Elucidation of the mechanism underlying different behaviors of muscle stem cells in loaded and sedentary muscle
| Project/Area Number |
19H04000
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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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| Review Section |
Basic Section 59020:Sports sciences-related
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| Research Institution | Osaka University |
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Principal Investigator |
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2021: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2020: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2019: ¥7,150,000 (Direct Cost: ¥5,500,000、Indirect Cost: ¥1,650,000)
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| Keywords | レジスタンストレーニング / 筋サテライト細胞 / 間葉系前駆細胞 / カルシトニン受容体 / Yap/Taz / トロンボスポンジン / 筋肥大 / Calcitonin receptor / 代償性筋肥大 / 過負荷 / 増殖 / 筋幹細胞 / 肥大 / Overload / Wheel running / 骨格筋 / PKA / Hippo |
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| Outline of Research at the Start |
筋サテライト細胞 (MuSC: Muscle Satellite Cell) は通常は、細胞周期G0期 (静止期) で維持されている。一方で、レジスタンストレーニング等の骨格筋への過負荷刺激により、MuSCは活性化・増殖後に筋線維へ新たな核を供給する事で筋肥大に働く。つまり、MuSCは「日常動作」と「レジスタンストレーニング」の動き（機械刺激）の違いを区別していると考えられる。しかしその分子メカニズムは不明である。本申請課題では、MuSCの能力を利用した筋疾患・筋萎縮治療法への応用を最終目標として、マウス筋肥大モデルやMuSCの静止期維持シグナルに焦点をあてる事でMuSCが異なる筋の動きを感知する分子機構解明に取り組む。
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| Outline of Final Research Achievements |
It is generally considered that muscle stem cell proliferation is triggered by the damages of myofibers in resistance training. However, in our previous study, we found that muscle stem cells proliferate even without the damages to myofibers (Elife. 2019;8:e48284.). In this proposal, we discovered the relayed signaling between interstitial cells and muscle stem cell via Yap/Taz-Thbs1-CD47 axis. We also founded that the down-regulation of calcitonin receptor ensure the proliferation of MuSC in training muscle.
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| Academic Significance and Societal Importance of the Research Achievements |
一般的には，物理的刺激により筋線維が壊れることがサテライト細胞の活性化・増殖を誘導すると考えられていました。そのため筋サテライト細胞が運動依存的に増殖するために，損傷は必要なく，間質の細胞が必要であることはこれまでの常識を塗り替える成果となりました。また，核は細胞のまさに「核」であり，老化や病気によってその質が低下します。損傷も物理的負荷もない条件でも，筋線維核を増加できる事は，筋線維核の機能が低下する疾患への応用が期待されます。
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Report
(4 results)
Research Products
(32 results)
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[Journal Article] Relayed signaling between mesenchymal progenitors and muscle stem cells ensures adaptive stem cell response to increased mechanical load.2021
Author(s)
Kaneshige A, Kaji T, Zhang L, Saito H, Nakamura A, Kurosawa T, Ikemoto-Uezumi M, Tsujikawa K, Seno S, Hori M, Saito Y, Matozaki T, Maehara K, Ohkawa Y, Potente M, Watanabe S, Braun T, Uezumi A, Fukada SI.
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Journal Title
Cell Stem Cell.
Volume: 29
Issue: 2
Pages: 265-280
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Calcitonin Receptor Neurons in the Mouse Nucleus Tractus Solitarius Control Energy Balance via the Non-aversive Suppression of Feeding.2020
Author(s)
Cheng W, Gonzalez I, Pan W, Tsang AH, Adams J, Ndoka E, Gordian D, Khoury B, Roelofs K, Evers SS, MacKinnon A, Wu S, Frikke-Schmidt H, Flak JN, Trevaskis JL, Rhodes CJ, Fukada SI, Seeley RJ, Sandoval DA, Olson DP, Blouet C, Myers MG Jr.
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Journal Title
Cell Metab
Volume: 31
Issue: 2
Pages: 301-12
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] The CalcR-PKA-Yap1 Axis Is Critical for Maintaining Quiescence in Muscle Stem Cells.2019
Author(s)
Zhang L, Noguchi YT, Nakayama H, Kaji T, Tsujikawa K, Ikemoto-Uezumi M, Uezumi A, Okada Y, Doi T, Watanabe S, Braun T, Fujio Y, Fukada SI.
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Journal Title
Cell Rep
Volume: 19
Issue: 8
Pages: 2154-63
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Sustained expression of HeyL is critical for the proliferation of muscle stem cells in overloaded muscle.2019
Author(s)
Fukuda S, Kaneshige A, Kaji T, Noguchi YT, Takemoto Y, Zhang L, Tsujikawa K, Kokubo H, Uezumi A, Maehara K, Harada A, Ohkawa Y, Fukada SI.
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Journal Title
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Reduced expression of calcitonin receptor is closely associated with age-related loss of the muscle stem cell pool.2019
Author(s)
Madoka Ikemoto-Uezumi, Akiyoshi Uezumi, Lidan Zhang, Heying Zhou, Naohiro Hashimoto, Kikuo Okamura, Yasumoto Matsui, Koji Tsukazaki, Tohru Hosoyama, Masashi Nakatani, Mitsuhiro Morita, Harumoto Yamada, Kunihiro Tsuchida, So-ichiro Fukada
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Journal Title
JSCM Rapid Communications
Volume: 2
Issue: 1
Pages: 1-13
DOI
Related Report
Peer Reviewed / Open Access
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