Key Laboratory of Non-coding RNA Transformation Research of Anhui Higher Education Institution, Wannan Medical College, Wuhu, China.
Department of Spine Surgery, Yijishan Hospital, The First Affiliated Hospital of Wannan Medical College, Wuhu, China.
Cell Biol Int. 2022 Oct;46(10):1637-1648. doi: 10.1002/cbin.11851. Epub 2022 Jul 12.
Disc herniation is a kind of disease caused by degenerative discs, which is common in the elderly, bringing substantial financial burden to families and society. Mechanical tension has a vital effect on the maintenance of cartilage function, however, the molecular mechanism by which mechanical tension causes degenerative discs to remain unclear. This study was the first to reveal Yes-associated protein 1(YAP1) is a key regulator in mechanical tension-mediated degenerative discs. Activation of YAP1 may be a valuable strategy to delays the degeneration of human cartilage chondrocytes. We found that YAP1 expression was significantly decreased in degenerative human endplate cartilage and tissue with the strength and time of mechanical stimulation, but the cell cycle distribution was significantly changed under the 10% cyclic mechanical tension(CMT). Besides, the degeneration of endplate cartilage can be delayed by activating the expression level of YAP1 in vitro and it has also been verified in the cartilage endplate tissue in vitro. Furthermore, We found that YAP1 and TEAD1 overexpression increased the activity of the ACAN or COL2A1 promoter to enhance the transcriptional activity of human chondrocyte collagen. The CMT activates the classic Hippo signaling pathway of YAP1, and piezo1 may regulate YAP1 expression through the Hippo signaling pathway. In conclusion, these results suggest the novel mechanism of YAP contributes to delaying the degeneration of endplate cartilage and targeting YAP in combination with Piezo1 is a potential therapeutic approach for the treatment of endplate cartilage degeneration.
椎间盘突出症是一种由退变的椎间盘引起的疾病，在老年人中较为常见，给家庭和社会带来了沉重的经济负担。机械张力对维持软骨功能有重要作用，然而，机械张力导致椎间盘退变的分子机制尚不清楚。本研究首次揭示了 Yes 相关蛋白 1（YAP1）是机械张力介导的椎间盘退变的关键调节因子。激活 YAP1 可能是延缓人软骨细胞退变的一种有价值的策略。我们发现，YAP1 在退变的人终板软骨和组织中的表达随着机械刺激的强度和时间而显著降低，但在 10%循环机械张力（CMT）下细胞周期分布显著改变。此外，在体外激活 YAP1 的表达水平可以延缓终板软骨的退变，并且在体外软骨终板组织中也得到了验证。此外，我们发现 YAP1 和 TEAD1 的过表达增加了 ACAN 或 COL2A1 启动子的活性，从而增强了人软骨细胞胶原的转录活性。CMT 激活了 YAP1 的经典 Hippo 信号通路，而 piezo1 可能通过 Hippo 信号通路调节 YAP1 的表达。总之，这些结果表明 YAP 的新机制有助于延缓终板软骨退变，靶向 YAP 结合 Piezo1 可能是治疗终板软骨退变的一种潜在治疗方法。
