EVIDENCE FOR METALLOPROTEINASE AND METALLOPROTEINASE INHIBITOR IMBALANCE IN HUMAN OSTEOARTHRITIC CARTILAGE
EVIDENCE FOR METALLOPROTEINASE AND METALLOPROTEINASE INHIBITOR IMBALANCE IN HUMAN OSTEOARTHRITIC CARTILAGE
复制标题
DOI：
10.1172/jci114215
复制
发表时间：
1989-08-01
影响因子：
15.9
通讯作者：
WOESSNER, JF
中科院分区：
文献类型：
--
作者：
DEAN, DD;MARTELPELLETIER, J;WOESSNER, JF
取1.3例骨性关节炎(OA)患者和7例对照组的胫骨平台软骨标本，取自A区、B区、C区三个区域，A区为纤维化区中心，B区为纤维化区，C区为远高原区。酸性、中性金属蛋白酶及其组织抑制因子(TIMP)用2-甲基胍提取。建立了选择性地破坏蛋白水解酶或TIMP的方法，以防止分析过程中的交叉反应。酸性和中性蛋白水解酶升高。OA150%，TIMP升高。50%。中性和酸性蛋白水解酶活性在骨性关节炎患者中呈正相关(r=0.50)，而在正常对照组中无相关性。两种蛋白水解酶活性在骨性关节炎中均有，但在对照组中不存在。两种蛋白水解酶在A、B和C区均升高两到三倍，但酸性金属蛋白酶的自活性形式仅在A和B区升高(200%)；它与Mankin评分有很好的相关性，而总活性则不是。TIMP仅在A区和B区升高(50%)，内侧的升高幅度和Mankin评分均大于外侧。TIMP对这两种金属蛋白酶的滴定表明，抑制物有少量过量增加，其程度与蛋白水解酶相同；由此产生的蛋白水解酶过量可能是软骨破坏的原因之一。
Cartilage specimens from tibial plateaus, obtained from 1.3 osteoarthritic (OA) patients and seven controls, were selected from three regions: zone A, center of fibrinated area; zone B, area adjacent to fibrillation, and zone C, remote region of plateau. Acid and neutral metalloproteinases and tissue inhibitor of metalloproteinase (TIMP) were extracted with 2 M guanidine. Methods were developed to selectively destroy either proteinases or TIMP to prevent cross-reaction during assay. Acid and neutral proteinases were elevated .apprx. 150% in OA; TIMP was elevated .apprx. 50%. A positive correlation (r = 0.50) was found between acid and neutral proteinase activities in OA, but not in controls. Both proteinase activities in OA, but not in controls. Both proteinases were elevated two- to threefold in zones A, B, and C. However, the self-active form of the acid metalloproteinase was elevated only in zones A and B (200%); it correlated well with the Mankin scores, whereas the total activities did not. TIMP was elevated (50%) only in zones A and B. Both the proteinase levels and the Mankin score were elevated to a greater extent in the medial, than in the lateral, compartment. Titration of TIMP against the two metalloproteinases indicates that there is a small excess of inhibitor increase to the same extent as the proteinases; the resultant excess of proteinase over TIMP may contribute to cartilage breakdown.