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

Abstract

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 of these interactions, we developed new biomimetic bone matrices containing low doses of natural uranium (up to 0.85 µg per cm 2 of uranium). These models were characterized by spectroscopic and microscopic approaches before being used as a support for the culture and differentiation of preosteoclastic 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.

Association between metal exposures and periodontitis among U.S. adults: the potential mediating role of biological aging

“…A Overall effect between mixed urinary metals and periodontitis. B Correlation of each univariate exposure with periodontitis that high concentrations of Ur in bone microenvironment inhibited osteoclastic bone resorption [43], which could reduce the risk of periodontitis. Our study shows that mixed metals exposure was strongly associated with periodontitis, which supported the previous studies regarding cadmium exposures as a risk for periodontitis [13].…”

Obesity and lipid metabolism in the development of osteoporosis (Review)

“…Compared with the increase in osteoclast activity, decreased osteogenesis is the most important factor in the occurrence and development of osteoporosis. On the one hand, bone resorption by osteoclasts contributes to the metabolism of bone tissue ( 8 ), while on the other hand, inhibiting osteoclastogenesis relieves further loss of bone mass, but does not improve bone mass, and patients are still in an osteoporotic state ( 9 ). Therefore, the role of osteoblasts is key to exploring the regulation of multiple types of osteoporosis.…”

The Janus face of uranium in toxicology

“…Thus, during the last 15 years, publications in Archives of Toxicology dealt with mechanistic aspects of both nephrotoxicity (Goldman et al 2006 ; Zhu et al 2009 ) and lung toxicity (Periyakaruppan et al 2007 , 2009 ) of uranium. But also other aspects were highlighted, namely effects of depleted uranium on CYP enzymes, with consequences on xenobiotic and vitamin D metabolism (Guéguen et al 2006 , 2014 ; Tissandie et al 2006 ), and effects on the bone matrix (Tasat et al 2007 ; Pierrefit-Carle et al 2017 ; Gritsaenko et al 2021 ).…”