The regulation mechanism of cartilage destruction m osteoarthritis

骨关节炎软骨破坏的调控机制

• 批准号: 14571386
• 负责人: MATSUMOTO Tomoko
• 金额: $ 2.18万
• 依托单位: Nagasaki University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14571386/
• 关键词: osteoarthritis; Insulin-like growth factor; interleukin-1β; articular cartilage; インターロイキン

Imbalances between synthesis and degradation of cartilage matrix lead the destruction of articular cartilage. To know the regulation mechanism of cartilage destruction in osteoarthritis, we have examined the effects of insulin-like growth factor (IGF)-I, dexamethasone, and mdomethacin on the action of interleukin (IL)-1β, which is the catabolic factor for cartilage tissue. We performed monolayer or three dimensional culture of chondrocytes. After adding the IL-I β with or without IGF-I, dexamethasone or indomethacin, the concentration of IL-6 and matrix metalloptroteinase (MMP)-3,-9,-13 in the culture medium was measured by ELISA. Further, total RNA was extracted from the cell layer, and the expression of aggrecan, collagen II, IL-6, and MMP-3,9,13 mRNA was measured by RT PCR.IGF-I induced the expression of aggrecan and collagen II mRNA both in the presence or absence of IL-β. IL-I β increased the expression of IL-6 and MMPs in the protein and mRNA levels. These effects of IL-Iβ was inhibited by dexamethasone and indomethacin but not by IGF-I. These results suggest that different mechanism may exist in the regulation of cartilage destruction.

软骨基质合成和降解的失衡导致关节软骨的破坏。为了解骨性关节炎软骨破坏的调控机制，我们观察了胰岛素样生长因子-I、地塞米松和美多美辛对软骨组织分解代谢因子白介素1-β作用的影响。我们进行了软骨细胞的单层或三维培养。将IL-Iβ与胰岛素样生长因子-I、地塞米松或吲哚美辛共同作用后，用ELISA法测定细胞培养上清液中IL-6和基质金属蛋白酶-3、-9、-13的浓度。进一步，提取细胞层总RNA，用RT-β法检测集聚糖、II型胶原、IL-6和MMP3、9、13mR-NA的表达，IGF-I在有或无IL-ICAM作用下均能诱导集聚扫描和II型胶原的表达。IL-Iβ促进IL-6和MMPs在蛋白和基因水平的表达。这些效应可被地塞米松和消炎痛抑制，但不能被β抑制。这些结果提示，软骨破坏的调控机制可能不同。

项目成果

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Taniguchi T 等人：“骨折愈合过程中骨钙素、碱性磷酸酶、IGF-I 和 IGF-结合蛋白-3 血清水平的变化”损伤。