Roles of skeletal muscle in whole body homeostasis

• Project/Area Number: 25560338
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Sports science
• Research Institution: Nagasaki University
• Principal Investigator: ONO Yusuke 長崎大学, 原爆後障害医療研究所, 講師 (60601119)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: 骨格筋 / 生体恒常性 / がんカヘキシア / 筋萎縮 / 筋可塑性 / 筋由来分泌因子 / 筋肥大 / マイオカイン / サテライト細胞

Outline of Final Research Achievements

We examined roles of skeletal muscle in whole body homeostasis using mouse models including cancer cachexia. Cancer cachexia was induced by injection of C26 mouse colon cancer cells. Several genes involved in regulating lipid metabolism in the body were abnormally expressed in atrophic muscles in the cancer cachexia model. We next investigated the function of μ-Crystallin (Crym) in skeletal muscle as well as whole body homeostasis. Crym was preferentially expressed in skeletal muscle. Crym-knockout mice exhibited an increase in grip strength and high intensity running ability. Genetic inactivation of Crym also improved high-fat-diet-induced metabolic abnormalities in vivo. These results indicate that the alteration in quality and mass of muscles potentially influences whole body homeostasis.

Research Products

• [Journal Article] Estrogens maintain skeletal muscle and satellite cell functions (2016)
  • Author(s): Kitajima Y and Ono Y
  • Journal Title: J Endocrinol Volume: 3 Issue: 3 Pages: 1-9
  • DOI: 10.1530/joe-15-0476
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] μ-Crystallin controls muscle function through thyroid hormone action (2016)
  • Author(s): Seko D, Ogawa S, Li TS, Taimura A, Ono Y
  • Journal Title: FASEB J Volume: 30 Issue: 5 Pages: 1733-40
  • DOI: 10.1096/fj.15-280933
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] サテライト細胞と細胞極性 (2016)
  • Author(s): 瀬古大暉，小川静香，小野悠介
  • Journal Title: 基礎老化研究 Volume: 40 Pages: 19-25
  • Peer Reviewed
• [Journal Article] Visualizing the functional heterogeneity in muscle stem cells (2016)
  • Author(s): Kitajima Y, Ogawa S and Ono Y
  • Journal Title: Methods Mol Biol Volume: 4 Pages: 1-11
  • DOI: 10.1007/7651_2016_349
  • ISBN: 9781493965496, 9781493965502
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Scribble dictates orderly stem cell fate (2015)
  • Author(s): Ryo Fujita, Daiki Seko, Yusuke Ono
  • Journal Title: Oncotarget Volume: 6 (22) Issue: 22 Pages: 18738-9
  • DOI: 10.18632/oncotarget.4923
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Muscle stem cell fate is controlled by the cell polarity protein Scrib (2015)
  • Author(s): Ono Y, Urata Y, Goto S, Nakagawa S, Humbert PO, Li TS & Zammit PS.
  • Journal Title: Cell Rep Volume: 10(7) Issue: 7 Pages: 1135-4
  • DOI: 10.1016/j.celrep.2015.01.045
  • NAID: 120006987131
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Time- and dose-dependent effects of total-body ionising radiation on muscle stem cells (2015)
  • Author(s): Masuda S, Hisamatsu T, Seko S, Urata Y, Goto S, Li TS & Ono Y
  • Journal Title: Physiol Rep Volume: 3(4) Issue: 4 Pages: e12377-e12377
  • DOI: 10.14814/phy2.12377
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Role of dietary flavonoids in oxidative stress and prevention of muscle atrophy (2013)
  • Author(s): R.Mukai, J. Terao
  • Journal Title: The Journal of Physical Fitness and Sports Medicine Volume: 2 Issue: 4 Pages: 385-392
  • DOI: 10.7600/jpfsm.2.385
  • NAID: 10031203875
  • ISSN: 2186-8123, 2186-8131
  • Peer Reviewed
• [Presentation] 骨格筋幹細胞における細胞極性因子の役割 (2015)
  • Author(s): 小野悠介
  • Organizer: 第3回若手による骨格筋細胞研究会
  • Place of Presentation: 九州大学（福岡・博多）
  • Year and Date: 2015-11-24
• [Presentation] Role of a FSHD-associated protein µ-Crystallin in skeletal muscle (2015)
  • Author(s): Daiki Seko, Tsubasa Hisamatsu, Ryo Fujita, Kiyoshi Yoshioka, Yoshishige Urata, Shinji Goto, Tao-Sheng Li, Akihiro Taimura and Yusuke Ono
  • Organizer: 20th WMS Congress
  • Place of Presentation: ロンドン（英国）
  • Year and Date: 2015-10-01
  • Int'l Joint Research
• [Presentation] The cell polarity protein Scrib dictates muscle stem cell fate (2015)
  • Author(s): Kiyoshi Yoshioka, Daiki Seko, Ryo Fujita, Tsubasa Hisamatsu, Shizuka Ogawa, Yoshishige Urata, Shinji Goto, Tao-Sheng Li, Yusuke Ono
  • Organizer: the 13th Protein Island Matsuyama International Symposium
  • Place of Presentation: 愛媛大学（愛媛・松山）
  • Year and Date: 2015-09-25
  • Int'l Joint Research
• [Presentation] 細胞極性因子による筋サテライト細胞の運命決定制御 (2015)
  • Author(s): 小野悠介
  • Organizer: 第1回日本筋学会
  • Place of Presentation: 国立精神神経医療研究センター（東京・小平市）
  • Year and Date: 2015-08-08
  • Invited
• [Presentation] The cell polarity protein Scrib controls muscle stem cell fate (2015)
  • Author(s): Yusuke Ono, Yoshishige Urata, Shinji Goto, Tao-Sheng Li.
  • Organizer: ISSCR2015
  • Place of Presentation: ストックホルム（スウェーデン）
  • Year and Date: 2015-06-25
  • Int'l Joint Research
• [Presentation] 新骨格筋生物学 (2015)
  • Author(s): 小野悠介
  • Organizer: 立命館大学・運動生理・生化学特論
  • Place of Presentation: 立命館大学（滋賀・草津市）
  • Year and Date: 2015-05-21
  • Invited
• [Presentation] 骨格筋サテライト細胞の幹細胞生物学 (2014)
  • Author(s): 小野悠介
  • Organizer: 第7回筋生理セミナー
  • Place of Presentation: 九州大学（博多）
  • Year and Date: 2014-10-03
  • Invited
• [Presentation] 細胞極性因子による骨格筋幹細胞の運命決定制御 (2014)
  • Author(s): 小野悠介
  • Organizer: 第181回 横浜市立大学医学会講演会
  • Place of Presentation: 横浜市立大学（横浜）
  • Year and Date: 2014-09-29
  • Invited
• [Presentation] The tumour suppressor Scrib plays a crucial role in maintenance of proliferative state in muscle stem cells. (2014)
  • Author(s): Yusuke Ono, Yoshishige Urata, Shinji Goto, Shunsuke Nakagawa, Patrick Humbert, Tao-Sheng Li, and Peter Zammit.
  • Organizer: 2014 FASEB Science Research Conferences “Lipids and Lipid Regulated Kinases in Cancer”
  • Place of Presentation: Steamboat Springs, Colorado (USA)
  • Year and Date: 2014-07-29
• [Presentation] The cell polarity protein Scrib is a novel regulator of myogenic progression in muscle satellite cells. (2014)
  • Author(s): Yusuke Ono, Yoshishige Urata, Shinji Goto, Shunsuke Nakagawa, Patrick Humbert, Tao-Sheng Li, and Peter Zammit.
  • Organizer: 2014 FASEB Science Research Conferences “Skeletal Muscle Satellite and Stem Cells”
  • Place of Presentation: Steamboat Springs, Colorado (USA)
  • Year and Date: 2014-07-24
• [Presentation] 骨筋可塑性の分子制御 (2014)
  • Author(s): 小野悠介
  • Organizer: 第22回日本運動生理学会
  • Place of Presentation: 川崎医療福祉大学（倉敷）
  • Year and Date: 2014-07-19
  • Invited
• [Presentation] Molecular and Cellular Mechanisms underlying Muscle Regeneration and Aging
  • Author(s): Yusuke Ono
  • Organizer: Asian Association of Aging Research
  • Place of Presentation: ソウル大学、ソウル
  • Invited
• [Presentation] 骨格筋可塑性を制御する分子基盤
  • Author(s): 小野悠介
  • Organizer: 第91回日本生理学会大会
  • Place of Presentation: 鹿児島大学、鹿児島
  • Invited
• [Presentation] 骨格筋糖代謝とNotchシグナリング
  • Author(s): 小野悠介
  • Organizer: 2014年度日本農芸化学学会
  • Place of Presentation: 明治大学、神奈川
  • Invited
• [Book] 生体の科学(特集：特殊な幹細胞としての骨格筋サテライト細胞 橋本有弘編, 「筋サテライト細胞の不均一性」) (2013)
  • Author(s): 小野悠介
  • Total Pages: 4
  • Publisher: 医学書院
• [Book] 再生医療事業の課題解決のための手引書（分担執筆）「再生医療で用いられる細胞種の培養～骨格筋幹細胞～」) (2013)
  • Author(s): 小野悠介
  • Total Pages: 8
  • Publisher: 技術情報協会出版
• [Remarks]
  • URL: http://www.nagasaki-u.ac.jp/ja/about/info/science/science84.html
• [Patent(Industrial Property Rights)] 筋力低下症および代謝性疾患の治療薬 (2015)
  • Inventor(s): 小野悠介
  • Industrial Property Rights Holder: 小野悠介
  • Industrial Property Rights Type: 特許
  • Filing Date: 2015-09-11