title: Tungsten Promotes Sex-Specific Adipogenesis in the Bone by Altering Differentiation of Bone Marrow-Resident Mesenchymal Stromal Cells.
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.
authors: *Lady Davis Institute for Medical Research; Department of Oncology;
authors: Alicia M
authors: AM
authors: Bolt
authors: *Lady Davis Institute for Medical Research;
authors: Michael P
authors: MP
authors: Grant
authors: *Lady Davis Institute for Medical Research; Division of Experimental Medicine;
authors: Ting Hua
authors: TH
authors: Wu
authors: *Lady Davis Institute for Medical Research;
authors: Manuel
authors: M
authors: Flores Molina
authors: *Lady Davis Institute for Medical Research;
authors: Dany
authors: D
authors: Plourde
authors: *Lady Davis Institute for Medical Research; Faculty of Medicine;
authors: Alexander D R
authors: AD
authors: Kelly
authors: *Lady Davis Institute for Medical Research; Division of Experimental Medicine;
authors: Luis Fernando
authors: LF
authors: Negro Silva
authors: *Lady Davis Institute for Medical Research; Department of Oncology;
authors: Maryse
authors: M
authors: Lemaire
authors: Department of Environmental Health, Boston University School of Public Health, Boston, Massachusetts, USA.
authors: Jennifer J
authors: JJ
authors: Schlezinger
authors: *Lady Davis Institute for Medical Research; Faculty of Medicine; Department of Surgery, McGill University, Montréal, Québec, Canada; and.
authors: Fackson
authors: F
authors: Mwale
authors: *Lady Davis Institute for Medical Research; Department of Oncology; Division of Experimental Medicine; koren.mann@mcgill.ca.
authors: Koren K
authors: KK
authors: Mann
mesh_terms: D050156:Adipogenesis / Q000187:drug effects*; D000375:Aging / Q000378:metabolism; D000818:Animals; D001853:Bone Marrow / Q000187:drug effects* / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000493:pharmacokinetics / Q000633:toxicity*; D005260:Female; D005269:Femur / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D066298:In Vitro Techniques; D008297:Male; D059630:Mesenchymal Stem Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D010012:Osteogenesis / Q000187:drug effects; D012727:Sex Characteristics; D014414:Tungsten / Q000493:pharmacokinetics / Q000633:toxicity*
chemical_list: D004785:Environmental Pollutants; D014414:Tungsten
keywords: adipogenesis; bone; mesenchymal stromal cell; metals.; osteogenesis; tungsten