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Osteoblastic Differentiation of Vascular Smooth Muscle Cells

Shuichi Jono, Yoshiki Nishizawa, Katsuhito Mori, Atsushi Shioi, Hirotoshi Morii

Atherosclerotic lesions are frequently associated with vascular calcification. Additionally, the process of atherosclerotic calcification shares a number of characteristics with skeletal tissue mineralization. At the onset of atherosclerotic lesions, we hypothesized that vascular smooth muscle cells might acquire osteoblastic characteristics.Using an in vitro calcification model, we examined the effect of dexamethasone (Dex), which is well known to be a potent stimulator of osteoblastic differentiation in vitro, on vascular calcification in this study. Dex increased the calcification of bovine vascular smooth muscle cells (BVSMCs) in a dose- and time-dependent manner, as we demonstrated. Alkaline phosphatase activity, procollagen type I carboxy-terminal peptide production, and cAMP responses to parathyroid hormone in BVSMCs were also enhanced by Dex in osteoblasts. In addition, we compared Dex’s effects on BVSMCs and Saos-2 cells and examined its effects on human osteoblast-like (Saos-2) cells. BVSMCs were less affected by Dex than Saos-2 cells were by its effects on alkaline phosphatase activity and the cAMP response to parathyroid hormone.We found that Dex increased the gene expression of both transcription factors, and that Osf2/Cbfa1, a key transcription factor in osteoblastic differentiation, was expressed in both BVSMCs and Saos-2 cells. According to these findings, in vitro osteoblastic differentiation of BVSMCs may be enhanced by Dex.