| Project/Area Number |
11671421
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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 |
Orthopaedic surgery
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| Research Institution | The Univ. of Tokyo |
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Principal Investigator |
IKEDA Toshiyuki (2000) Univ.of Tokyo, Assistant, 医学部・附属病院, 助手 (80322759)
坪井 寿和 (1999) 東京大学, 医学部・附属病院, 助手 (80302694)
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| Co-Investigator(Kenkyū-buntansha) |
TANAKA Sakae Univ.of Tokyo, Assistant, 医学部・附属病院, 助手 (50282661)
HIRAOKA Hisatada Univ.of Tokyo, Assistant, 医学部・附属病院, 助手 (10262007)
FUKUDA Akira Univ.of Tokyo, Assistant, 医学部・附属病院, 医員 (90302695)
NAKAMURA Kozo Univ.of Tokyo, Professor, 医学部・附属病院, 教授 (60126133)
池田 敏之 東京大学, 医学部・附属病院, 助手
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 2000: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1999: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Keywords | hyaluronic acid / hyaluronic acid synthetase type 2 / Osleoarthritis / Articular cartilage / adeno virus vector / gene therapy / ヒアルロン酸合成酵素タイプン / アデノウィルス / 変形性膝関節症 |
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| Research Abstract |
1, Through the courtesy of the Medical Science Center of longevity, the adenovirus vector encording hyaluronic acid synthetase type-2 gene (HAS2 virus) was presented and used to know whether the virus had the prevention effects or osteoarthritis (OA) by injection directly to the joint. The virus vector was injected in the knee joints or rabbit OA model. Then, hyaluronic acid (HA) concentration in joint fluid, macroscopic findings and histology of articular cartilage were evaluated at 6 weeks after HAS virus injection. The result showed that HA concentration in joint fluid of HA virus injected group (HA virus group) had no statistical difference between wild type virus injected group (wild group) and carrier vehicle injected group (carrier group). Macroscopic and histological examination also showed no apparent difference between three groups. Then, we ascertained whether HAS2 virus had the acceleration effects of HA synthesis for normal (non-OA) rabbit knee. HAS2 virus was injected in
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the rabbit normal knee joints. The results showed that HA concentration of HAS2 virus group had the tendency towards a little bit higher than that of wild group, but lower than that of carrier group. Thus, these results indicated that a kind of negative feedback mechanisms might affect the results or the concentration of the virus was too low to express the acceleration effects of HA synthesis.
2, We changed the strategy from in vivo study to in vitro study, in which articular chondrocytes were used. HA has some important roles also in cartilage tissue, and chondrocytes themselves synthesize HA.HAS2 virus was infected to the chondrocytes isolated from fetal cow articular cartilage, and condition medium was collected at 5 time points till 7 days. HA concentration in condition medium of HAS2 virus infected chondrocytes was higher than that of non-infeced chondrocytes at any time points till 7 days. Therefore it was verified that HAS virus had the acceleration effects of HA synthesis for articular chondrocytes in vitro. This acceleration effects can be used for tissue engineering technique of articular cartilage or prevention of OA progression. Less
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