Quercetin alleviates rat osteoarthritis by inhibiting inflammation and apoptosis of chondrocytes, modulating synovial macrophages polarization to M2 macrophages

摘要

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.