To investigate the potential value of icariin in the treatment of osteoarthritis and the regulatory effect of Icariin on nucleoside binding oligomerization domain like receptor protein 3(NLRP3) and caspase-1.Methods:In this study,lipopolysaccharide(LPS) was used to induce rat knee chondrocytes to establish an in vitro osteoarthritis model,and SD rats were treated with monosodium iodoacetate to establish an in vivo osteoarthritis model.The cytotoxicity was detected by the lactate dehydrogenase leakage test,and the cell viability was detected by the MTT test.The expression of NLRP3 mRNA was detected by qRT-PCR,and the protein expression of NLRP3,IL-1β,IL-18,MMP-1,MMP-13,collagen Ⅱ,Caspase-1,ASC and GSDMD was detected by Western Blotting.Immunofluorescence and immunohistochemical methods were used to detect the expression of NLRP3 in chondrocytes and rat cartilage.Safranin O/Fast Green staining evaluated cartilage lesions in rats.Results:Compared with LPS group,the LDH leakage rate and the expression levels of IL-1β,IL-18,MMP-1,MMP-13,NLRP3,Caspase-1,ASC,and GSDMD in LPS+ICA group were significantly reduced,while collagenⅡ was increased(P<0.05).Compared with the LPS+ICA+pcDNA3.1-NC group,the lactate dehydrogenase leakage rate and the expression level of NLRP3 inflammasome-related protein in the LPS+ICA+pcDNA3.1-NLRP3 group were significantly increased(P<0.05).Compared with the control group,the number of NLRP3 positive cells in the cartilage tissue of the OA group increased significantly,while the number of NLRP3 positive cells in the OA+ICA group was significantly reduced(P<0.05).Compared with the OA group,the protein expression levels of NRLP3,IL-1β,IL-18,MMP-1,MMP-13,Caspase-1,ASC and GSDMD in the OA+ICA group were significantly reduced,while the protein expression levels of collagen Ⅱ were significantly increased(P<0.05).Conclusion:Icariin inhibits lipopolysaccharide-induced chondrocyte damage and pyrolysis by inhibiting NLRP3 and Caspase-1 signaling,thereby reducing osteoarthritis in rats.