, miRNA-based treatment can be adopted to cure other diseases, such as TNF-α-induced let-7a in OP incommoded the Fas/FasL delivery, subsequently hobbling apoptotic emergence of T-cell, which manifested the downgraded immunologic suppression ability, in turn, the supply of the OP-based BMSCs with the let-7a downregulation made experimental colitis and GVHD get improved [\u003cspan citationid=\"CR93\" class=\"CitationRef\"\u003e93\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe distinctively existing target genes that miRNA aims at likely will yield novel and valuable insight for treating OP disease [\u003cspan citationid=\"CR100\" class=\"CitationRef\"\u003e100\u003c/span\u003e]. Simultaneously, we observed that the concurrent impulse and mutual feedback of a cluster of miRNAs may set off the explosive efficiency compared with a single miRNA, which is attributed to the intensive regulation of a specific gene that is targeted by several miRNAs [\u003cspan citationid=\"CR90\" class=\"CitationRef\"\u003e90\u003c/span\u003e], which guides our subsequent study direction.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis paper pointed out the different patterns of miRNAs and the effect of miRNAs on the biological course of BMSCs, insinuated the probability of miRNAs as the screening tools, confirmation guidance, treatment means, and prediction indicator of OP, paved the emerging road for clinical practice, and pushed the development of personalized remedy that breaks through regular remedies.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll data generated or analyzed data in the study are included in this article.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was supported by Key funded project for scientific research in higher education institutions in Hainan Province: The role and mechanism of chondrocyte exosomes regulating the Gremlin-1/MAPK pathway to induce phenotypic changes in subchondral bone progenitor cells. (NO. Hnky2024ZD-9) and Hainan Provincial Natural Science Foundation High level Talent Project:Mechanism study of TAF15 regulating chondrocyte apoptosis in anterior cruciate ligament injury induced PTOA through NF - \u0026kappa; B signaling pathway(NO. 824RC547).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eShunli Zhang and Yongxiong He Completed the study concept, manuscript drafting and study design, Rong Chen and Yuntao Gu completed the literature study and clinical studies, Chunzhao Xu completed the data acquisition Xiuqiong Du completed the data analysis, Guangji Wang completed the statistical analysis and Xiufan Du completed the manuscript review.All authors reviewed the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eWu J, Niu L, Yang K, Xu J, Zhang D, Ling J, et al. The role and mechanism of rna-binding proteins in bone metabolism and osteoporosis. Ageing Res Rev. 2024;96:102234.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhang B, Zhou Z, Zhang Y, Miu Y, Jin C, Ding W, et al. A sugary solution: harnessing polysaccharide-based materials for osteoporosis treatment. Carbohydr Polym. 2024;345:122549.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLuo Y, Liu H, Chen M, Zhang Y, Zheng W, Wu L, et al. Immunomodulatory nanomedicine for osteoporosis: current practices and emerging prospects. Acta Biomater. 2024;179:13\u0026ndash;35.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHu X, Wang Z, Wang W, Cui P, Kong C, Chen X, et al. Irisin as an agent for protecting against osteoporosis: a review of the current mechanisms and pathways. J Adv Res. 2024;62:175\u0026ndash;86.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMa S, Xing X, Huang H, Gao X, Xu X, Yang J, et al. Skeletal muscle-derived extracellular vesicles transport glycolytic enzymes to mediate muscle-to-bone crosstalk. Cell Metab. 2023;35(11):2028\u0026ndash;43.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYao Y, Cai X, Chen Y, Zhang M, Zheng C. Estrogen deficiency-mediated osteoimmunity in postmenopausal osteoporosis. Med Res Rev. 2024.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHuo S, Tang X, Chen W, Gan D, Guo H, Yao Q, et al. Epigenetic regulations of cellular senescence in osteoporosis. Ageing Res Rev. 2024;99:102235.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWanionok NE, Morel GR, Fernandez JM. Osteoporosis and alzheimer s disease (or alzheimer s disease and osteoporosis). Ageing Res Rev. 2024;99:102408.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAli M, Kim YS. A comprehensive review and advanced biomolecule-based therapies for osteoporosis. J Adv Res. 2024.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChen Y, Huang Y, Li J, Jiao T, Yang L. Enhancing osteoporosis treatment with engineered mesenchymal stem cell-derived extracellular vesicles: mechanisms and advances. Cell Death Dis. 2024;15(2):119.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOsteoporosis prevention. diagnosis, and therapy. JAMA. 2001;285(6):785\u0026ndash;95.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWang ZX, Luo ZW, Li FX, Cao J, Rao SS, Liu YW, et al. Aged bone matrix-derived extracellular vesicles as a messenger for calcification paradox. Nat Commun. 2022;13(1):1453.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLiu X, Chen C, Jiang Y, Wan M, Jiao B, Liao X, et al. Brain-derived extracellular vesicles promote bone-fat imbalance in alzheimer's disease. Int J Biol Sci. 2023;19(8):2409\u0026ndash;27.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFleischhacker V, Milosic F, Bricelj M, Kuhrer K, Wahl-Figlash K, Heimel P, et al. Aged-vascular niche hinders osteogenesis of mesenchymal stem cells through paracrine repression of wnt-axis. Aging Cell. 2024;23(6):e14139.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYates LA, Norbury CJ, Gilbert RJ. The long and short of microrna. Cell. 2013;153(3):516\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePritchard CC, Cheng HH, Tewari M. Microrna profiling: approaches and considerations. Nat Rev Genet. 2012;13(5):358\u0026ndash;69.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSun K, Lai EC. Adult-specific functions of animal micrornas. Nat Rev Genet. 2013;14(8):535\u0026ndash;48.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLuo XJ, Zhao Q, Liu J, Zheng JB, Qiu MZ, Ju HQ, et al. Novel genetic and epigenetic biomarkers of prognostic and predictive significance in stage ii/iii colorectal cancer. Mol Ther. 2021;29(2):587\u0026ndash;96.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBartel DP. Micrornas: target recognition and regulatory functions. Cell. 2009;136(2):215\u0026ndash;33.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGebert L, Macrae IJ. Regulation of microrna function in animals. Nat Rev Mol Cell Biol. 2019;20(1):21\u0026ndash;37.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eValenti MT, Deiana M, Cheri S, Dotta M, Zamboni F, Gabbiani D et al. Physical exercise modulates mir-21-5p, mir-129-5p, mir-378-5p, and mir-188-5p expression in progenitor cells promoting osteogenesis. Cells. 2019;8(7).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eXu T, Zhou P, Li H, Ding Q, Hua F. Microrna-577 aggravates bone loss and bone remodeling by targeting thyroid stimulating hormone receptor in hyperthyroid-associated osteoporosis. Environ Toxicol. 2022;37(3):539\u0026ndash;48.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMeder B, Backes C, Haas J, Leidinger P, Stahler C, Grossmann T, et al. Influence of the confounding factors age and sex on microrna profiles from peripheral blood. Clin Chem. 2014;60(9):1200\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAjit SK. Circulating micrornas as biomarkers, therapeutic targets, and signaling molecules. Sens (Basel). 2012;12(3):3359\u0026ndash;69.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAn JH, Ohn JH, Song JA, Yang JY, Park H, Choi HJ, et al. Changes of microrna profile and microrna-mrna regulatory network in bones of ovariectomized mice. J Bone Min Res. 2014;29(3):644\u0026ndash;56.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eInose H, Ochi H, Kimura A, Fujita K, Xu R, Sato S, et al. A microrna regulatory mechanism of osteoblast differentiation. Proc Natl Acad Sci U S A. 2009;106(49):20794\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHuang J, Zhao L, Xing L, Chen D. Microrna-204 regulates runx2 protein expression and mesenchymal progenitor cell differentiation. Stem Cells. 2010;28(2):357\u0026ndash;64.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLi H, Xie H, Liu W, Hu R, Huang B, Tan YF, et al. A novel microrna targeting hdac5 regulates osteoblast differentiation in mice and contributes to primary osteoporosis in humans. J Clin Invest. 2009;119(12):3666\u0026ndash;77.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKim KM, Park SJ, Jung SH, Kim EJ, Jogeswar G, Ajita J, et al. Mir-182 is a negative regulator of osteoblast proliferation, differentiation, and skeletogenesis through targeting foxo1. J Bone Min Res. 2012;27(8):1669\u0026ndash;79.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChen T, Wang C, Yu H, Ding M, Zhang C, Lu X, et al. Increased urinary exosomal micrornas in children with idiopathic nephrotic syndrome. EBioMedicine. 2019;39:552\u0026ndash;61.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLiu CJ, Xie GY, Miao YR, Xia M, Wang Y, Lei Q, et al. Evatlas: a comprehensive database for ncrna expression in human extracellular vesicles. Nucleic Acids Res. 2022;50(D1):D111\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLi D, Yuan Q, Xiong L, Li A, Xia Y. The mir-4739/dlx3 axis modulates bone marrow-derived mesenchymal stem cell (bmsc) osteogenesis affecting osteoporosis progression. Front Endocrinol (Lausanne). 2021;12:703167.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhou B, Peng K, Wang G, Chen W, Liu P, Chen F, et al. Mir\u0026ndash;483\u0026ndash;3p promotes the osteogenesis of human osteoblasts by targeting dikkopf 2 (dkk2) and the wnt signaling pathway. Int J Mol Med. 2020;46(4):1571\u0026ndash;81.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLi CJ, Cheng P, Liang MK, Chen YS, Lu Q, Wang JY, et al. Microrna-188 regulates age-related switch between osteoblast and adipocyte differentiation. J Clin Invest. 2015;125(4):1509\u0026ndash;22.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLi M, Cong R, Yang L, Yang L, Zhang Y, Fu Q. A novel lncrna lnc_000052 leads to the dysfunction of osteoporotic bmscs via the mir-96-5p-pik3r1 axis. Cell Death Dis. 2020;11(9):795.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMeng M, Wang J, Wang C, Zhao J, Wang H, Zhang Y, et al. Coenzyme q10 protects against hyperlipidemia-induced osteoporosis by improving mitochondrial function via modulating mir-130b-3p/pgc-1alpha pathway. Calcif Tissue Int. 2024;114(2):182\u0026ndash;99.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLiu H, Yi X, Tu S, Cheng C, Luo J. Kaempferol promotes bmsc osteogenic differentiation and improves osteoporosis by downregulating mir-10a-3p and upregulating cxcl12. Mol Cell Endocrinol. 2021;520:111074.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWang X, Chen T, Deng Z, Gao W, Liang T, Qiu X, et al. Melatonin promotes bone marrow mesenchymal stem cell osteogenic differentiation and prevents osteoporosis development through modulating circ_0003865 that sponges mir-3653-3p. Stem Cell Res Ther. 2021;12(1):150.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChen H, Shi Y, Zhu Y, Zheng Z, Xuzhou H, Wang Q. Effect of bone marrow stromal cells derived mir-26b on chondrocytes of osteoporosis rats. Ann Clin Lab Sci. 2024;54(4):466\u0026ndash;73.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHe P, Yang Z, Li H, Zhou E, Hou Z, Sang H. Mir-18a-5p promotes osteogenic differentiation of bmsc by inhibiting notch2. Bone. 2024;188:117224.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHu Z, Zhang L, Wang H, Wang Y, Tan Y, Dang L, et al. Targeted silencing of mirna-132-3p expression rescues disuse osteopenia by promoting mesenchymal stem cell osteogenic differentiation and osteogenesis in mice. Stem Cell Res Ther. 2020;11(1):58.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWang X, Zhao D, Zhu Y, Dong Y, Liu Y. Long non-coding rna gas5 promotes osteogenic differentiation of bone marrow mesenchymal stem cells by regulating the mir-135a-5p/foxo1 pathway. Mol Cell Endocrinol. 2019;496:110534.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTeng JW, Bian SS, Kong P, Chen YG. Icariin triggers osteogenic differentiation of bone marrow stem cells by up-regulating mir-335-5p. Exp Cell Res. 2022;414(2):113085.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYang X, Yang J, Lei P, Wen T. Lncrna malat1 shuttled by bone marrow-derived mesenchymal stem cells-secreted exosomes alleviates osteoporosis through mediating microrna-34c/satb2 axis. Aging. 2019;11(20):8777\u0026ndash;91.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJiang N, Jiang J, Wang Q, Hao J, Yang R, Tian X, et al. Strategic targeting of mir-183 and beta-catenin to enhance bmsc stemness in age-related osteoporosis therapy. Sci Rep. 2024;14(1):21489.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLi Y, Yang F, Gao M, Gong R, Jin M, Liu T, et al. Mir-149-3p regulates the switch between adipogenic and osteogenic differentiation of bmscs by targeting fto. Mol Ther Nucleic Acids. 2019;17:590\u0026ndash;600.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHuang J, Zhao L, Xing L, Chen D. Microrna-204 regulates runx2 protein expression and mesenchymal progenitor cell differentiation. Stem Cells. 2010;28(2):357\u0026ndash;64.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWang R, Zhang M, Hu Y, He J, Lin Q, Peng N. Mir-100-5p inhibits osteogenic differentiation of human bone mesenchymal stromal cells by targeting tmem135. Hum Cell. 2022;35(6):1671\u0026ndash;83.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEisa NH, Sudharsan PT, Herrero SM, Herberg SA, Volkman BF, Aguilar-Perez A, et al. Age-associated changes in micrornas affect the differentiation potential of human mesenchymal stem cells: novel role of mir-29b-1-5p expression. Bone. 2021;153:116154.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWu M, Dai M, Liu X, Zeng Q, Lu Y. Lncrna serpinb9p1 regulates sirt6 mediated osteogenic differentiation of bmscs via mir-545-3p. Calcif Tissue Int. 2023;112(1):92\u0026ndash;102.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLin Z, He H, Wang M, Liang J. Microrna-130a controls bone marrow mesenchymal stem cell differentiation towards the osteoblastic and adipogenic fate. Cell Prolif. 2019;52(6):e12688.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eXu L, Fu Y, Zhu W, Xu R, Zhang J, Zhang P, et al. Microrna-31 inhibition partially ameliorates the deficiency of bone marrow stromal cells from cleidocranial dysplasia. J Cell Biochem. 2019;120(6):9472\u0026ndash;86.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHuang Y, Hou Q, Su H, Chen D, Luo Y, Jiang T. Mir\u0026ndash;488 negatively regulates osteogenic differentiation of bone marrow mesenchymal stem cells induced by psoralen by targeting runx2. Mol Med Rep. 2019;20(4):3746\u0026ndash;54.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhang J, Xu N, Yu C, Miao K, Wang Q. Lncrna part1/mir-185-5p/runx3 feedback loop modulates osteogenic differentiation of bone marrow mesenchymal stem cells. Autoimmunity. 2021;54(7):422\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLiu YQ, Xu YC, Shuai ZW. Mir-142-3p regulates mapk protein family by inhibiting 14-3-3eta to enhance bone marrow mesenchymal stem cells osteogenesis. Sci Rep. 2023;13(1):22862.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWu J, Li X, Nie H, Shen Y, Guo Z, Huihan CC, et al. Phytic acid promotes high glucose-mediated bone marrow mesenchymal stem cells osteogenesis via modulating circeif4b that sponges mir-186-5p and complexes with igf2bp3. Biochem Pharmacol. 2024;222:116118.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLu Y, Liu YK, Wan FY, Shi S, Tao R. Circsmg5 stimulates the osteogenic differentiation of bone marrow mesenchymal stem cells by targeting the mir-194-5p/fzd6 axis and beta-catenin signaling. Environ Toxicol. 2022;37(3):593\u0026ndash;602.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eXiang J, Fu HQ, Xu Z, Fan WJ, Liu F, Chen B. Lncrna snhg1 attenuates osteogenic differentiation via the mir\u0026ndash;101/dkk1 axis in bone marrow mesenchymal stem cells. Mol Med Rep. 2020;22(5):3715\u0026ndash;22.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLi Y, Wang X, Pan C, Yuan H, Li X, Chen Z, et al. Myoblast-derived exosomal prrx2 attenuates osteoporosis via transcriptional regulation of lncrna-mir22hg to activate hippo pathway. Mol Med. 2023;29(1):54.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eXu C, Wang Z, Liu YJ, Duan K, Guan J. Harnessing gmnp-loaded bmsc-derived evs to target mir-3064-5p via meg3 overexpression: implications for diabetic osteoporosis therapy in rats. Cell Signal. 2024;118:111055.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLiu D, Lin Z, Huang Y, Qiu M. Role of microrna-19b-3p on osteoporosis after experimental spinal cord injury in rats. Arch Biochem Biophys. 2022;719:109134.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHu M, Zhu X, Yuan H, Li H, Liao H, Chen S. The function and mechanism of the mir-210-3p/kras axis in bone marrow-derived mesenchymal stem cell from patients with osteoporosis. J Tissue Eng Regen Med. 2021;15(8):699\u0026ndash;711.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHuang Y, Tao M, Yan S, He X. Long non-coding rna homeobox d gene cluster antisense growth-associated long noncoding rna/microrna-182-5p/homeobox protein a10 alleviates postmenopausal osteoporosis via accelerating osteoblast differentiation of bone marrow mesenchymal stem cells. J Orthop Surg Res. 2023;18(1):726.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLi J, Wu X, Shi Y, Zhao H. Fgd5-as1 facilitates the osteogenic differentiation of human bone marrow-derived mesenchymal stem cells via targeting the mir-506-3p/bmp7 axis. J Orthop Surg Res. 2021;16(1):665.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhong L, Sun Y, Wang C, Liu R, Ru W, Dai W, et al. Sp1 regulates bmsc osteogenic differentiation through the mir-133a-3p/mapk3 axis: sp1 regulates osteogenic differentiation of bmscs. J Orthop Surg Res. 2024;19(1):396.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWumiti T, Wang L, Xu B, Ma Y, Zhu Y, Zuo X, et al. Lnctimp3 promotes osteogenic differentiation of bone marrow mesenchymal stem cells via mir-214/smad4 axis to relieve postmenopausal osteoporosis. Mol Biol Rep. 2024;51(1):719.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWang G, Wan L, Zhang L, Yan C, Zhang Y. Microrna-133a regulates the viability and differentiation fate of bone marrow mesenchymal stem cells via mapk/erk signaling pathway by targeting fgfr1. DNA Cell Biol. 2021;40(8):1112\u0026ndash;23.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDeng L, Hu G, Jin L, Wang C, Niu H. Involvement of microrna-23b in tnf-alpha-reduced bmsc osteogenic differentiation via targeting runx2. J Bone Min Metab. 2018;36(6):648\u0026ndash;60.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhou Y, Jia H, Hu A, Liu R, Zeng X, Wang H. Nanoparticles targeting delivery antagomir-483-5p to bone marrow mesenchymal stem cells treat osteoporosis by increasing bone formation. Curr Stem Cell Res Ther. 2023;18(1):115\u0026ndash;26.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLiu N, Lu W, Qu X, Zhu C. Llli promotes bmsc proliferation through circrna_0001052/mir-124-3p. Lasers Med Sci. 2022;37(2):849\u0026ndash;56.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYu D, Li Z, Cao J, Shen F, Wei G. Microrna-25-3p suppresses osteogenic differentiation of bmscs in patients with osteoporosis by targeting itgb3. Acta Histochem. 2022;124(6):151926.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLiu N, Cao L, Peng L, Lu W, Dai X, Wang S, et al. Photobiomodulation (800 nm light-emitting diode) treatment promotes bone mesenchymal stem cell proliferation via long noncoding rna meg3-microrna-217-5p pathway. Photobiomodul Photomed Laser Surg. 2023;41(1):10\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHu H, Zhao C, Zhang P, Liu Y, Jiang Y, Wu E, et al. Mir-26b modulates oa induced bmsc osteogenesis through regulating gsk3beta/beta-catenin pathway. Exp Mol Pathol. 2019;107:158\u0026ndash;64.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eShen Y, Zhang Y, Wang Q, Jiang B, Jiang X, Luo B. Microrna-877-5p promotes osteoblast differentiation by targeting eif4g2 expression. J Orthop Surg Res. 2024;19(1):134.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhou Q, Zhou L, Li J. Mir-218-5p-dependent socs3 downregulation increases osteoblast differentiation inpostmenopausal osteoporosis. J Orthop Surg Res. 2023;18(1):109.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSun D, Chen Y, Liu X, Huang G, Cheng G, Yu C, et al. Mir-34a-5p facilitates osteogenic differentiation of bone marrow mesenchymal stem cells and modulates bone metabolism by targeting hdac1 and promoting er-alpha transcription. Connect Tissue Res. 2023;64(2):126\u0026ndash;38.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHe D, Zheng S, Cao J, Deng J, Ding R, Xu Y, et al. Circcox6a1 suppresses osteogenic differentiation and aggravates osteoporosis via mir-512-3p/dyrk2 axis. Mol Biol Rep. 2024;51(1):636.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhang DF, Jin XN, Ma X, Qiu YS, Ma W, Dai X, et al. Tumour necrosis factor alpha regulates the mir-27a-3p-sfrp1 axis in a mouse model of osteoporosis. Exp Physiol. 2024;109(7):1109\u0026ndash;23.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhang Z, Jiang W, Hu M, Gao R, Zhou X. Mir-486-3p promotes osteogenic differentiation of bmsc by targeting ctnnbip1 and activating the wnt/beta-catenin pathway. Biochem Biophys Res Commun. 2021;566:59\u0026ndash;66.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLi Z, Zhao H, Chu S, Liu X, Qu X, Li J, et al. Mir-124-3p promotes bmsc osteogenesis via suppressing the gsk-3beta/beta-catenin signaling pathway in diabetic osteoporosis rats. Vitro Cell Dev Biol Anim. 2020;56(9):723\u0026ndash;34.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhang Y, Cao X, Li P, Fan Y, Zhang L, Ma X, et al. Microrna-935-modified bone marrow mesenchymal stem cells-derived exosomes enhance osteoblast proliferation and differentiation in osteoporotic rats. Life Sci. 2021;272:119204.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eXu C, Wang Z, Liu Y, Wei B, Liu X, Duan K, et al. Extracellular vesicles derived from bone marrow mesenchymal stem cells loaded on magnetic nanoparticles delay the progression of diabetic osteoporosis via delivery of mir-150-5p. Cell Biol Toxicol. 2023;39(4):1257\u0026ndash;74.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eXu C, Wang Z, Liu Y, Duan K, Guan J. Delivery of mir-15b-5p via magnetic nanoparticle-enhanced bone marrow mesenchymal stem cell-derived extracellular vesicles mitigates diabetic osteoporosis by targeting gfap. Cell Biol Toxicol. 2024;40(1):52.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDuan J, Li H, Wang C, Yao J, Jin Y, Zhao J, et al. Bmsc-derived extracellular vesicles promoted osteogenesis via axin2 inhibition by delivering mir-16-5p. Int Immunopharmacol. 2023;120:110319.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLu GD, Cheng P, Liu T, Wang Z. Bmsc-derived exosomal mir-29a promotes angiogenesis and osteogenesis. Front Cell Dev Biol. 2020;8:608521.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eXu Y, Xin R, Sun H, Long D, Li Z, Liao H, et al. Long non-coding rnas loc100126784 and pom121l9p derived from bone marrow mesenchymal stem cells enhance osteogenic differentiation via the mir-503-5p/sorbs1 axis. Front Cell Dev Biol. 2021;9:723759.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEnsrud KE, Crandall CJ, Osteoporosis. Ann Intern Med. 2024;177(1):C1\u0026ndash;16.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhang YW, Song PR, Wang SC, Liu H, Shi ZM, Su JC. Diets intervene osteoporosis via gut-bone axis. Gut Microbes. 2024;16(1):2295432.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWang H, Jin J, Wu J, Qu H, Wu S, Bao W. Transcriptome and chromatin accessibility in porcine intestinal epithelial cells upon zearalenone exposure. Sci Data. 2019;6(1):298.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBang JH, Kim EH, Kim HJ, Chung JW, Seo WK, Kim GM et al. Machine learning-based etiologic subtyping of ischemic stroke using circulating exosomal micrornas. Int J Mol Sci. 2024;25(12).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKalia M. Biomarkers for personalized oncology: recent advances and future challenges. Metabolism. 2015;64(3 Suppl 1):S16\u0026ndash;21.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLi W, Liu JB, Hou LK, Yu F, Zhang J, Wu W, et al. Liquid biopsy in lung cancer: significance in diagnostics, prediction, and treatment monitoring. Mol Cancer. 2022;21(1):25.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLiao L, Yu Y, Shao B, Su X, Wang H, Kuang H, et al. Redundant let-7a suppresses the immunomodulatory properties of bmscs by inhibiting the fas/fasl system in osteoporosis. FASEB J. 2018;32(4):1982\u0026ndash;92.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNaesens M, Sarwal MM. Molecular diagnostics in transplantation. Nat Rev Nephrol. 2010;6(10):614\u0026ndash;28.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKato M, Natarajan R. Diabetic nephropathy\u0026ndash;emerging epigenetic mechanisms. Nat Rev Nephrol. 2014;10(9):517\u0026ndash;30.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMao Q, Liang XL, Wu YF, Pang YH, Zhao XJ, Lu YX. Ilk promotes survival and self-renewal of hypoxic mscs via the activation of lnctcf7-wnt pathway induced by il-6/stat3 signaling. Gene Ther. 2019;26(5):165\u0026ndash;76.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLiu D, Kou X, Chen C, Liu S, Liu Y, Yu W, et al. Circulating apoptotic bodies maintain mesenchymal stem cell homeostasis and ameliorate osteopenia via transferring multiple cellular factors. Cell Res. 2018;28(9):918\u0026ndash;33.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhang L, Li Q, Liu Z, Wang Y, Zhao M. The protective effects of bone mesenchymal stem cells on paraquat-induced acute lung injury via the muc5b and erk/mapk signaling pathways. Am J Transl Res. 2019;11(6):3707\u0026ndash;21.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChen Q, Zhang Y, Zhu H, Yuan X, Luo X, Wu X, et al. Bone marrow mesenchymal stem cells alleviate the daunorubicin-induced subacute myocardial injury in rats through inhibiting infiltration of t lymphocytes and antigen-presenting cells. Biomed Pharmacother. 2020;121:109157.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTsai MJ, Chang WA, Liao SH, Chang KF, Sheu CC, Kuo PL. The effects of epigallocatechin gallate (egcg) on pulmonary fibroblasts of idiopathic pulmonary fibrosis (ipf)-a next-generation sequencing and bioinformatic approach. Int J Mol Sci. 2019;20(8).\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"MiRNAs, BMSCs, Osteoporosis, Expression, Roles","lastPublishedDoi":"10.21203/rs.3.rs-5258994/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5258994/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eBone marrow mesenchymal stem cells (BMSCs) are core stem cells and their differentiation orientation directly manipulates the ongoing of osteoporosis (OP). MicroRNAs (miRNAs) are momentously characterized molecular in BMSCs. However, the leading pattern and trait of miRNAs in OP remain vague and mysterious. Full-scale research of BMSCs-existed miRNA expression between normal conditions and patients experiencing OP is the only way for us to pinpoint the effect of miRNA, making us rationally and effectively utilize miRNA.\u003c/p\u003e\u003ch2\u003eObjective\u003c/h2\u003e \u003cp\u003eThis review chiefly lies in exploring, selecting, verifying, and confirming the biomarker of miRNAs by dissecting miRNA patterns, which offer diagnosis reference, monitor value, customized feature therapy by developing related preparation, and emerging prognosis indicators.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eWe gathered miRNA-seq datasets from human BMSCs to detect the expression pattern of miRNA. Herein, we searched and distinguished microRNA expression levels of BMSCs, sifted the distinctively existing microRNAs, sought the preferentially expressed microRNAs, had knowledge of the target points of related microRNA biomarkers, and boosted our awareness of the role of miRNAs and the development of pharmaceutical preparation aimed at it.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eThese miRNAs manifested aberrant expression variation between matched control and OP cases, they mainly draw upon the Wnt/β-catenin, MAPK, and Notch pathways to perform signal delivery, mediating the osteogenesis, adipogenesis, the balance of these two kinds of differentiated conversion, the proliferation, migration, apoptosis, stemness, and senescence of BMSCs, and biological ongoing of chondrocytes and osteoclasts. In addition, the treatment based on miRNAs of \u003cem\u003ein vitro\u003c/em\u003e trials in combination with animal models defined the application of miRNA-linked therapy.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eThis paper accorded proof of miRNAs as screening tools, confirmation guidance, treatment means, and prediction indicators of OP, paved the emerging road for clinical practice, and pushed the development of personalized remedies that break through regular remedies.\u003c/p\u003e","manuscriptTitle":"MicroRNA expression profiling and potential biomarker exploration in BMSCs of osteoporosis patients based on high-throughput sequencing technology","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-10-31 07:24:49","doi":"10.21203/rs.3.rs-5258994/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"0124c627-b502-4fd1-aaee-79eb2ed59cc2","owner":[],"postedDate":"October 31st, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-11-25T13:24:07+00:00","versionOfRecord":[],"versionCreatedAt":"2024-10-31 07:24:49","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5258994","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5258994","identity":"rs-5258994","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}