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 M; Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. Electronic address: maria.herlin@ki.se., Sánchez-Pérez I; Instituto de Bioingeniería, Universidad Miguel Hernández de Elche, Elche, Alicante, Spain. Electronic address: ismael.sanchez@goumh.umh.es., Esteban J; Instituto de Bioingeniería, Universidad Miguel Hernández de Elche, Elche, Alicante, Spain. Electronic address: jesteban@umh.es., Korkalainen M; Environmental Health Unit, Finnish Institute for Health and Welfare (THL), Kuopio, Finland. Electronic address: merja.korkalainen@thl.fi., Barber X; Centro de Investigación Operativa, Universidad Miguel Hernández, Elche, Alicante, Spain. Electronic address: xbarber@umh.es., Finnilä MAJ; Research Unit of Medical Imaging, Physics, and Technology, Faculty of Medicine, University of Oulu, Oulu, Finland. Electronic address: mikko.finnila@oulu.fi., Hamscher G; Institute of Food Chemistry and Food Biotechnology, Justus Liebig University Giessen, 10 Giessen, Germany. Electronic address: gerd.hamscher@lcb.chemie.uni-giessen.de., Joseph B; Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. Electronic address: bertrand.joseph@ki.se., Viluksela M; Environmental Health Unit, Finnish Institute for Health and Welfare (THL), Kuopio, Finland; School of Pharmacy (Toxicology) and Department of Environmental and Biological Sciences, University of Eastern Finland, Kuopio, Finland. Electronic address: matti.viluksela@uef.fi., Håkansson H; Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. Electronic address: helen.hakansson@ki.se.
Jazyk: angličtina
Zdroj: Reproductive toxicology (Elmsford, N.Y.) [Reprod Toxicol] 2021 Oct; Vol. 105, pp. 25-43. Date of Electronic Publication: 2021 Aug 04.
DOI: 10.1016/j.reprotox.2021.07.013
Abstrakt: 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.
(Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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