2002 SSE Award Competition in Basic Science: Expression of major matrix metalloproteinases is associated with intervertebral disc degradation and resorption
2002 SSE Award Competition in Basic Science: Expression of major matrix metalloproteinases is associated with intervertebral disc degradation and resorption
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DOI：
10.1007/s00586-002-0472-0
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发表时间：
2002-08-01
影响因子：
2.8
通讯作者：
Boos, N
中科院分区：
文献类型：
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作者：
Weiler, C;Nerlich, AG;Boos, N
在退变过程中，由于组织吸收，椎间盘（IVD）的高度逐渐显着降低。椎间盘内裂隙和撕裂是椎间盘退变的主要标志。基质降解酶如基质金属蛋白酶（MMP）被认为在椎间盘组织降解和吸收中发挥着关键作用。因此，本研究的目的是研究 MMP 在导致椎间盘退变的细胞外基质降解中的潜在作用。本研究对 30 个年龄在 0 至 86 岁之间的尸体的腰椎 IVD 完整横截面进行福尔马林固定和 EDTA 脱钙。组织切片用于 MMP-1、-2、-3 和 -9 的免疫定位。通过形态测量分析评估标记细胞的数量，并与裂口和撕裂的形成、细胞增殖、颗粒基质变化和粘液变性统计相关。此外，使用脊柱手术期间获得的30个椎间盘标本进行MMP-2和-3-mRNA的原位杂交。此外，通过尸检材料中的原位酶谱测定酶促明胶分解活性。免疫组织化学显示所有四种 MMP 均在椎间盘内表达，并通过原位杂交证实，为髓核和纤维环细胞内酶的合成提供了明确的证据。通过原位酶谱法验证明胶分解酶活性。来自婴儿和青少年的 IVD 几乎完全未标记所有测试的 MMP，而在较年轻成人的椎间盘细胞中观察到的 MMP-1 和 -3 多于较年长者的椎间盘细胞，MMP-2 在成年时期保持不变，而 MMP-9 仅在相对较少的细胞中表达。这种模式与裂口和撕裂的发生显着相关。 MMP-1 的这种相关性最强 (P
During the process of degeneration, the inter-vertebral disc (IVD) shows a progressive and significant reduction in height due to tissue resorption. Intradiscal clefts and tears are major hallmarks of disc degeneration. Matrix-degrading enzymes such as matrix metalloproteinases (MMPs) are assumed to play a pivotal role in disc tissue degradation and resorption. The objective of this study was therefore to investigate the potential role of MMPs in extracellular matrix degradation leading to disc degeneration. This study was conducted on 30 formalin-fixed and EDTA-decalcified complete cross-sections of lumbar IVDs from cadavers of individuals aged between 0 and 86 years. Tissue sections were used for the immunolocalization of MMPs-1, -2, -3 and -9. The number of labeled cells was assessed by morphometric analyses, and was statistically correlated with the formation of clefts and tears, cellular proliferation, granular matrix changes and mucous degeneration. Furthermore, 30 disc specimens obtained during spinal surgery were used for in situ hybridization of MMP-2 and -3-mRNA. In addition, the enzymatic gelatinolytic activity was determined by in situ zymography in autopsy material. Immunohistochemistry showed the intradiscal expression of all four MMPs, which was confirmed by in situ hybridization, providing clear evidence for the synthesis of the enzymes within nucleus pulposus and annulus fibrosus cells. Gelatinolytic enzymatic activity was verified by in situ zymography. IVDs from infants and young adolescents remained almost completely unlabeled for all MMPs tested, while more MMPs-1 and -3 were seen in disc cells of younger adults than in those of a more advanced age, MMP-2 remained unchanged over the adult age periods, and MMP-9 was expressed in only relatively few cells. This pattern significantly correlated with the occurrence of clefts and tears. This correlation was strongest for MMP-1 (P