Bone morphogenetic protein-7 inhibits vascular calcification induced by high vitamin D in mice.
Vascular calcification refers to the deposition of calcium phosphate in cardiovascular tissues, including arteries and myocardium. Vascular calcification is frequently associated with cardiovascular disease. Recently, bone morphgenetic protein-7 (BMP-7) has been proposed to play an inhibitory role in vascular calcification, but its inhibitory effect has not been fully elucidated. We therefore tested the hypothesis that BMP-7 inhibits vascular calcification by using two conditions, high levels of vitamin D and phosphate, each of which could enhance vascular calcification. C57BL/6 mice were treated for 3 days with high vitamin D (500,000 IU/kg/day) in the presence or absence of recombinant human BMP-7 (rhBMP-7). Expression levels of osteopontin and osteocalcin, markers of the osteoblastic phenotype, were assessed by immunohistochemical staining or Western blotting analysis. Vitamin D increased calcium staining in thoracic aortas and hearts and the expression levels of osteopontin and osteocalcin in mice. Importantly, pretreatment for 7 days and subsequent treatment for 3 days with rhBMP-7 (10 microg/kg/day) abolished the vitamin D-mediated increases in the above parameters. In addition, human aortic smooth muscle cells (HASMCs) were cultured with high beta-glycerophosphate, a phosphate donor, for 2 weeks in the presence or absence of rhBMP-7. High beta-glycerophosphate increased expression levels of osteopontin and osteocalcin as well as calcium staining in HASMCs, but these changes were attenuated by treatment with BMP-7. Thus, BMP-7 inhibits vascular calcification associated with high levels of vitamin D or phosphate. We propose that BMP-7 treatment may be helpful in reducing the risks of cardiovascular disease related to vascular calcification.
Kang
Yang Ho
YH
Division of Endocrinology and Metabolism, Department of Internal Medicine, Pusan National University School of Medicine, Yangsan, Korea.
Jin
Jung Sook
JS
Yi
Dong Won
DW
Son
Seok Man
SM
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D055419:Bone Morphogenetic Protein 7 / Q000494:pharmacology*; D002114:Calcinosis / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D002762:Cholecalciferol / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004336:Drug Antagonism; D004338:Drug Combinations; D005994:Glycerophosphates / Q000037:antagonists & inhibitors / Q000494:pharmacology; D006321:Heart / Q000187:drug effects; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000473:pathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D015675:Osteocalcin / Q000378:metabolism; D053495:Osteopontin / Q000378:metabolism; D011994:Recombinant Proteins
D055419:Bone Morphogenetic Protein 7; D004338:Drug Combinations; D005994:Glycerophosphates; D011994:Recombinant Proteins; D015675:Osteocalcin; D053495:Osteopontin; D002762:Cholecalciferol; C031463:beta-glycerophosphoric acid