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Toxicol Sci. 2016 Apr;150(2):333-46. doi: 10.1093/toxsci/kfw008. Epub 2016 Feb 9.

Tungsten Promotes Sex-Specific Adipogenesis in the Bone by Altering Differentiation of Bone Marrow-Resident Mesenchymal Stromal Cells.

Author information

1
*Lady Davis Institute for Medical Research; Department of Oncology;
2
*Lady Davis Institute for Medical Research;
3
*Lady Davis Institute for Medical Research; Division of Experimental Medicine;
4
*Lady Davis Institute for Medical Research; Faculty of Medicine;
5
Department of Environmental Health, Boston University School of Public Health, Boston, Massachusetts, USA.
6
*Lady Davis Institute for Medical Research; Faculty of Medicine; Department of Surgery, McGill University, Montréal, Québec, Canada; and.
7
*Lady Davis Institute for Medical Research; Department of Oncology; Division of Experimental Medicine; koren.mann@mcgill.ca.

Abstract

Tungsten is a naturally occurring metal that increasingly is being incorporated into industrial goods and medical devices, and is recognized as an emerging contaminant. Tungsten preferentially and rapidly accumulates in murine bone in a concentration-dependent manner; however the effect of tungsten deposition on bone biology is unknown. Other metals alter bone homeostasis by targeting bone marrow-derived mesenchymal stromal cell (MSC) differentiation, thus, we investigated the effects of tungsten on MSCsin vitroandin vivoIn vitro, tungsten shifted the balance of MSC differentiation by enhancing rosiglitazone-induced adipogenesis, which correlated with an increase in adipocyte content in the bone of tungsten-exposed, young, male mice. Conversely, tungsten inhibited osteogenesis of MSCsin vitro; however, we found no evidence that tungsten inhibited osteogenesisin vivo Interestingly, two factors known to influence adipogenesis are sex and age of mice. Both female and older mice have enhanced adipogenesis. We extended our study and exposed young female and adult (9-month) male and female mice to tungsten for 4 weeks. Although tungsten accumulated to a similar extent in young female mice, it did not promote adipogenesis. Interestingly, tungsten did not accumulate in the bone of older mice; it was undetectable in adult male mice, and just above the limit of detect in adult female mice. Surprisingly, tungsten enhanced adipogenesis in adult female mice. In summary, we found that tungsten alters bone homeostasis by altering differentiation of MSCs, which could have significant implications for bone quality, but is highly dependent upon sex and age.

KEYWORDS:

adipogenesis; bone; mesenchymal stromal cell; metals.; osteogenesis; tungsten

PMID:
26865663
PMCID:
PMC4900133
DOI:
10.1093/toxsci/kfw008
[Indexed for MEDLINE]
Free PMC Article

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