TGF-beta 1 and 25-hydroxycholesterol stimulate osteoblast-like vascular cells to calcify.
Previous studies in our laboratory demonstrated messenger RNA for bone morphogenetic protein-2a in human calcified plaque, suggesting that arterial calcification is a regulated process, similar to osteogenesis. To further test this hypothesis, we have isolated and cloned a subpopulation of cells from bovine aortic media that show osteoblastic potential. These novel cells are primarily distinguished from smooth muscle cells by expression of a surface marker preliminarily identified as a modified form of the ganglioside sialyl-lactosylceramide (GM3). Osteoblastic potential was indicated by high levels of alkaline phosphatase and collagen I, expression of osteopontin and osteonectin (SPARC), and production of bone-specific osteocalcin and hydroxyapatite. Cultures of these cells were stimulated to form increased numbers of calcium-mineral-producing nodules by the oxysterol 25-hydroxycholesterol as well as by transforming growth factor-beta 1, both known to be present in atherosclerotic lesions. The stimulation of calcifying vascular cells in the artery wall by these two factors suggests a possible mechanism for the colocalization of calcification with atherosclerosis in vivo.
Watson
K E
KE
Department of Medicine, UCLA School of Medicine 90024-1679.
Boström
K
K
Ravindranath
R
R
Lam
T
T
Norton
B
B
Demer
L L
LL
D000469:Alkaline Phosphatase / Q000302:isolation & purification; D000818:Animals; D001011:Aorta / Q000166:cytology / Q000187:drug effects* / Q000473:pathology; D001161:Arteriosclerosis / Q000209:etiology; D015415:Biomarkers; D002114:Calcinosis / Q000139:chemically induced*; D002417:Cattle; D002999:Clone Cells; D016207:Cytokines / Q000494:pharmacology; D005679:G(M3) Ganglioside / Q000302:isolation & purification; D006651:Histocytochemistry; D006801:Humans; D006888:Hydroxycholesterols / Q000494:pharmacology*; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects*; D015675:Osteocalcin / Q000302:isolation & purification; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D015415:Biomarkers; D016207:Cytokines; D005679:G(M3) Ganglioside; D006888:Hydroxycholesterols; D016212:Transforming Growth Factor beta; D015675:Osteocalcin; C007997:25-hydroxycholesterol; D000469:Alkaline Phosphatase