SENTOS

The study of the biological mechanisms involved in chronic exposure of bone tissue to low doses of uranium corresponds to the focal area of interest "Assessment and detection of anthropogenic risks to human health, the environment and global change" by helping us better understand and assess the effects of this natural and anthropogenic toxicant on human health.

Our bones are complex and extremely dynamic organs, continuously remodeled (resorption and construction) throughout our lives. Their natural remodeling can be affected by unfavorable environmental conditions or chronic exposure to an external compound, in this case uranium, a radioelement naturally present in the soil or drinking water. This remodeling is the work of different cell types whose activities are closely coordinated: osteoclasts, responsible for resorption of the bone matrix, osteoblasts, responsible for construction of this matrix, and osteocytes, which act as coordinators relaying the information between the other two cell types. The research team working on the SEnTOs project is seeking to shed light on the effects of natural, moderate daily exposure to uranium, and to determine its impact on bone cell mechanisms. In order to explore these mechanisms, an internship supported by Academy 3 has focused specifically on modifications to the bone matrix generated in the presence of uranium, using a cell culture protocol and in vitro uranium exposure.
The unique feature of the project is its protocol, in which exposure of the bone matrix to uranium is chronic and moderate: ten days of exposure to two micromoles of uranium. At the end of this period, two effects could be observed: mineralization of the matrix by osteoblasts slowed down, and the component cells of osteoclasts were reduced. Experiments show that bones rebuild more slowly, and bone matrix resorption is slower, potentially disturbing bone tissue remodeling and leading to bone fragility. Over time, bones capture a number of toxic compounds and heavy metals, including uranium. The project has shown that the metal is more concentrated in areas of active remodeling and will therefore be trapped when the new matrix is built, only to be released again when the old matrix is resorbed. Uranium thus becomes trapped in the bones through this molecular cycle, which the team calls "the uranium cycle" linked to the environmental memory of bone cells.
To further understand this process, RT-PCR and Western blot analyses were performed to identify and confirm the genes and proteins affected by uranium exposure. Some proteins present in the matrix were over-expressed, while others were under-expressed compared with control conditions.
In the next stages of the project, the consequences of these differences in expression on bone molecular mechanisms will be investigated.

Scientific domain Biology, Health Risks	Key words Chronic exposure Bone cells Uranium
Total budget €250,000, including €7,000 from Academy 3	Students involved Arthur Gouraud (Master)
Partners TIRO-MATOs – Université Côte d’Azur, CEA ICN - Université Côte d’Azur, CNRS	Project members Georges Carle Sabine Santucci

Presentation of part of the results at a CEA science day.