| Project/Area Number |
15592099
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Surgical dentistry
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| Research Institution | The University of Tokyo |
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Principal Investigator |
HIKIJI Hisako The University of Tokyo, Faculty of medicine, Lecturer, 医学部附属病院, 講師 (50292876)
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| Co-Investigator(Kenkyū-buntansha) |
TAKATO Tuyoshi The University of Tokyo, Faculty of medicine, Professor, 医学部附属病院, 教授 (90171454)
MIZUKAMI Hiroaki Jichi Medical School, Faculty of medicine, Lecturer, 医学部, 講師 (20311938)
小泉 敏之 東京大学, 医学部附属病院, 助手 (80323575)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2004: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2003: ¥2,500,000 (Direct Cost: ¥2,500,000)
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| Keywords | iNOS / antisense / gene targeting / gene therapy / bone destruction |
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| Research Abstract |
Nitric oxide, a highly reactive free radical, is involved in the inflammation of bone tissues. We have shown that proinflammatry cytokines, tumor necrosis factor (TNF)-α combined with interleukin-1 (IL-1)-β, induce excessive production of nitric oxide (NO) and its cytotoxic metabolite, peroxynitrite (ONOO-) via inducible nitric oxide synthase (iNOS) in mouse osteoblasts. Among the nitric oxide synthases, inducible nitric oxide synthase (iNOS) has been considered as a potential target for gene therapy of chronic diseases including rheumatoid arthritis (RA). The recombinant adeno-associated virus (rAAV) vector offers new strategy for gene therapy, since it maintains transgene expression for alon time in vivo. AAV mediated the most effective gene expression in cells from arthritic rats. To identify the inhibitory effect of iNOS, rAAV, encoding iNOS antisense, was injected into ankle joints of arthritic rats. Compared to control animals, rAAV iNOS antisense injected rats were found to reduce paw volume, radiological and pathological scores. Thus, rAAV iNOS antisense gene therapy may be promising as a novel option in the treatment of RA.
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