Inhibition of YAP with siRNA prevents cartilage degradation and ameliorates osteoarthritis development

AbstractThe 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-1 β 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 in creased 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 messagesYAP was upregulated in human and mice osteoarthritis cartilage and chondrocytes.YAP siRNA decreased IL-1 β-induced catabolic gene expression.Intra-articular injection of YAP siRNA ameliorated OA development.Intra-articular injection of YAP siRNA r...
Source: Journal of Molecular Medicine - Category: Molecular Biology Source Type: research