Vanadate-induced nitric oxide production: role in osteoblast growth and differentiation

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 h igh doses are toxic to these cells. In this study, we measured NO productio n in two osteoblast-like cells (UMR106 and MC3T3E1) incubated with differen t concentrations (2.5-100 mu M) of vanadate. Vanadate induced NO release in a biphasic manner, with levels being significantly increased at concentrat ions over 50 mu M. The NO donor, sodium nitroprusside, mimicked the vanadat e effect: it inhibited cell growth and alkaline phosphatase activity in a d ose-dependent manner. Vanadate enhanced the NO synthases, the endothelial a nd inducible (eNOS and iNOS) isoforms, in a dose-dependent manner. Experime nts performed with the ionophore A23187 and EGTA suggested that vanadate-in duced NO production involves Ca2+-dependent and -independent mechanisms. Al together, our results suggest that NO may play a critical role in the bioac tivity of vanadium in osteoblast-like cells. (C) 2000 Elsevier Science B.V. All rights reserved.