Intra-articular Injection of Rebamipide Prevents Articular Cartilage Degeneration in Murine Post-Traumatic Osteoarthritis Models.

Objectives: Rebamipide is a protective drug used for gastric mucosal injuries, and it also exerts protective effects for a variety of other tissues. In this study, murine post-traumatic (PT) osteoarthritis (OA) models in vivo and human OA chondrocytes in vitro were used to examine the effects of rebamipide on articular cartilage degeneration. Methods: Male BALB/c mice were used. The knee ligaments were transected in both knees. Mice were injected with rebamipide into the knee joint every week. Human chondrocytes were stimulated with IL-1 beta, then treated with or without rebamipide. The levels of mRNA expression of COL2A, IL-1 beta, TNF alpha, NF-kappa B, MMP3, MMP13, ADAMTS5, TIMP3, FGF2, and TGF beta were estimated using real-time PCR. Results: Histological scores were significantly better in the rebamipide 1 mg/mL and 10 mg/mL groups than in the control group. Rebamipide up-regulated the mRNA expressions of COL2A, TIMP3, TGF beta, and FGF2 in chondrocytes and down-regulated IL-1 beta, TNF alpha, NF-kappa B, MMP3, MMP13, and ADAMTS5. Conclusion: Intra-articular injection of rebamipide prevents articular cartilage degeneration for 6 weeks in murine models of OA in vivo. Rebamipide down-regulates inflammatory cytokines and catabolic factors and up-regulates anabolic factors in human chondrocytes in vitro. Rebamipide could be an important treatment for prevention of articular cartilage degeneration.