Inhibition of YAP with siRNA prevents cartilage degradation and ameliorates osteoarthritis development
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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.
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.
KeywordsYAP siRNA Osteoarthritis Cartilage
This project was funded by the National Natural Science Foundation of China (grant number: 81371931 and 81301240) and the Natural Science Foundation of Guangdong Province, China (grant number: 2014A030313352 and 2014A030313310).
Compliance with ethical standards
This study was approved by the Institute Research Ethics Committee at the Southern Medical University. Written informed consent was obtained from each patient.
Conflict of interest
The authors declare that they have no competing interests.
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