Matrix gla protein (MGP) is a potent inhibitor of extracellular matrix (ECM) 
mineralization. MGP-deficiency in humans leads to Keutel syndrome, a rare 
genetic disease hallmarked by abnormal soft tissue calcification. MGP-deficient 
(Mgp(-/-)) mice show progressive deposition of hydroxyapatite minerals in the 
arterial walls and die within 2 months of age. The mechanism of 
antimineralization function of MGP is not fully understood. We examined the 
progression of vascular calcification and expression of several 
chondrogenic/osteogenic markers in the thoracic aortas of Mgp(-/-) mice at 
various ages. Although cells with chondrocyte-like morphology have been reported 
in the calcified aorta, our gene expression data indicate that 
chondrogenic/osteogenic markers are not upregulated in the arteries prior to the 
initiation of calcification. Interestingly, arterial calcification in Mgp(-/-) 
mice appears first in the elastic laminae. Considering the known mineral 
scaffolding function of elastin (ELN), a major elastic lamina protein, we 
hypothesize that elastin content in the laminae is a critical determinant for 
arterial calcification in Mgp(-/-) mice. To investigate this, we performed 
micro-computed tomography (µCT) and histological analyses of the aortas of 
Mgp(-/-);Eln(+/-) mice and show that elastin haploinsufficiency significantly 
reduces arterial calcification in this strain. Our data suggest that MGP 
deficiency leads to alterations of vascular ECM that may in turn initiate 
arterial calcification.