Takagi M, Konttinen Y T, Kemppinen P, Sorsa T, Tschesche H, Bläser J, Suda A, Santavirta S
Institute of Biomedicine and the Institute of Dentistry, University of Helsinki, Finland.
J Rheumatol. 1995 Dec;22(12):2285-90.
To study tissue inhibitor of metalloproteinase 1 (TIMP-1) in relation to collagenolytic and gelatinolytic potential, namely dinitrophenyl-Pro-Gln-Gly-Ile-Ala-Gly-Gln-D-Arg (DNP-S) sensitive proteolytic activity, in loose total hip arthroplasty (THA) endoprostheses.
Tissue localization of TIMP-1 was investigated immunohistochemically. TIMP-1 level of the periprosthetic tissues and fluid samples from 9 loose THA endoprostheses was measured by competitive ELISA, and DNP-S sensitive collagenolytic and gelatinolytic potential was evaluated by the degradation of synthetic DNP-S and reverse phase high performance liquid chromatography.
Immunohistochemical analysis revealed moderate to marked immunoreactivity of TIMP-1 in pseudosynovial lining cells, and weak to moderate immunoreactivity often in monocyte/macrophages, endothelial cells, and fibroblasts in both interface tissues between bone and implant and pseudocapsular tissues around the artificial joints. TIMP-1 level was low in interface tissue samples (795 +/- 203 ng/ml) compared to pseudosynovial fluid samples (2026 +/- 584 ng/ml). Degradation rate of the substrate was higher in interface tissue samples (56 +/- 6%) than in pseudocapsular tissue samples (32 +/- 4%) and pseudosynovial fluid samples (6 +/- 2%).
Low TIMP-1 level combined with high percentage of degradation of synthetic substrate DNP-S leads to high collagenolytic and gelatinolytic activity in interface tissue samples. This may in part explain the weakening of periprosthetic connective tissue. Weakening combined with cyclic mechanical loading may lead to loosening of THA endoprostheses.
研究金属蛋白酶组织抑制剂1（TIMP-1）与全髋关节置换术（THA）松动假体中胶原溶解和明胶溶解潜能（即二硝基苯基-脯氨酸-谷氨酰胺-甘氨酸-异亮氨酸-丙氨酸-甘氨酸-谷氨酰胺-D-精氨酸（DNP-S）敏感的蛋白水解活性）之间的关系。
采用免疫组织化学方法研究TIMP-1的组织定位。通过竞争性酶联免疫吸附测定法（ELISA）检测9个松动THA假体周围组织和液体样本中的TIMP-1水平，并通过合成DNP-S的降解和反相高效液相色谱法评估DNP-S敏感的胶原溶解和明胶溶解潜能。
免疫组织化学分析显示，在假滑膜衬里细胞中TIMP-1呈中度至明显的免疫反应性，在骨与植入物之间的界面组织和人工关节周围的假包膜组织中的单核细胞/巨噬细胞、内皮细胞和成纤维细胞中常呈弱至中度免疫反应性。与假滑液样本（2026±584 ng/ml）相比，界面组织样本中的TIMP-1水平较低（795±203 ng/ml）。界面组织样本中底物的降解率（56±6%）高于假包膜组织样本（32±4%）和假滑液样本（6±2%）。
低TIMP-1水平与合成底物DNP-S的高降解率相结合，导致界面组织样本中具有高胶原溶解和明胶溶解活性。这可能部分解释了假体周围结缔组织的弱化。弱化与周期性机械负荷相结合可能导致THA假体松动。
