Background Osteoarthritis (OA) is a degenerative joint disease characterized by the progressive loss of cartilage and pain. The development and progression of OA are believed to involve inflammation. Many studies have shown that OA is associated with oxidative stress. Rebamipide is a gastroprotective agent used for the treatment of gastritis and gastric ulcer. Substantial research shows that rebamipide acts as an oxygen radical scavenger and exhibits an anti-inflammatory property.
Objectives The objectives were to investigate the in vivo effects of treatment with rebamipide on pain severity and cartilage degeneration in an experimental model of rat OA and to explore its mode of action.
Methods OA was induced in rats by intra-articular injection of monosodium iodoacetate (MIA) into the knee. Rebamipide was administered orally every day after the MIA injection. Limb nociception was assessed by measuring the paw withdrawal latency and the paw withdrawal threshold. We analyzed the samples macroscopically and histomorphologically,and used immunohistochemistry to investigate the expression ofmatrix metalloproteinase 13 (MMP-13), interleukin-1b (IL-1b), hypoxia-inducible factor-2a (HIF-2a), inducible nitric oxide synthase (iNOS), and nitrotyrosine in knee joints. Real-time quantitative reverse transcription-polymerase chain reaction was used to quantify the mRNA for catabolic and anticatabolic factors in human OA chondrocytes.
Results Rebamipide showed an antinociceptive property and attenuated cartilage degeneration. Rebamipide reduced the expression of MMP-13, IL-1b, HIF-2a,iNOS, and nitrotyrosine in OA cartilage in a dose-dependent manner. Nitrotyrosine expression in the subchondral bone region was decreased in the rebamipide-treated joints. mRNA expression of MMP-1, -3, and -13, and ADAMTS5 was attenuated in IL-1b-stimulated human OA chondrocytes. By contrast, rebamipide induced the mRNA expression of tissue inhibitor of MMP-1 and -3.
Conclusions The results show the inhibitory effects of rebamipide on pain production and cartilage degeneration in experimentally induced OA. The suppression of oxidative damage and the restoration of extracellular matrix homeostasis of articular chondrocyte suggest that rebamipide is a potential therapeutic strategy for OA.
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Disclosure of Interest None Declared