Dexamethasone enhances In vitro vascular calcification by promoting osteoblastic differentiation of vascular smooth muscle cells.
Vascular calcification is often associated with atherosclerotic lesions. Moreover, the process of atherosclerotic calcification has several features similar to the mineralization of skeletal tissue. Therefore, we hypothesized that vascular smooth muscle cells might acquire osteoblastic characteristics 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 vascular calcification by using an in vitro calcification model. We demonstrated that 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 parathyroid hormone in BVSMCs. We also examined the effects of Dex on human osteoblast-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 cells. Interestingly, we detected that Osf2/Cbfa1, a key transcription factor in osteoblastic differentiation, was expressed in both BVSMCs and Saos-2 cells and that Dex increased the gene expression of both transcription factors. These findings suggest that Dex may enhance osteoblastic differentiation of BVSMCs in vitro.
Mori
K
K
Second Department of Internal Medicine, Osaka City University Medical School, Osaka, Japan.
Shioi
A
A
Jono
S
S
Nishizawa
Y
Y
Morii
H
H
D000469:Alkaline Phosphatase / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002114:Calcinosis / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002417:Cattle; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D050659:Core Binding Factor Alpha 1 Subunit; D000242:Cyclic AMP / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D009363:Neoplasm Proteins; D010006:Osteoblasts / Q000473:pathology*; D010281:Parathyroid Hormone / Q000494:pharmacology; D010446:Peptide Fragments / Q000378:metabolism; D011347:Procollagen / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics; D014652:Vascular Diseases / Q000378:metabolism*
D050659:Core Binding Factor Alpha 1 Subunit; D005938:Glucocorticoids; D009363:Neoplasm Proteins; D010281:Parathyroid Hormone; D010446:Peptide Fragments; D011347:Procollagen; D012333:RNA, Messenger; D014157:Transcription Factors; C042813:procollagen type I carboxy terminal peptide; D003907:Dexamethasone; D000242:Cyclic AMP; D000469:Alkaline Phosphatase; D002118:Calcium