ECTS2016 Poster Presentations Cell biology: osteoblasts and bone formation (36 abstracts)
Natural uranium triggers autophagy in osteoblasts
Valérie Pierrefite-Carle 1 , Sabine Santucci-Darmanin 1 , Véronique Breuil 1 , Claude Vidaud 2 , Gaëlle Creff 3 , Christophe Den Auwer 3 & Georges Carle 1
1TIRO-MATOs UMR E4320, Université Nice-Sophia Antipolis CEA, Nice, France; 2iBEB/DRF/CEA, Cadarache, France; 3ICN Université Nice Sophia-Antipolis, Nice, France.
Bone is a complex organ constituted of a mineralized matrix generated by osteoblasts (OB). Bone matrix is a major storage site for minerals but also for toxicants from the environment. Among them, uranium, a natural element of the earth crust, has a dual toxicity due to its radiological effects as an alpha emitter and its chemical effects due to its metal properties. In the case of natural uranium, the chemical toxicity is predominant. Uranium level in drinking water is usually in the range of microgram-per-liter but this value may be as much as 100 to 1000 times higher in some geographical areas and the effects of a chronic exposure on bone biology have been poorly explored. Using an osteoblastic cell line, we have shown that the presence of natural uranium, even at low and non-toxic concentrations, alters the main OB function i.e. matrix mineralization. A 24 h OB exposure to sub-toxic uranium level results in uranium precipitate formation which can be observed within autophagic vacuoles, multivesicular bodies, lysosomes as well as in the extracellular space. In addition, natural uranium triggers autophagy in OB after a 3 h exposure, with a block of the autophagic flux observed after a 24 h exposure. These results indicate that autophagy is activated in response to uranium in OB.
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