Protective Effect of Atorvastatin in Cultured Osteoarthritic Chondrocytes

The aim of our study was to evaluate the in vitro effect of an HMG-CoA reductase inhibitor, atorvastatin, on the expression of significant anabolic and catabolic genes in human osteoarthritic chondrocytes and to explore the metabolic pathways involved in this process. Human articular osteoarthritic chondrocytes were cultured in the presence and absence of atorvastatin (10 and 50 mu mol/L) for 24 h. Metalloproteinase 13 (MMP-13), collagen type II (COL2A1), and aggrecan (AGC) mRNA expression levels were evaluated by real-time PCR, and protein expression levels by Western blot analysis. IL-1 beta levels in culture medium was analyzed with ELISA. The effect of the treatment with the mevalonate isoprenoid derivatives farnesol and geranylgeraniol, or the cholesterol precursor squalene, was evaluated in the atorvastatin osteoarthritic chondrocyte cultures. Incubation of osteoarthritic chondrocyte cultures with atorvastatin produced a significant dose-dependent reduction in IL-1 beta production. Atorvastatin supplementation in cultures produced a decrease in MMP-13 mRNA and protein expression levels, which was reversed by the addition or farnesol. Regarding AGC and COL2A1 mRNA expression, a significant increase was observed only in chondrocytes cultures treated with 50 mu mol/L atorvastatin. Our findings suggest that atorvastatin may have potential chandroprotective effects mostly by reducing cartilage degradation. (C) 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:110-115, 201