Targeted overexpression of the long noncoding RNA ODSM can regulate osteoblast function in vitro and in vivo

长链非编码 RNA ODSM 的靶向过表达可在体内和体外调节成骨细胞功能

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作者:Yixuan Wang #, Ke Wang #, Lijun Zhang #, Yingjun Tan, Zebing Hu, Lei Dang, Hua Zhou, Gaozhi Li, Han Wang, Shu Zhang, Fei Shi, Xinsheng Cao, Ge Zhang

Abstract

Ameliorating bone loss caused by mechanical unloading is a substantial clinical challenge, and the role of noncoding RNAs in this process has attracted increasing attention. In this study, we found that the long noncoding RNA osteoblast differentiation-related lncRNA under simulated microgravity (lncRNA ODSM) could inhibit osteoblast apoptosis and promote osteoblast mineralization in vitro. The increased expression level of the lncRNA ODSM partially reduced apoptosis and promoted differentiation in MC3T3-E1 cells under microgravity unloading conditions, and the effect was partially dependent on miR-139-3p. LncRNA ODSM supplementation in hindlimb-unloaded mice caused a decrease in the number of apoptotic cells in bone tissue and an increase in osteoblast activity. Furthermore, targeted overexpression of the lncRNA ODSM in osteoblasts partially reversed bone loss induced by mechanical unloading at the microstructural and biomechanical levels. These findings are the first to suggest the potential value of the lncRNA ODSM in osteoporosis therapy and the treatment of pathological osteopenia.

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