| 摘要: |
| 椎间盘退变(intervertebral disc degeneration, IVDD)可导致多种脊柱相关疾病的发生。细胞外基质(extracellular matrix, ECM)的降解被认为是IVDD的主要病理过程。基质金属蛋白酶(matrix metalloproteinases, MMPs)及含凝血酶敏感蛋白模体的解整合素样金属蛋白酶(a disintegrin and metalloproteinase with thrombospondin motif, ADAMTSs)是参与ECM降解的主要蛋白酶类。本文总结在IVDD中MMPs、ADAMTSs及金属蛋白酶组织抑制剂(tissue inhibitors of metalloproteinases, TIMPs)的基因表达调控相关研究。研究发现人IVDD中MMP-1、2、3、7、8、10、13,ADAMTS-1、4、5出现表达上调,TIMP-3下调、TIMP-1上调。MMPs、ADAMTSs的表达受多因素共同调节,包括机械应力、炎症、氧化应激等,部分参与P38途径。遗传因素也在MMP-1、2、3、9的表达中起重要作用。MMPs、ADAMTSs蛋白表达及酶活性的上调导致ECM降解,进一步导致IVDD的发展。未来的治疗将靶向于导致ECM病理降解的特定MMPs及ADAMTSs。 |
| 关键词: 椎间盘退变 基质金属蛋白酶类 含凝血酶敏感蛋白模体的解整合素样金属蛋白酶 金属蛋白酶类组织抑制剂 |
| DOI：10.3724/SP.J.1008.2015.00201 |
| 投稿时间：2014-01-13修订日期：2014-04-01 |
| 基金项目:上海市基础研究重点项目(11JC1415600). |
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| Role of metalloproteinases and their inhibitors in intervertebral disc degeneration: research progress |
| SONG Qing-xin,WANG Kun,TANG Yi-xing,SHEN Hong-xing* |
(Department of Orthopedics, Changhai Hospital, Second Military Medical University, Shanghai 200433, China
*Corresponding author) |
| Abstract: |
| Intervertebral disc degeneration (IVDD) is characterized by the excessive degradation of extracellular matrix (ECM), which underlies many spine-related disorders. Matrix metalloproteinases (MMPs) and a disintegrin metalloproteinases with thrombospondin motifs (ADAMTSs) are believed to be the major proteolytic enzymes responsible for ECM degradation. This review summarizes the current literatures on gene expression and regulation of MMPs, ADAMTSs, and tissue inhibitors of metalloproteinases (TIMPs) in IVDD. Reports have showen that specific MMPs (MMP-1, -2, -3, -7, -8, -10, and -13) and ADAMTS (ADAMTS-1, -4, and -15) are upregulated in human degenerated intervertebral discs. Tissue inhibitor of metalloproteinase-3 is downregulated and TIMP-1 is upregulated in human degenerated intervertebral discs relative to nondegenerated intervertebral discs. Regulation of the MMP and ADAMTS expression is affected by many factors including mechanical, inflammatory, oxidative stress, and so on. Genetic predisposition also plays an important role in expression of MMP-1, -2, -3, and -9. Upregulation of MMP and ADAMTS expression is implicated in ECM destruction, which can lead to the development of IVDD. Future IVDD therapeutics may target specific MMPs and ADAMTSs which is essential in the pathological proteolysis of ECM. |
| Key words: intervertebral disc degeneration matrix metalloproteinases a disintegrin and metalloproteinase with thrombospondin motifs tissue inhibitor of metalloproteinases |
