Abstract
Age related changes to the skeleton, such as osteoporosis, increase the risk of fracture and morbidity in the elderly population. In osteoporosis, bone remodeling becomes unbalanced with an increase in bone resorption and a decrease in bone formation. Osteoclasts are large multinucleated cells that secrete acid and proteases to degrade and resorb bone. Understanding the molecular mechanisms that regulate osteoclast differentiation and activity will provide insight as to how hyper-active osteoclasts lead to pathological bone loss, contributing to diseases such as osteoporosis. Reversible modifications to the DNA such as histone acetylation, methylation, phosphorylation and ubiquitylation alters the access of transcriptional machinery to DNA and regulates gene expression and osteoclast differentiation and activity. It is critical for the management of bone related diseases to understand the role of these chromatin modifying proteins during osteoclast differentiation, as potential therapies targeting these proteins are currently under development.
Highlights
Introduction and Osteoclast BiologyOsteoclasts are large multinucleated cells of hematopoietic origin that degrade the bone matrix.They are formed by fusion of mononuclear precursors of the monocyte/macrophage lineage, and are the primary resorptive cells of the skeleton [1,2]
As is evident by the information contained in the above sections, there is mechanistic information known about the role of histone modifying proteins in regulating osteoclast differentiation; the information is limited due to the fact that most of these studies were done in cell culture
There have been a few studies characterizing the histone modifications that occur during osteoclast differentiation; studies analyzing interactions between multiple epigenetic regulators are still scarce [47,48,49,50,51]
Summary
Osteoclasts are large multinucleated cells of hematopoietic origin that degrade the bone matrix. Osteoclast gene expression is activated by a group of transcription factors. It has been shown that MITF plays an essential role in regulating gene expression during osteoclast differentiation. C-FOS is a member of the activator protein-1 (AP-1) family of transcription factors, and its expression is induced early during osteoclast differentiation [11,12]. Epigenetics are of external that do not change the DNA sequence but none the less become a major focus in understanding how these cells are transcriptionally regulated during aging regulate expression of target genes. There are three main types of(PTMs) proteinsofthat play anresult important role in in thechromatin epigenetic arrangement regulation of gene translational modifications histones in changes and transcription:. There are three main types of proteins that play an important role in histone modifications to histone tailstranscription: to either activate or repress gene transcription. We will describe what is currently known about epigenetic
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