title: Uremia induces the osteoblast differentiation factor Cbfa1 in human blood vessels.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Medicine, Indiana University School of Medicine and Roudebush Veterans Affairs Medical Center, Indianapolis, Indiana 46202, USA. smoe@iupui.edu
authors.forename: Sharon M
authors.initials: SM
authors.lastname: Moe
authors.forename: Danxia
authors.initials: D
authors.lastname: Duan
authors.forename: Brian P
authors.initials: BP
authors.lastname: Doehle
authors.forename: Kalisha D
authors.initials: KD
authors.lastname: O'Neill
authors.forename: Neal X
authors.initials: NX
authors.lastname: Chen
mesh_terms: D000818:Animals; D001798:Blood Proteins / Q000494:pharmacology; D002114:Calcinosis / Q000473:pathology; D002417:Cattle; D002454:Cell Differentiation / Q000187:drug effects; D024042:Collagen Type I / Q000235:genetics; D050659:Core Binding Factor Alpha 1 Subunit; D019074:Epigastric Arteries / Q000473:pathology* / Q000502:physiology; D015870:Gene Expression; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000166:cytology; D009363:Neoplasm Proteins; D010006:Osteoblasts / Q000473:pathology*; D053495:Osteopontin; D012795:Sialoglycoproteins / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*; D014511:Uremia / Q000473:pathology*
chemical_list: D001798:Blood Proteins; D024042:Collagen Type I; D050659:Core Binding Factor Alpha 1 Subunit; D009363:Neoplasm Proteins; C506895:SPP1 protein, human; D012795:Sialoglycoproteins; D014157:Transcription Factors; D053495:Osteopontin