Journal article

Publication year: 2021

Pages: 25-43

Journal: Reproductive Toxicology

Volume number: 105

ISSN: 0890-6238

eISSN: 1873-1708

Open access status: Hybrid

DOI Link: https://doi.org/10.1016/j.reprotox.2021.07.013

Publisher: Elsevier

Abstract: 
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.

Harvard Citation style: Herlin, M., Sanchez-Perez, I., Esteban, J., Korkalainen, M., Barber, X., Finnilä, M., et al. (2021) 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, Reproductive Toxicology, 105, pp. 25-43. https://doi.org/10.1016/j.reprotox.2021.07.013

APA Citation style: Herlin, M., Sanchez-Perez, I., Esteban, J., Korkalainen, M., Barber, X., Finnilä, M., Hamscher, G., Joseph, B., Viluksela, M., & Håkansson, H. (2021). 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. Reproductive Toxicology. 105, 25-43. https://doi.org/10.1016/j.reprotox.2021.07.013