SAME RESTORES THE CHANGES IN THE PROLIFERATION AND IN THE SYNTHESIS OF FIBRONECTIN AND PROTEOGLYCANS INDUCED BY TUMOR-NECROSIS-FACTOR-ALPHAON CULTURED RABBIT SYNOVIAL-CELLS

S-Adenosyl-L-methionine (SAMe) is a naturally occurring compound invol ved in transmethylation and trans-sulphuration reactions. The administ ration of SAMe to patients with osteoarthritis (OA) seems to have a pr otective effect, although the mechanisms of its action are largely unk nown. We have studied the effect of SAMe as a protective agent against the modifications induced by tumour necrosis factor alpha (TNF alpha) on synovial cell proliferation and extracellular matrix protein synth esis, two important hallmarks of progressive articular diseases. The s timulation of cells with 100 U/ml TNF alpha for 24 h decreased the pro liferative rate (58 +/- 14% with TNF alpha vs basal 100%, P < 0.05), f ibronectin (FN) mRNA expression (36 +/- 14% vs basal, P < 0.05) and FN synthesis (79 +/- 20% vs basal, P > 0.05). By contrast, TNF alpha rai sed total protein and proteoglycan synthesis (127 +/- 12% vs basal and 239 +/- 40% vs basal, respectively, P < 0.05). The addition of increa sing concentrations of SAMe (10(-10)-10(-6) M) to synoviocytes incubat ed with TNF alpha reversed the effects induced by the cytokine, while SAMe alone did not modify significantly the metabolic processes studie d. These results indicate that, in cultured synovial cells, SAMe resto res basal conditions after cell damage elicited by TNF alpha stimulati on.