Possible novel therapy of degenerated intervertebral disc by ADAMTS10
| Project/Area Number |
17K10924
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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 | The University of Tokyo |
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Principal Investigator |
Taniguchi Yuki 東京大学, 医学部附属病院, 特任准教授 (80722165)
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| Co-Investigator(Kenkyū-buntansha) |
齋藤 琢 東京大学, 医学部附属病院, 准教授 (30456107)
松林 嘉孝 東京大学, 医学部附属病院, 助教 (50747962)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | ADAMTS10 / ADAMTS17 / 成長障害 / フィブリリン / 椎間板 / ADAMTSファミリー |
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| Outline of Final Research Achievements |
In this study, we mainly investigated the function of Adamts17, which is known to be a causative gene for Weill-Marchesani syndrome (WMS), as well as Adamts10. Thorough analysis of Adamts17-/- mice, we identified those facts: a) Adamts17-/- mice recapitulated WMS with shorter long bones, brachydactyly, and thick skin, b) the hypertrophic zone of the growth plate in Adamts17-/- mice was shortened with enhanced extracellular fibrillin-2 deposition, and c) BMP signaling is decreased in the terminal differentiation of the chondrocytes in limb cartilage in Adamts17-/- mice. Our data indicated that Adamts17 is involved in skeletal formation by modulating BMP-Smad1/5/8 pathway, possibly through inhibiting the incorporation of fibrillin-2 into microfibrils. These results were published as a peer-reviewed article. Now we are analyzing the phenotype of the intervertebral disc of Adamts17-/- mice and analyzing the function of ADAMTS17 in intervertebral disc.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究では遺伝子改変マウスの解析を通じてADAMTS17遺伝子の機能の解析をすることに成功した。当初目的とした椎間板での機能の解析や変性椎間板の治療効果というところまでは解析を進めることができなかったが、ノックアウトマウスの作出に成功し、また本遺伝子の軟骨内骨化過程における分子生物学的な機能を解明できた利点は大きい。現在同様のストラテジーで椎間板における機能解析を継続して行っており、新たな知見が得られつつある。本研究により椎間板変性における新たな機序が明らかになることが期待され、今後の創薬開発につなげうることが期待される。
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Report
(4 results)
Research Products
(1 results)
