Proteoglycan's activation by adhesion molecules and L metalloproteases in rheumatoid arthritis and osteoarthritis.

H L Montrull, C I Meirovich, A M Strusberg, N Y Brizuela
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Abstract

Two groups of patients were studied, both in accordance with ACR criteria. First group (41 cases) suffering R.A. Second group (36 cases) suffering O.A. In both pathologies MMPs, ICAM and VCAM from synovial fluid and plasma were studied. Measurements were made with ELISA-sandwich in a Metrolab spectrophotometer at 410 nm for MMPs, and 491 nm for ICAM and VCAM. As control, samples of patients with noninflammatory muscle skeletal disorders or traumatic arthritis and healthy witness were used. Synovial concentration of MMPs in R.A. was 1402 +/- 76 ng/ml, a higher significant value (p < 0.0001) compared with osteoarthritis: 353 +/- 23 ng/ml. In the witness plasma, MMPs were not detected. Plasmatic and synovial levels of the adhesion molecules present different values in both pathologies and between them. Synovial ICAM level in R.A. (280 +/- 9.8 ng/ml) is significantly higher than in O.A. (163 +/- 10 ng/ml) (p < 0.001), but lower than the plasmatic ones (370 +/- 35 ng/ml) (p < 0.001). All these values are significantly higher than the normal plasma (121 +/- 6.5 ng/ml) (p < 0.01, p < 0.005, and p < 0.0001, respectively) VCAM increase regarding basal values (140 +/- 5.6 ng/ml) (p < 0.001) and in a similar proportion for both pathologies (R.A.: 186 +/- 9.3 ng/ml and O.A.: 207 +/- 14.3 ng/ml). Their plasmatic levels were higher (270 +/- 45 and 320 +/- 38 ng/ml) (p < 0.001) but without significative difference between them. There is correlation among MMPs, ICAM and VCAM variations. The variability can be explained by concomitance several evolutive steps. Each pathology shows a different grade of cellularity, inverted predominance in the relation TIMPs/ collagenase and different generator mechanisms of MMPs. Our findings reinforce the importance as diagnostic guide of adhesion molecules dosage, and possible therapeutic use of MMPs inhibitors and ICAM or VCAM antagonists en R.A. and related pathologies.

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类风湿性关节炎和骨关节炎中粘附分子和L金属蛋白酶对蛋白聚糖的激活作用。
研究了两组患者,均符合ACR标准。第1组(41例)为ra,第2组(36例)为oa。两组患者均观察滑液和血浆中MMPs、ICAM和VCAM的变化。用ELISA-sandwich在Metrolab分光光度计上测定MMPs的波长为410 nm, ICAM和VCAM的波长为491 nm。作为对照,使用非炎症性肌肉骨骼疾病或创伤性关节炎患者和健康证人的样本。骨性关节炎滑膜中MMPs的浓度为1402 +/- 76 ng/ml,高于骨关节炎的353 +/- 23 ng/ml (p < 0.0001)。在证人血浆中,未检测到MMPs。黏附分子的血浆和滑膜水平在两种病理和它们之间呈现不同的值。ra滑膜ICAM水平(280 +/- 9.8 ng/ml)显著高于oa (163 +/- 10 ng/ml) (p < 0.001),低于血浆(370 +/- 35 ng/ml) (p < 0.001)。所有这些值均显著高于正常血浆(121 +/- 6.5 ng/ml) (p < 0.01, p < 0.005和p < 0.0001)。VCAM升高与基础值(140 +/- 5.6 ng/ml) (p < 0.001)有关,两种病理的比例相似(R.A: 186 +/- 9.3 ng/ml, O.A: 207 +/- 14.3 ng/ml)。血浆水平较高(270 +/- 45和320 +/- 38 ng/ml) (p < 0.001),但两者之间无显著差异。MMPs、ICAM和VCAM的变化之间存在相关性。这种变异性可以用同时发生的几个进化步骤来解释。每种病理表现出不同级别的细胞结构,TIMPs/胶原酶关系的反向优势和MMPs的不同产生机制。我们的研究结果加强了粘附分子剂量作为诊断指南的重要性,以及MMPs抑制剂和ICAM或VCAM拮抗剂在ra和相关病理中的可能治疗应用。
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