Silencing of miR-138-5p sensitizes bone anabolic action to mechanical stimuli.
Silencing of miR-138-5p sensitizes bone anabolic action to mechanical stimuli.
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miR-138-5p 沉默使骨合成代谢作用对机械刺激敏感
作者：
Chen Z;Zhao F;Liang C;Hu L;Li D;Zhang Y;Yin C;Chen L;Wang L;Lin X;Su P;Ma J;Yang C;Tian Y;Zhang W;Li Y;Peng S;Chen W;Zhang G;Qian A
新出现的证据表明，microRNAs （miRNAs）在调节成骨的机械传感中起着重要作用。然而，在人骨标本中尚未发现机械反应性mirna。方法：采用卧床和老年患者、后肢卸车和老年小鼠、随机定位机和原代老龄成骨细胞分别模拟人、动物和细胞水平的机械卸车条件。采用跑步机运动和Flexcell循环机械拉伸分别模拟体内和体外机械负荷。结果：在这里，我们发现卧床和老年患者的骨标本中miR-138-5p水平升高，骨形成程度降低。功能缺失和功能获得研究表明，miR-138-5p直接靶向微管肌动蛋白交联因子1 (MACF1)，在不同机械条件下抑制成骨细胞分化。在转化医学方面，骨靶向抑制miR-138-5p可减轻后肢卸车小鼠机械骨合成代谢反应的下降。此外，骨靶向抑制miR-138-5p使miR-138-5p转基因小鼠和老年小鼠对机械负荷的骨合成代谢反应增敏，从而促进骨形成。结论：这些数据表明，miR-138-5p作为一种机械反应性miRNA，可以解释骨合成代谢反应的机械敏感性，抑制成骨细胞中的miR-138-5p可能是一种新的骨合成代谢增敏策略，可以改善废用性或老年性骨质疏松症。
Emerging evidence is revealing that microRNAs (miRNAs) play essential roles in mechanosensing for regulating osteogenesis. However, no mechanoresponsive miRNAs have been identified in human bone specimens. Methods: Bedridden and aged patients, hindlimb unloaded and aged mice, and Random Positioning Machine and primary aged osteoblasts were adopted to simulate mechanical unloading conditions at the human, animal and cellular levels, respectively. Treadmill exercise and Flexcell cyclic mechanical stretching were used to simulate mechanical loading in vivo and in vitro, respectively. Results: Here, we found increased miR-138-5p levels with a lower degree of bone formation in bone specimens from bedridden and aged patients. Loss- and gain-of-function studies showed that miR-138-5p directly targeted microtubule actin crosslinking factor 1 (MACF1) to inhibit osteoblast differentiation under different mechanical conditions. Regarding translational medicine, bone-targeted inhibition of miR-138-5p attenuated the decrease in the mechanical bone anabolic response in hindlimb unloaded mice. Moreover, bone-targeted inhibition of miR-138-5p sensitized the bone anabolic response to mechanical loading in both miR-138-5p transgenic mice and aged mice to promote bone formation. Conclusion: These data suggest that miR-138-5p as a mechanoresponsive miRNA accounts for the mechanosensitivity of the bone anabolic response and that inhibition of miR-138-5p in osteoblasts may be a novel bone anabolic sensitization strategy for ameliorating disuse or senile osteoporosis.
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破骨细胞来源的外泌体 miR-214-3p 抑制成骨细胞骨形成
影响因子：
16.6
作者：
Li D;Liu J;Guo B;Liang C;Dang L;Lu C;He X;Cheung HY;Xu L;Lu C;He B;Liu B;Shaikh AB;Li F;Wang L;Yang Z;Au DW;Peng S;Zhang Z;Zhang BT;Pan X;Qian A;Shang P;Xiao L;Jiang B;Wong CK;Xu J;Bian Z;Liang Z;Guo DA;Zhu H;Tan W;Lu A;Zhang G
通讯作者：
Zhang G
影响因子：
5.4
作者：
Li B;Bai L;Shen P;Sun Y;Chen Z;Wen Y
通讯作者：
Wen Y
靶向沉默 miRNA-132-3p 表达可通过促进小鼠间充质干细胞成骨分化和成骨来挽救废用性骨质减少。
影响因子：
7.5
作者：
Hu, Zebing;Zhang, Lijun;Zhang, Ge
通讯作者：
Zhang, Ge
DOI：
10.1007/978-1-61779-415-5_2
发表时间：
2012-01-01
期刊：
BONE RESEARCH PROTOCOLS, SECOND EDITION
影响因子：
--
作者：
Bakker, Astrid D.;Klein-Nulend, Jenneke
通讯作者：
Klein-Nulend, Jenneke
DOI：
10.1002/jbmr.2900
发表时间：
2016-12
期刊：
Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research
影响因子：
--
作者：
Holguin N;Brodt MD;Silva MJ
通讯作者：
Silva MJ