Sequential dynamics of inflammatory cytokine, angiogenesis inducing factor and matrix degrading enzymes during spontaneous resorption of the herniated disc
Sequential dynamics of inflammatory cytokine, angiogenesis inducing factor and matrix degrading enzymes during spontaneous resorption of the herniated disc
复制标题
DOI：
10.1016/j.orthres.2003.11.008
复制
发表时间：
2004-07-01
影响因子：
2.8
通讯作者：
Shinomiya, K
中科院分区：
文献类型：
--
作者：
Kato, T;Haro, H;Shinomiya, K
椎间盘突出症（HD）是最常见的骨科疾病之一。 HD 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似乎导致炎症细胞因子的产生。此外，炎症细胞因子如肿瘤坏死因子-α (TNF-α) 是诱导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 和纤溶酶所必需的。我们假设这些分子在自发性 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检查了这些分子的顺序表达，该系统由活化的巨噬细胞和椎间盘组织的相互作用组成，作为 HID 中发生的炎症急性反应的模型。我们还考虑了 HD 吸收过程中激活潜在 MMP 的机制。目前我们的结果表明，TNF-α mRNA 和蛋白质表达的上调首先发生在 HD 诱导的炎症中。 VEGF 上调伴随着 TNF-α 表达水平的增加。纤溶酶和 MMP-3 在稍后的时间点均上调。我们还证明 TNF-α 和 VEGF 均可诱导尿激酶型纤溶酶原激活剂 (u-PA) 表达上调。我们之前的工作表明，TNF-α可以上调共培养系统中VEGF、MMP-3和MMP-7的表达。据报道，纤溶酶可以影响激活潜在的MMP。基于这些发现，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引发剂，而纤溶酶和 u-PA 在 MMP 的激活中发挥着至关重要的作用。我们提出了自发的 HD 吸收级联。对吸收过程的进一步了解可能为未来的 HID 提供新的治疗方法。 (C) 2003 年骨科研究学会。由爱思唯尔有限公司出版。保留所有权利。
intervertebral disc herniation (HD) is one of the most common orthopaedic conditions. MRI analysis of HD has revealed a spontaneous resorption mechanism related with neo-vascularization. It appears that the interaction of activated macrophages with disc tissues leads to the generation of inflammatory cytokines. Moreover, inflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha) 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 this study, we have examined the sequential expression of these molecules using a co-culture system which is composed of the interaction of activated macrophages and disc tissues as a model of the acute response of inflammation occurred in HID. We have also considered the mechanism of activating latent MMPs during HD resorption process. Current our results indicate that upregulation of both TNF-alpha mRNA and protein expressions occur first in the inflammation induced by HD. VEGF upregulation follows the increased level of TNF-alpha expression. Both plasmin and MMP-3 are upregulated at later time points. We also demonstrate that both TNF-alpha and VEGF induce upregulated expression of urokinase-type plasminogen activator (u-PA). Our previous work has demonstrated that TNF-alpha could upregulate the expression of VEGF, MMP-3 and MMP-7 in the co-culture system. It has been reported that plasmin could affect to activate latent MMPs. Based on these findings, we suggest that TNF-alpha acts as the initiator of inflammation following contact between macrophages and disc chondrocytes and that plasmin and u-PA play a crucial role in activation of MMPs. We propose a spontaneous HD resorption cascade. Further understanding of the resorption process may provide future novel therapies for HID. (C) 2003 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved.