Simvastatin Induces Apoptosis of Fibroblast-Like Synoviocytes~!2009-02-16~!2009-03-24~!2009-09-07~!

Background: Statins (3-Hydroxy-3-methylglutaryl-CoA reductase inhibitors) exert favorable effects on lipopro- tein metabolism, but appeared to possess anti-inflammatory properties among others, as suggested by their ability to in- hibit 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 cul- tured in Petri dishes with test materials, as previously described. FLS were incubated for 48 hours with 1 μmol/ml, 5 μmol/ml, 15 μmol/ml and 50 μmol/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 rest- ing or activated with lipopolysaccharide (LPS; 3 μg/ml) FLS, not treated with simvastatin, was 21%. At 48 hours, the rate of apoptosis of activated fibroblasts, incubated with 1 μmol/ml, 5 μmol/ml, 15 and 50 μmol/ml was 22%, 32%, 48% and 41% respectively. Synovial cell viability evaluated by tetrazolium salt XXT was unaffected by the simvastatin concentra- tion 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.