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Research in veterinary science2025; 193; 105800; doi: 10.1016/j.rvsc.2025.105800

Epigenetic signatures in in vitro-expanded equine chondrocytes induced by a histone deacetylase inhibitor.

Abstract: We have explored the impact of DNA methylation changes on gene transcription in expanded equine chondrocytes treated with the histone deacetylase inhibitor (HDACi), Trichostatin A (TSA). The subjects were DNA and RNA samples prepared from articular cartilage cells derived from four animals in our previous study. Using Reduced Representation Bisulfite Sequencing (RRBS), we determined differentially methylated sites (DMS) and regions (DMRs) in the genomes of TSA-treated cells. We linked them to gene differential expression, as obtained from 3' mRNA sequencing data and the single-locus quantification results of mRNA abundance (Real-time PCR) for the four chondrocyte cell lines. We have identified a set of genes exhibiting a negative correlation between methylation and gene expression, which are involved in cartilage development, cell proliferation, and chromatin organization. While TSA was found to hypermethylate and downregulate genes crucial for chondrocyte function, it also hypomethylated and upregulated genes involved in cartilage and bone formation. The findings highlight the TSA's selective activity in modifying epigenetic marks, suggesting its potential as well as limitations in promoting chondrocyte differentiation and regeneration, which is notably relevant for regenerative medicine applications in treating cartilage damage.
Publication Date: 2025-07-08 PubMed ID: 40645097DOI: 10.1016/j.rvsc.2025.105800Google Scholar: Lookup
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  • Journal Article

Summary

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The research article discusses how a histone deacetylase inhibitor called Trichostatin A (TSA) affects the DNA methylation and as a result gene expression in equine chondrocytes, with implications for cartilage development and regeneration.

Methodology and Subjects

  • The researchers used DNA and RNA samples taken from articular cartilage cells derived from four different animals. These samples were used to study the effect of TSA on their genomes.
  • The process they used to determine the effects involves a technique called Reduced Representation Bisulfite Sequencing (RRBS), through which they were able to identify differentially methylated sites (DMS) and regions (DMRs) in the genomes of cells treated with TSA.

Findings and their Significance

  • The researchers found that TSA induced changes to the methylation of certain genes, altering their expression. Notably, they found a negative correlation between methylation and gene expression in a set of genes associated with cartilage development, cell proliferation and chromatin organization. This suggests that TSA has a specific, selective effect on these genes.
  • On one hand, TSA was found to increase methylation (hypermethylate) and decrease the expression (downregulate) of certain genes important for chondrocyte function. This could potentially inhibit the functionality of these cartilage cells. On the other hand, TSA also decreased methylation (hypomethylated) and increased the expression (upregulated) of certain genes involved in the formation of cartilage and bone, suggesting a potential regenerative effect.
  • The authors conclude that these effects highlight TSA’s selective impact on modifying epigenetic marks and its potential role in promoting chondrocyte differentiation and regeneration. However, the concomitant downregulation of some genes crucial for chondrocyte function may pose limitations to its efficacy.
  • The results of this research could have implications for regenerative medicine, particularly in developing treatments for cartilage damage.

Cite This Article

APA
Ząbek T, Witarski W, Szmatoła T, Semik-Gurgul E, Sawicki S, Ropka-Molik K. (2025). Epigenetic signatures in in vitro-expanded equine chondrocytes induced by a histone deacetylase inhibitor. Res Vet Sci, 193, 105800. https://doi.org/10.1016/j.rvsc.2025.105800

Publication

ISSN: 1532-2661
NlmUniqueID: 0401300
Country: England
Language: English
Volume: 193
Pages: 105800
PII: S0034-5288(25)00274-7

Researcher Affiliations

Ząbek, Tomasz
  • Department of Animal Molecular Biology, National Research Institute of Animal Production, Poland. Electronic address: tomasz.zabek@iz.edu.pl.
Witarski, Wojciech
  • Department of Animal Molecular Biology, National Research Institute of Animal Production, Poland.
Szmatoła, Tomasz
  • Department of Animal Molecular Biology, National Research Institute of Animal Production, Poland; Centre of Experimental and Innovative Medicine, University of Agriculture in Kraków, Poland.
Semik-Gurgul, Ewelina
  • Department of Animal Molecular Biology, National Research Institute of Animal Production, Poland.
Sawicki, Sebastian
  • Centre of Experimental and Innovative Medicine, University of Agriculture in Kraków, Poland.
Ropka-Molik, Katarzyna
  • Department of Animal Molecular Biology, National Research Institute of Animal Production, Poland.

MeSH Terms

  • Animals
  • Chondrocytes / drug effects
  • Chondrocytes / metabolism
  • Histone Deacetylase Inhibitors / pharmacology
  • Horses / genetics
  • Hydroxamic Acids / pharmacology
  • Epigenesis, Genetic / drug effects
  • DNA Methylation / drug effects

Conflict of Interest Statement

Declaration of competing interest We notify that there's no financial/personal interest or belief that could affect our objectivity. We disclose any actual or potential conflict of interest including any financial, personal or other relationships with other people or organizations within three years of beginning the submitted work that could inappropriately influence, or be perceived to influence, their work.

Citations

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