Effects of Raloxifene (RAL) on proliferation in healthy (H) and rheumatoid arthritis (RA) synoviocytes. (a) Proliferation of H and RA synoviocytes as a function of RAL concentration. Synoviocytes were seeded in 24 multi-well plates (15,000 cells/well) with 10% FCS in RPMI 1640. After 24 h incubation, cells were treated with increasing concentrations of RAL (0.5 to 2 μM). (b) Proliferation of H and RA synoviocytes under control conditions (0.2% FCS as a negative control, and 10% FCS as a positive control), in 0.2% FCS under the effect of 500 ng/ml urokinase-type plasminogen activator (u-PA) and in the presence of 0.5 and 1 μM RAL or the monoclonal antibodies (mAbs) 5B4 and 3936, which impair u-PA/u-PAR binding (see text for details). In both (a) and (b), each point represents the mean ± standard deviation of three experiments performed in triplicate on four normal and four RA synovial cell lines. § = p < 0.01 versus basal (0.2% FCS); # = p < 0.001 versus 10% FCS or u-PA, for both H and RA.