About this Research Topic
Longitudinal bone growth is driven by a process called endochondral ossification, where cartilage scaffold resulted from chondrocyte proliferation and differentiation were constantly remodeled into newly formed bone. Studies from recent years have shown that epigenetic mechanisms play an important role in the regulation of longitudinal bone growth. For example, mutations in DNA methyltransferase DNMT3A causes skeletal overgrowth in Tatton-Brown-Rahman Syndrome, while mutations in histone methyltransferases EZH2 and NSD1 causes two additional overgrowth conditions, Weaver syndrome and Sotos syndrome, respectively. Advances on clinical genetics, next-generation sequencing and genome editing have catalyzed the expansion of our knowledge on histone modifications, chromatin remodeling, non-coding RNAs, and their implications on skeletal development and pathophysiology.
Important questions/challenges relevant to this research topic:
1. What additional epigenetic modifiers (e.g. histone methyltransferases) could play a role on skeletal development?
2. What is the interplay between different epigenetic modifications, and their interplay with genes involving skeletal development and chondrocyte biology?
3. What other novel genetic variants cause growth disorders or overgrowth in humans?
4. What are the molecular mechanisms by which epigenetic modifications causes overgrowth?
5. Could novel therapeutics targeting epigenetic mechanisms be developed to treat growth disorders?
This Research Topic calls for original research articles and reviews regarding the understanding of role of epigenetic regulations on skeletal development and skeletal growth disorders, as listed but not limited to the following:
• in vivo models (e.g. transgenic or knockout mouse models) elucidating the role of epigenetic regulation of skeletal growth and development
• in vitro studies on the molecular mechanisms of epigenetic regulation of chondrocyte functions
• studies on structural biology involved in epigenetic regulation, focusing on its implications on skeletal biology and growth disorders
• clinical studies of novel human mutations or genetic variants affecting epigenetic modifications, preferably with a skeletal and/or growth phenotype
• observational studies of genome-wide epigenetic modifications and/or chromatin structure in humans or animal models in tissues or cell types relevant to skeletal biology
• review article on the recent advances on the role of epigenetic regulations on skeletal growth and/or growth disorders
Keywords: Growth plate, chondrocytes, histone, growth disorders, stature
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