1,25-Dihydroxyvitamin D3 increases in vitro vascular calcification by modulating secretion of endogenous parathyroid hormone-related peptide.
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 1alpha,25-dihydroxyvitamin D3 [1,25(OH)2D3] may have a direct impact on the calcium-regulating system of vascular smooth muscle cells, resulting in deposition of calcium in vascular wall.


RESULTS
We investigated the effect of 1,25(OH)2D3 on in vitro calcification by bovine vascular smooth muscle cells (BVSMCs). 1,25(OH)2D3 dose dependently increased BVSMC calcification and alkaline phosphatase activity. 1,25(OH)2D3 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)2D3 on BVSMCs. Finally, 1,25(OH)2D3 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)2D3 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)2D3 on alkaline phosphatase activity and osteopontin expression may contribute to its promoting action in vascular calcification.
Jono
S
S
Second Department of Internal Medicine, Osaka City University Medical School, Osaka 545, Japan.
Nishizawa
Y
Y
Shioi
A
A
Morii
H
H
D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D002114:Calcinosis / Q000139:chemically induced*; D002117:Calcitriol / Q000494:pharmacology*; D002417:Cattle; D002478:Cells, Cultured; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000473:pathology; D053495:Osteopontin; D010024:Osteoporosis / Q000188:drug therapy; D044162:Parathyroid Hormone-Related Protein; D011506:Proteins / Q000378:metabolism*; D012795:Sialoglycoproteins / Q000235:genetics; D014807:Vitamin D / Q000502:physiology
D044162:Parathyroid Hormone-Related Protein; D011506:Proteins; D012795:Sialoglycoproteins; D053495:Osteopontin; D014807:Vitamin D; D000469:Alkaline Phosphatase; D002117:Calcitriol