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Nutrients 2018, 10(10), 1426; https://doi.org/10.3390/nu10101426

Potential Role for Osteocalcin in the Development of Atherosclerosis and Blood Vessel Disease

1
Institute for Health and Sport (IHES), Victoria University, Melbourne, VIC 3011, Australia
2
Australian Institute for Musculoskeletal Science, Department of Medicine, Western Health, Melbourne Medical School, University of Melbourne, Melbourne, VIC 3021, Australia
3
Department of Physiology and Bosch Institute for Medical Research, University of Sydney, Sydney, NSW 2006, Australia
*
Author to whom correspondence should be addressed.
Received: 1 September 2018 / Revised: 27 September 2018 / Accepted: 29 September 2018 / Published: 4 October 2018
(This article belongs to the Special Issue Vitamin K in Human Health and Disease)
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Abstract

There is increasing evidence for the involvement of the skeleton in the regulation of atherosclerotic vascular disease. Osteocalcin, an osteoblast derived protein, exists in two forms, carboxylated and undercarboxylated osteocalcin. Undercarboxylated osteocalcin has been linked to the regulation of metabolic functions, including glucose and lipid metabolism. Features of atherosclerosis have been associated with circulating osteocalcin; however, this association is often conflicting and unclear. Therefore, the aim of this review is to examine the evidence for a role of osteocalcin in atherosclerosis development and progression, and in particular endothelial dysfunction and vascular calcification. The current literature suggests that undercarboxylated osteocalcin stimulates the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) signaling pathway to upregulate nitric oxide and nuclear factor kappa β (NF-кβ) in vascular cells, possibly protecting endothelial function and preventing atherogenesis. However, this effect may be mediated by metabolic factors, such as improvements in insulin signaling, rather than through a direct effect on the vasculature. Total osteocalcin is frequently associated with vascular calcification, an association that may occur as a result of vascular cells eliciting an osteogenic phenotype. Whether osteocalcin acts as a mediator or a marker of vascular calcification is currently unclear. As such, further studies that examine each form of osteocalcin are required to elucidate if it is a mediator of atherogenesis, and whether it functions independently of metabolic factors. View Full-Text
Keywords: undercarboxylated osteocalcin; carboxylated osteocalcin; endothelial dysfunction; vascular calcification; atherosclerosis; humans; animal models undercarboxylated osteocalcin; carboxylated osteocalcin; endothelial dysfunction; vascular calcification; atherosclerosis; humans; animal models
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Tacey, A.; Qaradakhi, T.; Brennan-Speranza, T.; Hayes, A.; Zulli, A.; Levinger, I. Potential Role for Osteocalcin in the Development of Atherosclerosis and Blood Vessel Disease. Nutrients 2018, 10, 1426.

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