Osteocalcin positive mononuclear cells are associated with the severity of aortic calcification

Abstract

Objective: To assess the association of circulating bone marrow-derived osteo-progenitors with vascular calcification in mouse models and patients with peripheral artery disease.

Methods: We estimated the percentage of circulating mononuclear cells expressing osteocalcin in 2 mouse models of aortic calcification developed in osteoprotegerin-deficient mice (OPG−/−) using flow cytometry. Aortic calcification was assessed in mice principally by a bioassay of harvested aortas. In patients with peripheral artery disease osteocalcin-positive cells (estimated by flow cytometry) were related to aortic calcification volume assessed from computed tomography.

Results: The amount of extractable aortic calcium was increased in both mouse models used in comparison to controls. The percentage of circulating mononuclear cells expressing osteocalcin was correlated to the amount of extractable aortic calcium in male (r = 0.525, p = 0.02) and female OPG−/− (r = 0.564, p = 0.02) mice and also in animals in which calcification was accelerated using calcitriol (r = 0.64, p = 0.01). Patients with more severe aortic calcification had a greater percentage of circulating OCN+ MNCs (median 4.07%, IQR 3.76–4.39, n = 12) than those with less severe aortic calcification (median 3.10%, IQR 2.32–3.60, n = 11, p = 0.05).

Conclusions: This study demonstrates that aortic calcification can be robustly quantified in 2 mouse models. In these models and patients with peripheral artery disease circulating osteocalcin positive mononuclear cells are associated with the severity of aortic calcification.