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

Valeria Sibilia, Daniele Bottai, Roberto Maggi, Francesca Pagani, Raffaella Chiaramonte, Domenica Giannandrea, Valentina Citro, Natalia Platonova and Lavinia Casati
Additional contact information
Valeria Sibilia: Department of Medical Biotechnology and Translational Medicine, Università degli Studi di Milano, 20129 Milano, Italy
Daniele Bottai: Department of Health Sciences, Università degli Studi di Milano, 20142 Milano, Italy
Roberto Maggi: Department of Pharmaceutical Sciences, Università degli Studi di Milano, 20133 Milano, Italy
Francesca Pagani: Department of Medical Biotechnology and Translational Medicine, Università degli Studi di Milano, 20129 Milano, Italy
Raffaella Chiaramonte: Department of Health Sciences, Università degli Studi di Milano, 20142 Milano, Italy
Domenica Giannandrea: Department of Health Sciences, Università degli Studi di Milano, 20142 Milano, Italy
Valentina Citro: Department of Health Sciences, Università degli Studi di Milano, 20142 Milano, Italy
Natalia Platonova: Department of Health Sciences, Università degli Studi di Milano, 20142 Milano, Italy
Lavinia Casati: Department of Health Sciences, Università degli Studi di Milano, 20142 Milano, Italy

IJERPH, 2021, vol. 18, issue 22, 1-23

Abstract: 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.

Keywords: bone; steroids milieu; histone modification; oxidative stress; H3K4me3; H4 acetylation (search for similar items in EconPapers)
JEL-codes: I I1 I3 Q Q5 (search for similar items in EconPapers)
Date: 2021
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.mdpi.com/1660-4601/18/22/12168/pdf (application/pdf)
https://www.mdpi.com/1660-4601/18/22/12168/ (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:gam:jijerp:v:18:y:2021:i:22:p:12168-:d:683552

Access Statistics for this article

IJERPH is currently edited by Ms. Jenna Liu

More articles in IJERPH from MDPI
Bibliographic data for series maintained by MDPI Indexing Manager ().