Quercetin Alleviates Osteoarthritis Progression In Rats By Suppressing Inflammation And Apoptosis Via Inhibition Of Irak1/Nlrp3 Signaling

Introduction: Quercetin was recently reported to help protect against osteoarthritis (OA) progression, but the molecular mechanism for that protective affect remains unclear. Methods: Here, OA model rats were intraperitoneally injected with quercetin, and the severity of cartilage damage in the rats was evaluated by H&E, Safranin O, and Toluidine blue, as well as by using the Osteoarthritis Research Society International (OARSI) Scoring System. Additionally, rat chondrocytes were treated with quercetin and then stimulated with IL-10. The levels of pro-inflammatory cytokines (IL-10, IL-18, and TNF-alpha) were detected by ELISA.Cell apoptosis was evaluated by flow cytometry and Hoechst staining. ROS levels were measured using a DCFH-DA probe. Protein expression was evaluated by Western blotting, immunohistochemical staining, and immunofluorescence. Results: Our data showed that quercetin attenuated the degeneration and erosion of articular cartilage, suppressed inflammation and apoptosis, and downregulated the levels of IRAK1, NLRP3, and caspase-3 expression. In vitro data showed that overexpression of NLRP3 could reverse the suppressive effect of quercetin on IL-10-induced rat chondrocyte injuries. Importantly, rescue experiments confirmed that quercetin inhibited IL-10-induced rat chondrocyte injuries in vitro by suppressing the IRAK1/NLRP3 signaling pathway. Conclusion: Our study indicated that quercetin inhibits IL-10-induced inflammation and cartilage degradation by suppressing the IRAK1/NLRP3 signaling pathway.