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

Author

Listed:
  • 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)

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.

Suggested Citation

  • Valeria Sibilia & Daniele Bottai & Roberto Maggi & Francesca Pagani & Raffaella Chiaramonte & Domenica Giannandrea & Valentina Citro & Natalia Platonova & Lavinia Casati, 2021. "Sex Steroid Regulation of Oxidative Stress in Bone Cells: An In Vitro Study," IJERPH, MDPI, vol. 18(22), pages 1-23, November.
  • Handle: RePEc:gam:jijerp:v:18:y:2021:i:22:p:12168-:d:683552
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    References listed on IDEAS

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    1. Colin Jamora & Ramanuj DasGupta & Pawel Kocieniewski & Elaine Fuchs, 2003. "Erratum: Links between signal transduction, transcription and adhesion in epithelial bud development," Nature, Nature, vol. 424(6951), pages 974-974, August.
    2. Colin Jamora & Ramanuj DasGupta & Pawel Kocieniewski & Elaine Fuchs, 2003. "Links between signal transduction, transcription and adhesion in epithelial bud development," Nature, Nature, vol. 422(6929), pages 317-322, March.
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    More about this item

    Keywords

    bone; steroids milieu; histone modification; oxidative stress; H3K4me3; H4 acetylation;
    All these keywords.

    JEL classification:

    • H4 - Public Economics - - Publicly Provided Goods

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