Celecoxib Attenuates Cartilage Matrix Damage in Arthritis Rats by Inhibiting NF-kappa B

Objective: Celecoxib selectively inhibits the activity of COX-2 and the production of prostaglandin (PG), and plays a therapeutic role in treating osteoarthritis (OA). NE-kappa B signaling and IL-1 beta and TNF alpha are involved in OA pathogenesis. This study explored whether Celecoxib might exert therapeutic effects on OA through regulating NE-kappa B signaling and IL-1 beta and TNF alpha release in OA rat model. Methods The contents of MMP-13, Hyp, IL-1 beta and TNF alpha in synovial fluid were detected by ELISA. The protein expressions of NF--kappa B p-p65, COL2A1 and the activity of caspase-3 were detected. OA model rats were separated into OA group and OA +Celecoxib group followed by analysis of MMP-13, Hyp, IL-1 beta and TNF alpha level in articular fluid by ELISA and p-p65 and COL2A1 level and caspase-3 activity by western blot. Rat cartilage tissue was cultured and divided into control group, LPS group and LPS+ Celecoxib group followed by analysis of expressions of p-p65 and COL2A1 in cartilage tissue, IL-1 beta and TNF alpha content in culture supernatant, and chondrocyte apoptosis. Results: Compared with Sham group, p-p65 expression and caspase-3 activity in cartilage tissue of OA rats was increased and COL2A1 level was reduced. Meanwhile the expression of MMP-13, Hyp, IL-1 beta and TNF alpha in articular fluid of OA rats was increased. Compared to OA group, p-p65 expression and caspase-3 activity was decreased and COL2A1 expression was increased in OA + Celecoxib treatment group along with decreased MMP-13, Hyp, IL-1 beta and TNF alpha level in articular fluid. p-p65 expression and caspase-3 activity in LPS group was increased and COL2A1 expression was decreased with increased IL-1 beta and TNF alpha content. Compared to LPS group, p-p65 expression and caspase-3 activity was decreased and COL2A1 expression was increased in LPS +Celecoxib group with decreased content of IL-1 beta and TNF alpha. Conclusion: Celecoxib can protect cartilage in OA by inhibiting NE-kappa B activation and IL-1 beta and TNF alpha release, and decreasing cell apoptosis in inflammatory environment.