Division of Rheumatology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Bucheon City, Kyunggi-Do, Republic of Korea.
Osteoarthritis Cartilage. 2012 Nov;20(11):1426-38. doi: 10.1016/j.joca.2012.08.002. Epub 2012 Aug 10.
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 osteoarthritis (OA) and to explore its mode of action.
OA was induced in rats by intra-articular injection of monosodium iodoacetate (MIA). Oral administration of rebamipide was initiated on the day of MIA injection, 3 or 7 days after. Limb nociception was assessed by measuring the paw withdrawal latency and threshold. We analyzed the samples macroscopically and histomorphologically, and used immunohistochemistry to investigate the expression of matrix metalloproteinase-13 (MMP-13), interleukin-1β (IL-1β), hypoxia-inducible factor-2α (HIF-2α), 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.
Rebamipide showed an antinociceptive property and attenuated cartilage degeneration. Rebamipide reduced the expression of MMP-13, IL-1β, HIF-2α, 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-1β-stimulated human OA chondrocytes. By contrast, rebamipide induced the mRNA expression of tissue inhibitor of metalloproteinase-1 and -3.
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.
研究瑞巴派特治疗实验性大鼠骨关节炎（OA）模型中疼痛严重程度和软骨退变的体内作用，并探讨其作用机制。
通过关节内注射单碘乙酸（MIA）诱导大鼠 OA。在 MIA 注射当天、注射后 3 天或 7 天开始给予瑞巴派特口服治疗。通过测量足底回缩潜伏期和阈值来评估肢体痛觉过敏。我们对样本进行了宏观和组织形态学分析，并使用免疫组织化学方法检测膝关节中基质金属蛋白酶-13（MMP-13）、白细胞介素-1β（IL-1β）、缺氧诱导因子-2α（HIF-2α）、诱导型一氧化氮合酶（iNOS）和硝基酪氨酸的表达。实时定量逆转录聚合酶链反应用于定量人 OA 软骨细胞中分解代谢和抗分解代谢因子的 mRNA。
瑞巴派特具有镇痛作用，并能减轻软骨退变。瑞巴派特呈剂量依赖性降低 OA 软骨中 MMP-13、IL-1β、HIF-2α、iNOS 和硝基酪氨酸的表达。在瑞巴派特治疗的关节中，软骨下骨区域的硝基酪氨酸表达减少。在 IL-1β 刺激的人 OA 软骨细胞中，MMP-1、-3 和 -13 以及 ADAMTS5 的 mRNA 表达减弱。相比之下，瑞巴派特诱导组织抑制剂金属蛋白酶-1 和 -3 的 mRNA 表达。
结果表明瑞巴派特对实验性诱导的 OA 中疼痛产生和软骨退变具有抑制作用。抑制氧化损伤和恢复关节软骨细胞细胞外基质稳态表明瑞巴派特是 OA 的一种潜在治疗策略。
