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.

椎间盘突出 (HP) 的 MRI 分析揭示了与新生血管形成相关的自发吸收机制，活化的巨噬细胞与椎间盘组织的相互作用导致炎症细胞因子的产生，例如肿瘤坏死因子-α。 TNF-α）是诱导血管生成诱导因子（例如血管内皮生长因子（VEGF））或基质降解酶（例如 MMP-3）所必需的， MMP-7 和纤溶酶。我们发现这些分子在自发性 HD 吸收过程中发挥着至关重要的作用。在这项研究中，我们使用共培养系统作为椎间盘突出急性期的模型来检查这些分子的顺序表达。结果表明，TNF-α 表达上调首先发生在椎间盘突出引起的炎症中，随后 TNF-α 表达水平增加。研究表明，在共培养系统下，TNF-α 可以上调 VEGF、MMP-3 和 MMP-7 的表达，因此，我们提出 TNF-α 作为巨噬细胞和椎间盘软骨细胞接触后炎症的引发剂。 TNF-α 还可以加速血管生成和基质的级联反应，从而促进降解，促进 HD 吸收。对再吸收过程的进一步了解可能为 HD 提供未来的新疗法。