Abstract
Epigenetics describes mechanisms which control gene expression and cellular processes without changing the DNA sequence. The main mechanisms in epigenetics are DNA methylation in CpG-rich promoters, histone modifications and non-coding RNAs (ncRNAs). DNA methylation modifies the function of the DNA and correlates with gene silencing. Histone modifications including acetylation/deacetylation and phosphorylation act in diverse biological processes such as transcriptional activation/inactivation and DNA repair. Non-coding RNAs play a large part in epigenetic regulation of gene expression in addition to their roles at the transcriptional and post-transcriptional level. Osteoporosis is the most common skeletal disorder, characterized by compromised bone strength and bone micro-architectural deterioration that predisposes the bones to an increased risk of fracture. It is most often caused by an increase in bone resorption that is not sufficiently compensated by a corresponding increase in bone formation. Nowadays it is well accepted that osteoporosis is a multifactorial disorder and there are genetic risk factors for osteoporosis and bone fractures. Here we review emerging evidence that epigenetics contributes to the machinery that can alter DNA structure, gene expression, and cellular differentiation during physiological and pathological bone remodeling.
Highlights
The human skeleton is a metabolically active organ that undergoes continuous bone remodeling throughout life [1]
Non-coding RNAs can be divided into two main groups: infrastructural and regulatory non-coding RNAs (ncRNAs). Since they are involved in the modification and regulation of other RNAs, regulatory ncRNAs are considered as epigenetic modifiers
They can be categorized into six groups: microRNAs, P-element induced wimpy testis-interacting RNAs, short interference RNA (siRNA), long non-coding RNAs, enhancer RNAs, and promoter-associated RNAs (PARs)
Summary
The human skeleton is a metabolically active organ that undergoes continuous bone remodeling throughout life [1]. Rojas et al showed that the epigenetically-forced expression of Runx and osteocalcin, classical bone-related target genes, under myoblastic differentiation is accompanied by enrichment of the H3K4me and H3K27ac marks at the Runx promoter region [44] These authors identified JARID1B, known as lysine (K)-specific demethylase (KDM)5B, as a key and potent epigenetic switch which controls mesenchymal cell differentiation into myogenic and osteogenic lineages. Knockdown of HDAC1 by the short interference RNA (siRNA) stimulated osteoblast differentiation It was shown in a recent study that the treatment of non-osteogenic cells with TSA allows Wnt3a to promote osteogenesis in these cells, suggesting that direct conversion of non-osteogenic cells into osteoblastic cell types without inducing pluripotency might be controlled by histone modifiers [17]
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