Epigenetic Regulation of the Musculoskeletal System in Health, Disease, and Aging

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Background

Epigenetic regulation of the musculoskeletal (MSK) system is well-recognized and is evolving in biomedical research. The epigenetic apparatus controls various cellular processes of physiological conditions such as bone cell differentiation and muscle response to stress, but also directs integration of environmental changes, for example adaptation to nutritional status. On the other hand, altered epigenetic pathways can lead to musculoskeletal pathologies, such as osteoporosis and age-related sarcopenia or osteoarthritis. Following the first human genome sequencing, accomplished almost twenty years ago, epigenomics play an important role at the forefront of understanding the molecular mechanisms that regulate musculoskeletal pathophysiology in health, disease, and aging. Thus, recently developed experimental advances, such as histone ChIP-seq and WGBS, as well as bioinformatics have become pioneering tools for uncovering the multicellular interactions that drive epigenetic gene regulation events associated with DNA, RNA, and chromatin modifications and the non-coding RNA machinery.

Doubtlessly, the epigenome plays an important role in controlling gene expression and results in MSK disorders when dysregulated. For example, hypermethylation of CpG islands of bone regulators, like SOST and DKK1, are present in postmenopausal osteoporotic women, while m6A modification can serve as a novel epitranscriptomic marker. A plethora of microRNAs (miRs) have also been shown to affect skeletal (osteomiRs) and muscle (myomiRs) tissues. In addition, non-coding RNAs are being revealed as increasingly important in epigenetic regulation of MSK tissues. For instance, lncRNAS can act as sponges of miRs, and circRNAs are confirmed to play important roles in regulating cellular processes and diseases via large and complex networks involving mRNAs, miRNAs, and proteins. However, the detailed epigenetic mapping and how this regulates normal homeostasis, MSK pathogenesis, as well as the interaction with aging has not been described for a number of genes. In this Research Topic we welcome articles that encompass the latest advances and provide a comprehensive update in the field.

This Research Topic welcomes basic, clinical, and translational researchers in the musculoskeletal field regarding the epigenetic basis of gene regulation to submit original research articles, reviews, and hypothesis-driven papers addressing important issues such as, but not limited to:
• New advances in understanding the epigenome (novel modifiers, microRNAs etc.) and how these molecules affect the musculoskeletal tissues in health, disease, and aging
• Use of animal models (rodents, equine etc.) to unravel how epigenetic mechanisms can regulate gene expression and control the (patho)physiology of the musculoskeletal system
• Development of in vitro models to elucidate the epigenetic effect on cellular functions of bone cells, myocytes, chondrocytes, tendinocytes, etc. 
• Genome-wide human or animal studies to detect epigenetic modifications in age-related musculoskeletal disorders and utilization of these changes as biomarkers (e.g. circulating microRNAs, epitranscriptomics)
• Use of bioinformatics to incorporate epigenetic changes in musculoskeletal pathologies and unravel pathogenetic mechanisms by systems biology approaches

Keywords: Histone modifications, DNA methylation, epitranscriptomics, non-coding RNAs, musculoskeletal aging

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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