Zheng Tiansheng, Zhou Qingluo, Huang Jishang, Lai Jinliang, Ji Guanglin, Kong Dechao
Department of Orthopedics, The First Affiliated Hospital of Gannan Medical University, Ganzhou, China.
Department of Emergency, The First Affiliated Hospital of Gannan Medical University, Ganzhou, China.
Front Pharmacol. 2021 Sep 10;12:737552. doi: 10.3389/fphar.2021.737552. eCollection 2021.
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.
骨关节炎（OA）在组织病理学上的特征是关节软骨中的细胞外基质（ECM）降解。对关节软骨的异常机械刺激可能导致ECM退变和OA发展。基质金属蛋白酶13（MMP-13）是导致ECM降解的分解代谢酶之一，并且已成为OA治疗管理的潜在生物标志物。黄腐酚（XH）是一种天然存在的来源于啤酒花和啤酒的异戊烯基黄酮，显示出对OA发展的保护活性。然而，其潜在机制仍需深入研究。在本文中，机械刺激可显著增加MMP-13和长链非编码RNA GAS5（GAS5）的表达，并促进ECM降解。这些作用可通过给予XH有效逆转。GAS5表达受抑制可改善机械刺激诱导的MMP-13表达。预测并验证miR-27a是GAS5的一个靶点，miR-27a过表达可下调MMP-13的表达。总体而言，XH通过介导OA软骨细胞中的GAS5/miR-27a信号通路，对机械刺激诱导的ECM降解具有保护作用。
