High glucose promotes vascular smooth muscle cell calcification by activating WNT signaling pathway

Objective To investigate whether high glucose- induced vascular calcification is associated with WNT signaling pathway. Methods An in vitro model of human vascular smooth muscle cell(VSMC) calcification was induced by exposure of the cells to high glucose. The expressions of WNT signal molecules and bone-related proteins including Cbfa1, Osx, OCN and BMP2 were analyzed with q RT-PCR, and the cell calcification was assessed by alizarin red staining. The effect of Dkk1, a WNT signaling inhibitor, on high glucose- induced cell calcification was tested with alizarin red staining and calcium content analysis. Results High glucose activated WNT signaling pathway in human VSMCs by up-regulating the expressions of WNT signal molecules including Wnt3 a, Wnt7 a, Fzd4 and Wisp1 m RNA by 1.86, 1.68, 2.1, and 2.3 folds, respectively, and by promoting the phosphorylation of β-catenin(2.70±0.22, P0.05), a key mediator of WNT signaling pathway. Inhibition of WNT signaling pathway by Dkk1 attenuated high glucose-induced VSMC calcification and down-regulated the expression of bonerelated proteins Cbfa1, Osx, OCN, and BMP2 by(51 ± 9)%,(58 ± 11)%,(56 ± 10)%, and(62 ± 10)%(P0.01). Conclusion WNT signaling pathway is involved in high glucose-induced VSMC calcification.