Statin Enhances Osteoblast Differentiation by Suppression of Runx2 Overexpression

Abstract

It has recently been reported that statins, the cholesterol-lowering drug, activate the promoter of the bone morphogenic protein-2 (BMP-2) gene, and stimulate bone forma-tion. However, the mechanism of the stimulation of bone metabolism by statins is not precisely clarified. In this study, we investigated whether statins effect the expression of osteogenic master transcription factors, Runx2/Cbfa1 and Dlx5, as a downstream target of BMP-2. The human osteoblastic osteosarcoma cell line, SaOS-2, was used for this experiment. RT-PCR analysis demonstrated continuous overexpression of Runx2 in SaOS-2, though the expression was hardly observed in normal human osteoblasts. Therefore we considered SaOS-2 a model for the overexpression of the transcription factor. When the osteosarcoma cells were incubated with compactin, there was a significant decrease in mRNA level of Runx2 compared with controls (p<0.01). There appeared to be no overall changes in Dlx5. These results demonstrate that statins suppress the overexpression of Runx2 mRNA, and it hardly effects the expression of Dlx5. It is known that Runx2 is essential for the initial osteoblastic differentiation, but it inhibits the final differentiation. Hence, it is indicated that statins promote not only the initial osteoblastic differentiation but also the final differentiation through regulation of transcription factors.