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

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.

Serum Osteocalcin Level is Negatively Associated with Vascular Reactivity Index by Digital Thermal Monitoring in Kidney Transplant Recipients

“…Some studies have demonstrated an inverse relationship between osteocalcin level and arterial calcification (carotid or coronary atherosclerosis) [16]. However, despite the seemingly favorable metabolic and cardiovascular effects associated with osteocalcin, it is also implicated in the pathogenesis of vascular calcification, which occurs in the chronic stage of atherosclerosis [17]. In bone formation, γ-carboxylated osteocalcin has been determined to bind to calcium and hydroxyapatite as part of bone mineralization [17].…”

Increased Serum Parathyroid Hormone, Osteocalcin and Alkaline Phosphatase Are Associated with a Long-Term Adverse Cardiovascular Outcome after Coronary Artery Bypass Graft Surgery

“…Osteocalcin is a pleiotropic protein regulating glucose and lipid metabolism, nitric oxide release, and endothelial homeostasis depending on its carboxylation status [30]. Opposite to PTH, an association of serum osteocalcin with cardiovascular death is unclear, being U-shaped as well as gender-and age-dependent [31][32][33].…”

Fundamental and practical aspects of coronary artery calcification

“…Этому спо собствует ряд факторов инициации и прогрессирования атеросклероза: дислипидемия, активация маркеров оксидативного стресса (С-реактивный белок), системы интерлейкинов и факторов роста, что, в свою очередь, приводит к эндотелиальной дисфункции, локальному повышению концентрации металлопротеиназ, запуску системы RANK/RANKL/остеопротегерин и выделению ряда катепсинов с формированием участков коллагеновых волокон как центров будущей кальцификации в проекции атеросклеротической бляшки. Предполагается, что это и есть общие механизмы кальцификации аорты и коронарных артерий, а также нарушения минеральной плотности костной ткани [50].…”