Uremia induces the osteoblast differentiation factor Cbfa1 in human blood vessels

Kidney Int. 2003 Mar;63(3):1003-11. doi: 10.1046/j.1523-1755.2003.00820.x.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Blood Proteins / pharmacology
  • Calcinosis / pathology
  • Cattle
  • Cell Differentiation / drug effects
  • Collagen Type I / genetics
  • Core Binding Factor Alpha 1 Subunit
  • Epigastric Arteries / pathology*
  • Epigastric Arteries / physiology
  • Gene Expression
  • Humans
  • Muscle, Smooth, Vascular / cytology
  • Neoplasm Proteins*
  • Osteoblasts / pathology*
  • Osteopontin
  • Sialoglycoproteins / genetics
  • Transcription Factors / genetics*
  • Uremia / pathology*


  • Blood Proteins
  • Collagen Type I
  • Core Binding Factor Alpha 1 Subunit
  • Neoplasm Proteins
  • SPP1 protein, human
  • Sialoglycoproteins
  • Transcription Factors
  • Osteopontin