Journal of Orthopaedic Surgery and Research (Jun 2024)

Alterations in DNA methylation machinery in a rat model of osteoarthritis of the hip

  • Yuya Kawarai,
  • Junichi Nakamura,
  • Shigeo Hagiwara,
  • Miyako Suzuki-Narita,
  • Kazuhide Inage,
  • Seiji Ohtori

DOI
https://doi.org/10.1186/s13018-024-04847-0
Journal volume & issue
Vol. 19, no. 1
pp. 1 – 12

Abstract

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Abstract Background This study aimed to validate alterations in the gene expression of DNA methylation-related enzymes and global methylation in the peripheral blood mononuclear cell (PBMC) and synovial tissues of animal hip osteoarthritis (OA) models. Methods Animals were assigned to the control (no treatment), sham (25 µL of sterile saline), and OA (25 µL of sterile saline and 2 mg of monoiodoacetate) groups. Microcomputed tomography scan, histopathological assessment and pain threshold measurement were performed after induction. The mRNA expression of the DNA methylation machinery genes and global DNA methylation in the PBMC and hip synovial tissue were evaluated. Results The OA group presented with hip joint OA histopathologically and radiologically and decreased pain threshold. The mRNA expression of DNA methyltransferase (Dnmt 3a), ten–eleven translocation (Tet) 1 and Tet 3 in the synovial tissue of the OA group was significantly upregulated. Global DNA methylation in the synovial tissue of the OA group was significantly higher than that of the control and sham groups. Conclusions The intra-articular administration of monoiodoacetate induced hip joint OA and decreased pain threshold. The DNA methylation machinery in the synovial tissues of hip OA was altered.

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