Mesenchyme-specific Knockout of ESET Histone Methyltransferase Causes Ectopic Hypertrophy and Terminal Differentiation of Articular Chondrocytes

Lawson, Kevin A.; Teteak, Colin J.; Zou, Jie; Hacquebord, Jacques; Ghatan, Andrew C.; Zielinska-Kwiatkowska, Anna; Fernandes, Russell J.; Chansky, Howard A.; Yang, Liu

doi:10.1074/jbc.m113.473827

Cited by 19 publications

(16 citation statements)

References 28 publications

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“…In growth plate chondrocytes, ESET associates with HDAC4 to suppress Runx2 activity and hypertrophy; thus, ESET‐deficient chondrocytes undergo accelerated hypertrophy. Interestingly, the authors also saw increased ectopic hypertrophic differentiation of articular chondrocytes (Lawson et al, ; Yang et al, ), a feature of OA as discussed below. A second histone methyltransferase, DOT1L, was recently identified as another potential regulator of chondrocyte differentiation in a genome‐wide association study (GWAS) for hip OA susceptibility loci (Castano Betancourt et al, ; Evangelou et al, ), but detailed studies on the role of this gene in chondrocyte differentiation are required.…”

Section: Regulation Of Chondrocyte Hypertrophymentioning

confidence: 95%

“…In addition to acetylation, many other posttranslational modifications control histone and nucleosome function, but very few of these have been studied in the context of chondrocyte differentiation. Two recent studies have demonstrated a role for the histone methyltransferase ESET in hypertrophy (Lawson et al, ; Yang et al, ). In growth plate chondrocytes, ESET associates with HDAC4 to suppress Runx2 activity and hypertrophy; thus, ESET‐deficient chondrocytes undergo accelerated hypertrophy.…”

Section: Regulation Of Chondrocyte Hypertrophymentioning

confidence: 99%

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Chondrocyte hypertrophy in skeletal development, growth, and disease

Sun

Beier

2014

Birth Defects Research Pt C

119

118

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Most of our bones form through the process of endochondral ossification, which is tightly regulated by the activity of the cartilage growth plate. Chondrocyte maturation through the various stages of growth plate physiology ultimately results in hypertrophy. Chondrocyte hypertrophy is an essential contributor to longitudinal bone growth, but recent data suggest that these cells also play fundamental roles in signaling to other skeletal cells, thus coordinating endochondral ossification. On the other hand, ectopic hypertrophy of articular chondrocytes has been implicated in the pathogenesis of osteoarthritis. Thus, a better understanding of the processes that control chondrocyte hypertrophy in the growth plate as well as in articular cartilage is required for improved management of both skeletal growth disorders and osteoarthritis. This review summarizes recent findings on the regulation of hypertrophic chondrocyte differentiation, the cellular mechanisms involved in hypertrophy, and the role of chondrocyte hypertrophy in skeletal physiology and pathophysiology.

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Section: Regulation Of Chondrocyte Hypertrophymentioning

confidence: 95%

Section: Regulation Of Chondrocyte Hypertrophymentioning

confidence: 99%

Chondrocyte hypertrophy in skeletal development, growth, and disease

Sun

Beier

2014

Birth Defects Research Pt C

119

118

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“…ESET, a H3K9-specific histone methyltransferase also called Set domain protein bifurcated 1 (SETDB1), is transiently upregulated in prehypertrophic chondrocytes in newborn mice. ESET controls hypertrophic differentiation of growth plate chondrocytes and formation of epiphyseal plates (80) , as well as the terminal differentiation of articular chondrocytes (81) . ESET conditional deletion in mesenchymal cells causes acceleration of chondrocyte hypertrophy during embryonic and prenatal development, resulting in a defect in long bone growth and trabecular bone formation.…”

Section: Histone Methylationmentioning

confidence: 99%

Epigenetic dynamic during endochondral ossification and articular cartilage development

Allas¹,

Boumédiene²,

Baugé³

2019

Bone

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Within the last decade epigenetics has emerged as fundamental regulator of numerous cellular processes, including those orchestrating embryonic and fetal development. As such, epigenetic factors play especially crucial roles in endochondral ossification, the process by which bone tissue is created, as well during articular cartilage formation. In this review, we summarize the recent discoveries that characterize how DNA methylation, histone posttranslational modifications and non-coding RNA (e.g., miRNA and lcnRNA) epigenetically regulate endochondral ossification and chondrogenesis.

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“…Herlofsen et al have demonstrated that the methylation level of H3K4me3 and H3K36me3 is largely associated with chondrocyte differentiation of human mesenchymal stem cells, assessed by Chip-Seq analysis [64]. Setdb1 (SET domain, bifurcated1) regulates chondrocyte hypertrophy by inhibiting Runx2 activity through H3K9 methylation [65,66]. However, despite its significance in gene expression pathways, only the role of histone acetylation has been predominantly studied in chondrogenesis, with little attention given to the regulatory mechanism of histone methylation/demethylation during chondrocyte differentiation.…”

Section: Histone Methylationmentioning

confidence: 98%

Epigenetic regulation of chondrocyte differentiation

Hata

2015

Japanese Dental Science Review

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Chondrocytes play an essential role in endochondral bone development, which is requisite for mammalian skeletal development. During endochondral bone development, chondrocytes undergo well-organized stages of sequential differentiation, including proliferation and hypertrophy, a process harmoniously modulated by various transcription factors. Epigenetics, including DNA methylation and histone modification, has recently emerged as an essential regulatory system for gene expression, not only in physiological conditions, but also in human disease. During chondrocyte differentiation, transcriptional co-regulators, which form transcriptional protein complexes with specific transcription factors, are predominantly involved in this epigenetic process and cooperatively regulate chondrocyte gene expression. Importantly, several studies indicate that epigenetic regulators correlate with cartilage-related diseases, such as osteoarthritis, and are noted as a potential therapeutic target. Here, current studies of epigenetic regulation of chondrocyte differentiation are reviewed and novel aspects for the molecular mechanisms involved in chondrogenesis are introduced.

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Mesenchyme-specific Knockout of ESET Histone Methyltransferase Causes Ectopic Hypertrophy and Terminal Differentiation of Articular Chondrocytes

Cited by 19 publications

References 28 publications

Chondrocyte hypertrophy in skeletal development, growth, and disease

Chondrocyte hypertrophy in skeletal development, growth, and disease

Epigenetic dynamic during endochondral ossification and articular cartilage development

Epigenetic regulation of chondrocyte differentiation

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