title: Vanadate-induced nitric oxide production: role in osteoblast growth and differentiation.
abstract: Nitric oxide (NO) has been shown to act as a mediator of cytokines in bone tissue. We have previously demonstrated that vanadium compounds are insulin- and growth factor-mimetic compounds in osteoblasts in culture, although high doses are toxic to these cells. In this study, we measured NO production in two osteoblast-like cells (UMR106 and MC3T3E1) incubated with different concentrations (2.5-100 microM) of vanadate. Vanadate induced NO release in a biphasic manner, with levels being significantly increased at concentrations over 50 microM. The NO donor, sodium nitroprusside, mimicked the vanadate effect: it inhibited cell growth and alkaline phosphatase activity in a dose-dependent manner. Vanadate enhanced the NO synthases, the endothelial and inducible (eNOS and iNOS) isoforms, in a dose-dependent manner. Experiments performed with the ionophore A23187 and EGTA suggested that vanadate-induced NO production involves Ca(2+)-dependent and -independent mechanisms. Altogether, our results suggest that NO may play a critical role in the bioactivity of vanadium in osteoblast-like cells.
authors.affiliation: Cátedra de Bioquímica Patológica, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, 47 y 115 (1900), La Plata, Argentina. cortizo@nahuel.biol.unlp.edu.ar
authors.forename: A M
authors.initials: AM
authors.lastname: Cortizo
authors.forename: M
authors.initials: M
authors.lastname: Caporossi
authors.forename: G
authors.initials: G
authors.lastname: Lettieri
authors.forename: S B
authors.initials: SB
authors.lastname: Etcheverry
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D003470:Culture Media; D051379:Mice; D009569:Nitric Oxide / Q000096:biosynthesis* / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D009599:Nitroprusside / Q000494:pharmacology; D010006:Osteoblasts / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D014638:Vanadates / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D003470:Culture Media; D014665:Vasodilator Agents; D009599:Nitroprusside; D009569:Nitric Oxide; D014638:Vanadates; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496317:Nos2 protein, mouse; C496318:Nos2 protein, rat; C496315:Nos3 protein, mouse; C496316:Nos3 protein, rat; D000469:Alkaline Phosphatase; D002118:Calcium