Exploring the Impact of Gut Microbiota-Mediated miRNA in Exosomes of Bone Marrow Mesenchymal Stem Cells on the Regulation of Bone Metabolism

Abstract Background Osteoporosis, a prevalent metabolic bone disease, is intricately linked to an imbalance in gut microbiota. Methods The ovaries were surgically removed from female 6 months SD rats to induce osteoporosis. Subsequently, 16S rRNA sequencing was employed to identify gut microbiota in osteoporotic rats. Bone marrow mesenchymal stem cells (BMSCs) were isolated and cultured separately from the osteoporotic rats, and their osteogenic and adipogenic differentiation was observed. Furthermore, exosomes were extracted from these cells, and miRNA sequencing was performed on the exosomes to identify key miRNAs. Osteoporotic rats were then subjected to intervention with gut microbiota to observe any changes in the osteogenic and adipogenic differentiation of bone marrow mesenchymal stem cells. ResultsIn our investigation, we observed a changed proportion of Firmicutes and Bacteroidetes in the gut of ovariectomized rats, contributing to dysbiosis and consequential changes in intestinal permeability. The BMSCs exhibited disrupted osteogenic/adipogenic differentiation, coupled with structural damage to the bone. Through the isolation of exosomes from BMSCs and subsequent miRNA analysis, we identified miR-151-3p and miR-23b-3p as potential pivotal regulators of bone metabolism. Furthermore, employing 16S rDNA sequencing, we identified g_Ruminococcus and its remarkable capacity to ameliorate the imbalance in BMSCs osteogenic/adipogenic differentiation. This intervention demonstrated promising outcomes, mitigating bone loss and structural damage in the tibia and femur of ovariectomized rats. Conclusion These findings underscore the significant role of g_Ruminococcusin alleviating osteoporosis induced by estrogen deficiency, suggesting its therapeutic potential in addressing postmenopausal osteoporosis through the targeted modulation of BMSCs exosome miR-151-3p and miR-23b-3p.