Osteoarthritis (OA) is a chronic disease that is mainly characterized by chondrocyte degeneration. Inflammatory mediators participate in the development of OA, leading to chondrocyte apoptosis and destruction of the cartilage. Genistein is the major active component of isoflavone, with a chemical composition and a biological effect that is similar to that of estrogens, which prevents the degradation of cartilage; however, its underlying mechanisms of action remain unknown. The aim of the present study was to investigate the anti-apoptotic effects of genistein on chondrocytes for the treatment of inflammation-induced OA. Interleukin (IL)-1β was used to establish a chondrocyte OA model. After treatment with different concentrations of genistein, western blotting identified that expression levels of collagen II and aggrecan were increased in a concentration-dependent manner, while caspase 3 expression gradually decreased after genistein application. Moreover, flow cytometry and ELISA results demonstrated that genistein could decrease chondrocyte apoptosis and reduce the levels of tumor necrosis factor (TNF)-α in a dose-dependent manner. Furthermore, the in vitro data were evaluated in an OA rat model. Genistein increased the collagen and acid glycosaminoglycan content, as well as decreased the levels of TNF-α and IL-1β. Genistein also promoted the expression levels of collagen II and aggrecan in the articular cartilage, and decreased the expression of caspase 3, thus alleviating cartilage degradation. In conclusion, the results indicated that genistein mediated inflammation and had an anti-apoptotic role in treating OA. Therefore, genistein may serve as an alternative treatment for OA.

Background: Knee osteoarthritis (KOA) is one of the leading causes of disability, and its etiopathogenesis is not completely understood. Polydatin has the potential effect on the treatment of KOA, but the mechanism is not clear.Methods: After an KOA rat model was established by anterior cruciate ligament transection, KOA rats were treated with polydatin (4 mg/kg) for 30 days. Subsequently, cartilage tissues were collected from rats and detected by HE, TUNEL staining and Western blotting to evaluate the pathological damage, apoptosis and autophagy activity. Then, human chondrocyte C28/I2 cells were stimulated by LPS to induce a KOA model in vitro, and the effects of polydatin on the C28/I2 cell viability, apoptosis and autophagy were also detected. In addition, the mechanism of polydatin on KOA in C28/I2 cells was investigated, and the effect of an AMPK inhibitor (Dorsomorphin 2HCl) on the proliferation and apoptosis of polydatin administrated-cells were also detected. Results: After treated with polydatin, the pathological damage of rat cartilage tissues were ameliorated, cells apoptosis was inhibited and autophagy was activated in KOA rats. Meanwhile, polydatin also ameliorated the proliferation and apoptosis of C28/I2 cells, the expression of autophagy-related proteins, LC3II/LC3I, Beclin-1, and p-AMPK/AMPK were up-regulated, p-mTOR/mTOR was down-regulated by polydatin in C28/I2 cells. Interestingly, relative results showed that the improvement effect of polydatin on LPS-sdtimulated-C28/I2 cells was blocked by AMPK/mTOR inhibitor, Dorsomorphin 2HCl. Conclusion: Our research showed that polydatin reduces apoptosis and activate autophagy both in a rat model of KOA and C28/I2 cell model by AMPK/mTOR signaling pathway, which provides the basis for further investigations into the potential therapeutic impact of polydatin in KOA.

Cartilage degeneration is reported to be one of the pathological symptoms of osteoarthritis (OA). Pyroptosis is highly involved in the development of cartilage degeneration and is regulated by the NLRP3 inflammasome. The present study aims to check the impact of Wufuyin granules (WFYG) against cartilage degeneration and explore the potential mechanism. Knee osteoarthritis (KOA) model was constructed in rats. The IL-1β and IL-18 level in chondrocytes and peripheral blood of KOA rats was detected by ELISA. Western Blot, qRT-PCR and immunofluorescence assay were applied to determine the IL-1β, IL-18, NLRP3, ASC and Caspase-1 levels in chondrocytes. The ROS level was visualized via immunofluorescence assay. The pyroptosis rate of chondrocytes was evaluated by flow cytometry and AO/EB staining. The release of IL-1β and IL-18 was repressed by WFYG both in-vitro and in-vivo. The pyroptosis rate of chondrocytes isolated from KOA rats was suppressed by a high dosage of WFYG. ROS in the cartilage tissue was significantly inhibited by the introduction of WFYG. IL-1β, IL-18, NLRP3, ASC and caspase-1 were downregulated by WFYG both in-vitro and in-vivo. WFYG ameliorates cartilage degeneration by inhibiting pyroptosis, possibly through suppressing the activation of NLRP3 inflammasomes.