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Transgenic mice with a constitutively active aryl hydrocarbon receptor (CA-AhR) display a gender specific bone phenotype
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
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2010 (English)In: Toxicological Sciences, ISSN 1096-6080, E-ISSN 1096-0929, Vol. 114, no 1, 48-58 p.Article in journal (Refereed) Published
Abstract [en]

Bone tissue homeostasis is governed by hormones, growth factors and cytokines and can be distorted by environmental pollutants such as ligands to the aryl hydrocarbon receptor (AhR). A transgenic mouse expressing a constitutively active AhR (CA-AhR), mimicking continuous low-dose exposure to AhR-ligands, was used to explore potential long-term effects of these ligands on bone The density, content and dimensions of cortical and trabecular bone, as well as physical properties, were significantly altered in female transgenic mice, while almost no alterations were detected in males. Osteoclast volume density and serum level of CTX, reflecting osteoclast activity, were both increased by approximately 60% in female CA-AhR mice, while serum TRAP 5b, reflecting osteoclast numbers, was unchanged. Subsequently, the resorption index (CTX/TRAP 5b) was increased by 90% indicating increased osteoclast activity in female CA-AhR. Moreover, the protein level of the osteoclast collagenase cathepsin K was increased by 40 % in bone extracts of female CA-AhR mice. The mRNA expression of several osteoclast and osteoblast associated genes were altered in female transgenic mice, but not in males. Notably, early markers for osteoclast and osteoblast differentiation were normal, while the expression of functional markers of osteoclasts and osteoblasts were reduced. In conclusion, a low continuous activation of the AhR leads to a skeletal phenotype with increased bone resorption associated with more ductile bones in females but not in males. The results indicate the presence of an interaction between the AhR and a female specific mechanism implicated in inhibition of osteoclast development and function. Female bone tissue appears more susceptible to dioxins and other AhR-ligands than male bone tissue.

Place, publisher, year, edition, pages
2010. Vol. 114, no 1, 48-58 p.
Keyword [en]
dioxin, Ah receptor, osteoclast, osteoblast, bone, transgenic mouse mode
National Category
Medical and Health Sciences
Research subject
URN: urn:nbn:se:uu:diva-111744DOI: 10.1093/toxsci/kfp284ISI: 000274499800006PubMedID: 19934163OAI: oai:DiVA.org:uu-111744DiVA: diva2:282615
Available from: 2009-12-21 Created: 2009-12-21 Last updated: 2012-03-02Bibliographically approved

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