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Molecular analysis for the mechanisms of intervertebral disc degeneration using experimental animal model

实验动物模型对椎间盘退变机制的分子分析

基本信息

批准号：
17591553
负责人：
ASOU Yoshinori
金额：
$ 2.18万
依托单位：
Tokyo Medical and Dental University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2006
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17591553/
关键词：
degeneration of intervertebral disc animal model Runx2 間歇的軸圧負荷モデル Runx2

项目摘要

We have developed continuous weight bearing disc degeneration model for mouse tail. In this model, degradation of IVD was observed within two weeks after operation. Using this model, we tested if weight loading, a most common cause of intervertebral disc (IVD) degeneration, induces Runx2 expression, which may cause chondrocyte hypertrophy. Indeed, weight loading of the IVD by compression for a day significantly increased Runx2 expression. Thus, we next examined the expression of Runx2 with other disc degradation markers in canine IVD, The expression of RUNX2, type-X collagen and MMP-13 mRNA in young intact and degenerated IVD were examined by semi-quantitative RT-PCR analysis. The localization of Runx2 and type-X collagen protein in control and degenerated IVD were examined by imunohistochemistly. The expression of RUNX2 transcript and protein, in combination with type-X collagen and MMP-13, was enhanced in degenerated IVDs of the dog. RUNX2 co-localizes with MMP-13 in clusters of chondrocytes in fibrillated OA cartilage, and MMP-13 expression is regulated by Runx2 in osteoarthritis chondrocytes. Type-X collagen and MMP13 are downstream targets of Runx2 in the growth plate chondrocytes. Considering IVD cells all express cartilage-specific matrix proteins with quantitative differences, depending on their anatomic situation, the comparable molecular regulation may exist in IVD cells, articular chondrocytes and growth plate chondrocytes.

建立了小鼠尾部连续承重椎间盘退变模型。在该模型中，术后两周内观察到IVD的降解。使用该模型，我们测试了体重负荷（椎间盘（IVD）退变的最常见原因）是否诱导Runx2表达，这可能导致软骨细胞肥大。事实上，通过压缩一天的IVD重量负荷显著增加了Runx2的表达。因此，我们接下来检测了Runx2与其他椎间盘降解标志物在犬IVD中的表达，并采用半定量RT-PCR分析了Runx2、x型胶原和MMP-13 mRNA在幼年完整和退化IVD中的表达。免疫组织化学检测Runx2和x型胶原蛋白在对照组和退行性IVD中的定位。RUNX2转录物及蛋白与x型胶原蛋白和MMP-13的表达在犬变性ivd中增强。RUNX2与MMP-13共定位于骨性关节炎软骨细胞簇中，骨性关节炎软骨细胞中MMP-13的表达受RUNX2调控。x型胶原和MMP13是Runx2在生长板软骨细胞中的下游靶点。考虑到IVD细胞均表达软骨特异性基质蛋白，且数量不同，根据其解剖情况，IVD细胞、关节软骨细胞和生长板软骨细胞中可能存在类似的分子调控。