Protective effects of Erdosteine on interleukin-1 beta-stimulated inflammation via inhibiting the activation of MAPK, NF-kappa B, and Wnt/beta-catenin signaling pathways in rat osteoarthritis

摘要

Osteoarthritis (OA), a degenerative arthropathy, is featured with progressive degradation of cartilage and a chondrocyte inflammatory response. Erdosteine (ER) showed the anti-oxidant properties and various anti-inflammatory effects in various diseases. However, whether it protects against OA remains unknown. In this study, we explore the potential therapeutic properties of ER on IL-beta-stimulated rat chondrocytes and its underlying mechanism in vitro and vivo. Cell viability, pro-inflammatory cytokines and the degradation of ECM biomarkers were tested to determine the effects of ER at 10, 20, and 40 mu M doses on IL-1 beta-induced rat chondrocytes for 24 h in virto. In vivo, intra-articular injections of 50 mu l of 100 mg/ml ER twice a week for 8 weeks. The results showed ER significantly suppressed the expressions of IL-1 beta-induced the production of inflammatory factors in a dose-dependent pattern (4.30-fold decrease in COX-2, p < 0.05; 4.77-fold decrease in iNOS, p < 0.05 at 40 mu M in protein levels). Moreover, ER could attenuate the degradation of ECM in IL-1 beta-induced rat chondrocytes by repressing the expression of OA-related factors (2.40-fold decrease in ADAMTS-5, p < 0.05; 3.12-fold decrease in MMP1, p < 0.05; 3.97-fold decrease in MMP3, p < 0.05; and 2.62-fold decrease in MMP-13, p < 0.05 at 40 mu M in protein levels). Furthermore, our study revealed that ER could inhibit the activations of IL-1 beta-induced MAPK and Wnt/beta-catenin. Besides, ER could suppress the process of IL-1 beta-induced P65 from the cytoplasm into the nucleus. In vivo, ER delaied the osteoarthritis progression in rat OA models. Collectively, ER might become a new therapeutic agent for OA.