Simvastatin Induces Apoptosis of Fibroblast-Like Synoviocytes
Ira Litinsky*, Itshak Golan, Michael Yaron, Ilana Yaron, Dan Caspi, Ori Elkayam
Identifiers and Pagination:Year: 2009
First Page: 35
Last Page: 40
Publisher ID: TORJ-3-35
Article History:Received Date: 16/2/2009
Revision Received Date: 26/2/2009
Acceptance Date: 24/3/2009
Electronic publication date: 7/9/2009
Collection year: 2009
open-access license: This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.
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.
To evaluate the effect of varying doses of simvastatin on apoptosis of FLS.
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 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.
Different concentrations of simvastatin induced apoptosis of FLS. The level proportion of apoptotic cells of resting 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 concentration used.
Varying concentrations of simvastatin induce apoptosis of activated fibroblast-like synoviocytes, suggesting another possible mechanism of anti-inflammatory effects of statins in inflammatory conditions.