Among the signaling molecules, we document here the relevance of Rho to the pathogenesis of RA synovitis, based on the following results: high expression of thrombin receptor on RA SFs and thrombin markedly increased the proliferation of these cells and progression of the cell cycle to S phase; thrombin induced the activation of Rho; Rho activation as well as proliferation and S-phase progression were completely blocked by either p115RGS or Gα13-ct; and thrombin-induced IL-6 secretion was also reduced by p115RGS and Gα13-ct. Here, F2R is linked to rheumatoid arthritis.