c-Jun mediates IL-1β regulation of TIMP-4/MMP-2 expression in articular chondrocytes of OA joint
Refereed conference paper presented and published in conference proceedings


摘要The tissue inhibitor of metalloproteinase-4 (TIMP-4) is a member of TIMP family and a potent inhibitor of several matrix metalloproteinases (MMPs) including MMP-2 expressed in normal and/or osteoarthritis (OA) articular cartilage. The roles of TIMP-4 in the pathogenesis of OA remain unknown. This study aims to determine the mechanisms
of regulation of TIMP-4 expression in OA articular chondrocytes. Protein expression of TIMP-4, MMP-2 and c-Jun in OA and non-OA articular cartilage was compared by immunohistochemistry. The transcriptional control of TIMP-4 by c-Jun was identified by chromatin immunoprecipitation (ChIP) assay and confirmed using the TIMP-4-promoter luciferase reporter system. The responses of TIMP-4 and MMP-2 expression to IL-1 Beta treatment were examined in the non-OA articular chondrocytes with or without siRNAmediated knockdown of c-Jun. We found that the protein expression of TIMP-4, MMP-2 and c-Jun was simultaneously upregulated in OA articular cartilage. The mRNA and
protein levels of the above genes in articular chondrocytes of none-OA patients were elevated following treatment with IL-1 Beta. We demonstrated that c-Jun transcriptionally controlled the expression of TIMP-4 through its putative binding site in its promoter region. siRNA mediated knockdown of c-Jun in chondrocytes eliminated the effect of IL-
1 Beta on TIMP-4 expression. c-Jun knockdown significantly decreased the ratio of TIMP4 to MMP2 mRNA expression in chondrocytes, which was accompanied by downregulation of aggrecan expression and upregulation of hypertrophic chondrocyte markers MMP-13 and Col10α1. Our results suggest that c-Jun functions as an important mediator of IL-1 Beta regulation on TIMP-4 and MMP-2 expression in articular chondrocytes. The c-Jun/TIMP-4 axis may serve as a potential target for prevention or treatment of articular cartilage degeneration.
著者WU Yufeng, ZHANG Fengjie, ZHAO Yichen, TSANG Wing Pui, HE Qiling, HUANG Ziqi, TAN Guangyi, WAN CHAO
會議名稱The 4th International Chinese Musculoskeletal Research Conference (ICMRC-2019)

上次更新時間 2020-27-11 於 11:25