AGER and diabetes mellitus: In a study by Suga et al. [29], RAGE overexpression induced the expression of ALP and Msx2 and calcium deposition in human aortic VSMCs that were cultured with the sera of patients with diabetes; on the contrary, silencing of Msx2 effectively inhibited osteogenic differentiation of VSMCs, which indicates that activation of Notch/Msx2 signal pathway under high glucose induces osteogenic differentiation of VSMCs and contributes to aortic calcification.