Piascledine modulates the production of VEGF and TIMP-1 and reduces the invasiveness of rheumatoid arthritis synoviocytes

Background: In rheumatoid arthritis (RA), hypertrophy of the synovial membrane generates a tumour-like pannus that invades the joint cavity and erodes cartilage and bone. Invasion of the extracellular matrix (ECM) is accompanied by angiogenesis, in which vascular endothelial growth factor (VEGF) and tissue inhibitors of metalloproteinases (TIMPs), produced by synoviocytes lining the parmus, have a primary role. Piascledine (PSD) is used in the treatment of osteoarthritis and has anti-inflammatory effects in vitro. Objective: To study the effects of PSD on levels of VEGF and TIMP-1 and chemoinvasion in RA synoviocytes and healthy controls. Methods: The effects of PSD 5, 10, and 20 mu g/mL were evaluated, with/without interleukin-1 beta (IL-1 beta) and tumour necrosis factor-alpha (TNF alpha) 20 ng/mL, on synoviocytes. The levels of VEGF and TIMP-1 were assayed in the culture medium by enzyme-linked immunosorbent assay (ELISA). Chemoinvasion was measured by the Boyden chamber invasion assay. Results: RA synoviocytes treated with PSD showed, compared to basal, lower levels of VEGF (41080 +/- 830 vs. 79210 +/- 920 pg/10(6) cells, p < 0.001) and increased levels of TIMP-1 (23540 +/- 93.2 vs. 12860 +/- 42.9 ng/10(6) cells, p < 0.001). PSD decreased dose-dependently IL-1 beta and TNF alpha induced migration. Conclusions: In RA synoviocytes, and also to a lesser extent in control cells, PSD modulates VEGF and TIMP-1 and decreases chemoinvasion. PSD might have a role in the treatment of RA synovitis controlling invasiveness.