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Research for angiogenesis mechanism in hemialed disc (HD) resorption process and development of new therapies for HD using the resorption process

研究半盘椎间盘（HD）吸收过程中的血管生成机制并利用吸收过程开发HD新疗法

基本信息

批准号：
13671494
负责人：
HARO Hirotaka
金额：
$ 2.69万
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：
2001
资助国家：
日本
起止时间：
2001 至 2002
项目状态：
已结题

项目摘要

MRI analysis of herniated discs(HP)has revealed a spontaneous resorption mechanism related with neo-vascnlarization. It appears that interaction of activated macrophages with disc tissues leads to the generation of inflammnatory cytokines. Moreover, inflammatory cytokines such as tumor necrosis factor-α(TNF-α)is required for the induction of angiogenesis inducing factors such as vascular endothelial growth factor((VEGF) or matrix degrading enzymes such as MMP-3, MMP-7 and Plasmin.We hypothesized that these molecules play a crucial role during spontaneous HD resorption. In the study we have examined the sequential expression of these molecules using a co-culture system as a model of the acute phase of disc herniation. Our results indicate that upregulation of TNF-α expression occurs first in the inflammation induced by disc herniation. VEGF upregluation follows flie increased level of TNF-α expression. Both plasmin and MMP-3 are upregulated at later time points.Our previous work has demonstrated that TNF-α can upregulate the expression of VEGF, MMP-3 and MMP-7 under the co-culture system. Therefore, we propose that TNF-α acts as the initiator of inflammation following contact between macrophages and disc chondrocytes. TNF-α could also act to accelerate the cascade of both angiogenesis and matrix degradation thereby facilitating HD resorption. Further understanding of the resorption process may provide future novel therapies for HD.

MRI分析揭示了与新生血管形成相关的自发性吸收机制。激活的巨噬细胞与椎间盘组织的相互作用似乎会导致炎性细胞因子的产生。此外，肿瘤坏死因子-α等炎性细胞因子在诱导血管生成诱导因子如血管内皮生长因子或基质降解酶如基质金属蛋白酶-3、基质金属蛋白酶-7和纤溶酶等方面也是必需的，我们推测这些分子在自发性HD吸收过程中起着至关重要的作用。在这项研究中，我们使用共培养系统作为腰椎间盘突出症急性期的模型，检查了这些分子的顺序表达。我们的结果表明，肿瘤坏死因子-α的表达上调首先发生在椎间盘突出所致的炎症中。随着肿瘤坏死因子-α表达水平的升高，血管内皮生长因子表达上调。纤溶酶和基质金属蛋白酶-3在以后的时间点均上调，我们先前的工作已经证明，在共培养体系中，肿瘤坏死因子-α可以上调血管内皮生长因子、基质金属蛋白酶-3和基质金属蛋白酶-7的表达。因此，我们认为肿瘤坏死因子-α是巨噬细胞与关节盘软骨细胞接触后炎症反应的始发者。肿瘤坏死因子-α还可以加速血管生成和基质降解的级联反应，从而促进HD的吸收。对吸收过程的进一步了解可能为HD未来的治疗提供新的方法。