論文

査読有り 国際誌
2019年

Genome-wide analysis of DNA methylation profile identifies differentially methylated loci associated with human intervertebral disc degeneration.

PloS one
  • Akihiro Ikuno
  • ,
  • Koji Akeda
  • ,
  • Shin-Ichiro Takebayashi
  • ,
  • Motomu Shimaoka
  • ,
  • Katsuzumi Okumura
  • ,
  • Akihiro Sudo

14
9
開始ページ
e0222188
終了ページ
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1371/journal.pone.0222188

BACKGROUND: Environmental and endogenous factors under genetic predisposition are considered to initiate the human intervertebral disc (IVD) degeneration. DNA methylation is an essential mechanism to ensure cell-specific gene expression for normal development and tissue stability. Aberrant epigenetic alterations play a pivotal role in several diseases, including osteoarthritis. However, epigenetic alternations, including DNA methylation, in IVD degeneration have not been evaluated. The purpose of this study was to comprehensively compare the genome-wide DNA methylation profiles of human IVD tissues, specifically nucleus pulpous (NP) tissues, with early and advanced stages of disc degeneration. METHODS: Human NP tissues were used in this study. The samples were divided into two groups: early stage degeneration (n = 8, Pfirrmann's MRI grade: I-III) and advanced stage degeneration (n = 8, grade: IV). Genomic DNA was processed for genome-wide DNA methylation profiling using the Infinium MethylationEPIC BeadChip array. Extraction of raw methylation data, clustering and scatter plot of each group values of each sample were performed using a methylation module in GenomeStudio software. The identification of differentially methylated loci (DMLs) and the Gene Ontology (GO) analysis were performed using R software with the ChAMP package. RESULTS: Unsupervised hierarchical clustering revealed that early and advanced stage degenerated IVD samples segregated into two main clusters by their DNA methylome. A total of 220 DMLs were identified between early and advanced disc degeneration stages. Among these, four loci were hypomethylated and 216 loci were hypermethylated in the advanced disc degeneration stage. The GO enrichment analysis of genes containing DMLs identified two significant GO terms for biological processes, hemophilic cell adhesion and cell-cell adhesion. CONCLUSIONS: We conducted a genome-wide DNA methylation profile comparative study and observed significant differences in DNA methylation profiles between early and advanced stages of human IVD degeneration. These results implicate DNA methylation in the process of human IVD degeneration.

リンク情報
DOI
https://doi.org/10.1371/journal.pone.0222188
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/31513634
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6742346
ID情報
  • DOI : 10.1371/journal.pone.0222188
  • PubMed ID : 31513634
  • PubMed Central 記事ID : PMC6742346

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