| Project/Area Number |
23390358
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 University of Tokyo |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
KAWAGUCHI Hiroshi 東京大学, 医学部附属病院, 届出診療医 (40282660)
OHASHI Satoru 東京大学, 医学部附属病院, 助教 (20466767)
唐司 寿一 東京大学, 医学部附属病院, 助教 (40597762)
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| Project Period (FY) |
2011-04-01 – 2014-03-31
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥18,980,000 (Direct Cost: ¥14,600,000、Indirect Cost: ¥4,380,000)
Fiscal Year 2013: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2012: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2011: ¥8,970,000 (Direct Cost: ¥6,900,000、Indirect Cost: ¥2,070,000)
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| Keywords | 関節軟骨 / 変形性関節症 / Notchシグナル |
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| Research Abstract |
Notch signaling consists of 5 ligands and 4 receptors (Notch1-4). Upon ligand binding, the Notch receptor is cleaved and its intracellular domain (ICD) translocates to the nucleus, where it binds to Rbpj, a transcription repressor, and activates expression of target genes including Hes/Hey family member. Notch1 and 2 were expressed in mouse and human articular chondrocytes, and their ICDs were translocated to the nucleus with cartilage degradation. When we deleted Rbpj in chondrocytes after skeletal growth using tamoxifen-inducible Cre mice and created an experimental OA model, cartilage degradation and Mmp13 expression were suppressed. We further investigated functions of Hes1, only target gene expressed abundantly in chondrocytes, using Hes1-flox mice. When we deleted Hes1 in the same way, OA development was suppressed while skeletal development was not affected.
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