Osteocalcin and vascular function: is there a cross-talk?

Abstract

Background The bone-derived protein osteocalcin (OC), in its undercarboxylated (ucOC) form, has a beneficial effect on energy metabolism and may be a future therapeutic target for metabolic diseases. Increasing evidence suggests a link between ucOC and cardiovascular disease (CVD) development; however, the exact relationship is conflicting and unclear. Scope of review The aim of this review was to summarise the current research examining the interaction between OC and vascular dysfunction, the initiating stage in the development of atherosclerosis and CVD. Major conclusions In humans, the association between OC and vascular function is inconsistent. Several studies report that total OC (tOC) is associated with adverse function or beneficial function, whereas others report that tOC and ucOC has no effect on vascular function. The conflicting data are likely due to several methodological inconsistencies, in particular the lack of studies reporting circulating ucOC levels. In animal models, the direct administration of ucOC to isolated blood vessels ex vivo produced minimal changes in endothelial function, but importantly, no adverse responses. Finally, in human endothelial and vascular smooth muscle cells, ucOC treatment did not influence classical markers of cellular function, including endothelin-1, vascular adhesion molecule-1 and monocyte chemoattractant protein-1 after exposure to high glucose and inflammatory conditions. The lack of adverse effects in ex vivo and in vitro studies suggests that ucOC may be targeted as a future therapeutic for metabolic diseases, without the risk of detrimental effects in the vasculature. However, further studies are needed to confirm these findings and to investigate whether there is a direct beneficial influence of ucOC.

Osteocalcin association with vascular function in chronic kidney disease

“…Osteocalcin (OCN), a vitamin K dependent hormone derived from osteoblasts, plays a role in bone mineralization, implicates the activity of osteoblasts and osteoclasts, and regulates the energy metabolism of glucose and lipids 1 . As a marker of bone turnover, increasing studies suggest that OCN is also associated with vascular health, including endothelial function and vascular calcification 2–4 . Uremia and abnormal mineral metabolism are significant factors affecting vascular health, which precede the onset of cardiovascular disease (CVD) and lead to morbidity and mortality of chronic kidney disease (CKD) 5,6 .…”

The Emerging Role of Bone-Derived Hormones in Diabetes Mellitus and Diabetic Kidney Disease

“…OC is an osteoblast-secreted and vitamin K–dependent protein and is comprised of two forms: undercarboxylated osteocalcin (ucOCN) and carboxylated osteocalcin (cOCN) ( 54 , 55 ). Circulating OC is accessible to measurement, and ucOCN is considered to be the bioactive form of OC that plays a role in regulating energy metabolism and glucose homeostasis ( 56 ). OCN maintains calcium homeostasis and facilitates bone mineralization and growth ( 55 ).…”

Osteocalcin-expressing endothelial progenitor cells and serum osteocalcin forms are independent biomarkers of coronary atherosclerotic disease severity in male and female patients

“…Through the secretion of OC, the bone regulates glucose homeostasis [8,13] and male reproductive functions [17,18]. In addition, clinical studies suggest a more complex role for OC in human metabolism, which led to investigations exploring its associations with CV disease (CVD) [19][20][21][22], and to clarify whether OC is a vital mediator or a nonparticipant bystander in energy metabolism and vascular function [23][24][25]. Another candidate potentially providing a link between bone metabolism and CVD are endothelial progenitor cells (EPCs), which are nucleated bone marrow-derived cells, that can be mobilized in response to vascular injury, and contribute to vascular repair [26,27].…”