OBJECTIVE: To evaluate the molecular mechanism underlying the beneficial effect of Bushen Qiangjin capsule ((sic), BSQJ), a Traditional Chinese 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-BSQJ), and low-dose BSQJ (L-BSQJ). After successfully establishing the KOA model by intra-articular injection of papain, H-BS-QJ and L-BSQJ groups were intragastrically administered 0.243 and 0.122 g/kg BSQJ, 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-1 beta and tumor necrosis factor-alpha levels of rats were detected with an enzyme-linked immunosorbent assay method. Gene expression of Wnt-4, beta-catenin, Frizzled-2, glycogen synthase kinase-3 beta (GSK-3 beta), cysteinyl aspartate-specific proteinases 3 and 9 (caspases 3 and 9), collagen type. alpha 1 (Col2a1), and matrix metalloproteinases 1 and 13 (MMP-1 and MMP-3) of rat knee articular cartilage was quantified by reverse transcription-quantitative polymerase chain reaction analysis. Wnt-4, beta-catenin, Frizzled-2, GSK-3 beta, 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 cartilage in KOA rats. Compared with the KOA group, H-BSQJ rats exhibited downregulated mRNA and protein expression of Wnt-4, beta-catenin, Frizzled-2, and caspase-3, as well as upregulated mRNA and protein expression of GSK-3 beta. 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/beta-catenin pathway, which inhibited both cartilage extracellular matrix degradation and chondrocyte apoptosis to ameliorate KOA in rats. (C) 2021 JTCM. All rights reserved.