| Project/Area Number |
07557098
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
Orthopaedic surgery
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| Research Institution | Osaka University |
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Principal Investigator |
OCHI Takahiro Osaka University Medical School, Professor, 医学部, 教授 (80112035)
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| Co-Investigator(Kenkyū-buntansha) |
TOMITA Tetsuya Osaka University Medical School, Assistant Professor, 医学部, 助手 (30283766)
HAYASHIDA Kenji Osaka University Medical School, Assistant Professor, 医学部, 助手 (50273686)
KANEDA Yasufumi Osaka University, Associate Professor, 細胞工学センター, 助教授 (10177537)
大脇 肇 大阪大学, 医学部, 助手 (60223872)
木村 友厚 大阪大学, 医学部, 助手 (80167379)
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| Project Period (FY) |
1995 – 1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥21,200,000 (Direct Cost: ¥21,200,000)
Fiscal Year 1997: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1996: ¥4,700,000 (Direct Cost: ¥4,700,000)
Fiscal Year 1995: ¥14,500,000 (Direct Cost: ¥14,500,000)
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| Keywords | Rheumatoid arthritis / Gene therapy / Sendai virus / Liposome / Joint destruction / Tissue repair / 肝細胞増殖因子 / 転写因子 / おとり型核酸医薬 / 創修復 / Hemagglutinating virus of Japan(HVJ) / NFkB / おとり型核酸医薬(デコイ) / Hemagglutinating virus of Japan (HVJ) / 滑膜細胞 / リポゾーム / 遺伝子導入 / Hemagglutinating virus of Japan / 関節軟骨 / 修復靱帯 / ヒト血小板由来増殖因子 |
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| Research Abstract |
We previously established a transfection method of intra-articular injection using Sendai virus/HVj in vivo. In this study we constructed and transfected genes into an animal arthritis model in vivo as well as into human synovial fibroblasts obtained from patients with rheumatoid arthritis (RA) in vitro, in search of possibility of gene therapy for RA.Furthermore we achieved a novel transfection method into ligaments in animal models and investigated in vivo effect of transfection of a gene relating to wound healing.
I.Anti-inflammatory effect in an arthritis model
We constructed a "decoy" against transcription factor, NFkB which closely associated with production of inflammatory cytokines and expression of adhesion molecules. Its intra-articular transfection in CIA rats showed significant improvement of arthritic grades, paw swelling and arthritis index, and also markedly suppressed histological findings of joint destruction.
Next we constructed plasmid DNA encoding p21 locating downstream of p53, the mutation of which had repeatedly been reported in RA.p21 is also thought to associate with apoptosis. The transfection of the gene into human synovial fibroblasts from RA patients by use of HVJ-liposomes demonstrated apoptosis of the cells as well as marked suppression of cell proliferation in vitro.
2. Ligament healing model
We established a novel method of direct transfection in rat patellar ligaments by intra-arterial delivery of HVJ-liposomes. Moreover we transfected plasmid DNA encoding hepatocyte growth factor (HGF) into healing patellar ligament in rats and observed the expression of collagen type I with parallel alignment of fibers, which resembled normal ligaments.
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