Exosomal miR-140-5p inhibits osteogenesis by targeting IGF1R and regulating mTOR pathway in ossification of the posterior longitudinal ligament

Yifan Tang, Yanqing Sun, Junkai Zeng, Bo Yuan, Yin Zhao, Xiangwu Geng, Lianshun Jia, Shengyuan Zhou, Xiongsheng Chen
In: Research Square · 2022 · doi:10.21203/rs.3.rs-1669995/v1 · W4281773766
preprint OA: green CC0
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Abstract

Abstract Background Ossification of the posterior longitudinal ligament (OPLL) is a disabling disease, of which the pathogenesis is still unclear, and there are no effective cure or prevention methods. Exosomal miRNA play an important role in osteogenesis of the ectopic bone. Therefore, we focused on the down-regulation miR-140-5p from OPLL cell-derived exosomes in order to explore the mechanism of exosomal miR-140-5p in inhibiting osteogenesis in OPLL. Results Exosomes were isolated by differential centrifugation and identified by transmission electron microscopy, nanoparticle tracking analysis, and exosomal markers. Exosomal RNA was extracted to perform miRNA sequencing and disclose the differentially expressed miRNAs, among which miR-140-5p was significantly down-regulated. The confocal microscopy was used to trace the exosomal miR-140-5p delivered from OPLL cells to human mesenchymal stem cells (hMSCs). In vitro, we verified exosomal miR-140-5p inhibited osteoblast differentiation of hMSCs by targeting IGF1R and suppressing the phosphorylation of IRS1/PI3K/Akt/mTOR pathway. In vivo, we verified that exosomal miR-140-5p inhibited the ectopic bone formation in mice assessed by micro-CT and immunohistochemistry. Conclusions We found that exosomal miR-140-5p could inhibit the osteogenic differentiation of hMSCs by targeting IGF1R and regulating the mTOR pathway, prompting a further potential means of drug treatment and a possible target for molecular therapy of OPLL.

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