Quercetin alleviates rat osteoarthritis by inhibiting inflammation and apoptosis of chondrocytes, modulating synovial macrophages polarization to M2 macrophages
Quercetin alleviates rat osteoarthritis by inhibiting inflammation and apoptosis of chondrocytes, modulating synovial macrophages polarization to M2 macrophages
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槲皮素通过抑制软骨细胞炎症和凋亡、调节滑膜巨噬细胞极化为 M2 巨噬细胞来减轻大鼠骨关节炎
DOI：
10.1016/j.freeradbiomed.2019.09.024
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发表时间：
2019-12-01
影响因子：
7.4
通讯作者：
Xu, Yuanjin
中科院分区：
文献类型：
--
作者：
Hu, Yue;Gui, Zhipeng;Xu, Yuanjin
骨关节炎（OA）是一种进行性关节疾病，其主要特征是关节软骨的变性和破坏。关节软骨基质的降解、炎症介质的产生、软骨细胞的凋亡和巨噬细胞的活化参与了OA的发病机制。目前OA的非手术治疗主要是缓解疼痛，但几乎不能缓解OA的进展。槲皮素是一种天然存在的黄酮类化合物，具有较强的抗炎作用，但其对OA的作用机制尚未系统阐明。本研究旨在探讨槲皮素对OA诱导的软骨损伤的保护作用及其可能的机制。体外实验表明，槲皮素能显著抑制白细胞介素1 β（IL-1 β）诱导的大鼠软骨细胞基质降解蛋白酶和炎症介质的表达，同时促进软骨合成代谢因子的产生。此外，槲皮素通过降低细胞内活性氧（ROS），恢复线粒体膜电位（MMP）和抑制凋亡大鼠软骨细胞中的Caspase-3途径表现出抗凋亡作用。此外，槲皮素诱导巨噬细胞的M2极化并上调转化生长因子β（TGF-1 β）和胰岛素样生长因子（IGF）的表达，这反过来又为软骨细胞创造了促软骨形成的微环境并促进软骨细胞中糖胺聚糖（GAG）的合成。在体内实验中，关节腔内注射槲皮素可减轻大鼠OA模型的软骨退化和软骨细胞凋亡。此外，滑膜液中TGF-1 β和TGF-β 2的表达以及滑膜中M2巨噬细胞的比例升高。总之，我们的研究证明，槲皮素通过抑制软骨细胞的炎症和凋亡，调节滑膜巨噬细胞向M2巨噬细胞的极化，为软骨细胞创造促软骨形成环境，以增强OA环境下的软骨修复，从而发挥软骨保护作用。槲皮素有可能成为治疗OA的潜在药物。
Osteoarthritis (OA) is a progressive joint disorder that is primarily characterized by the degeneration and destruction of the articular cartilage. Cartilage matrix degradation, production of proinflammatory mediators, chondrocyte apoptosis and activation of macrophages in the synovial are involved in OA pathogenesis. Current non-surgical therapies for OA mainly aim at relieving pain but can barely alleviate the progression of OA. Quercetin, a naturally occurring flavonoid has shown potent anti-inflammatory effects, however, its effects and underlying mechanisms on OA have seldom been systematically illuminated. In this study, we explored the protective effects of quercetin on repairing OA-induced cartilage injuries and its possible mechanisms. In vitro, quercetin remarkably suppressed the expression of matrix degrading proteases and inflammatory mediators, meantime promoted the production of cartilage anabolic factors in interleukin-1 beta-induced (IL-1 beta) rat chondrocytes. In addition, quercetin exhibited anti-apoptotic effects by decreasing intracellular reactive oxygen species (ROS), restoring mitochondrial membrane potential (MMP) and inhibiting the Caspase-3 pathway in apoptotic rat chondrocytes. Moreover, quercetin induced M2 polarization of macrophages and upregulated the expression of transforming growth factor beta (TGF-1 beta) and insulin-like growth factor (IGF), which in turn created a pro-chondrogenic microenvironment for chondrocytes and promoted the synthesis of glycosaminoglycan (GAG) in chondrocytes. In vivo, intra-articular injection of quercetin alleviated the degradation of the cartilage and the apoptosis of chondrocytes in a rat OA model. Moreover, the expression of TGF-1 beta and TGF-beta 2 in the synovial fluid and the ratio of M2 macrophages in the synovial membrane were elevated. In summary, our study proves that quercetin exerts chondroprotective effects by inhibiting inflammation and apoptosis of chondrocytes, modulating synovial macrophages polarization to M2 macrophages and creating a pro-chondrogenic environment for chondrocytes to enhance cartilage repair under OA environment. It is suggested that quercetin may serve as a potential drug for OA treatment.