TGF-beta 1 and 25-hydroxycholesterol stimulate osteoblast-like vascular cells to calcify.

TLDR

Arterial calcification appears to be a regulated, osteogenesis‑like process, as indicated by BMP‑2a mRNA in human calcified plaque. The study aimed to isolate and clone a bovine aortic media subpopulation with osteoblastic potential to test this hypothesis. The isolated cells were identified by a unique GM3 ganglioside surface marker that distinguishes them from smooth muscle cells. These cells expressed osteogenic markers and, when stimulated with 25‑hydroxycholesterol or TGF‑β1, produced abundant calcium‑mineral nodules, supporting a role for these factors in vascular calcification.

Abstract

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.