Protective effects of biochanin A on articular cartilage: in vitro and in vivo studies

BACKGROUND: Increased production of matrix metalloproteinases (MMPs) is closely related to the progression of osteoarthritis (OA). The present study was performed to investigate the potential value of biochanin A in inhibition of MMP expression in both rabbit chondrocytes and an animal model of OA. METHODS: MTT assay was performed to assess chondrocyte survival in monolayers. The mRNA and protein expression of MMPs (including MMP-1, MMP-3, and MMP-13) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in interleukin-1 < beta > (IL-1β)-induced rabbit chondrocytes were determined by quantitative real-time PCR and enzyme-linked immunosorbent assay (ELISA), respectively. The involvement of the NF-kappaB (NF-κB) pathway activated by IL-1β was determined by western blotting. The in vivo effects of biochanin A were evaluated by intra-articular injection in an experimental OA rabbit model induced by anterior cruciate ligament transection (ACLT). RESULTS: Biochanin A downregulated the expression of MMPs and upregulated TIMP-1 at both the mRNA and protein levels in IL-1β-induced chondrocytes in a dose-dependent manner. In addition, IL-1β-induced activation of NF-κB was attenuated by biochanin A, as determined by western blotting. Moreover, biochanin A decreased cartilage degradation as determined by both morphological and histological analyses in vivo. CONCLUSIONS: Taken together, these findings suggest that biochanin A may be a useful agent in the treatment and prevention of OA.