Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, 1- 8-1 Inohana, Chuo-ku, Chiba City, Chiba, 260-8677, Japan.
Department of Bioenvironmental Medicine, Graduate School of Medicine, Chiba University, 1- 8-1 Inohana, Chuo-ku, Chiba City, Chiba, 260-8677, Japan.
J Orthop Surg Res. 2024 Jun 16;19(1):357. doi: 10.1186/s13018-024-04847-0.
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.
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.
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.
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.
本研究旨在验证 DNA 甲基化相关酶和外周血单个核细胞 (PBMC) 及关节滑膜组织中整体甲基化在动物髋关节骨关节炎 (OA) 模型中的变化。
动物被分为对照组（无治疗）、假手术组（25 μL 无菌生理盐水）和 OA 组（25 μL 无菌生理盐水和 2mg 单碘乙酸）。诱导后进行微计算机断层扫描、组织病理学评估和痛阈测量。评估 PBMC 和髋关节滑膜组织中 DNA 甲基化机制基因的 mRNA 表达和整体 DNA 甲基化水平。
OA 组在髋关节组织学和影像学上表现为骨关节炎，痛阈降低。OA 组滑膜组织中 DNA 甲基转移酶 (Dnmt3a)、十 - 十一易位酶 1 (Tet1) 和 Tet3 的 mRNA 表达明显上调。OA 组滑膜组织中的整体 DNA 甲基化水平明显高于对照组和假手术组。
关节内注射单碘乙酸可诱导髋关节 OA 并降低痛阈。髋关节 OA 滑膜组织中的 DNA 甲基化机制发生改变。
