Giannelli G, Erriquez R, Iannone F, Marinosci F, Lapadula G, Antonaci S
Department of Internal Medicine, Immunology, and Infectious Diseases, Section of Internal Medicine, University of Bari Medical School, Bari, Italy.
Clin Exp Rheumatol. 2004 May-Jun;22(3):335-8.
Rheumatoid arthritis (RA) and psoriatic arthritis (PA) are both chronic rheumatic inflammatory diseases characterized by disruption of the extra-cellular matrix (ECM) protein of the cartilage, likely induced by proteolytic enzymes such as matrix metalloproteases (MMPs). The goal of this study was to quantify the expression of MMPs such as MMP-2 and MMP-9, and their physiological tissue inhibitors TIMP-2 and TIMP-1, respectively, in serum and synovial fluid.
Serum and synovial fluid from 24 RA patients and 17 PA patients were studied to determine the levels of MMP-2 and MMP-9 proteolytic activity using a modified gelatin zymography procedure. TIMP-1 and TIMP-2 were measured by a commercially available ELISA kit.
Our results show that MMP-2 was detected in the latent form only, while MMP-9 was present in latent and active form. Both gelatinases were more concentrated in synovial fluid than in serum, and TIMP-1 and TIMP-2 concentrations were also more elevated in synovial fluid than in serum.
To investigate the remodelling of cartilage ECM proteins, the evaluation of synovial fluid concentrations of MMP-2, MMP-9, TIMP-1 and TIMP-2 is more reliable than that determined in serum. In view of these data, MMPs inhibitors might represent a possible target for new therapies delivered directly in the joint space.
类风湿性关节炎(RA)和银屑病关节炎(PA)均为慢性风湿性炎症疾病,其特征是软骨细胞外基质(ECM)蛋白遭到破坏,这可能是由诸如基质金属蛋白酶(MMPs)等蛋白水解酶所诱导的。本研究的目的是分别定量测定血清和滑液中MMP-2和MMP-9等基质金属蛋白酶及其生理性组织抑制剂TIMP-2和TIMP-1的表达。
对24例RA患者和17例PA患者的血清和滑液进行研究,采用改良的明胶酶谱法测定MMP-2和MMP-9的蛋白水解活性水平。TIMP-1和TIMP-2通过市售ELISA试剂盒进行检测。
我们的结果显示,仅检测到潜伏形式的MMP-2,而MMP-9以潜伏形式和活性形式存在。两种明胶酶在滑液中的浓度均高于血清,TIMP-1和TIMP-2的浓度在滑液中也比血清中更高。
为研究软骨ECM蛋白的重塑,评估滑液中MMP-2、MMP-9、TIMP-1和TIMP-2的浓度比测定血清中的浓度更可靠。鉴于这些数据,基质金属蛋白酶抑制剂可能是直接在关节腔给药的新疗法的一个潜在靶点。