Abstract
Epigenetic mechanisms modify gene activity in a stable manner without altering DNA sequence. They participate in the adaptation to the environment, as well as in the pathogenesis of common complex disorders. We provide an overview of the role of epigenetic mechanisms in bone biology and pathology. Extensive evidence supports the involvement of epigenetic mechanisms (DNA methylation, post-translational modifications of histone tails, and non-coding RNAs) in the differentiation of bone cells and mechanotransduction. A variety of epigenetic abnormalities have been described in patients with osteoporosis, osteoarthritis, and skeletal cancers, but their actual pathogenetic roles are still unclear. A few drugs targeting epigenetic marks have been approved for neoplastic disorders, and many more are being actively investigated. Advances in the field of epigenetics underscore the complex interactions between genetic and environmental factors as determinants of osteoporosis and other common disorders. Likewise, they help to explain the mechanisms by which prenatal and post-natal external factors, from nutrition to psychological stress, impact our body and influence the risk of later disease.
Highlights
Genetics, epigenetics, and adaptationLike other animals, humans need molecular and functional stability to survive
Technical developments are allowing to have a better understanding of the “chromosomal conformation signatures”, a term describing the collection of DNA contacts associated with specific gene expression profiles
In a genomewide methylation screening of bone tissue samples of patients with either osteoporotic hip fractures or hip osteoarthritis, we found significant differences in the methylation of a number of genes, which were enriched in the Wnt signaling pathway and other pathways related to skeletal development [60,61]
Summary
Humans need molecular and functional stability to survive. cells must preserve their main characteristics through mitosis and cell division. The stress response includes a number of changes in catecholamines, glucocorticoids, and other hormones that reinforce the ability of the body to fight against the adverse environment (either internal or external) [1] Unlike genetic changes, these modifications are fast, but transitory. As described epigenetic marks include a number of mechanisms, triggered by environmental influences and other stimuli, which are capable of modifying gene activity in a stable manner, without altering DNA sequence These mechanisms play a central role in another particular process of adaptation: the differentiation of cells, which must express and repress unique sets of genes and display distinct tissue-specialized functions despite the fact that all they have an identical genome [2]
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