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

MRI分析突出的椎间盘（HP）揭示了与新生血管化相关的自发性吸收机制。似乎活化的巨噬细胞与椎间盘组织的相互作用导致炎性细胞因子的产生。此外，炎症因子如肿瘤坏死因子-α（TNF-α）也参与了血管生成诱导因子如血管内皮生长因子（VEGF）或基质降解酶如MMP-3、MMP-7和纤溶酶的诱导，我们推测这些分子在HD的自发性吸收过程中起着至关重要的作用。在这项研究中，我们已经检查了这些分子的顺序表达使用共培养系统作为模型的急性期椎间盘突出。我们的结果表明，TNF-α表达的上调首先发生在椎间盘突出诱导的炎症中。TNF-α表达增加后VEGF表达增加。我们的前期工作已经证实TNF-α可以上调共培养体系中VEGF、MMP-3和MMP-7的表达。因此，我们认为TNF-α是巨噬细胞和椎间盘软骨细胞接触后炎症的起始物。TNF-α还可加速血管生成和基质降解的级联反应，从而促进HD再吸收。对吸收过程的进一步了解可能为HD提供未来的新疗法。

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.