Rebamipide attenuates pain severity and cartilage degeneration in a rat model of osteoarthritis by downregulating oxidative damage and catabolic activity in chondrocytes
Rebamipide attenuates pain severity and cartilage degeneration in a rat model of osteoarthritis by downregulating oxidative damage and catabolic activity in chondrocytes
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DOI：
10.1016/j.joca.2012.08.002
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发表时间：
2012-11-01
影响因子：
7
通讯作者：
Min, J. -K.
中科院分区：
文献类型：
--
作者：
Moon, S-J;Woo, Y. -J.;Min, J. -K.
目的：目的是探讨在体内治疗与瑞巴派特对疼痛的严重程度和软骨退化的大鼠骨关节炎（OA）的实验模型的影响，并探讨其模式的action.Materials and Methods：OA诱导大鼠通过关节内注射碘乙酸（MIA）。瑞巴派特的口服给药在MIA注射当天、注射后3天或7天开始。通过测量缩爪潜伏期和阈值来评估肢体伤害感受。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研究了基质金属蛋白酶-13（MMP-13）、白细胞介素-1 β（IL-1 β）、缺氧诱导因子-2 α（HIF-2 α）、诱导型一氧化氮合酶（iNOS）和硝基酪氨酸在膝关节中的表达。实时定量逆转录-聚合酶链反应被用来定量mRNA的分解代谢和anticatabolic因子在人OA软骨cytos.Results：瑞巴派特表现出抗伤害性和衰减软骨退变。瑞巴派特以剂量依赖性方式降低OA软骨中MMP-13、IL-1 β、HIF-2 α、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-β刺激的人OA软骨细胞中，MMP-1、MMP-3和MMP-13以及ADAMTS 5的mRNA表达减弱。结论：瑞巴派特对实验性骨关节炎的疼痛产生和软骨退变有抑制作用。瑞巴派特对氧化损伤的抑制和对关节软骨细胞外基质稳态的恢复表明瑞巴派特是一种潜在的OA治疗策略。皇冠版权所有（C）2012由爱思唯尔有限公司代表国际骨关节炎研究学会发布。All rights reserved.
Objective: 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.Materials and methods: 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-1 beta (IL-1 beta), hypoxia-inducible factor-2 alpha (HIF-2 alpha), 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-1 beta, HIF-2 alpha, 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-beta-stimulated human OA chondrocytes. By contrast, rebamipide induced the mRNA expression of tissue inhibitor of metalloproteinase-1 and -3.Conclusion: 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. Crown Copyright (C) 2012 Published by Elsevier Ltd on behalf of Osteoarthritis Research Society International. All rights reserved.