Transgenic mice with a constitutively active aryl hydrocarbon receptor display a gender-specific bone phenotype

Toxicological Sciences : an Official Journal of the Society of Toxicology
Carolina WejhedenAnnika Hanberg

Abstract

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 aryl hydrocarbon receptor (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 C-telopeptide of type I collagen (CTX), reflecting osteoclast activity, were both increased by approximately 60% in female CA-AhR mice, while serum tartrate-resistant acid phosphatase (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 messenger RNA expression of several osteoclast- and osteoblast-associated genes was ...Continue Reading

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Jun 19, 2013·Proceedings of the National Academy of Sciences of the United States of America·Jameel IqbalNarayan G Avadhani
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