Anti-arthritic effects of crocin in interleukin-1β-treated articular chondrocytes and cartilage in a rabbit osteoarthritic model

Interleukin-1 beta-mediated production of matrix metalloproteinases (MMPs) plays a pivotal role in the process of osteoarthritis. Crocin, a pharmacologically active component of Crocus sativus L. (saffron), has been used in Chinese traditional medicine. In this study, we aimed to investigate the effects of crocin on MMP-1, MMP-3 and MMP-13 expression in rabbit chondrocytes induced by interleukin-1 beta (IL-1 beta) and in an experimental rabbit model induced by anterior cruciate ligament transection. Chondrocytes isolated from the articular cartilage of 4-week-old rabbits were cultured and passaged. Confluent chondrocytes were treated with various concentrations of crocin in the presence or absence of IL-1 beta (10 ng/ml) for 24 h. Quantitative real-time polymerase chain reaction, enzyme-linked immunosorbent assay, and Western blotting were used to investigate the expression of inducible MMP-1, MMP-3 and MMP-13. In addition, the in-vivo effects of crocin were assessed by morphological and histological analysis. IL-1 beta markedly upregulated the expression of MMP-1, -3 and -13 in chondrocytes, and this activation was inhibited by co-incubation with crocin in a dose-dependent manner, in contrast with the control group. Moreover, crocin inhibited IL-1 beta-induced activation of the nuclear factor kappa B pathway through suppressing degradation of inhibitory-kappa-B-alpha. In-vivo investigations showed that crocin ameliorated cartilage degeneration and that expression of the MMP-1, -3 and -13 genes in cartilage was significantly inhibited by crocin. Taken together, our findings suggest that the anti-inflammatory activity of crocin may be of potential value in the prevention and treatment of osteoarthritis.