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

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    Author
    Tacey, A; Qaradakhi, T; Brennan-Speranza, T; Hayes, A; Zulli, A; Levinger, I
    Date
    2018-10-01
    Source Title
    Nutrients
    Publisher
    MDPI
    University of Melbourne Author/s
    Hayes, Alan; Levinger, Itamar
    Affiliation
    Medicine and Radiology
    Metadata
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    Document Type
    Journal Article
    Citations
    Tacey, A., Qaradakhi, T., Brennan-Speranza, T., Hayes, A., Zulli, A. & Levinger, I. (2018). Potential Role for Osteocalcin in the Development of Atherosclerosis and Blood Vessel Disease. NUTRIENTS, 10 (10), https://doi.org/10.3390/nu10101426.
    Access Status
    Open Access
    URI
    http://hdl.handle.net/11343/253356
    DOI
    10.3390/nu10101426
    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.

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