OBJECTIVE: To clarify which proteases are specifically activated in the lesions of rheumatoid arthritis (RA) and osteoarthritis (OA). METHODS: The activity levels of the serine proteases of the coagulation and fibrinolytic systems, and of elastase and collagenase as controls, in synovial fluid from 27 RA patients and 28 OA patients were measured using fluorogenic synthetic substrates which had methylcoumarylamide (MCA) at their COOH-termini. The thrombin-antithrombin III complex (TAT) content was also measured by ELISA. RESULTS: Among the proteases, thrombin-like activity was the highest in both RA and OA. The profiles of protease activity were similar in RA and OA, but their activities were in general significantly higher in RA than in OA (p < 0.01). The levels of both thrombin-like activity and TAT were about 7.5-fold higher in RA than in OA, while the levels of CRP and fibrinogen were only about 2-fold higher. Biochemical characterization of the thrombin-like activity in the synovial fluid of RA patients showed that this activity was due to thrombin. Thrombin-like activity positively correlated with the TAT concentration in RA (r = 0.750, p < 0.0001), but not in OA. CONCLUSION: Activation of the coagulation system was more marked in RA than in OA, strongly suggesting that in RA there is an imbalance between thrombin and its inhibitors, and that thrombin is more closely linked to the pathogenesis of RA than to that of OA. Our results also show that analysis of the synovial fluid may be useful to estimate the activation of the coagulation system in RA, but not that of the fibrinolytic system.
OBJECTIVE: To clarify which proteases are specifically activated in the lesions of rheumatoid arthritis (RA) and osteoarthritis (OA). METHODS: The activity levels of the serine proteases of the coagulation and fibrinolytic systems, and of elastase and collagenase as controls, in synovial fluid from 27 RA patients and 28 OA patients were measured using fluorogenic synthetic substrates which had methylcoumarylamide (MCA) at their COOH-termini. The thrombin-antithrombin III complex (TAT) content was also measured by ELISA. RESULTS: Among the proteases, thrombin-like activity was the highest in both RA and OA. The profiles of protease activity were similar in RA and OA, but their activities were in general significantly higher in RA than in OA (p < 0.01). The levels of both thrombin-like activity and TAT were about 7.5-fold higher in RA than in OA, while the levels of CRP and fibrinogen were only about 2-fold higher. Biochemical characterization of the thrombin-like activity in the synovial fluid of RA patients showed that this activity was due to thrombin. Thrombin-like activity positively correlated with the TAT concentration in RA (r = 0.750, p < 0.0001), but not in OA. CONCLUSION: Activation of the coagulation system was more marked in RA than in OA, strongly suggesting that in RA there is an imbalance between thrombin and its inhibitors, and that thrombin is more closely linked to the pathogenesis of RA than to that of OA. Our results also show that analysis of the synovial fluid may be useful to estimate the activation of the coagulation system in RA, but not that of the fibrinolytic system.
Authors: Andrew D Grant; Graeme S Cottrell; Silvia Amadesi; Marcello Trevisani; Paola Nicoletti; Serena Materazzi; Christophe Altier; Nicolas Cenac; Gerald W Zamponi; Francisco Bautista-Cruz; Carlos Barajas Lopez; Elizabeth K Joseph; Jon D Levine; Wolfgang Liedtke; Stephen Vanner; Nathalie Vergnolle; Pierangelo Geppetti; Nigel W Bunnett Journal: J Physiol Date: 2006-11-23 Impact factor: 5.182
Authors: Beth Friedman; Michael A Whitney; Elamprakash N Savariar; Christa Caneda; Paul Steinbach; Qing Xiong; Dina V Hingorani; Jessica Crisp; Stephen R Adams; Michael Kenner; Csilla N Lippert; Quyen T Nguyen; Monica Guma; Roger Y Tsien; Maripat Corr Journal: Arthritis Rheumatol Date: 2017-11-29 Impact factor: 10.995
Authors: Yuan H Yang; Pam Hall; Georgia Milenkovski; Laveena Sharma; Paul Hutchinson; Els Melis; Peter Carmeliet; Peter Tipping; Eric Morand Journal: Am J Pathol Date: 2004-01 Impact factor: 4.307