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- Title
Tungsten Promotes Sex-Specific Adipogenesis in the Bone by Altering Differentiation of Bone Marrow-Resident Mesenchymal Stromal Cells.
- Authors
Bolt, Alicia M.; Grant, Michael P.; Ting Hua Wu; Molina, Manuel Flores; Plourde, Dany; Kelly, Alexander D. R.; Negro Silva, Luis Fernando; Lemaire, Maryse; Schlezinger, Jennifer J.; Mwale, Fackson; Mann, Koren K.
- Abstract
Tungsten is a naturally occurringmetal that increasingly is being incorporated into industrial goods andmedical devices, and is recognized as an emerging contaminant. Tungsten preferentially and rapidly accumulates inmurine bone in a concentration-dependentmanner; however the effect of tungsten deposition on bone biology is unknown. Othermetals alter bone homeostasis by targeting bonemarrow-derived mesenchymal stromal cell (MSC) differentiation, thus, we investigated the effects of tungsten on MSCs in vitro and in vivo. In vitro, tungsten shifted the balance ofMSC differentiation by enhancing rosiglitazone-induced adipogenesis, which correlated with an increase in adipocyte content in the bone of tungsten-exposed, young, malemice. Conversely, tungsten inhibited osteogenesis ofMSCs in vitro; however, we found no evidence that tungsten inhibited osteogenesis in vivo. Interestingly, two factors known to influence adipogenesis are sex and age of mice. Both female and oldermice have enhanced adipogenesis. We extended our study and exposed young female and adult (9-month)male and femalemice to tungsten for 4 weeks. Although tungsten accumulated to a similar extent in young femalemice, it did not promote adipogenesis. Interestingly, tungsten did not accumulate in the bone of oldermice; it was undetectable in adultmale mice, and just above the limit of detect in adult femalemice. Surprisingly, tungsten enhanced adipogenesis in adult female mice. In summary, we found that tungsten alters bone homeostasis by altering differentiation ofMSCs, which could have significant implications for bone quality, but is highly dependent upon sex and age.
- Subjects
BONE marrow physiology; ADIPOGENESIS; MESENCHYMAL stem cells; HOMEOSTASIS; BONE physiology
- Publication
Toxicological Sciences, 2016, Vol 150, Issue 2, p333
- ISSN
1096-6080
- Publication type
Article
- DOI
10.1093/toxsci/kfw008