| Project/Area Number |
08407046
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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 | 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 |
HARII Kiyonori University of Tokyo, Faculty of Medicine, Professor, 医学部・附属病院, 教授 (50111539)
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| Co-Investigator(Kenkyū-buntansha) |
EGUCHI Tomoaki University of Tokyo, Faculty of Medicine, Assistant, 医学部・附属病院, 助手 (00302688)
YOSHIMURA Kotaro University of Tokyo, Faculty of Medicine, Lecturer, 医学部・附属病院, 講師 (60210762)
ASATO Hirotaka University of Tokyo, Faculty of Medicine, Associate Professor, 医学部・附属病院, 助教授 (20222581)
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| Project Period (FY) |
1996 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥34,200,000 (Direct Cost: ¥34,200,000)
Fiscal Year 1999: ¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1998: ¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 1997: ¥6,300,000 (Direct Cost: ¥6,300,000)
Fiscal Year 1996: ¥22,800,000 (Direct Cost: ¥22,800,000)
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| Keywords | myosin / apoptosis / embryonic myosin / aging / denervation / regeneration / atrophy / muscle / 再神経支配 / MyoD / 筋衛星細胞 / モーターユニット / 等尺性収縮力 / 長趾伸筋 |
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| Research Abstract |
The purpose of this study is to examined the cellular and molecular events coincident with muscle denervation, especially a regenerative change seen following muscle denervation, the role of satellite cells involved in the process, and the possibility of apoptotic degeneration of myonuclei as a mechanism of myonuclei loss during muscle denervation atrophy. Myosin heavy chain (MHC) isoform expression during muscle denervation was examined using pyrophosphate acrylamide gel electrophoresis and immunohistochemistry. DNA fragmentation (apoptosis) in myonuclei of denervated fibers was investigated using agarose gel electrophoresis, the TUNEL technique and ELISA. Immunohistchemistry for MyoD and BrdU, and an ultrastructural survey were also performed. Following muscle denervation, embroyonic MHC which is not expressed in adult healthy muscles was expressed in some denervated fibers as well as small activated satellite cells ; maximal expression was observed two to three weeks after denervation. Activation and proliferation of satellite cells were observed, while few typical regenerating fibers were identified, suggesting that activated satellite cells fused to the denervated maternal fibers to try to repair them instead of fusing to each other to form new fibers, likely as a mechanism to compensate for atrophic changes after denervation. DNA fragmentation was detected by the TUNEL technique and ELISA, although DNA ladder formation was not observed with agarose gel electrophoresis. Apoptotic degeneration of myonuclei of denervated fibers was not confirmed, but it may contribute to loss of myoneuclei associated with denervation atrophy and induce activation of satellite cells.
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