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  • Title: Thrombin in the synovial fluid of patients with rheumatoid arthritis mediates proliferation of synovial fibroblast-like cells by induction of platelet derived growth factor.
    Author: Ohba T, Takase Y, Ohhara M, Kasukawa R.
    Journal: J Rheumatol; 1996 Sep; 23(9):1505-11. PubMed ID: 8877916.
    Abstract:
    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.
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