Uremia induces the osteoblast differentiation factor Cbfa1 in human blood vessels

Sharon M. Moe, Danxia Duan, Brian P. Doehle, Kalisha D. O'Neill, Neal X. Chen

Research output: Contribution to journalArticle

267 Scopus citations

Abstract

Background. Bone matrix proteins are expressed in calcified arteries from dialysis patients, suggesting that vascular smooth muscle cells (VSMCs) may transform to osteoblast-like cells. One of the key transcriptional regulators of osteoblast differentiation is Cbfa1. Thus, we hypothesized that this may be a key factor in arterial calcification. Methods. To test this hypothesis, we examined sections of the inferior epigastric artery from uremic patients for the presence of Cbfa1 and type I collagen and osteopontin by in situ hybridization and immunostaining. We also examined the effect of pooled uremic sera from dialysis patients on the expression of Cbfa1 by reverse transcription-polymerase chain reaction (RT-PCR) in bovine VSMCs in vitro. Results. Cbfa1 and osteopontin were expressed in both the media and the intima in vessels that were calcified, but there was only minimal staining in non-calcified vessels. In vitro studies demonstrated that pooled uremic serum, compared to pooled control human serum induced the expression of Cbfa1 by RT-PCR in bovine VSMCs in a time-dependent, nonphosphorus-mediated mechanism. Conclusion. These results support that Cbfa1 is a key regulatory factor in the vascular calcification observed in dialysis patients and is up-regulated in response to many uremic toxins.

Original languageEnglish (US)
Pages (from-to)1003-1011
Number of pages9
JournalKidney international
Volume63
Issue number3
DOIs
StatePublished - Mar 1 2003

Keywords

  • Cbfa1
  • Dialysis
  • Osteopontin
  • Type 1 collagen
  • Vascular calcification

ASJC Scopus subject areas

  • Nephrology

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