Abstract：
Ankle osteoarthritis is a relatively understudied condition and the molecular mechanisms involved in its development are not well understood. This investigation aimed to explore the role and underlying molecular mechanisms of Yes-associated protein (YAP) in rat ankle osteoarthritis. The results demonstrated that YAP expression levels were abnormally increased in the ankle osteoarthritis cartilage model. In addition, knockdown of YAP expression was shown to hinder the imbalance in ECM metabolism induced by IL-1β in chondrocytes, as demonstrated by the regulation of matrix metalloproteinase (MMP)-3, MMP-9, and MMP-13, a disintegrin, metalloprotease with thrombospondin motifs, aggrecan, and collagen II expression. Additional studies revealed that downregulation of YAP expression markedly inhibited the overexpression of β-catenin stimulated by IL-1β. Furthermore, inhibition of the Wnt/β-catenin signaling pathway reversed the ECM metabolism imbalance caused by YAP overexpression in chondrocytes. It is important to note that the YAP-specific inhibitor verteporfin (VP) significantly delayed the progression of ankle osteoarthritis. In conclusion, the findings highlighted the crucial role of YAP as a regulator in modulating the progression of ankle osteoarthritis via the Wnt/β-catenin signaling pathway. These findings suggest that pharmacological inhibition of YAP can be an effective and critical therapeutic target for alleviating ankle osteoarthritis.
摘要：
踝关节关节炎是一种相对较少研究的疾病，其发展过程中涉及的分子机制尚不清楚。本研究旨在探讨Yes相关蛋白(YAP)在大鼠踝关节骨性关节炎中的作用及其分子机制。结果表明，YAP表达水平在踝关节骨性关节炎软骨模型中异常升高。此外,YAP表达的敲低被证明阻碍了软骨细胞中IL-1β诱导的ECM代谢失衡，正如基质金属蛋白酶（MMP）-3，MMP-9和MMP-13的调节所证明的那样，具有血小板反应蛋白基序的金属蛋白酶，aggrecan,和胶原蛋白II表达。其他研究表明，YAP表达的下调显着抑制了IL-1β刺激的β-catenin的过表达。此外，抑制Wnt/β-catenin信号通路逆转了YAP在软骨细胞中过度表达引起的ECM代谢失衡。值得注意的是，YAP特异性抑制剂维替泊芬（VP）显着延迟了踝关节骨关节炎的进展。总之,研究结果强调了YAP作为调节因子通过Wnt/β-catenin信号通路调节踝关节关节炎进展的关键作用.这些发现表明，药物抑制YAP可能是缓解踝关节骨性关节炎的有效和关键的治疗靶点。
