title: Effect of vitamin D receptor activator therapy on vitamin D receptor and osteocalcin expression in circulating endothelial progenitor cells of hemodialysis patients.
abstract: BACKGROUND
  The effects of vitamin D receptor (VDR) and osteocalcin (OC) expression as well as VDR agonist (VDRA) therapy on circulating endothelial progenitor cells (EPCs) has not been elucidated yet.
  
  
  METHODS
  We therefore analyzed EPCs in 30 healthy controls and 82 patients undergoing dialysis (no VDRA therapy: 28; oral calcitriol: 30, and intravenous paricalcitol, PCTA: 24). The percentage of EPCs (CD34+/CD133-/KDR+/CD45-) expressing VDR or OC, and VDR and OC expression defined by mean fluorescence intensity (MFI) were analyzed using flow cytometry. The in vitro effect of VDRAs was evaluated in EPCs isolated from each patient group.
  
  
  RESULTS
  The percentage of VDR+ EPCs correlated positively with VDRA therapy and 25(OH)D, and negatively with diabetes, C-reactive protein, hemoglobin and osteopontin. VDR-MFI correlated positively with VDRA therapy, parathyroid hormone (PTH) and 25(OH)D, and negatively with diabetes and osteopontin. The percentage of OC+ EPCs correlated positively with the calcium score, PTH and phosphate, and negatively with 25(OH)D. OC-MFI correlated positively with calcium score, PTH, phosphate and hemoglobin, and negatively with albumin, 25(OH)D and osteopontin. Cell cultures from patients without VDRA therapy had the highest levels of calcium deposition and OC expression, which both significantly decreased following in vitro VDRA administration: in particular extracellular calcium deposition was only reduced by adding PCTA.
  
  
  CONCLUSIONS
  Our data suggest that 25(OH)D serum levels and VDRA therapy influence VDR and OC expression on circulating EPCs. Since OC expression may contribute to vascular calcification, we hypothesize a putative protective role of VDRA therapy.
authors.affiliation: Section of Nephrology, Department of Internal Medicine, Aging and Renal Disease, University of Bologna, Bologna, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Cianciolo
authors.forename: Gaetano
authors.initials: G
authors.lastname: La Manna
authors.forename: Elena
authors.initials: E
authors.lastname: Della Bella
authors.forename: Maria Laura
authors.initials: ML
authors.lastname: Cappuccilli
authors.forename: Maria Laura
authors.initials: ML
authors.lastname: Angelini
authors.forename: Ada
authors.initials: A
authors.lastname: Dormi
authors.forename: Irene
authors.initials: I
authors.lastname: Capelli
authors.forename: Claudio
authors.initials: C
authors.lastname: Laterza
authors.forename: Roberta
authors.initials: R
authors.lastname: Costa
authors.forename: Francesco
authors.initials: F
authors.lastname: Alviano
authors.forename: Gabriele
authors.initials: G
authors.lastname: Donati
authors.forename: Claudio
authors.initials: C
authors.lastname: Ronco
authors.forename: Sergio
authors.initials: S
authors.lastname: Stefoni
mesh_terms: D015652:25-Hydroxyvitamin D 2 / Q000097:blood; D015703:Antigens, CD / Q000097:blood / Q000235:genetics; D002097:C-Reactive Protein; D002118:Calcium / Q000097:blood; D016022:Case-Control Studies; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D056892:Mediator Complex / Q000494:pharmacology*; D015675:Osteocalcin / Q000097:blood / Q000235:genetics*; D053495:Osteopontin / Q000097:blood / Q000235:genetics; D010281:Parathyroid Hormone / Q000097:blood / Q000235:genetics; D018167:Receptors, Calcitriol / Q000097:blood / Q000235:genetics*; D006435:Renal Dialysis; D051436:Renal Insufficiency, Chronic / Q000097:blood / Q000188:drug therapy*; D013234:Stem Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology
chemical_list: D015703:Antigens, CD; C491863:MED4 protein, human; D056892:Mediator Complex; D010281:Parathyroid Hormone; D018167:Receptors, Calcitriol; D015675:Osteocalcin; D053495:Osteopontin; D015652:25-Hydroxyvitamin D 2; D002097:C-Reactive Protein; D002118:Calcium