Nawrocki B, Polette M, Burlet H, Birembaut P, Adnet J J
INSERM U314, IFR 53 and Laboratoire Pol Bouin, Hôpital Maison Blanche, CHU Reims, Reims, France.
J Bone Miner Res. 1999 Feb;14(2):288-94. doi: 10.1359/jbmr.1999.14.2.288.
Wear debris of polyethylene prosthetic components is known to induce a host 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 (IHC) 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 IHC and ISH, 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.
已知聚乙烯假体部件的磨损碎屑会引发宿主肉芽肿反应，该反应会募集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在导致假体无菌性松动的骨溶解过程中起关键作用。基质金属蛋白酶（MMPs）因其能够降解骨和相邻结缔组织的细胞外基质成分而与这一破坏过程有关。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在聚乙烯假体无菌性松动中的作用，对假体周围假滑膜界面组织进行了免疫组织化学（IHC）和原位杂交（ISH）检测。在与聚乙烯磨损碎屑接触的巨噬细胞和多核巨细胞中免疫组织化学强烈检测到明胶酶A和MT1-MMP。与MT1-MMP不同，吞噬细胞中未发现明胶酶A的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存在协作。通过IHC和ISH评估，TIMP-1主要在增生的假滑膜细胞中表达，而TIMP-2、MT1-MMP和明胶酶A共定位于吞噬细胞中。这些数据支持了前明胶酶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，本研究表明明胶酶A及其激活剂可能导致聚乙烯假体的无菌性松动。
