Inhibition of experimental arthritis in mice by small interfering RNA targeting histone deacetylase 1 (siHDAC1) using in vivo electroporation method

使用体内电穿孔方法通过靶向组蛋白脱乙酰酶 1 (siHDAC1) 的小干扰 RNA 抑制小鼠实验性关节炎

• 批准号: 23592215
• 负责人: NISHIDA Keiichiro
• 金额: $ 2.25万
• 依托单位: Okayama University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23592215/
• 关键词: 関節リウマチ; ヒストン脱アセチル化酵素; 遺伝子導入; エレクトロポレーション; 抗コラーゲン抗体誘導関節炎; Lipofection法; エピジェネティクス; 関節炎; lipofecton法; ヒストン脱アセチル化酵素阻害剤; HDAC1; コラーゲン抗体誘導関節炎; siRNA; electroporation

We examined the therapeutic effects of siRNA targeting histone deacetylase 1 (siHDAC1) using in vivo electroporation method. Intraarticular injection of siHDAC did not affected redness or paw swelling of anti-collagen antibody-induced arthritiis in mice. However, synovial proliferation, bone erosion, and degeneration of articular cartilage were milder in the knee joints treated with siHDAC1 than in the control group and the non-specific siRNA group. TUNEL stain revealed increased number of positive cells in the synovial tissue of siHADC group. Decreased HDAC1 expression was noted in the synovial fibroblasts isolated from arthritic knee joints treated by siHDAC, but no significant difference was shown by RT-PCR in IL-6, TNF, and MMP-3 mRNA expression with those from control and non-specific siRNA group. Our results suggested therapeutic effects of intraarticular siHDAC1 with electroporation was derived by its anti-proliferative property by induction of synovial cell apoptosis.

我们使用体内电穿孔方法检测了靶向组蛋白去乙酰化酶1（siHDAC 1）的siRNA的治疗效果。关节内注射siHDAC不影响小鼠中抗胶原抗体诱导的关节炎的发红或爪肿胀。然而，用siHDAC 1治疗的膝关节的滑膜增生、骨侵蚀和关节软骨退行性变比对照组和非特异性SiRNA组轻。TUNEL染色显示siHADC组滑膜组织中阳性细胞数量增加。siHDAC处理组滑膜成纤维细胞HDAC 1表达明显降低，而IL-6、TNF和MMP-3 mRNA表达与对照组和非特异性siRNA组相比无显著性差异。我们的研究结果表明，关节内siHDAC 1与电穿孔的治疗效果是通过诱导滑膜细胞凋亡的抗增殖特性。

项目成果

関節炎モデルマウスに対するヒストン脱アセチル化酵素1(Hdac1) siRNAの治療効果の検討

组蛋白脱乙酰酶1 (Hdac1) siRNA对关节炎模型小鼠的治疗效果研究

• 发表时间: 2012
• 作者: 金澤智子;他
• 通讯作者: 他