Dexamethasone enhances in vitro vascular calcification by promoting osteoblastic differentiation of vascular smooth muscle cells

Vascular calcification is often associated with atherosclerotic lesions. Mo reover, the process of atherosclerotic calcification has several features s imilar to the mineralization of skeletal tissue. Therefore, we hypothesized that vascular smooth muscle cells might acquire osteoblastic characteristi cs during the development of atherosclerotic lesions. In the present study, we investigated the effect of dexamethasone (Dex), which is well known to be a potent stimulator of osteoblastic differentiation in vitro, on vascula r calcification by using an in vitro calcification model. We demonstrated t hat Dex increased bovine vascular smooth muscle cell (BVSMC) calcification in a dose- and time-dependent manner, Dex also enhanced several phenotypic markers of osteoblasts, such as alkaline phosphatase activity, procollagen type I carboxy-terminal peptide production, and cAMP responses to parathyro id hormone in BVSMCs. We also examined the effects of Dex on human osteobla st-like (Saos-2) cells and compared its effects on BVSMCs and Saos-2 cells. The effects of Dex on alkaline phosphatase activity and the cAMP response to parathyroid hormone in BVSMCs were less prominent than those in Saos-2 c ells. Interestingly, we detected that Osf2/Cbfa1, a key transcription facto r in osteoblastic differentiation, was expressed in both BVSMCs and Saos-2 cells and that Dex increased the gene expression of both transcription fact ors. These findings suggest that Dex may enhance osteoblastic differentiati on of BVSMCs in vitro.