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 μM) of vanadate. Vanadate induced NO release in a biphasic manner, with levels being significantly increased at concentrations over 50 μM. 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.