Inhibition of YAP with SiRNA Prevents Cartilage Degradation and Ameliorates Osteoarthritis Development

Overview

Journal J Mol Med (Berl)

Specialty General Medicine

Date 2018 Nov 23

PMID 30465058

Citations 38

Authors

Yong Gong

Song-Jian Li

Rui Liu

Jian-Feng Zhan

Chao Tan

Yi-Fei Fang

Yan Chen

Bo Yu

Affiliations

Soon will be listed here.

Abstract

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.

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