Simvastatin induces differentiation in rabbit articular chondrocytes via Wnt/ β-catenin pathway.

This study was conducted to evaluate the effects and signalling pathway of simvastatin on chondrocyte differentiation. We found that simvastatin induced chondrocyte differentiation, as confirmed by increased type II collagen expression and induced sulphated proteoglycan synthesis. Western blotting results showed that expression of type II collagen increased 6-fold in a dose-dependent manner compared with that in the control. Further, nuclear/cytosol fraction analysis revealed that simvastatin reduced the expression and translocation of β-catenin into the nucleus from the cytoplasm by approximately 50% compared with that in the control. A luciferase assay using a T cell factor/lymphoid enhancer factor reporter construct was performed to test the transcriptional activity of β-catenin. Simvastatin-induced differentiation was dependent on inactivation of β-catenin, as simvastatin inhibited accumulation of β-catenin, which was characterized by translocation of β-catenin to the nucleus as shown by immunofluorescence staining and the luciferase assay. Prevention of β-catenin degradation by inhibition of the proteasome with z-Leu-Leu-Leu-CHO blocked the increase in type II collagen expression. Simvastatin treatment reduced chondrocyte dedifferentiation induced by retinoic acid or serial monolayer culturing by 50% compared to that in the non-treated cells. Our findings demonstrate that simvastatin increases differentiation of rabbit articular chondrocytes via the β-catenin path...
Source: European Journal of Pharmacology - Category: Drugs & Pharmacology Authors: Tags: Eur J Pharmacol Source Type: research