1,25-DIHYDROXYVITAMIN D-3 INCREASES IN-VITRO VASCULAR CALCIFICATION BY MODULATING SECRETION OF ENDOGENOUS PARATHYROID HORMONE-RELATED PEPTIDE

Background-A significant association between vascular calcification an d osteoporosis has been noted, suggesting that calcium homeostasis is important in vascular calcification as well as in osteoporosis. Moreov er, results of our previous studies suggest that calcium-regulating ho rmones such as parathyroid hormone-related peptide (PTHrP) may modulat e vascular calcification. Therefore we hypothesized that 1 alpha,25-di hydroxyvitamin D-3 [1,25(OH)(2)D-3] may have a direct impact on the ca lcium-regulating system of vascular smooth muscle cells, resulting in deposition of calcium in vascular wall. Methods and Results-We investi gated 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 dependentl y increased BVSMC calcification and alkaline phosphatase activity. 1,2 5(OH)(2)D-3 also decreased secretion of PTHrP by BVSMCs in a dose-depe ndent 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 th e expression of the osteopontin gene, one of the bone matrix proteins in BVSMCs, contributing to its stimulatory action on BVSMC calcificati on. Conclusions-These data suggest that 1,25(OH)(2)D-3 exerts a stimul atory effect on vascular calcification through direct inhibition of th e 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 contribu te to its promoting action in vascular calcification.