Fish as a model to assess chemical toxicity in bone

Environmental toxicology has been expanding as growing concerns on the impact of produced and released chemical compounds over the environment and human health are being demonstrated. Among the toxic effects observed in organisms exposed to pollutants, those affecting skeletal tissues (osteotoxicity) have been somehow overlooked in comparison to hepato-, immune-, neuro- and/or reproductive toxicities. Nevertheless, sub-lethal effects of toxicants on skeletal development and/or bone maintenance may result in impaired growth, reduced survival rate, increased disease susceptibility and diminished welfare. Osteotoxicity may occur by acute or chronic exposure to different environmental insults. Because of biologically and technically advantagous features - easy to breed and inexpensive to maintain, external and rapid rate of development, translucent larvae and the availability of molecular and genetic tools - the zebrafish (Danio rerio) has emerged in the last decade as a vertebrate model system of choice to evaluate osteotoxicity. Different experimental approaches in fish species and analytical tools have been applied, from in vitro to in vivo systems, from specific to high throughput methodologies. Current knowledge on osteotoxicity and underlying mechanisms gained using fish, with a special emphasis on zebrafish systems, is reviewed here. Osteotoxicants have been classified into four categories according to the pathway involved in the transduction of the osteotoxic effects: activation/inhibition of membrane and/or nuclear receptors, alteration of redox condition, mimicking of bone constituents and unknown pathways. Knowledge on these pathways is also reported here as it may provide critical insights into the development, production and release of future chemical compounds with none or low osteotoxicity, thus promoting the green/environmental friendly chemistry.