Low doses of uranium and osteoclastic bone resorption: key reciprocal effects evidenced using new in vitro biomimetic models of bone matrix

Description

Uranium is widely spread in the environment due to its natural and anthropogenic occurrences, hence the importance of understanding its impact on human health. The skeleton is the main site of long-term accumulation of this actinide. However, interactions of this metal with biological processes involving the mineralized extracellular matrix and bone cells are still poorly understood. To get a better insight into these interactions, we developed new biomimetic bone matrices containing low doses of natural uranium (up to 0.85 µg of uranium per cm2). These models were characterized by spectroscopic and microscopic approaches before being used as a support for the culture and differentiation of pre-osteoclastic cells. In doing so, we demonstrate that uranium can exert opposite effects on osteoclast resorption depending on its concentration in the bone microenvironment. Our results also provide evidence for the first time that resorption contributes to the remobilization of bone matrix-bound uranium. In agreement with this, we identified, by HRTEM, uranium phosphate internalized in vesicles of resorbing osteoclasts. Thanks to the biomimetic matrices we developed, this study highlights the complex mutual effects between osteoclasts and uranium. This demonstrates the relevance of these 3D models to further study the cellular mechanisms at play in response to uranium storage in bone tissue, and thus better understand the impact of environmental exposure to uranium on human bone health.

Abstract

The authors would like to thank Chantal Cros and Colette Ricort for helpful technical assistance. The authors acknowledge the MARS beamline of SOLEIL synchrotron (Gif sur Yvette, France) that was used to perform XAS experiments and the IRCAN's Molecular and Cellular Core Imaging (PICMI) Facility which is supported by grants from the Ministère de l'Enseignement Supérieur, the Région PACA, the Conseil Départemental des Alpes Maritimes, INSERM, the FEDER, the GIS IBiSA, the Canceropole PACA and the foundation ARC.Funding

Abstract

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