1,25-Dihydroxyvitamin D 3 Increases In Vitro Vascular Calcification by Modulating Secretion of Endogenous Parathyroid Hormone–Related Peptide

Abstract

Background —A significant association between vascular calcification and osteoporosis has been noted, suggesting that calcium homeostasis is important in vascular calcification as well as in osteoporosis. Moreover, results of our previous studies suggest that calcium-regulating hormones such as parathyroid hormone–related peptide (PTHrP) may modulate vascular calcification. Therefore, we hypothesized that 1α,25-dihydroxyvitamin D 3 [1,25(OH) 2 D 3 ] may have a direct impact on the calcium-regulating system of vascular smooth muscle cells, resulting in deposition of calcium in vascular wall. Methods and Results —We investigated the effect of 1,25(OH) 2 D 3 on in vitro calcification by bovine vascular smooth muscle cells (BVSMCs). 1,25(OH) 2 D 3 dose dependently increased BVSMC calcification and alkaline phosphatase activity. 1,25(OH) 2 D 3 also decreased secretion of PTHrP by BVSMCs in a dose-dependent manner and depressed its gene expression. Furthermore, exogenous PTHrP (fragment 1-34) antagonized the stimulatory effect of 1,25(OH) 2 D 3 on BVSMCs. Finally, 1,25(OH) 2 D 3 dose dependently increased the expression of the osteopontin gene, one of the bone matrix proteins in BVSMCs, contributing to its stimulatory action on BVSMC calcification. Conclusions —These data suggest that 1,25(OH) 2 D 3 exerts a stimulatory effect on vascular calcification through direct inhibition of the expression of PTHrP in BVSMCs as an endogenous inhibitor of vascular calcification. Moreover, the stimulatory effects of 1,25(OH) 2 D 3 on alkaline phosphatase activity and osteopontin expression may contribute to its promoting action in vascular calcification.