title: [Effect of desferrioxamine and deferiprone on osteocalcin secretion in osteoblast-type cells].
abstract: Desferrioxamine and deferiprone are both metal-chelating drugs often used in aluminum-overloaded dialysis patients. In these patients, desferrioxamine produces an improvement on bone mineralisation without a relevant decrease in bone aluminum. Thus, desferrioxamine might have a direct effect on bone cells. The aim of this study was to assess the effect of desferrioxamine and deferiprone on 1,25(OH)2D3-stimulated osteocalcin secretion in osteoblast--like cells. The study was carried out in MG-63 cell cultures. Cells were seeded at a density of 15,000 cel/cm2 and grown to confluence for 72 hours in DMEM supplemented with 10% FCS. The medium was then replaced by another medium containing 1% BSA, 10(-9) M 1,25(OH)2D3 and desferrioxamine 5, 10, 20, 40, 60, 80 microM or deferiprone 15, 30, 60, 120, 180, 240 microM. Tris-HCl at pH 7.4 was used as control. After 48 hours, supernatants were collected for the measurement of secreted osteocalcin. Desferrioxamine and deferiprone, at high doses (desferrioxamine: 60 microM, 80 microM; deferiprone: 180 microM, 240 microM), inhibited the 1,25(OH)2D3-induced osteocalcin secretion. On the contrary, at lower doses (desferrioxamine 5 microM; deferiprone 15 microM) stimulated the secretion. In summary, these results suggest that desferrioxamine and deferiprone exert a direct effect on bone cell metabolism that might be independent from their metal-chelating properties.
authors.affiliation: Servicio de Metabolismo Oseo y Mineral, Instituto Reina Sofía de Investigación, Hospital Universitario Central de Asturias, Universidad de Oviedo, Oviedo.
authors.forename: I
authors.initials: I
authors.lastname: González Suárez
authors.forename: J L
authors.initials: JL
authors.lastname: Fernández Martín
authors.forename: M
authors.initials: M
authors.lastname: Naves Díaz
authors.forename: J B
authors.initials: JB
authors.lastname: Cannata Andía
mesh_terms: D000535:Aluminum; D000818:Animals; D001859:Bone Neoplasms / Q000473:pathology; D002117:Calcitriol / Q000037:antagonists & inhibitors / Q000494:pharmacology; D002417:Cattle; D002614:Chelating Agents / Q000008:administration & dosage / Q000494:pharmacology; D003470:Culture Media / Q000494:pharmacology; D000077543:Deferiprone; D003676:Deferoxamine / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism; D015675:Osteocalcin / Q000378:metabolism*; D012516:Osteosarcoma / Q000473:pathology; D011728:Pyridones / Q000008:administration & dosage / Q000494:pharmacology*; D012636:Secretory Rate / Q000187:drug effects; D012710:Serum Albumin, Bovine / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
chemical_list: D002614:Chelating Agents; D003470:Culture Media; D011728:Pyridones; D015675:Osteocalcin; D012710:Serum Albumin, Bovine; D000077543:Deferiprone; D000535:Aluminum; D002117:Calcitriol; D003676:Deferoxamine