Nutrients | |
Potential Role for Osteocalcin in the Development of Atherosclerosis and Blood Vessel Disease | |
Tara Brennan-Speranza1  Tawar Qaradakhi2  Anthony Zulli2  Itamar Levinger2  Alan Hayes2  Alexander Tacey2  | |
[1] Department of Physiology and Bosch Institute for Medical Research, University of Sydney, Sydney, NSW 2006, Australia;Institute for Health and Sport (IHES), Victoria University, Melbourne, VIC 3011, Australia; | |
关键词: undercarboxylated osteocalcin; carboxylated osteocalcin; endothelial dysfunction; vascular calcification; atherosclerosis; humans; animal models; | |
DOI : 10.3390/nu10101426 | |
来源: DOAJ |
【 摘 要 】
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.
【 授权许可】
Unknown