Platelets express and release osteocalcin and co‐localize in human calcified atherosclerotic plaques

Background: Although vascular‐calcification mechanisms are only partially understood, the role of circulating calcifying cells and non‐collagenous bone matrix proteins in the bone–vascular axis is emerging. In spite of the fact that platelets represent a cellular interface between hemostasis, inflammation and atherosclerosis, and have a myeloid precursor, a possible involvement in the modulation of vascular calcification has rarely been investigated. We investigated if osteocalcin (OC) is released by platelets and described OC expression in patients with carotid artery occlusive disease. Methods: Expression and release of OC were determined by Western blot, immunofluorescence, fluorescence‐activated cell sorting (FACS) and ELISA in human resting and activated platelets and megakaryocytes. Co‐localization of platelet aggregates, macrophages, OC and calcifications was studied in carotid endarterectomy specimens and normal tissues. Results: Human platelets expressed OC and co‐localized with CD63 in δ‐granules. Upon activation with an endogenous mechanism, platelets released OC in the extracellular medium. Expression of OC in megakaryocytes suggested lineage specificity. The OC count in circulating platelets and the released amount were significantly higher in patients with carotid artery occlusive disease than in healthy controls (P