Xanthohumol Inhibited Mechanical Stimulation-Induced Articular ECM Degradation by Mediating lncRNA GAS5/miR-27a Axis

Tiansheng Zheng; Qingluo Zhou; Jishang Huang; Jinliang Lai; Guanglin Ji; Dechao Kong

doi:10.3389/fphar.2021.737552

Xanthohumol Inhibited Mechanical Stimulation-Induced Articular ECM Degradation by Mediating lncRNA GAS5/miR-27a Axis

Front Pharmacol. 2021 Sep 10:12:737552. doi: 10.3389/fphar.2021.737552. eCollection 2021.

Authors

Tiansheng Zheng¹, Qingluo Zhou¹, Jishang Huang¹, Jinliang Lai², Guanglin Ji¹, Dechao Kong³

Affiliations

¹ Department of Orthopedics, The First Affiliated Hospital of Gannan Medical University, Ganzhou, China.
² Department of Emergency, The First Affiliated Hospital of Gannan Medical University, Ganzhou, China.
³ Department of Trauma Center, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Abstract

Osteoarthritis (OA) is histopathologically marked by extracellular matrix (ECM) degradation in joint cartilage. Abnormal mechanical stimulation on joint cartilage may result in ECM degeneration and OA development. Matrix metalloproteinase 13 (MMP-13) is one of the catabolic enzymes contributing to the degradation of ECM, and it has become the potential biomarker for the therapeutic management of OA. Xanthohumol (XH), a naturally occurring prenylflavonoid derived from hops and beer, shows the protective activity against OA development. However, the potential mechanisms still need great effort. In this article, mechanical stimulation could significantly increase the expression of MMP-13 and lncRNA GAS5 (GAS5) and promoting ECM degradation. These could be effectively reversed by XH administration. Suppressed expression GAS5 ameliorated mechanical stimulation-induced MMP-13 expression. MiR-27a was predicted and verified as a target of GAS5, and overexpression of miR-27a down regulated the expression of MMP-13. Collectively, XH exhibited protective effects against mechanical stimulation-induced ECM degradation by mediating the GAS5/miR-27a signaling pathway in OA chondrocytes.

Keywords: Gas5; extracellular matrix; miR-27a; mmp-13; osteoarthritis; xanthohumol.