Zhang Ming, Zhang Rui, Zheng Tiansheng, Chen Zhixi, Ji Guanglin, Peng Fang, Wang Wei
Department of Orthopedics, Taizhou People's Hospital, Taizhou, China.
College of Pharmacy, Gannan Medical University, Ganzhou, China.
Front Pharmacol. 2021 May 4;12:680585. doi: 10.3389/fphar.2021.680585. eCollection 2021.
Osteoarthritis (OA) is the most frequent and disabling disease in developed countries. The progressive degeneration of articular cartilage characterized as thinner and erosive. Inflammation is well-known to be involved in OA development. However, there are no effective therapeutic strategies to cure it. Xanthohumol (XH) is a natural prenylflavonoid isolated from hops and beer. The protective activity of XH against OA chondrocytes inflammation and ECM degradation is unclear. In this article, we found that XH significantly inhibited inflammatory responses, attenuated catabolic enzymes expression, and ameliorated ECM degradation, as showed by decreased production of NO, PGE2, TNFα, and IL-6, decreased expression of MMP-3/-13 and ADAMTS-4/-5, and increased expression of collagen-II and aggrecan. In addition, XH activated HO-1 signaling and attenuated IL-1β-induced C/EBPβ. XH promoted the interaction between HO-1 and C/EBPβ, inhibiting the nuclear translocation of C/EBPβ. HO-1 knockdown could abrogate the protective effects of XH in IL-1β-treated chondrocytes. Collectively, XH attenuated inflammatory responses and ECM degradation by mediating HO-1 and C/EBPβ signaling pathways in osteoarthritis chondrocytes.
骨关节炎（OA）是发达国家最常见且使人致残的疾病。其特征为关节软骨进行性退变，表现为变薄和糜烂。众所周知，炎症参与了骨关节炎的发展。然而，目前尚无有效的治疗策略来治愈该病。黄腐酚（XH）是一种从啤酒花和啤酒中分离出的天然异戊烯基黄酮。XH对骨关节炎软骨细胞炎症和细胞外基质（ECM）降解的保护作用尚不清楚。在本文中，我们发现XH显著抑制炎症反应，减弱分解代谢酶的表达，并改善ECM降解，表现为一氧化氮（NO）、前列腺素E2（PGE2）、肿瘤坏死因子α（TNFα）和白细胞介素-6（IL-6）的产生减少，基质金属蛋白酶-3/-13（MMP-3/-13）和含血小板反应蛋白基序的解聚蛋白样金属蛋白酶-4/-5（ADAMTS-4/-5）的表达降低，以及胶原蛋白-II和聚集蛋白聚糖的表达增加。此外，XH激活血红素加氧酶-1（HO-1）信号通路并减弱白细胞介素-1β（IL-1β）诱导的C/EBPβ。XH促进HO-1与C/EBPβ之间的相互作用，抑制C/EBPβ的核转位。敲低HO-1可消除XH对IL-1β处理的软骨细胞的保护作用。总体而言，XH通过介导骨关节炎软骨细胞中的HO-1和C/EBPβ信号通路减弱炎症反应和ECM降解。
