Osteocalcin Regulates Arterial Calcification Via Altered Wnt Signaling and Glucose Metabolism.
Rashdan NA., Sim AM., Cui L., Phadwal K., Roberts FL., Carter R., Ozdemir DD., Hohenstein P., Hung J., Kaczynski J., Newby DE., Baker AH., Karsenty G., Morton NM., MacRae VE.
Arterial calcification is an important hallmark of cardiovascular disease and shares many similarities with skeletal mineralization. The bone-specific protein osteocalcin (OCN) is an established marker of vascular smooth muscle cell (VSMC) osteochondrogenic transdifferentiation and a known regulator of glucose metabolism. However, the role of OCN in controlling arterial calcification is unclear. We hypothesized that OCN regulates calcification in VSMCs and sought to identify the underpinning signaling pathways. Immunohistochemistry revealed OCN co-localization with VSMC calcification in human calcified carotid artery plaques. Additionally, 3 mM phosphate treatment stimulated OCN mRNA expression in cultured VSMCs (1.72-fold, p