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- New insights into mineralogenic effects of vanadatePublication . Laizé, Vincent; Tiago, Daniel; Aureliano, M.; Cancela, LeonorVanadium is a transition metal that occurs naturally in a variety of minerals and exhibits an exceptional complex chemistry in solution, e.g., several oxidation states ranging from ?2 to ?5, and formation of vanadium oligomers such as decameric vanadate (?5) species [1–4]. Besides its metallurgical role in steel alloys, vanadium is also an ultra trace element known to participate in many biological processes and considered to be essential for living organisms [5, 6]. It accumulates in a variety of organisms ranging from microbes to vertebrates, where it modulates the activity of an array of key enzymes or participates as a cofactor in the active centre of others [1, 2, 5–9]. In mammals, vanadium compounds can mimic insulin action and may prevent chemical carcinogenesis, most probably through the inhibition of cellular tyrosine phosphatases and subsequent activation of signalling pathways, suggesting their use as pharmacological tools to treat human diabetes mellitus and cancer, respectively [10–14]. Anti-tumoral action of vanadium is, however, controversial as several studies have proposed that vanadium could act as a mitogen, tumor promoter and co-carcinogen (see [15] and references therein). Other studies have reported an osteogenic role for vanadium compounds and suggest that vanadium could also have a therapeutic application in bone-related diseases, such as osteoporosis [16–18]. Decades of research have thus provided evidence for vanadium’s physiological and pharmacological properties, supporting the claim that it may represent a promising therapeutic agent for diseases targeting billions of human beings and affecting a wide range of pathological conditions. However, the development of vanadium-based pharmaceuticals will probably take some time since various issues related to vanadium toxicity, speciation and multiple targeting will need to be solved before advancing to clinical trials. Despite being used for decades by researchers as an inhibitor of protein tyrosine phosphatases, it is still not totally clear which vanadium species induce or which signalling pathways transduce physiological and pharmacological effects. Vanadium chemistry is complex, and different species or complexes may induce different pathways [5], affecting different biological processes. This work intends to review what is presently known about the bone-related role of vanadium in mammals and present recent in vitro data on the mineralogenic effect of vanadate in fish, which have become promising model organisms for vertebrate bone-related studies.
- Vanadate proliferative and anti-mineralogic effects are mediated by MAPK and PI-3K/Ras/Erk pathways in a fish chondrocyte cell linePublication . Tiago, Daniel; Cancela, Leonor; Aureliano, M.; Laizé, VincentWe recently reported proliferative and anti-mineralogenic effects of vanadate on fish chondrocytes and here we investigate the signalling pathways associated with these effects. Our data show that vanadate stimulates chondrocyte proliferation through the MAPK pathway, using signalling mechanisms similar to those used by IGF-1, while it inhibits chondrocyte differentiation/mineralization through a putative PI-3K/Ras/ Erk signalling, a pathway shared with insulin. Our data also suggest that vanadate impairs ECM mineralization not only by interfering with regulatory pathways but also by inhibiting enzymatic activity of ALP. Finally, this work provides additional evidence for the conservation, throughout evolution, of mechanisms regulating chondrocyte proliferation and differentiation.