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Integrated Analysis of DNA Methylation and Gene Expression Profiles in a Rat Model of Osteoarthritis.
Chun, Jin Mi; Kim, Joong-Sun; Kim, Chul.
Afiliação
  • Chun JM; Digital Health Research Division, Korea Institute of Oriental Medicine, Yuseong-daero 1672, Daejeon 34054, Republic of Korea.
  • Kim JS; College of Veterinary Medicine, Chonnam National University, Gwangju 61186, Republic of Korea.
  • Kim C; KM Data Division, Korea Institute of Oriental Medicine, Daejeon 34054, Republic of Korea.
Int J Mol Sci ; 25(1)2024 Jan 02.
Article em En | MEDLINE | ID: mdl-38203768
ABSTRACT
Osteoarthritis (OA) is common and affected by several factors, such as age, weight, sex, and genetics. The pathogenesis of OA remains unclear. Therefore, using a rat model of monosodium iodoacetate (MIA)-induced OA, we examined genomic-wide DNA methylation using methyl-seq and characterized the transcriptome using RNA-seq in the articular cartilage tissue from a negative control (NC) and MIA-induced rats. We identified 170 genes (100 hypomethylated and upregulated genes and 70 hypermethylated and downregulated genes) regulated by DNA methylation in OA. DNA methylation-regulated genes were enriched in functions related to focal adhesion, extracellular matrix (ECM)-receptor interaction and the PI3K-Akt and Hippo signaling pathways. Functions related to extracellular matrix organization, extracellular matrix proteoglycans, and collagen formation were involved in OA. A molecular and protein-protein network was constructed using methylated expression-correlated genes. Erk1/2 was a downstream target of OA-induced changes in DNA methylation and RNA expression. We found that the integrin subunit alpha 2 (ITGA2) gene is important in focal adhesion, alpha6-beta4 integrin signaling, and the inflammatory response pathway in OA. Overall, gene expression changes because DNA methylation influences OA pathogenesis. ITGA2, whose gene expression changes are regulated by DNA methylation during OA onset, is a candidate gene. Our findings provide insights into the epigenetic targets of OA processes in rats.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Osteoartrite / Cartilagem Articular Idioma: En Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Osteoartrite / Cartilagem Articular Idioma: En Ano de publicação: 2024 Tipo de documento: Article