MicroRNA-139-3p regulates osteoblast differentiation and apoptosis by targeting ELK1 and interacting with long noncoding RNA ODSM.

MicroRNA-139-3p regulates osteoblast differentiation and apoptosis by targeting ELK1 and interacting with long noncoding RNA ODSM.
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MicroRNA-139-3p 通过靶向 ELK1 并与长非编码 RNA ODSM 相互作用调节成骨细胞分化和凋亡

DOI:
10.1038/s41419-018-1153-1
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发表时间:
2018-10-31
影响因子:
9
通讯作者:
Shi F
Shi F
中科院分区:
生物学1区
文献类型:
--
作者:
Wang Y;Wang K;Hu Z;Zhou H;Zhang L;Wang H;Li G;Zhang S;Cao X;Shi F

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最近的研究证实microRNA和lncRNA可以影响骨细胞分化和骨形成。在这项研究中,miR-139- 3 p在模拟微重力条件下后肢卸载小鼠股骨和MC 3 T3-E1细胞中上调;这种效应与成骨细胞分化和凋亡有关。沉默miR-139- 3 p可减弱模拟微重力对MC 3 T3-E1细胞分化的抑制和对细胞凋亡的促进作用。ELK 1是miR-139- 3 p的靶点,是miR-139- 3 p调节成骨细胞分化和凋亡所必需的。在模拟微重力条件下,在MC 3 T3-E1细胞中鉴定出一种与miR-139- 3 p相互作用的成骨细胞分化相关lncRNA(lncRNA ODSM)。进一步的研究表明lncRNA ODSM可以促进MC 3 T3-E1细胞的分化。因此,本研究首次揭示了lncRNA ODSM/miR-139- 3 p/ELK 1通路在成骨细胞中的关键作用,这些发现表明miR-139- 3 p在骨质疏松症诊断和治疗中的潜在价值。
Recent studies have confirmed that microRNAs and lncRNAs can affect bone cell differentiation and bone formation. In this study, miR-139-3p was upregulated in the femurs of hindlimb unloading mice and MC3T3-E1 cells under simulated microgravity; this effect was related to osteoblast differentiation and apoptosis. Silencing miR-139-3p attenuated the suppression of differentiation and the promotion of MC3T3-E1 cell apoptosis induced by simulated microgravity. ELK1 is a target of miR-139-3p and is essential for miR-139-3p to regulate osteoblast differentiation and apoptosis. An osteoblast differentiation-related lncRNA that could interact with miR-139-3p (lncRNA ODSM) was identified in MC3T3-E1 cells under simulated microgravity. Further investigations demonstrated that lncRNA ODSM could promote MC3T3-E1 cell differentiation. Therefore, this research was the first to reveal the critical role of the lncRNA ODSM/miR-139-3p/ELK1 pathway in osteoblasts, and these findings suggest the potential value of miR-139-3p in osteoporosis diagnosis and therapy.
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