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Yoshiaki Suzuki, Masahiro Hasegawa, Yuriyo Matsui, Hironori Unno, Takahiro Iino, Toshimichi Yoshida, Akihiro Sudo, Intra-articular injection of rebamipide prevents articular cartilage degeneration in murine post-traumatic osteoarthritis models, Modern Rheumatology, Volume 30, Issue 4, 3 July 2020, Pages 765–772, https://doi.org/10.1080/14397595.2019.1641912
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Abstract
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-1β, then treated with or without rebamipide. The levels of mRNA expression of COL2A, IL-1β, TNFα, NF-κB, MMP3, MMP13, ADAMTS5, TIMP3, FGF2, and TGFβ 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, TGFβ, and FGF2 in chondrocytes and down-regulated IL-1β, TNFα, NF-κB, 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.
