G Giannelli1, R Erriquez, F Iannone, F Marinosci, G Lapadula, S Antonaci. 1. Department of Internal Medicine, Immunology, and Infectious Diseases, Section of Internal Medicine, University of Bari Medical School, Bari, Italy. g.giannelli@intmed.uniba.it
Abstract
OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
OBJECTIVE: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. METHODS: Serum and synovial fluid from 24 RApatients 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. RESULTS: 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. CONCLUSIONS: 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.
Authors: Katherine P Liao; Michael E Weinblatt; Jing Cui; Christine Iannaccone; Lori B Chibnik; Bing Lu; Jonathan S Coblyn; Nancy A Shadick; Daniel H Solomon Journal: Rheumatology (Oxford) Date: 2011-03-29 Impact factor: 7.580