Osteomodulin mRNA and protein levels were found to be linked with plaque calcification in human atherosclerosis. Furthermore, osteomodulin mRNA, but not protein levels, was shown to be related to plaque stability.

• Osteomodulin, originally found in bones, is expressed by bone synthesizing osteoblasts and implicated in mineralization.

• From patients with or without cerebrovascular symptoms, carotid plaques were obtained by endarterectomy were analyzed for osteomodulin gene expression (OMD; n=82) and osteomodulin protein levels (n=45).

• Plaques from asymptomatic patients exhibited elevated OMD levels than symptomatic.

• During follow-up, fewer cardiovascular events occurred in patients with high OMD levels.

• OMD showed a positive correlation with smooth muscle α-actin and collagen but had an inverse correlation with CD68 gene expression, lipids, intraplaque hemorrhage, inflammatory cytokine, and matrix metalloproteinase plaque contents.

• OMD demonstrated a positive link with MSX2 (Msh Homeobox 2), a marker of preosteoblast differentiation, BMP4 (bone morphogenetic protein) and BMP6, plaque calcification.

• OMD was identified to be strongly upregulated in osteogenically stimulated smooth muscle cells, which was further increased upon BMP stimulation.

• In calcified regions, the presence of osteomodulin protein was evident.

• Osteomodulin protein levels were found to be linked with plaque calcification and elevated in macrocalcified plaques.