Abstract: 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 qRT-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 Wnt3a, Wnt7a, Fzd4 and Wisp1 mRNA by 1.86, 1.68, 2.1, and 2.3 folds, respectively, and by
promoting the phosphorylation of β-catenin (2.70±0.22, P<0.05), 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
bone-related proteins Cbfa1, Osx, OCN, and BMP2 by (51±9)%, (58±11)%, (56±10)%, and (62±10)% (P<0.01). Conclusion WNT
signaling pathway is involved in high glucose-induced VSMC calcification.