Emodin ameliorates cartilage degradation in osteoarthritis by inhibiting NF-κB and Wnt/β-catenin signaling in-vitro and in-vivo.

The overproduction of MMPs (matrix metalloproteinases) and members of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) protein family plays an important role in the pathogenesis of osteoarthritis (OA). The potential of selective MMPs or ADAMTS inhibitors as chemopreventive agents for OA has been demonstrated in several studies. In this study, we investigated the protective effects of emodin (1,3,8-trihydroxy-6-methylanthaquinone), isolated from the root of Rheum palmatum L., in the inhibition of MMP and ADAMTS expression in both rat chondrocytes and an animal model of OA. The expression of MMP-3, MMP-13, ADAMTS-4, ADAMTS-5, aggrecan, and collagen II mRNA and protein in interleukin-1beta (IL-1β)-induced rat chondrocytes was followed by quantitative real-time PCR and western blot. The activation of the NF-κB and Wnt/β-catenin pathways by IL-1β was assessed by western blot. The in vivo effects of emodin were evaluated by intra-articular injection in rats in an experimental model of OA induced by anterior cruciate ligament transection. Emodin dose-dependently down-regulated the expression of MMP-3, MMP-13, ADAMTS-4 and ADAMTS-5 at both the mRNA and protein level in IL-1β-stimulated rat chondrocytes. In addition, the IL-1β-induced activation of NF-κB and Wnt signals was attenuated by emodin, as determined by western blotting. The intra-articular injection of emodin in a rat OA model ameliorated OA progression, as determined in morphological and histological analyses in vivo. Taken together, our findings demonstrate that emodin is a promising therapeutic agent for the prevention and treatment of OA.