Histone H3K27 demethylase, Utx, regulates osteoblast-to-osteocyte differentiation

Xia, Yuhan; Ikedo, Aoi; Lee, Jiwon; Iimura, Tadahiro; Inoue, Kenzo; Imai, Yuuki

doi:10.1016/j.bbrc.2021.12.102

Cited by 7 publications

(3 citation statements)

References 34 publications

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“…In postmenopausal women, increased SOST promoter methylation resulted in lower serum SOST level and stimulated bone formation by inhibition of Wnt signaling activity ( 13 ). During the OCY differentiation process, H3K27me3 in the loci of osteocyte-expressing genes decreased and H3K27me3 demethylase was attached to those genes ( 14 ). Osteocytogenesis is also accompanied by increased expression of dentin matrix protein 1 (DMP1), matrix metalloproteinases (MMPs), and fibroblast growth factor 23 (FGF23), which is critical for OCY maturation, dendritic formation, and elongation together with phosphate metabolism ( 15 , 16 ).…”

Section: Ocy In Physiologic Conditionsmentioning

confidence: 99%

Novel insights into osteocyte and inter-organ/tissue crosstalk

Zhang,

Chen

2024

Front. Endocrinol.

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Osteocyte, a cell type living within the mineralized bone matrix and connected to each other by means of numerous dendrites, appears to play a major role in body homeostasis. Benefiting from the maturation of osteocyte extraction and culture technique, many cross-sectional studies have been conducted as a subject of intense research in recent years, illustrating the osteocyte–organ/tissue communication not only mechanically but also biochemically. The present review comprehensively evaluates the new research work on the possible crosstalk between osteocyte and closely situated or remote vital organs/tissues. We aim to bring together recent key advances and discuss the mutual effect of osteocyte and brain, kidney, vascular calcification, muscle, liver, adipose tissue, and tumor metastasis and elucidate the therapeutic potential of osteocyte.

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Section: Ocy In Physiologic Conditionsmentioning

confidence: 99%

Novel insights into osteocyte and inter-organ/tissue crosstalk

Zhang,

Chen

2024

Front. Endocrinol.

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“…KMT2D NCC deletion also impaired expression of extracellular matrix components within osteoblasts of the developing palatal shelf (Shpargel et al, 2020 ). KDM6A deletion downstream of osteoblast specification produced a loss of skeletal bone volume and mineralization that resulted from alterations in osteocyte differentiation from osteoblasts (Xia et al, 2022 ). Collectively, these studies highlight the importance of Kabuki‐causative histone modifiers in multiple stages of osteoblast differentiation.…”

Section: Mouse Neural Crest‐specific Mutation Of Kmt2d ...mentioning

confidence: 99%

SETting up the genome: KMT2D and KDM6A genomic function in the Kabuki syndrome craniofacial developmental disorder

Shpargel,

Quickstad

2023

Birth Defects Research

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BackgroundKabuki syndrome is a congenital developmental disorder that is characterized by distinctive facial gestalt and skeletal abnormalities. Although rare, the disorder shares clinical features with several related craniofacial syndromes that manifest from mutations in chromatin‐modifying enzymes. Collectively, these clinical studies underscore the crucial, concerted functions of chromatin factors in shaping developmental genome structure and driving cellular transcriptional states. Kabuki syndrome predominantly results from mutations in KMT2D, a histone H3 lysine 4 methylase, or KDM6A, a histone H3 lysine 27 demethylase.AimsIn this review, we summarize the research efforts to model Kabuki syndrome in vivo to understand the cellular and molecular mechanisms that lead to the craniofacial and skeletal pathogenesis that defines the disorder.DiscussionAs several studies have indicated the importance of KMT2D and KDM6A function through catalytic‐independent mechanisms, we highlight noncanonical roles for these enzymes as recruitment centers for alternative chromatin and transcriptional machinery.

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“…Transition of osteoblasts-to-osteocytes results in progressive changes in cell morphology from a cuboidal to a stellate shape, a process that requires coordinated regulation and interplay between transcriptional and epigenetic mechanisms, such as histone modifications (e.g., H3K27 trimethylation). Using an integrative genome-wide transcriptomic (RNA-seq) and epigenomic (ChIP-seq) approach, Xia et al [ 48 •] recently profiled the expression of genes and epigenetic modifications during osteoblast-to-osteocyte differentiation of IDG-SW3 cells. Transcriptomics analyses identified 1239 osteocyte signature genes, 318 (including Sost, DMp1, Mepe, and Dkk1) of which were upregulated during osteocyte differentiation.…”

Section: An Introduction To Bone Omicsmentioning

confidence: 99%

Bone Trans-omics: Integrating Omics to Unveil Mechanistic Molecular Networks Regulating Bone Biology and Disease

Mullin

Ribet

Pavlos

2023

Curr Osteoporos Rep

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Purpose of Review Recent advancements in “omics” technologies and bioinformatics have afforded researchers new tools to study bone biology in an unbiased and holistic way. The purpose of this review is to highlight recent studies integrating multi-omics data gathered from multiple molecular layers (i.e.; trans-omics) to reveal new molecular mechanisms that regulate bone biology and underpin skeletal diseases. Recent Findings Bone biologists have traditionally relied on single-omics technologies (genomics, transcriptomics, proteomics, and metabolomics) to profile measureable differences (both qualitative and quantitative) of individual molecular layers for biological discovery and to investigate mechanisms of disease. Recently, literature has grown on the implementation of integrative multi-omics to study bone biology, which combines computational and informatics support to connect multiple layers of data derived from individual “omic” platforms. This emerging discipline termed “trans-omics” has enabled bone biologists to identify and construct detailed molecular networks, unveiling new pathways and unexpected interactions that have advanced our mechanistic understanding of bone biology and disease. Summary While the era of trans-omics is poised to revolutionize our capacity to answer more complex and diverse questions pertinent to bone pathobiology, it also brings new challenges that are inherent when trying to connect “Big Data” sets. A concerted effort between bone biologists and interdisciplinary scientists will undoubtedly be needed to extract physiologically and clinically meaningful data from bone trans-omics in order to advance its implementation in the field.

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Histone H3K27 demethylase, Utx, regulates osteoblast-to-osteocyte differentiation

Cited by 7 publications

References 34 publications

Novel insights into osteocyte and inter-organ/tissue crosstalk

Novel insights into osteocyte and inter-organ/tissue crosstalk

SETting up the genome: KMT2D and KDM6A genomic function in the Kabuki syndrome craniofacial developmental disorder

Bone Trans-omics: Integrating Omics to Unveil Mechanistic Molecular Networks Regulating Bone Biology and Disease

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