Circulating concentrations of stem-cell-mobilizing cytokines are associated with levels of osteoprogenitor cells and aortic calcification severity.

BACKGROUND To investigate the association between aortic calcification, concentrations of stem-cell-mobilizing cytokines and osteocalcin-positive mononuclear cells in a mouse model and patients with peripheral artery disease. METHODS AND RESULTS We estimated the concentration of the stem-cell-mobilizing cytokines stromal cell-derived factor α (SDF-1α), granulocyte colony stimulating factor and stem cell factor in a mouse model of aortic calcification developed in osteoprotegerin-deficient (OPG(-/-)) mice, as well as in patient plasma samples. Calcification was estimated by a colorimetric assay of extracts of harvested mice aortas and by computed tomographic angiogram images in patients. The cytokine concentrations were assessed for association with the severity of calcification and the percentage of osteocalcin-positive mononuclear cells (OCN(+) MNC) using non-parametric analysis. The serum concentration of stromal SDF-1α and granulocyte-colony stimulating factor (G-CSF) were significantly greater in OPG(-/-) compared to control mice. The percentage of circulating OCN(+) MNC was correlated to the concentration of SDF-1α in OPG(-/-) mice. These cytokines also correlated with the severity of calcification in OPG(-/-) mice. Patients with more severe calcification had a higher plasma concentration of the cytokines than those with less marked aortic calcification. The concentrations also correlated with circulating OCN(+) MNC and aortic calcification volumes. CONCLUSIONS The association between stem cell cytokines, OCN(+) MNC and calcification suggests a possible role of bone-derived osteoprogenitor cells in the pathogenesis of vascular calcification.