MiR-582-3p alleviates osteoarthritis progression by targeting YAP1
MiR-582-3p alleviates osteoarthritis progression by targeting YAP1
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DOI：
10.1016/j.molimm.2020.10.022
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发表时间：
2020-12-01
影响因子：
3.6
通讯作者：
Xie, Wenwei
中科院分区：
文献类型：
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作者：
He, Jun;Su, Xiaotao;Xie, Wenwei
骨关节炎（OA）是一种广泛存在的退行性关节疾病，影响着全球超过3.5亿人。虽然YAP 1在OA发病中起着关键作用，但其生物学功能和作用机制仍需进一步研究。在本研究中，我们证明了YAP 1在OA大鼠软骨细胞中高度表达。近年来，研究发现生长中的microRNAs（miRNAs）在OA的发生发展中起重要作用。其中，miR-582- 3 p是为数不多的显著下调的miRNAs之一，引起了我们的关注。功能研究表明，miR-582- 3 p抑制软骨细胞凋亡，减少促炎细胞因子的产生，并抑制细胞外基质（ECM）降解。随后的分子机制研究提示YAP 1是miR-582- 3 p的下游靶点。此外，救援试验表明，YAP 1扩增可以逆转miR-582- 3 p模拟物介导的对软骨细胞凋亡、炎症反应和ECM降解的影响。建立OA大鼠模型，探讨miR-582- 3 p/YAP 1轴在体内的功能。结果表明，YAP 1过表达可以恢复由注射AAV-miR-582- 3 p模拟物诱导的对OA进展的影响。综上所述，这些发现暗示了miR-582- 3 p/YAP 1轴在OA中的关键作用，这可能为OA提供有希望的治疗策略。
Osteoarthritis (OA) is a widespread degenerative joint disease that affects more than 350 million people worldwide. Although YAP1 has been proved to play a key role in OA, the biological function and mechanism of YAP1 in OA still need further investigation. In the present study, we demonstrated that YAP1 was highly expressed in OA rat chondrocytes. Recently, growing microRNAs (miRNAs) have been reported to play important roles in OA development. Among them, miR-582-3p is one of the few significantly downregulated miRNAs and attracted our attention. Functional investigations indicated that miR-582-3p inhibited chondrocyte apoptosis, reduced the proinflammatory cytokine production and suppressed extracellular matrix (ECM) degradation. Subsequently, molecular mechanism exploration implied that YAP1 is a downstream target of miR-582-3p. Furthermore, rescue assays revealed that YAP1 amplification can reverse miR-582-3p mimic-mediated effects on chondrocyte apoptosis, inflammatory response, and ECM degradation. Moreover, the OA rat model was established to explore the function of miR-582-3p/YAP1 axis in vivo. The results showed that YAP1 overexpression can recover the effects induced by injection of AAV-miR-582-3p mimic on OA progression. To sum up, these findings implied a crucial role of miR-582-3p/YAP1 axis in OA, which may provide a promising therapeutic strategy for OA.