Simvastatin Induces Apoptosis of Fibroblast-Like Synoviocytes

BACKGROUND Statins (3-Hydroxy-3-methylglutaryl-CoA reductase inhibitors) exert favorable effects on lipoprotein metabolism, but appeared to possess anti-inflammatory properties among others, as suggested by their ability to inhibit collagen-induced arthritis in mice. Their activity in fibroblast-like synovial cells (FLS) has not yet been studied. OBJECTIVES To evaluate the effect of varying doses of simvastatin on apoptosis of FLS. METHODS Synovial tissue, obtained during total knee replacement due to osteoarthritis, was cut into small pieces and cultured in Petri dishes with test materials, as previously described. FLS were incubated for 48 hours with 1 mumol/ml, 5 mumol/ ml, 15 mumol/ml and 50 mumol/ml of simvastatin. Following incubation, apoptosis was analyzed by two-dimensional flow cytometry (FACS) using annexin V/PI staining according to the manufacturer's instructions. RESULTS Different concentrations of simvastatin induced apoptosis of FLS. The level proportion of apoptotic cells of resting or activated with lipopolysaccharide (LPS; 3 mug/ml) FLS, not treated with simvastatin, was 21%. At 48 hours, the rate of apoptosis of activated fibroblasts, incubated with 1 mumol/ml, 5 mumol/ml, 15 and 50 mumol/ml was 22%, 32%, 48% and 41% respectively. Synovial cell viability evaluated by tetrazolium salt XXT was unaffected by the simvastatin concentration used. CONCLUSION Varying concentrations of simvastatin induce apoptosis of activated fibroblast-like synoviocytes, suggesting another possible mechanism of anti-inflammatory effects of statins in inflammatory conditions.