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Bone toxicity induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and the retinoid system: A causality analysis anchored in osteoblast gene expression and mouse data


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Título :
Bone toxicity induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and the retinoid system: A causality analysis anchored in osteoblast gene expression and mouse data
Autor :
Herlin, Maria
Sánchez-Pérez, Ismael
Esteban Mozo, Javier
Korkalainen, Merja  
Barber, Xavier  
Jalmari Finnilä, Mikko Arttu
Hamscher, Gerd  
Joseph, Bertrand  
Viluksela, Matti  
Hǻkansson, Helen
Editor :
Elsevier
Departamento:
Departamentos de la UMH::Biología Aplicada
Fecha de publicación:
2021-10
URI :
https://hdl.handle.net/11000/37575
Resumen :
Dioxin exposures impact on bone quality and osteoblast differentiation, as well as retinoic acid metabolism and signaling. In this study we analyzed associations between increased circulating retinol concentrations and altered bone mineral density in a mouse model following oral exposure to 2,3,7,8-tetrachlordibenzo-p-dioxin (TCDD). Additionally, effects of TCDD on differentiation marker genes and genes involved with retinoic acid metabolism were analysed in an osteoblast cell model followed by benchmark dose-response analyses of the gene expression data. Study results show that the increased trabecular and decreased cortical bone mineral density in the mouse model following TCDD exposure are associated with increased circulating retinol concentrations. Also, TCDD disrupted the expression of genes involved in osteoblast differentiation and retinoic acid synthesis, degradation, and nuclear translocation in directions compatible with increasing cellular retinoic acid levels. Further evaluation of the obtained results in relation to previously published data by the use of mode-of-action and weight-of-evidence inspired analytical approaches strengthened the evidence that TCDD-induced bone and retinoid system changes are causally related and compatible with an endocrine disruption mode of action.
Palabras clave/Materias:
Vitamin A
Dioxin
Mode of action
Adverse outcome pathway
Weight of evidence
Effect biomarkers
Metabolism and endocrinology
Endocrine disruption
Área de conocimiento :
CDU: Ciencias puras y naturales: Biología
Tipo de documento :
info:eu-repo/semantics/article
Derechos de acceso:
info:eu-repo/semantics/openAccess
Attribution-NonCommercial-NoDerivatives 4.0 Internacional
DOI :
https://doi.org/10.1016/j.reprotox.2021.07.013
Publicado en:
Reproductive Toxicology, Volume 105, October 2021, Pages 25-43
Aparece en las colecciones:
Artículos Biología Aplicada



Creative Commons La licencia se describe como: Atribución-NonComercial-NoDerivada 4.0 Internacional.