Epigenetic regulation of chondrocyte differentiation

Hata, Kenji

doi:10.1016/j.jdsr.2015.05.001

Cited by 9 publications

(13 citation statements)

References 95 publications

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“…On the other hand, CRET stimulation might also influence epigenetic mechanisms that regulate gene expression during chondrogenic differentiation. Such mechanisms include, among others, methylation of cartilage-specific promoter genes, or acetylation, methylation, phosphorylation and SUMOylation of histones, which depending on the case, are able of promoting or repressing the transcriptional activation of chondrogenic genes such as SOX9 (see [49] for a review). In fact, in contrast to the observations in this paper, ERK1/2 signaling pathway has shown able to facilitate chondrogenic differentiation in the dental pulp stem cells (DPSCs) [50], what indicates that MAPK pathway activation might play distinct roles in the differentiation of stem cells from different lineages.…”

Section: Discussionmentioning

confidence: 99%

Chondrogenic Differentiation of Adipose-Derived Stem Cells by Radiofrequency Electric Stimulation

Hernández-Bule¹,

Trillo²,

Martínez‐García³

et al. 2017

J Stem Cell Res Ther

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Objective: Although capacitive-resistive electric transfer (CRET) therapies, based on transdermal application of electrothermal radiofrequency currents, have shown promising therapeutic effectiveness in regeneration of traumatic or degenerative tissue lesions, their potential effects on tissues like cartilage, having poor regenerative capabilities, have not been studied sufficiently. Here we investigate the effects of the exposure to a 448 kHz current typically used in CRET therapy, on the early chondrogenic differentiation of human, adipose-derived stem cells (ADSC). Materials and methods: Stem cells obtained from healthy donors were differentiated in chondrogenic medium for 16 days. During the last 2 days of incubation the cultures were intermittently exposed or sham-exposed to a 448-kHz, sine wave current, administered at a 50 µA/mm 2 subthermal density. The cellular response was assessed by: XTT proliferation assay, glycosaminoglycans (GAG) and collagen quantification (image analysis, Blyscan assay and immunoblot) and analysis of the expression of chondrogenic factors Sox5 and Sox6, and of the transcription factor ERK1/2 and its active form p-ERK1/2 (immunoflorescence, immunoblot and RT-PCR). Results: The electric stimulus significantly increased the levels of both, cartilage-specific collagen type II and GAG in the extracellular matrix of the differentiating cultures. Although no changes were observed in the expression of the SOX genes at the end of the 48-hour treatment, the stimulus did induce significant overexpression of transcription factors L-Sox5, Sox6 and p-ERK1/2. Since these proteins are crucial regulators of the synthesis of the extracellular matrix during chondrogenic differentiation, it is likely that their overexpression is involved in the observed increases in the content of extracellular collagen and GAG. Conclusion: The present data set provides support to the hypothesis that the electric component of the electrothermal treatment applied in CRET therapies could stimulate cartilage repair by promoting chondrogenic differentiation. These data, coupled with previously reported results that in vitro treatment with the same type of subthermal electric signal promotes proliferation of undifferentiated ADSC, identify molecular phenomena underlying the potential repairing and regenerative effects of such radiofrequency currents.

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Section: Discussionmentioning

confidence: 99%

Chondrogenic Differentiation of Adipose-Derived Stem Cells by Radiofrequency Electric Stimulation

Hernández-Bule¹,

Trillo²,

Martínez‐García³

et al. 2017

J Stem Cell Res Ther

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“…Effects of 5-azaC on cell proliferation (b) and cell viability (mitochondrial activity) (c) in primary murine high density cultures. Cell viability was determined by using MTT assay and cell proliferation was examined by 3 H-thymidine incorporation assay on day 4 or day 6, following treatment with 5-azaC. Statistically significant differences between proliferation rate and mitochondrial activity of cells in cultures that received the inhibitor versus vehicle control cultures are marked by asterisks (*P < 0.05, **P < 0.01, ***P < 0.001).…”

Section: Ecm Morphology Cell Proliferation and Cell Viability Of Earmentioning

confidence: 99%

“…The accessibility of a specific DNA segment for transcription factors is influenced by different epigenetic marks such as DNA methylation or histone modifications. miRNA interactions are recently discovered epigenetic factors that may alter the transcriptional regulation of mRNA [3]. DNA methylation, the most widely studied epigenetic modulation, causes gene repression or silencing by adding a methyl group from the ubiquitous methyl donor S-adenosyl methionine to the carbon 5 position of cytosine rings of the DNA.…”

Section: Introductionmentioning

confidence: 99%

Modulation of DNA Methylation Influences Cartilage Formation in Murine Chondrogenic Models

Vágó¹,

Kiss²,

Karanyicz³

et al. 2021

Preprint

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The aim of this study was to investigate the role of DNA methylation in the regulation of in vitro and in vivo cartilage formation. Based on the data of an RNA chip-assay performed on chondrifying BMP2-overexpressing C3H10T1/2 cells, the relative expression of Tet1 (tet methylcytosine dioxygenase 1), Dnmt3a (DNA methyltransferase 3) and Ogt (O-linked N-acetylglucosamine transferase) genes was examined with RT-qPCR in mouse cell-line based and primary micromass cultures. RNA probes for in situ hybridization were used on frozen sections of 15-day-old mouse embryos. DNA methylation was inhibited with 5-azacytidine during culturing. We found very strong but gradually decreasing expression of Tet1 throughout the entire course of in vitro cartilage differentiation along with strong signals in the cartilaginous embryonic skeleton. Dnmt3a and Ogt expressions did not show significant changes with RT-qPCR and gave weak in situ hybridization signals. Inhibition of DNA methylation applied during early stages of differentiation reduced cartilage-specific gene expression and cartilage formation. In contrast, it had stimulatory effect when added to differentiated chondrocytes. Our results indicate that the DNA demethylation-inducing Tet1 is a significant epigenetic factor of chondrogenesis, and inhibition of DNA methylation exerts distinct effects in different phases of in vitro cartilage formation.

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“…For example, several studies have shown that the expression of miR-145 is blunted during chondrocyte differentiation of mouse mesenchymal cells [55,56]. This finding is recapitulated when miR-145 is inhibited, which triggers chondrocyte differentiation [57]. Conversely, overexpression of this miRNA attenuates chondrocyte differentiation by reducing the expression of various chondrocyte proteins such as COL2A1 and ACAN.…”

Section: Mirnas Contribute To Chondrocyte Differentiationmentioning

confidence: 99%

Non-Coding RNAs in Cartilage Development: An Updated Review

Razmara

Bitaraf

Yousefi

et al. 2019

IJMS

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In the development of the skeleton, the long bones are arising from the process of endochondral ossification (EO) in which cartilage is replaced by bone. This complex process is regulated by various factors including genetic, epigenetic, and environmental elements. It is recognized that DNA methylation, higher-order chromatin structure, and post-translational modifications of histones regulate the EO. With emerging understanding, non-coding RNAs (ncRNAs) have been identified as another mode of EO regulation, which is consist of microRNAs (miRNAs or miRs) and long non-coding RNAs (lncRNAs). There is expanding experimental evidence to unlock the role of ncRNAs in the differentiation of cartilage cells, as well as the pathogenesis of several skeletal disorders including osteoarthritis. Cutting-edge technologies such as epigenome-wide association studies have been employed to reveal disease-specific patterns regarding ncRNAs. This opens a new avenue of our understanding of skeletal cell biology, and may also identify potential epigenetic-based biomarkers. In this review, we provide an updated overview of recent advances in the role of ncRNAs especially focus on miRNA and lncRNA in the development of bone from cartilage, as well as their roles in skeletal pathophysiology.

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Epigenetic regulation of chondrocyte differentiation

Cited by 9 publications

References 95 publications

Chondrogenic Differentiation of Adipose-Derived Stem Cells by Radiofrequency Electric Stimulation

Chondrogenic Differentiation of Adipose-Derived Stem Cells by Radiofrequency Electric Stimulation

Modulation of DNA Methylation Influences Cartilage Formation in Murine Chondrogenic Models

Non-Coding RNAs in Cartilage Development: An Updated Review

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