Department of Orthopedics, St. Jansdal Ziekenhuis, Harderwijk, The Netherlands.
Acta Histochem. 2011 Sep;113(5):556-63. doi: 10.1016/j.acthis.2010.06.001. Epub 2010 Jul 24.
In vitro and in vivo studies have suggested that polyethylene wear particles are the main cause for osteolysis in prosthetic loosening. Elevated amounts of proteases including gelatinases (or matrix metalloproteinases MMP-2 and MMP-9) have been found in fibrous tissue interfaces of loosened total hip arthroplasties suggesting that proteolysis plays a role in osteolysis. The presence of proteases does not mean that they are active, because activity of proteases is highly regulated at the post-translational level. We investigated whether the activity of two major proteases that are active extracellularly and have been associated with loosening, MMP-2 and MMP-9, is involved in loosening of non-cemented hip implants with polyethylene acetabular components. Eight interface tissues retrieved during revision were studied with light and electron microscopy and by in situ zymography to localize MMP-2 and MMP-9 activity in combination with immunohistochemistry to localize MMP-2 and MMP-9 proteins. All interface tissues contained large amounts of polyethylene wear particles, either in large accumulations or dispersed in the extracellular matrix or intracellularly in fibroblasts. Particles were not encountered in association with MMP-2 or MMP-9 activity or leukocytes. Inflammation was never found. MMP-9 activity was restricted to macrophages and MMP-2 activity was restricted to microvascular endothelial cells mainly outside areas where particles were present. Our data indicate that wear particles do not induce activation of leukocytes or MMP-2 or MMP-9 activity. Therefore, aseptic loosening may not be particle induced but initiated by other mechanisms such as mechanical stress.
体外和体内研究表明,聚乙烯磨损颗粒是导致假体松动性骨溶解的主要原因。在松动的全髋关节置换术的纤维组织界面中发现了大量的蛋白酶,包括明胶酶(基质金属蛋白酶 MMP-2 和 MMP-9),这表明蛋白水解在骨溶解中起作用。蛋白酶的存在并不意味着它们具有活性,因为蛋白酶的活性在翻译后水平受到高度调节。我们研究了两种主要的蛋白酶(MMP-2 和 MMP-9)的活性是否与非骨水泥髋关节植入物中聚乙烯髋臼组件的松动有关,这两种蛋白酶在细胞外具有活性,并与松动有关。对 8 个在翻修过程中取出的界面组织进行了光镜和电镜研究,并通过原位酶谱法定位 MMP-2 和 MMP-9 活性,同时结合免疫组织化学定位 MMP-2 和 MMP-9 蛋白。所有界面组织都含有大量的聚乙烯磨损颗粒,要么是大量聚集,要么是分散在细胞外基质中,要么是在成纤维细胞内。在与 MMP-2 或 MMP-9 活性或白细胞相关的情况下,没有遇到颗粒。从未发现炎症。MMP-9 活性仅限于巨噬细胞,MMP-2 活性仅限于主要存在颗粒的区域外的微血管内皮细胞。我们的数据表明,磨损颗粒不会诱导白细胞或 MMP-2 或 MMP-9 活性的激活。因此,无菌性松动可能不是由颗粒引起的,而是由其他机制如机械应力引起的。