Runt-Related Transcription Factor 2 Induction During Differentiation of Wharton’s Jelly Mesenchymal Stem Cells to Osteoblasts Is Regulated by Jumonji AT-Rich Interactive Domain 1B Histone Demethylase

Bustos, Francisco; Sepúlveda, Hugo; Prieto, Catalina P.; Carrasco, Margarita E.; Díaz, Leonor; Palma, José Luis; Lattus, José; Montecino, Martín; Palma, Verónica

doi:10.1002/stem.2704

Cited by 22 publications

(22 citation statements)

References 68 publications

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“…Maintenance of chromatin with low H3K4me3 enrichment (and hence elevated H3K4me1) at the Runx2 promoter can be also achieved by binding and activity of the H3K4 demethylase Jarid1b/Kdm5b (Figure 1; Rojas et al, 2015Rojas et al, , 2019Bustos et al, 2017;Sepulveda et al, 2017a), which converts H3K4me3 to H3K4me1 (Christensen et al, 2007;Iwase et al, 2007;Yamane et al, 2007). Targeted depletion of Jarid1b/Kdm5b in mice results in elevated lethality at early post-natal stages, exhibiting these animals cranial dysmorphic parameters and skeletal alterations (Albert et al, 2013).…”

Section: Methylation At Histone H3k4 and H3k27 Residuesmentioning

confidence: 99%

Epigenetic Control of Osteogenic Lineage Commitment

Montecino

Carrasco

Nardocci

2021

Front. Cell Dev. Biol.

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Within the eukaryotic nucleus the genomic DNA is organized into chromatin by stably interacting with the histone proteins as well as with several other nuclear components including non-histone proteins and non-coding RNAs. Together these interactions distribute the genetic material into chromatin subdomains which can exhibit higher and lower compaction levels. This organization contributes to differentially control the access to genomic sequences encoding key regulatory genetic information. In this context, epigenetic mechanisms play a critical role in the regulation of gene expression as they modify the degree of chromatin compaction to facilitate both activation and repression of transcription. Among the most studied epigenetic mechanisms we find the methylation of DNA, ATP-dependent chromatin remodeling, and enzyme-mediated deposition and elimination of post-translational modifications at histone and non-histone proteins. In this mini review, we discuss evidence that supports the role of these epigenetic mechanisms during transcriptional control of osteoblast-related genes. Special attention is dedicated to mechanisms of epigenetic control operating at the Runx2 and Sp7 genes coding for the two principal master regulators of the osteogenic lineage during mesenchymal stem cell commitment.

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Section: Methylation At Histone H3k4 and H3k27 Residuesmentioning

confidence: 99%

Epigenetic Control of Osteogenic Lineage Commitment

Montecino

Carrasco

Nardocci

2021

Front. Cell Dev. Biol.

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“…Current study by Bustos and colleagues have demonstrated that JARID1B (Jumonji AT-rich interactive domain 1B) histone demethylase represses Runx2 in undifferentiated WJ-MSCs. In JARID1B knockdown murine, it can be seen that Runx2 is highly expressed and ready for osteogenic commitment indicating that this molecular mechanism is relevant to modulating osteoblastic lineage commitment [ 63 ].…”

Section: Introductionmentioning

confidence: 99%

Osteogenic Induction of Wharton’s Jelly-Derived Mesenchymal Stem Cell for Bone Regeneration: A Systematic Review

Ansari

Yazid

Sainik

et al. 2018

Stem Cells International

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Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) are emerging as a promising source for bone regeneration in the treatment of bone defects. Previous studies have reported the ability of WJ-MSCs to be induced into the osteogenic lineage. The purpose of this review was to systematically assess the potential of WJ-MSC differentiation into the osteogenic lineage. A comprehensive search was conducted in Medline via Ebscohost and Scopus, where relevant studies published between 1961 and 2018 were selected. The main inclusion criteria were that articles must be primary studies published in English evaluating osteogenic induction of WJ-MSCs. The literature search identified 92 related articles, but only 18 articles met the inclusion criteria. These include two animal studies, three articles containing both in vitro and in vivo assessments, and 13 articles on in vitro studies, all of which are discussed in this review. There were two types of osteogenic induction used in these studies, either chemical or physical. The studies demonstrate that WJ-MSCs are able to differentiate into osteogenic lineage and promote osteogenesis. In light of these observations, it is suggested that WJ-MSCs can be a potential source of stem cells for osteogenic induction, as an alternative to bone marrow-derived mesenchymal stem cells.

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“…Among the multiple factors that are known to affect epigenetic state, histone modifications have been identified as a process that is vital to the fate decision of MSCs [7][8][9]. Histone modifications affect gene expression via changes in the configuration of chromatin.…”

Section: Introductionmentioning

confidence: 99%

Epigenetic Control of Mesenchymal Stem Cell Fate Decision via Histone Methyltransferase Ash1l

Yin

Wang

et al. 2018

Stem Cells

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Previous research indicates that knocking out absent, small, or homeotic-like (Ash1l) in mice, a histone 3 lysine 4 (H3K4) trimethyltransferase, can result in arthritis with more severe cartilage and bone destruction. Research has documented the essential role of Ash1l in stem cell fate decision such as hematopoietic stem cells and the progenitors of keratinocytes. Following up on those insights, our research seeks to document the function of Ash1l in skeletal formation, specifically whether it controls the fate decision of mesenchymal progenitor cells. Our findings indicate that in osteoporotic bones, Ash1l was significantly decreased, indicating a positive correlation between bone mass and the expression of Ash1l. Silencing of Ash1l that had been markedly upregulated in differentiated C3H10T1/2 (C3) cells hampered osteogenesis and chondrogenesis but promoted adipogenesis. Consistently, overexpression of an Ash1l SET domain-containing fragment 3 rather than Ash1lΔN promoted osteogenic and chondrogenic differentiation of C3 cells and simultaneously inhibited adipogenic differentiation. This indicates that the role of Ash1l in regulating the differentiation of C3 cells is linked to its histone methyltransferase activity. Subcutaneous ex vivo transplantation experiments confirmed the role of Ash1l in the promotion of osteogenesis. Further experiments proved that Ash1l can epigenetically affect the expression of essential osteogenic and chondrogenic transcription factors. It exerts this impact via modifications in the enrichment of H3K4me3 on their promoter regions. Considering the promotional action of Ash1l on bone, it could potentially prompt new therapeutic strategy to promote osteogenesis. STEM CELLS 2019; 37:115-127 SIGNIFICANCE STATEMENTThe authors' research first discovered that Ash1l can epigenetically affect the expression of essential osteogenic and chondrogenic transcription factors via modifications in the enrichment of H3K4me3 on their promoter regions. These findings helped to further understand the role of Ash1l in the epigenetic regulation of C3H10T1/2 MSCs differentiation, which also makes it potential therapeutic target of bone diseases. Considering the promotional action of Ash1l on bone, it could potentially prompt new therapeutic strategy to promote osteogenesis.

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Runt-Related Transcription Factor 2 Induction During Differentiation of Wharton’s Jelly Mesenchymal Stem Cells to Osteoblasts Is Regulated by Jumonji AT-Rich Interactive Domain 1B Histone Demethylase

Cited by 22 publications

References 68 publications

Epigenetic Control of Osteogenic Lineage Commitment

Epigenetic Control of Osteogenic Lineage Commitment

Osteogenic Induction of Wharton’s Jelly-Derived Mesenchymal Stem Cell for Bone Regeneration: A Systematic Review

Epigenetic Control of Mesenchymal Stem Cell Fate Decision via Histone Methyltransferase Ash1l

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