Expression of gelatinase A and its activator MT1-MMP in the inflammatory periprosthetic response to polyethylene
Expression of gelatinase A and its activator MT1-MMP in the inflammatory periprosthetic response to polyethylene
复制标题
DOI：
10.1359/jbmr.1999.14.2.288
复制
发表时间：
1999-02-01
影响因子：
6.2
通讯作者：
Adnet, JJ
中科院分区：
文献类型：
--
作者：
Nawrocki, B;Polette, M;Adnet, JJ
已知聚乙烯假体部件的磨损碎片会诱发软管肉芽肿反应，从而招募大量巨噬细胞和多核巨细胞。通过释放非特异性炎症反应的细胞介质，活化的吞噬细胞被认为发挥着以下作用：在导致假体无菌性松动的骨溶解中发挥关键作用。基质金属蛋白酶 (MMP) 具有降解骨和邻近结缔组织的细胞外基质成分的能力，因此参与了这一破坏过程。为了研究明胶酶 A、其激活剂 MT1-MMP 以及 MMP 抑制剂 TIMP-1 和 TIMP-2 在聚乙烯假体无菌松动中的作用，对假体周围假滑膜界面组织进行了免疫组织化学 (WC) 和原位杂交 (ISH)。免疫组织化学方法在与聚乙烯磨损碎片接触的巨噬细胞和多核巨细胞中强烈检测到明胶酶 A 和 MT1-MMP。与 MT1-MMP 相比，在吞噬细胞中未发现明胶酶 A mRNA，而是在周围的成纤维细胞中发现，从而表明在此过程中巨噬细胞和成纤维细胞之间的合作。虽然通过 MC 和 LSH 评估，TIMP-1 基本上在增生性假滑膜细胞中表达，但 TIMP-2、MT1-MMP 和明胶酶 a 共定位于吞噬细胞中。这些数据支持原明胶酶 A 激活涉及三分子复合物 (MT1-MMP-TIMP-2-明胶酶 A) 机制的概念。因此，本研究证明明胶酶 A 及其激活剂可能导致聚乙烯假体的无菌松动。
Wear debris of polyethylene prosthetic components is known to induce a hose granulomatous reaction which recruits numerous macrophages and multinucleated giant cells, By releasing cellular mediators of a nonspecific inflammatory reaction, activated phagocytic cells are thought to play: a key role in osteolysis leading to aseptic loosening of the prosthesis. Matrix metalloproteinases (MMPs) have been implicated in this destructive process by their ability to degrade extracellular matrix components of bone and adjacent connective tissue. To investigate the roles of gelatinase A, its activator MT1-MMP, and the MMP inhibitors TIMP-1 and TIMP-2 in aseptic loosening of polyethylene prostheses, immunohistochemistry (WC) and in situ hybridization (ISH) were performed on periprosthetic pseudosynovial interface tissues. Gelatinase A and MT1-MMP were strongly detected immunohistochemically in macrophages and multinucleated giant cells in contact with polyethylene wear debris, In contrast to MT1-MMP, gelatinase A mRNAs were not found in phagocytic cells but in surrounding fibroblasts, thereby suggesting cooperation between macrophages and fibroblasts in this process. While TIMP-1 was expressed essentially in hyperplastic pseudosynoviocytes as assessed by MC and LSH, TIMP-2, MT1-MMP, and gelatinase a were colocalized in phagocytic cells. These data support the concept of progelatinase A activation involving a trimolecular complex (MT1-MMP-TIMP-2-gelatinase A) mechanism. Thus, this study demonstrated that gelatinase A and its activator might contribute to the aseptic loosening of polyethylene prostheses.