Sex Steroid Regulation of Oxidative Stress in Bone Cells: An In Vitro Study

Environmental stimuli, including sex hormones and oxidative stress (OS), affect bone balance, modifying the epigenetic profiles of key osteogenic genes. Nonetheless, the interplay between sex steroids, epigenome and OS has yet be fully elucidated. This paper aims to study in vitro the role of sex st...

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Autores principales:	Valeria Sibilia, Daniele Bottai, Roberto Maggi, Francesca Pagani, Raffaella Chiaramonte, Domenica Giannandrea, Valentina Citro, Natalia Platonova, Lavinia Casati
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	bone steroids milieu histone modification oxidative stress H3K4me3 H4 acetylation Medicine R
Acceso en línea:	https://doaj.org/article/b1e88c93a87140f3b37ec34091ee3617
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spelling	oai:doaj.org-article:b1e88c93a87140f3b37ec34091ee36172021-11-25T17:51:47ZSex Steroid Regulation of Oxidative Stress in Bone Cells: An In Vitro Study10.3390/ijerph1822121681660-46011661-7827https://doaj.org/article/b1e88c93a87140f3b37ec34091ee36172021-11-01T00:00:00Zhttps://www.mdpi.com/1660-4601/18/22/12168https://doaj.org/toc/1661-7827https://doaj.org/toc/1660-4601Environmental stimuli, including sex hormones and oxidative stress (OS), affect bone balance, modifying the epigenetic profiles of key osteogenic genes. Nonetheless, the interplay between sex steroids, epigenome and OS has yet be fully elucidated. This paper aims to study in vitro the role of sex steroids in OS-induced alteration in bone cells’ homeostasis, and to assess the possible contribution of epigenetic modifications. Toward this purpose, osteoblast (MC3T3-E1) and osteocyte (MLOY-4) cell lines were exposed to two different sources of free oxygen radicals, i.e., tert-butyl hydroperoxide and dexamethasone, and the protective effect of pre-treatment with androgens and estrogens was evaluated. In particular, we analyzed parameters that reflect bone cell homeostasis such as cell viability, cell migration, transcriptomic profile, transcriptional activity, and epigenetic signature. Our findings indicate that estrogens and androgens counteract OS effects. Using partially overlapping strategies, they reduce OS outcomes regarding cell viability, cell migration, the transcriptomic profile of gene families involved in bone remodeling, and epigenetic profile, i.e., H3K4me3 level. Additionally, we demonstrated that the protective effect of steroids against OS on bone homeostasis is partially mediated by the Akt pathway. Overall, these results suggest that the hormonal milieu may influence the mechanisms of age-related bone disease.Valeria SibiliaDaniele BottaiRoberto MaggiFrancesca PaganiRaffaella ChiaramonteDomenica GiannandreaValentina CitroNatalia PlatonovaLavinia CasatiMDPI AGarticlebonesteroids milieuhistone modificationoxidative stressH3K4me3H4 acetylationMedicineRENInternational Journal of Environmental Research and Public Health, Vol 18, Iss 12168, p 12168 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	bone steroids milieu histone modification oxidative stress H3K4me3 H4 acetylation Medicine R
spellingShingle	bone steroids milieu histone modification oxidative stress H3K4me3 H4 acetylation Medicine R Valeria Sibilia Daniele Bottai Roberto Maggi Francesca Pagani Raffaella Chiaramonte Domenica Giannandrea Valentina Citro Natalia Platonova Lavinia Casati Sex Steroid Regulation of Oxidative Stress in Bone Cells: An In Vitro Study
description	Environmental stimuli, including sex hormones and oxidative stress (OS), affect bone balance, modifying the epigenetic profiles of key osteogenic genes. Nonetheless, the interplay between sex steroids, epigenome and OS has yet be fully elucidated. This paper aims to study in vitro the role of sex steroids in OS-induced alteration in bone cells’ homeostasis, and to assess the possible contribution of epigenetic modifications. Toward this purpose, osteoblast (MC3T3-E1) and osteocyte (MLOY-4) cell lines were exposed to two different sources of free oxygen radicals, i.e., tert-butyl hydroperoxide and dexamethasone, and the protective effect of pre-treatment with androgens and estrogens was evaluated. In particular, we analyzed parameters that reflect bone cell homeostasis such as cell viability, cell migration, transcriptomic profile, transcriptional activity, and epigenetic signature. Our findings indicate that estrogens and androgens counteract OS effects. Using partially overlapping strategies, they reduce OS outcomes regarding cell viability, cell migration, the transcriptomic profile of gene families involved in bone remodeling, and epigenetic profile, i.e., H3K4me3 level. Additionally, we demonstrated that the protective effect of steroids against OS on bone homeostasis is partially mediated by the Akt pathway. Overall, these results suggest that the hormonal milieu may influence the mechanisms of age-related bone disease.
format	article
author	Valeria Sibilia Daniele Bottai Roberto Maggi Francesca Pagani Raffaella Chiaramonte Domenica Giannandrea Valentina Citro Natalia Platonova Lavinia Casati
author_facet	Valeria Sibilia Daniele Bottai Roberto Maggi Francesca Pagani Raffaella Chiaramonte Domenica Giannandrea Valentina Citro Natalia Platonova Lavinia Casati
author_sort	Valeria Sibilia
title	Sex Steroid Regulation of Oxidative Stress in Bone Cells: An In Vitro Study
title_short	Sex Steroid Regulation of Oxidative Stress in Bone Cells: An In Vitro Study
title_full	Sex Steroid Regulation of Oxidative Stress in Bone Cells: An In Vitro Study
title_fullStr	Sex Steroid Regulation of Oxidative Stress in Bone Cells: An In Vitro Study
title_full_unstemmed	Sex Steroid Regulation of Oxidative Stress in Bone Cells: An In Vitro Study
title_sort	sex steroid regulation of oxidative stress in bone cells: an in vitro study
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/b1e88c93a87140f3b37ec34091ee3617
work_keys_str_mv	AT valeriasibilia sexsteroidregulationofoxidativestressinbonecellsaninvitrostudy AT danielebottai sexsteroidregulationofoxidativestressinbonecellsaninvitrostudy AT robertomaggi sexsteroidregulationofoxidativestressinbonecellsaninvitrostudy AT francescapagani sexsteroidregulationofoxidativestressinbonecellsaninvitrostudy AT raffaellachiaramonte sexsteroidregulationofoxidativestressinbonecellsaninvitrostudy AT domenicagiannandrea sexsteroidregulationofoxidativestressinbonecellsaninvitrostudy AT valentinacitro sexsteroidregulationofoxidativestressinbonecellsaninvitrostudy AT nataliaplatonova sexsteroidregulationofoxidativestressinbonecellsaninvitrostudy AT laviniacasati sexsteroidregulationofoxidativestressinbonecellsaninvitrostudy
_version_	1718411941980930048

Sex Steroid Regulation of Oxidative Stress in Bone Cells: An In Vitro Study

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