Woessner J F, Gunja-Smith Z
Department of Biochemistry, University of Miami School of Medicine, FL 33101.
J Rheumatol Suppl. 1991 Feb;27:99-101.
Extracts of human articular cartilage have been examined for the presence of metalloproteinases that degrade proteoglycans and collagen of the extracellular matrix. Two enzymes (stromelysin and acid metalloproteinase) that degrade proteoglycan are elevated at least 150% in osteoarthritis (OA), whereas the tissue inhibitor of metalloproteinases (TIMP) shows only a small increase. We postulate an imbalance of enzyme over inhibitor that leads to net matrix destruction in OA. Stromelysin is shown to have an acid pH optimum of about 5.5. At this pH it can become spontaneously active and is less susceptible to TIMP inhibition than at pH 7.5. We postulate that the chondrocytes may secrete acid into the pericellular space, leading to localized enzyme activation and proteoglycan digestion.
已对人关节软骨提取物进行检测，以确定是否存在可降解细胞外基质中蛋白聚糖和胶原蛋白的金属蛋白酶。在骨关节炎（OA）中，两种可降解蛋白聚糖的酶（基质溶素和酸性金属蛋白酶）至少升高了150%，而金属蛋白酶组织抑制剂（TIMP）仅略有增加。我们推测酶与抑制剂之间的失衡会导致OA中的净基质破坏。基质溶素的最适酸性pH约为5.5。在此pH下，它可自发激活，且比在pH 7.5时更不易受TIMP抑制。我们推测软骨细胞可能会向细胞周隙分泌酸性物质，导致局部酶激活和蛋白聚糖消化。
