Inhibition of experimental arthritis in mice by small interfering RNA targeting histone deacetylase 1 (siHDAC1) using in vivo electroporation method
| Project/Area Number |
23592215
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Orthopaedic surgery
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| Research Institution | Okayama University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
OOHASHI Toshitaka 岡山大学, 大学院医歯薬学総合研究科, 准教授 (50194262)
KAWABATA Tomoko 岡山大学, 大学院医歯薬学総合研究科, 助教 (90600669)
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| Project Period (FY) |
2011 – 2013
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2013: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000)
Fiscal Year 2012: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | 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 |
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| Research Abstract |
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.
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Report
(4 results)
Research Products
(2 results)
