Bone Morphogenetic Protein-7 Inhibits Vascular Calcification Induced by High Vitamin D in Mice

Kang, Yang Ho; Jin, Jong Sook; Yi, Dongwon; Son, Seok Man

doi:10.1620/tjem.221.299

Cited by 38 publications

(36 citation statements)

References 33 publications

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“…29 USP grade cholecalciferol (C1357; Sigma, St. Louis, MO) was dissolved in 100% ethanol and diluted freshly to 1.65 mg/mL containing 5% ethanol for each injection. Ten-week-old Runx2 f/f and Runx2 DSM mice received cholecalciferol subcutaneously at a dosage of 500,000 IU/kg/ day for 4 consecutive days, and 5% ethanol in sterile water was used as a vehicle control.…”

Section: Vitamin D Induction Of Amc In Micementioning

confidence: 99%

Runx2 Expression in Smooth Muscle Cells Is Required for Arterial Medial Calcification in Mice

Lin

Chen

Leaf

et al. 2015

The American Journal of Pathology

122

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Arterial medial calcification (AMC) is a hallmark of aging, diabetes, and chronic kidney disease. Smooth muscle cell (SMC) transition to an osteogenic phenotype is a common feature of AMC, and is preceded by expression of runt-related transcription factor 2 (Runx2), a master regulator of bone development. Whether SMC-specific Runx2 expression is required for osteogenic phenotype change and AMC remains unknown. We therefore created an improved targeting construct to generate mice with floxed Runx2 alleles (Runx2(f/f)) that do not produce truncated Runx2 proteins after Cre recombination, thereby preventing potential off-target effects. SMC-specific deletion using SM22-recombinase transgenic allele mice (Runx2(ΔSM)) led to viable mice with normal bone and arterial morphology. After vitamin D overload, arterial SMCs in Runx2(f/f) mice expressed Runx2, underwent osteogenic phenotype change, and developed severe AMC. In contrast, vitamin D-treated Runx2(ΔSM) mice had no Runx2 in blood vessels, maintained SMC phenotype, and did not develop AMC. Runx2 deletion did not affect serum calcium, phosphate, fibroblast growth factor-23, or alkaline phosphatase levels. In vitro, Runx2(f/f) SMCs calcified to a much greater extent than those derived from Runx2(ΔSM) mice. These data indicate a critical role of Runx2 in SMC osteogenic phenotype change and mineral deposition in a mouse model of AMC, suggesting that Runx2 and downstream osteogenic pathways in SMCs may be useful therapeutic targets for treating or preventing AMC in high-risk patients.

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Section: Vitamin D Induction Of Amc In Micementioning

confidence: 99%

Runx2 Expression in Smooth Muscle Cells Is Required for Arterial Medial Calcification in Mice

Lin

Chen

Leaf

et al. 2015

The American Journal of Pathology

122

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“…Moreover, in another experimental study, BMP-7 was found to inhibit VC by using two conditions, high levels of vitamin D and phosphate, each of which could enhance VC. In this study, vitamin D was found to increase Ca staining in thoracic aortas and hearts, while BMP-7 treatment inhibited VC [260].…”

Section: Bone Morphogenetic Proteins-7 (Bmp-7)mentioning

confidence: 48%

Novel Biomarkers Assessing the Calcium Deposition in Coronary Artery Disease

Tousoulis

Siasos²,

Maniatis³

et al. 2012

CMC

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Coronary atherosclerosis is the pathophysiologic background of coronary artery disease. Vascular calcification is an actively regulated form of calcified tissue metabolism and a common feature of coronary atherosclerotic plaques. Interestingly, systematic research has revealed that vascular mineralization, is also a strong and independent predictor of cardiovascular morbidity and mortality. Recently, several biomarkers, including osteopontin, fetuin-A, matrix-carboxyglutamic acid protein, pyrophosphates, bone morphogenetic proteins, leptin, osteoprotegerin have emerged as surrogate markers of coronary calcification. Furthermore, biomarkers of vascular calcification can be used as prognostic markers of coronary artery disease and can predict future cardiovascular events and mortality. Nevertheless, there is little knowledge on the usefulness of these biomarkers in evaluating the results of treatments targeting coronary artery disease. Within this context, the present review sets out to discuss the role of new biomarkers assessing calcium deposition in coronary arteries and their role in the prognosis, progression, and treatment of cardiovascular disease.

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“…There are no human intake studies with respect to CV calcification, probably because dietary vitamin D provides only a relatively small contribution to serum 25(OH)D. Animal studies, however, show that high vitamin D intake can induce CV calcification and impair endothelial function 128,129 but they also show that a vitamin D deficient diet can induce an increase in calcified lesions [130][131][132] , indicating that both excess and deficiency are detrimental. Several epidemiological studies measuring serum 25(OH)D demonstrate an absence of association with presence or extent of CAC, MAC, cIMT, degree of carotid stenosis or mean arterial pressure 22,[133][134][135] , although patients with calcific aortic stenosis 136 and poor coronary collateral circulation 137 140 and with the calcification score in peripheral arterial disease 27 .…”

Section: Ectopic Calcificationmentioning

confidence: 99%

Cardiovascular Calcification and Bone: A Comparison of The Effects of Dietary and Serum Calcium, Phosphorous, Magnesium and Vitamin D

Nicoll¹

2015

ICFJ

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This comparison of the effects of calcium, phosphorus, magnesium and vitamin D on cardiovascular (CV) calcification and bone has shown that in general the micronutrients that promote bone health also protect the arteries. We have shown that adequate amounts of all three minerals should be ingested, paying particular attention to supplementing calcium to bind high phosphorus and to ensure the maximum benefit from supplementing vitamin D. It appears that the optimum intake for bone is >800 mg/d calcium, with postmenopausal women possibly requiring a total intake of >1100mg/d. Both CV and bone studies suggest achieving a serum 25(OH)D level of >75nmol/l. These relationships are valid for a Caucasian population, however, and may not hold in African Americans and Asians. The recent concerns that calcium supplementation may increase CV disease risk has largely proved groundless, with higher calcium intake improving dyslipidaemia, hypertension and mortality. With respect to higher serum phosphate, there is an association with CV calcification and CVD risk even within the normal range, suggesting that the reference ranges may need to be redefined for ‘at risk’ patients. CV calcification was reduced in CKD patients with magnesium intake in the range 384-669mg/d. When considering the complex interplay of the action of the minerals together with their regulators vitamin D, PTH and FGF23, it is clear that this is a very sophisticated system which attempts to maintain calcium homeostasis to the possible detriment of bone and arteries. This reinforces the need to ensure adequate calcium intake before supplementing vitamin D.

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Bone Morphogenetic Protein-7 Inhibits Vascular Calcification Induced by High Vitamin D in Mice

Cited by 38 publications

References 33 publications

Runx2 Expression in Smooth Muscle Cells Is Required for Arterial Medial Calcification in Mice

Runx2 Expression in Smooth Muscle Cells Is Required for Arterial Medial Calcification in Mice

Novel Biomarkers Assessing the Calcium Deposition in Coronary Artery Disease

Cardiovascular Calcification and Bone: A Comparison of The Effects of Dietary and Serum Calcium, Phosphorous, Magnesium and Vitamin D

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