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.
Highlights
IntroductionThe sexual steroid milieu (estrogens and androgens) is involved in acquiring bone mass during puberty and maintains this throughout adult life
The sexual steroid milieu is involved in acquiring bone mass during puberty and maintains this throughout adult life
This paper aims to analyze in vitro the involvement of sex steroids in disruptions in bone metabolism associated with aging induced by free radicals and clarify the epigenome contribution
Summary
The sexual steroid milieu (estrogens and androgens) is involved in acquiring bone mass during puberty and maintains this throughout adult life. A reduction in estrogen levels in females during menopause or estrogens and androgens in males later in life causes bone mass loss and lowers strength [1]. This unbalance contributes to the development of osteoporosis, one of the most common metabolic aging disorders [1]. The correct acquisition and maintenance of bone mass are essential for bone integrity and regeneration. Any factor that destroys the coupling between OB and OC action leads to a reduction in the quality and density of bone mass, resulting in decreased bone strength and increased fracture risk, as occurs in osteoporosis [2]
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