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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Author: | Herlin, Maria1; Sánchez-Pérez, Ismael2; Esteban, Javier2; |
Organizations: |
1Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden 2Instituto de Bioingeniería, Universidad Miguel Hernández de Elche, Elche, Alicante, Spain 3Environmental Health Unit, Finnish Institute for Health and Welfare (THL), Kuopio, Finland
4Centro de Investigación Operativa, Universidad Miguel Hernández, Elche, Alicante, Spain
5Research Unit of Medical Imaging, Physics, and Technology, Faculty of Medicine, University of Oulu, Oulu, Finland 6Institute of Food Chemistry and Food Biotechnology, Justus Liebig University Giessen, 10 Giessen, Germany 7School of Pharmacy (Toxicology) and Department of Environmental and Biological Sciences, University of Eastern Finland, Kuopio, Finland |
Format: | article |
Version: | published version |
Access: | open |
Online Access: | PDF Full Text (PDF, 4.2 MB) |
Persistent link: | http://urn.fi/urn:nbn:fi-fe2021092947481 |
Language: | English |
Published: |
Elsevier,
2021
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Publish Date: | 2021-09-29 |
Description: |
AbstractDioxin 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. see all
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Series: |
Reproductive toxicology |
ISSN: | 0890-6238 |
ISSN-E: | 1873-1708 |
ISSN-L: | 0890-6238 |
Volume: | 105 |
Pages: | 25 - 43 |
DOI: | 10.1016/j.reprotox.2021.07.013 |
OADOI: | https://oadoi.org/10.1016/j.reprotox.2021.07.013 |
Type of Publication: |
A1 Journal article – refereed |
Field of Science: |
317 Pharmacy 1172 Environmental sciences 217 Medical engineering 3111 Biomedicine |
Subjects: | |
Funding: |
The authors gratefully acknowledge financial support for the European Commission R&D project BoneTox (QLK4-CT-2002-02528) and for contractual work by the Nordic Chemical Group (2016-023, 2017-003). The authors are solely responsible for the contents of this paper, which does not necessarily represent the opinion of the European Community. |
Copyright information: |
© 2021 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
https://creativecommons.org/licenses/by/4.0/ |