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  • Vanadate effects on bone metabolism: fish cell lines as an alternative to mammalian in vitro systems
    Publication . Tiago, Daniel; Laizé, Vincent; Aureliano, M.; Cancela, Leonor
    Vanadate, one of the most relevant forms of vanadium in solution, has been associated with the regulation of various enzyme activities (e.g. phosphatases, ribonucleases, ATPases, etc.) and shown to exhibit important biological effects. Several in vivo and in vitro studies have clearly demonstrated that any deficiency or excess of vanadium can seriously affect bone formation and its metabolism. Bone-related effects result largely from vanadium insulino-mimetic capabilities mediated by specific inhibition of protein tyrosine phosphatases (PTPases) and consequent activation of tyrosine kinase receptors (e.g. insulin receptor). Although mammals have been repetitively shown to be appropriate models to study vanadate mechanisms of action, fish have recently emerged as alternative models. Fish has been recognized as suitable model to study vertebrate bone formation and the natural presence of high quantities of vanadium in water makes it even more suitable to investigate vanadium effect on bone formation. Recent data obtained using fish bone-derived cells revealed that micromolar concentrations (5 mM) of monomeric and decameric vanadate slightly stimulate growth performances while strongly inhibiting extracellular matrix mineralization through mechanisms involving both alkaline phosphatase and MAPK pathways. Recent data obtained in fish cells will be discussed here and further compared to results obtained in mammalian systems.
  • Vanadate and bone metabolism: effect on proliferation and mineralization of fish bone-derived cells
    Publication . Tiago, Daniel; Laizé, Vincent; Cancela, Leonor; Aureliano, M.
    Vanadate is known for mimicking insulin action through activation of insulin and/or insulin like growth factor 1 (IGF 1) receptors. Vanadate insulin- like effect on bone-related metabolism has been previously investigated using mammalian in vitro cell systems but other vertebrate systems have rarely been used. We have recently demonstrated the suitability of a fish bone derived cell line (VSa13) to study anti-mineralogenic effects of vanadate. Here, we propose that vanadate stimulation of cell proliferation involves MAPK signalling pathway and IGF 1 receptor activation, while impairment of extracellular matrix (ECM) mineralization is likely to involve both MAPK and PI 3K pathways and insulin receptor activation.