Li Ci, Wu Wenliang, Jiao Guangjun, Chen Yunzhen, Liu Haichun
Department of Orthopedics, Qilu Hospital of Shandong University 107# Wenhua West Road Jinan 250012 China
RSC Adv. 2018 Jun 4;8(36):20202-20210. doi: 10.1039/c8ra00993g. eCollection 2018 May 30.
Resveratrol (Res), a naturally occurring polyphenolic compound, has been reported to exert many biological effects like anti-inflammatory and anti-oxidant effects. In this study, we investigated the role of Res on IL-1β-induced osteoarthritis (OA) chondrocytes and its possible mechanism. Results demonstrated that Res suppressed IL-1β-induced IL-1, IL-6 and TNF-α production in a dose-dependent manner. Res also decreased MMP-1, MMP-3 and MMP-13 production in IL-1β-induced OA chondrocytes. These results suggested that Res suppressed IL-1β-induced inflammation and matrix-metalloproteases (MMP) expression in OA chondrocytes. In addition, Res was found to reverse the decreased autophagy level through increasing the expression of Beclin1, LC3 II/I ratio and LC3 puncta in IL-1β-induced OA chondrocytes. Inhibition of autophagy by 3-methyladenine (3-MA) abolished the inhibitory effect of Res on inflammation and MMP expression in IL-1β-induced OA chondrocytes. Moreover, the Wnt/β-catenin signaling pathway was activated in IL-1β-induced OA chondrocytes. However, Res was found to suppress this activated Wnt/β-catenin signaling pathway. Activation of the Wnt/β-catenin signaling pathway counteracted the promoted effect on autophagy and inhibitory effect on inflammation and MMP expression of Res in IL-1β-induced OA chondrocytes. Taken together, our data demonstrated that Res attenuated inflammation and reduced MMP expression through inducing autophagy inhibiting the Wnt/β-catenin signaling pathway in IL-1β-induced OA chondrocytes. Res may be used as a potential therapeutic agent for OA treatment.
白藜芦醇(Res)是一种天然存在的多酚化合物,据报道具有多种生物学效应,如抗炎和抗氧化作用。在本研究中,我们研究了Res对白细胞介素-1β(IL-1β)诱导的骨关节炎(OA)软骨细胞的作用及其可能机制。结果表明,Res以剂量依赖性方式抑制IL-1β诱导的IL-1、IL-6和肿瘤坏死因子-α(TNF-α)的产生。Res还降低了IL-1β诱导的OA软骨细胞中基质金属蛋白酶-1(MMP-1)、基质金属蛋白酶-3(MMP-3)和基质金属蛋白酶-13(MMP-13)的产生。这些结果表明,Res抑制了IL-1β诱导的OA软骨细胞中的炎症和基质金属蛋白酶(MMP)表达。此外,发现Res通过增加IL-1β诱导的OA软骨细胞中Beclin1的表达、LC3 II/I比值和LC3斑点来逆转自噬水平的降低。用3-甲基腺嘌呤(3-MA)抑制自噬消除了Res对IL-1β诱导的OA软骨细胞中炎症和MMP表达的抑制作用。此外,在IL-1β诱导的OA软骨细胞中Wnt/β-连环蛋白信号通路被激活。然而,发现Res抑制了这种激活的Wnt/β-连环蛋白信号通路。Wnt/β-连环蛋白信号通路的激活抵消了Res对IL-1β诱导的OA软骨细胞自噬的促进作用以及对炎症和MMP表达的抑制作用。综上所述,我们的数据表明,Res通过诱导自噬和抑制IL-1β诱导的OA软骨细胞中的Wnt/β-连环蛋白信号通路来减轻炎症并降低MMP表达。Res可能用作OA治疗的潜在治疗剂。