OBJECTIVE:To evaluate the molecular mechanism underlying the beneficial effect of Bushen Qiangjin capsule(补肾强筋胶囊,BSQJ),a Traditional Chi-nese Medicine,on knee osteoarthritis (KOA).METHODS:In the present study,32 female Sprague-Dawley rats were randomly divided into four groups:control,KOA,high-dose BSQJ (H-BS-Q J),and low-dose BSQJ (L-BSQJ).After successfully establishing the KOA model by intra-articular injec-tion of papain,H-BSQJ and L-BSQJ groups were in-tragastrically administered 0.243 and 0.122 g/kg BS-Q J,respectively,daily for 6 weeks.At the end of the experiment,knee articular cartilage tissues of rats were collected for evaluation by hematoxylin and eosin staining,Safranin O-Fast Green staining,and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay.Serum interleukin-1β and tumor necrosis factor-α levels of rats were de-tected with an enzyme-linked immunosorbent as-say method.Gene expression of Wnt-4,β-catenin,Frizzled-2,glycogen synthase kinase-3β (GSK-3β),cysteinyl aspartate-specific proteinases 3 and 9(caspases 3 and 9),collagen type Ⅱ alpha 1(Col2a1),and matrix metalloproteinases 1 and 13(MMP-1 and MMP-3) of rat knee articular cartilage was quantified by reverse transcription-quantita-tive polymerase chain reaction analysis.Wnt-4,β-catenin,Frizzled-2,GSK-3β,cleaved caspase-3,and cleaved caspase-9 protein expression in rat knee articular cartilage was determined by western blot analysis.RESULTS:BSQJ obviously reduced pathological damage and matrix degradation of articular carti-lage in KOA rats.Compared with the KOA group,H-BSQJ rats exhibited downregulated mRNA and protein expression of Wnt-4,β-catenin,Frizzled-2,and caspase-3,as well as upregulated mRNA and protein expression of GSK-3β.In addition,H-BSQJ significantly increased mRNA expression of Col2a1 and decreased mRNA expression of MMP-1 and MMP-13.CONCLUSION:BSQJ exerted a beneficial effect on KOA by a mechanism involving downregulation of the Wnt/β-catenin pathway,which inhibited both cartilage extracellular matrix degradation and chondrocyte apoptosis to ameliorate KOA in rats.