A novel approach to measure the contribution of matrix metalloproteinase in the overall net proteolytic activity present in synovial fluids of patients with arthritis

Autor: Nathalie, Simard, Gilles, Boire, Artur J, de Brum-Fernandes, Yves, St-Pierre
Přispěvatelé: Institut Armand Frappier (INRS-IAF), Institut National de la Recherche Scientifique [Québec] (INRS)-Réseau International des Instituts Pasteur (RIIP), Division of Rheumatology, Department of Medicine, Université de Sherbrooke (UdeS)-Centre Hospitalier Universitaire de Sherbrooke, The work was supported by a grant from the Canadian Arthritis Network. YS-P and AJdBF are scholars of the Fonds de la Recherche en Santé du Québec.
Jazyk: angličtina
Rok vydání: 2006
Předmět:
Zdroj: Arthritis Research and Therapy
Arthritis Research and Therapy, BioMed Central, 2006, 8 (4), pp.R125. ⟨10.1186/ar2014⟩
Arthritis Research & Therapy
ISSN: 1478-6354
DOI: 10.1186/ar2014⟩
Popis: International audience; Despite decades of research, only a very limited number of matrix metalloproteinase (MMP) inhibitors have been successful in clinical trials of arthritis. One of the central problems associated with this failure may be our inability to monitor the local activity of proteases in the joints since the integrity of the extracellular matrix results from an equilibrium between noncovalent, 1:1 stoichiometric binding of protease inhibitors to the catalytic site of the activated forms of the enzymes. In the present work, we have measured by flow cytometry the net proteolytic activity in synovial fluids (SF) collected from 95 patients with osteoarthritis and various forms of inflammatory arthritis, including rheumatoid arthritis, spondyloarthropathies, and chronic juvenile arthritis. We found that SF of patients with inflammatory arthritis had significantly higher levels of proteolytic activity than those of osteoarthritis patients. Moreover, the overall activity in inflammatory arthritis patients correlated positively with the number of infiltrated leukocytes and the serum level of C-reactive protein. No such correlations were found in osteoarthritis patients. Members of the MMP family contributed significantly to the proteolytic activity found in SF. Small-molecular-weight MMP inhibitors were indeed effective for inhibiting proteolytic activity in SF, but their effectiveness varied greatly among patients. Interestingly, the contribution of MMPs decreased in patients with very high proteolytic activity, and this was due both to a molar excess of tissue inhibitor of MMP-1 and to an increased contribution of other proteolytic enzymes. These results emphasize the diversity of the MMPs involved in arthritis and, from a clinical perspective, suggest an interesting alternative for testing the potential of new protease inhibitors for the treatment of arthritis.
Databáze: OpenAIRE
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