Department of Orthopedics, Zhujiang Hospital, Southern Medical University, Guangzhou, 510282, China.
Department of Ultrasonic Diagnosis, Zhujiang Hospital, Southern Medical University, Guangzhou, 510282, China.
J Mol Med (Berl). 2019 Jan;97(1):103-114. doi: 10.1007/s00109-018-1705-y. Epub 2018 Nov 21.
The Hippo/YAP signaling pathway is important for mediating organ size and tissue homeostasis, but its role in osteoarthritis (OA) remains unclear. We aimed to investigate the role of Hippo/YAP signaling pathway in OA development. YAP expression in OA cartilage was assessed by immunohistochemistry, RT-qPCR, and Western blotting. The effects of YAP overexpression or knockdown on gene expression related to chondrocyte hypertrophy induced by IL-1β were examined. The in vivo effects of YAP inhibition were studied. Subchondral bone was analyzed by micro-CT. YAP was increased in mice and human OA articular cartilage and chondrocytes. YAP mRNA expression level was also increased in IL-1β-induced chondrocytes. YAP overexpression resulted in increased expression of catabolic genes in response to IL-1β. Suppression of YAP by siRNA inhibited IL-1β stimulated catabolic genes expression and chondrocytes apoptosis. Intra-articular injection of YAP siRNA ameliorated OA development in mice. Micro-CT results showed the aberrant subchondral bone formation was also reduced. We provided evidence that YAP was upregulated in OA cartilage. Inhibition of YAP using YAP siRNA is a promising way to prevent cartilage degradation in OA. KEY MESSAGES: YAP was upregulated in human and mice osteoarthritis cartilage and chondrocytes. YAP siRNA decreased IL-1β-induced catabolic gene expression. Intra-articular injection of YAP siRNA ameliorated OA development. Intra-articular injection of YAP siRNA reduced aberrant subchondral bone formation.
Hippo/YAP 信号通路对于调节器官大小和组织稳态至关重要，但它在骨关节炎（OA）中的作用尚不清楚。我们旨在研究 Hippo/YAP 信号通路在 OA 发展中的作用。通过免疫组织化学、RT-qPCR 和 Western blot 评估 OA 软骨中的 YAP 表达。通过 IL-1β 诱导的软骨细胞肥大检测 YAP 过表达或敲低对相关基因表达的影响。研究了 YAP 抑制的体内效应。通过 micro-CT 分析软骨下骨。YAP 在小鼠和人类 OA 关节软骨和软骨细胞中增加。IL-1β 诱导的软骨细胞中 YAP mRNA 表达水平也增加。YAP 过表达导致对 IL-1β 的反应性分解代谢基因表达增加。用 siRNA 抑制 YAP 抑制了 IL-1β 刺激的分解代谢基因表达和软骨细胞凋亡。关节内注射 YAP siRNA 改善了小鼠的 OA 发展。micro-CT 结果表明，异常的软骨下骨形成也减少。我们提供了证据表明 YAP 在 OA 软骨中上调。使用 YAP siRNA 抑制 YAP 是预防 OA 软骨降解的一种有前途的方法。 关键信息：YAP 在人类和小鼠 OA 软骨和软骨细胞中上调。YAP siRNA 降低了 IL-1β 诱导的分解代谢基因表达。关节内注射 YAP siRNA 改善了 OA 发展。关节内注射 YAP siRNA 减少了异常的软骨下骨形成。
