OBJECTIVE: To investigate the clotting and fibrinolytic activities in synovial fluid (SF) from patients with rheumatoid arthritis (RA) and to examine the role of thrombin in synovial hyperplasia. METHODS: We measured the amounts of thrombin-antithrombin-III complex (TAT), antithrombin-III (AT-III), thrombin, plasminogen, alpha 2-plasmin inhibitor (alpha 2-PI), and plasmin-alpha 2-antiplasmin complex (PAP) in SF of 20 patients with RA and 16 patients with osteoarthritis (OA). The proliferative response of synovial fibroblast-like cells to thrombin was measured using [3H] thymidine incorporation. Expression of platelet derived growth factors (PDGF) in conditioned medium was analyzed using a Western blot method, and expression of the mRNA of PDGF and their receptors was analyzed by reverse transcription polymerase chain reaction. RESULTS: The amounts of clotting factors (TAT, AT-III) and fibrinolytic factors (plasminogen, alpha 2-PI, and PAP) were significantly higher in the patients with RA than in patients with OA (p < 0.01). Moreover, SF thrombin concentrations of patients with RA correlated significantly with erythrocyte sedimentation rates (rs = 0.751, p < 0.01) and serum C-reactive protein concentrations (rs = 0.531, p < 0.05). Thrombin exhibits mitogenic activity toward synovial fibroblast-like cells in vitro, and this mitogenic activity is associated with an increase in the expression of mRNA of both PDGF-alpha receptor and PDGF-beta-receptor. CONCLUSION: The high levels of thrombin activity in the SF of patients with RA and strong mitogenic activity of thrombin toward the synovial fibroblast-like cells suggest that thrombin plays an important role in the pathogenesis of RA.
OBJECTIVE: To investigate the clotting and fibrinolytic activities in synovial fluid (SF) from patients with rheumatoid arthritis (RA) and to examine the role of thrombin in synovial hyperplasia. METHODS: We measured the amounts of thrombin-antithrombin-III complex (TAT), antithrombin-III (AT-III), thrombin, plasminogen, alpha 2-plasmin inhibitor (alpha 2-PI), and plasmin-alpha 2-antiplasmin complex (PAP) in SF of 20 patients with RA and 16 patients with osteoarthritis (OA). The proliferative response of synovial fibroblast-like cells to thrombin was measured using [3H] thymidine incorporation. Expression of platelet derived growth factors (PDGF) in conditioned medium was analyzed using a Western blot method, and expression of the mRNA of PDGF and their receptors was analyzed by reverse transcription polymerase chain reaction. RESULTS: The amounts of clotting factors (TAT, AT-III) and fibrinolytic factors (plasminogen, alpha 2-PI, and PAP) were significantly higher in the patients with RA than in patients with OA (p < 0.01). Moreover, SF thrombin concentrations of patients with RA correlated significantly with erythrocyte sedimentation rates (rs = 0.751, p < 0.01) and serum C-reactive protein concentrations (rs = 0.531, p < 0.05). Thrombin exhibits mitogenic activity toward synovial fibroblast-like cells in vitro, and this mitogenic activity is associated with an increase in the expression of mRNA of both PDGF-alpha receptor and PDGF-beta-receptor. CONCLUSION: The high levels of thrombin activity in the SF of patients with RA and strong mitogenic activity of thrombin toward the synovial fibroblast-like cells suggest that thrombin plays an important role in the pathogenesis of RA.
Authors: M Sen; K Lauterbach; H El-Gabalawy; G S Firestein; M Corr; D A Carson Journal: Proc Natl Acad Sci U S A Date: 2000-03-14 Impact factor: 11.205
Authors: H Shin; I Kitajima; T Nakajima; Q Shao; T Tokioka; I Takasaki; N Hanyu; T Kubo; I Maruyama Journal: Ann Rheum Dis Date: 1999-01 Impact factor: 19.103
Authors: Matthew J Flick; Anil K Chauhan; Malinda Frederick; Kathryn E Talmage; Keith W Kombrinck; Whitney Miller; Eric S Mullins; Joseph S Palumbo; Xunzhen Zheng; Naomi L Esmon; Charles T Esmon; Sherry Thornton; Ann Becker; Leslie A Pelc; Enrico Di Cera; Denisa D Wagner; Jay L Degen Journal: Blood Date: 2011-03-24 Impact factor: 22.113