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Difference in expression of the plasminogen activation system in synovial tissue of patients with rheumatoid arthritis and osteoarthritis

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Author: Ronday, H.K. · Smits, H.H. · Muijen, G.N.P. van · Pruszczynski, M.S.M. · Dolhain, R.J.E.M. · Langelaan, E.J. van · Breedveld, F.C. · Verheijen, J.H.
Institution: Gaubius Instituut TNO
Source:British Journal of Rheumatology, 5, 35, 416-423
Identifier: 233358
Keywords: Biology · Immunohistochemistry · Osteoarthritis · Plasminogen activation · Rheumatoid arthritis · Urokinase · fibrin · plasminogen activator · plasminogen activator inhibitor · urokinase · article · clinical article · gene expression · human tissue · immunohistochemistry · nonhuman · osteoarthritis · priority journal · rheumatoid arthritis · synovium · Arthritis, Rheumatoid · Enzyme Activation · Humans · Immunohistochemistry · Osteoarthritis · Plasminogen · Plasminogen Activator Inhibitor 1 · Plasminogen Activator Inhibitor 2 · Plasminogen Activators · Receptors, Cell Surface · Synovial Membrane · Tissue Plasminogen Activator · Urinary Plasminogen Activator


Proteolytic joint destruction in inflammatory and non-inflammatory arthropathy is believed to be mediated, at least in part, by the plasminogen activation (PA) system. To further investigate possible involvement of the PA system, we quantified immunoreactive urokinase-type plasminogen activator (u-PA), tissue-type plasminogen activator (t-PA), both plasminogen activator inhibitors (PAI-1 and PAI-2) and u-PA-receptor (u-PAR) in synovial tissue extracts of 14 patients with rheumatoid arthritis (RA) and 12 with osteoarthritis (OA). u-PA, PAI-1, PAI-2 and u-PAR concentrations were significantly higher in RA than in OA patients, t-PA antigen levels were significantly lower in RA than in OA synovial tissue extracts. Immunohistochemistry was performed to compare the distribution and staining intensity of these components in samples of RA and OA synovial tissue. Intense immunostaining of u-PA, u-PAR, PAI-1 and, to a lesser degree, PAI-2 was observed predominantly in the synovial lining of RA patients. In OA patients, u-PA, PAI-1, PAI-2 and u-PAR were barely detectable. t-PA immunostaining was restricted to the endothelial side of vascular wall's in both groups. We conclude that the observed increase of u-PA, u-PAR and PAI expression, distributed mainly in the synovial lining area of proliferative and invasively growing synovial tissue in RA patients, supports a pathogenic role for the PA system in destructive arthritis. Depressed t-PA-mediated plasminogen activation might contribute to delayed intra-articular fibrin removal. Chemicals/CAS: Plasminogen Activator Inhibitor 1; Plasminogen Activator Inhibitor 2; plasminogen activator, urokinase receptors; Plasminogen Activators, EC 3.4.21.-; Plasminogen, 9001-91-6; Receptors, Cell Surface; Tissue Plasminogen Activator, EC; Urinary Plasminogen Activator, EC