Is collagen breakdown during periodontitis linked to inflammatory cells and expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases in human gingival tissue?
Is collagen breakdown during periodontitis linked to inflammatory cells and expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases in human gingival tissue?
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DOI：
10.1902/jop.2001.72.10.1398
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发表时间：
2001-10
影响因子：
4.3
通讯作者：
S. Séguier;B. Gogly;A. Bodineau;Gaston Godeau;Nicole Brousse
中科院分区：
文献类型：
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作者：
S. Séguier;B. Gogly;A. Bodineau;Gaston Godeau;Nicole Brousse
背景：由牙周组织中的常驻细胞和炎性细胞产生的基质金属蛋白酶（MMPs）在牙周组织破坏中的作用已经得到了很好的证实。本研究的目的是量化，在健康和患病的上牙龈结缔组织中，胶原纤维所占的面积分数（AA%），属于炎性细胞亚群的细胞数量，以及MMPs和TIMPs（MMPs的组织抑制剂）的量，以研究这些分子，胶原损失和炎性细胞亚群之间可能存在的相关性。方法将6例健康对照者（C组）和6例重度牙周炎患者（P组）的牙龈组织标本分为两组。第一组标本冷冻后，用天狼星红F3 Ba对胶原纤维进行染色，并用抗CD 8、CD 4、CD 22、CD 68和TIA-1分子的抗体进行免疫组织化学染色。第二组用于器官培养、酶谱、Western印迹和斑点印迹。进行形态测量和自动图像分析，以评估胶原纤维所占的面积分数、炎性细胞亚群的数量和MMPs所产生的酶活性，以及牙周病期间表达的TIMPs的量。结果P组胶原纤维面积分数（33 ± 10%）较C组（60 ± 7%）明显减少（P < 0.0002），且与炎性细胞数、MMPs和TIMPs含量相关。在P组中，CD 8+、CD 22+、CD 68+和TIA-1+细胞显著增加，以及MMP-1、MMP-2、MMP-3、MMP-9和MMP-9活性形式的量增加。MMP-9的活性形式和TIMP-1的含量与CD 22+、CD 68+和TIA-1+细胞数呈正相关。结论：目前的研究表明MMPs和TIMPs之间的失衡与牙周炎时细胞外基质的病理性破坏有关。MMP-9的活性形式可以作为牙周病临床严重程度的标志物。
BACKGROUND Evidence of the role of matrix metalloproteinases (MMPs) produced by resident and inflammatory cells in periodontal destruction is now well established. The purpose of this study was to quantify, in healthy and diseased upper gingival connective tissue, the area fraction (AA%) occupied by collagen fibers, the cell number belonging to inflammatory cell subsets, and the amounts of MMPs and TIMPs (tissue inhibitors of MMPs) in order to investigate the possible correlations, if any, between such molecules, collagen loss, and inflammatory cell subsets. METHODS Gingival tissue specimens from 6 healthy controls (C) and 6 patients with severe periodontitis (P) were divided into 2 groups. The first group of specimens was frozen and used for the staining of collagen fibers by sirius red F3Ba and for immunohistochemistry with antibodies against CD8, CD4, CD22, CD68, and TIA-1 molecules. The second group was used for organ culture, zymography, Western blotting, and dot blotting. Morphometric and automated image analysis was performed for the evaluation of the area fraction occupied by collagen fibers, the number of inflammatory cell subsets and for enzymatic activities developed by MMPs, and the amounts of TIMPs expressed during periodontal disease. RESULTS In group P, the area fraction of collagen fibers (33 +/- 10%) was significantly decreased (P < 0.0002) when compared to group C (60 +/- 7%), and was correlated with the number of all inflammatory cells and amounts of MMPs and TIMPs. In group P, there were significant increases of CD8+, CD22+, CD68+, and TIA-1+ cells, as well as increases in the amounts of MMP-1, MMP-2, MMP-3, MMP-9, and the active form of MMP-9. The active form of MMP-9 and the amount of TIMP-1 were positively correlated with the number of CD22+, CD68+, and TIA-1+ cells. CONCLUSIONS The present study showed an imbalance between MMPs and TIMPs associated with the pathologic breakdown of the extracellular matrix during periodontitis. The active form of MMP-9 could be a marker for the clinical severity of periodontal disease.