Cryptotanshinone protects against IL-1β-induced inflammation in human osteoarthritis chondrocytes and ameliorates the progression of osteoarthritis in mice

Osteoarthritis (OA) is a common degenerative disease characterized by progressive erosion of articular cartilage, subchondral bone sclerosis and synovitis. Cryptotanshinone (CTS), an active component extracted from the root of Salvia miltiorrhiza Bunge, has been shown to have potent anti-inflammatory effects. However, its effects on OA have not been clearly elucidated. This study aimed to assess the effect of CTS on human OA chondrocytes and mice OA models. Human OA chondrocytes were pretreated with CTS (5, 10 and 20 mu M) for 2 h and subsequently stimulated with IL-1 beta for 24 h. Production of NO, PGE2, IL-6, TNF-alpha was evaluated by the Griess reaction and ELISA. The protein expression of COX-2, iNOs, MMP-3, MMP13, COX-2, ADAMTS-5, JNK, p-JNK, ERK, p-ERK, p38, p-p38, p-IICK alpha/beta, p65, p-p65, I kappa B-alpha, and p-I kappa B-alpha was tested by Western blot. In vivo, the severity of OA was determined by histological analysis. We found that CTS significantly inhibited the IL-1 beta-induced production of NO and PGE2; expression of COX-2, iNOS, MMP-3, MMP-13, and ADAMTS-5. Furthermore, CTS in dramatically suppressed IL-1 beta-stimulated NF-kappa B and MAPK activation. Immunofluorescence staining demonstrated that CTS could suppress IL-1 beta-induced phosphorylation of p65 nuclear translocation. In vivo, treatment of CTS prevented the destruction of cartilage and the thickening of subchondral bone in mice OA models. These results indicate that the therapeutic effect of CTS on OA is accomplished through the inhibition of both NF-kappa B and MAPK signaling pathways. Our findings provide the evidence to develop CTS as a potential therapeutic agent f or patients with OA.