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Regulation of pluripotency of skeletal muscle-derived stem cells and application to muscular diseases

Research Project

Project/Area Number 24590363
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field General medical chemistry
Research InstitutionFujita Health University

Principal Investigator

TSUCHIDA Kunihiro  藤田保健衛生大学, 総合医科学研究所, 教授 (30281091)

Research Collaborator NAKATANI Masashi  藤田保健衛生大学, 総合医科学研究所, 助教 (00421264)
HITACHI Keisuke  藤田保健衛生大学, 総合医科学研究所, 助教 (10508469)
UEZUMI Akiyoshi  藤田保健衛生大学, 総合医科学研究所, 講師 (60434594)
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords筋分化 / 筋衛星細胞 / 間葉系前駆細胞 / 脂肪分化 / 筋萎縮 / miRNA / lncRNA / 筋疾患 / 間葉系幹細胞 / 脂肪化 / 幹細胞システム / 細胞分化 / 小分子RNA / 幹細胞 / 筋サテライト細胞 / 再生医療 / 異所性骨化 / 線維化
Outline of Final Research Achievements

Muscle atrophies are observed both in genetic and non-genetic muscular disorders. Satellite cells play an important role in muscle repair, regeneration and muscle mass. Recently, non-myogenic mesenchymal progenitors/stem cells have been identified in muscles. They do not adopt a myogenic fate, however, they differentiate to adipocytes, fibroblasts and osteogenic cells. We have established an elegant method to purify myogenic cells and mesenchymal stem cells. Myostatin, a muscle-specific TGF-beta superfamily, is a pivotal negative regulator of muscle mass. Using myostatin knockout mice, we investigated the global microRNA expression profile. miR486, a positive regulator of IGF-1/Akt pathway, was, identified as a target of myostatin signaling. Overexpression of miR486 induced myotube hypertrophy. miR486 is one of the intermediate molecules linking myostatin signaling and the IGF-1/Akt/mTOR pathway in the regulation of skeletal muscle size.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (56 results)

All 2015 2014 2013 2012 Other

All Journal Article (17 results) (of which Peer Reviewed: 13 results,  Acknowledgement Compliant: 3 results,  Open Access: 4 results) Presentation (27 results) (of which Invited: 6 results) Book (6 results) Remarks (6 results)

  • [Journal Article] Pro-IGF-II ameliorates age-related inefficient regenerative response by orchestrating self-reinforcement mechanism of muscle regeneration.2015

    • Author(s)
      Ikemoto-Uezumi M, Uezumi A, Tsuchida K, Fukada S, Yamamoto H, Yamamoto N, Shiomi K, Hashimoto N.
    • Journal Title

      Stem Cells

      Volume: in press Issue: 8 Pages: 2456-2468

    • DOI

      10.1002/stem.2045

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Myostatin signaling regulates Akt activity via the regulation of miR-486 expression.2014

    • Author(s)
      Hitachi K, Nakatani M, Tsuchida K.
    • Journal Title

      Int J Biochem Cell Biol

      Volume: 47 Pages: 93-103

    • DOI

      10.1016/j.biocel.2013.12.003

    • Related Report
      2014 Annual Research Report 2013 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Role of microRNAs in muscle hypertrophy.2014

    • Author(s)
      Hitachi K, Tsuchida K.
    • Journal Title

      Frontiers in Physiology

      Volume: 408 Pages: 1-7

    • DOI

      10.3389/fphys.2013.00408

    • Related Report
      2014 Annual Research Report 2013 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Role for nonmyogenic mesenchymal progenitors in pathogenesis and regeneration of skeletal muscle.2014

    • Author(s)
      Uezumi A, Ikemoto-Uezumi M, Tsuchida K.
    • Journal Title

      Frontiers in Physiology

      Volume: 5 Pages: 1-11

    • DOI

      10.3389/fphys.2014.00068

    • Related Report
      2014 Annual Research Report 2013 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Myokines and signal crosstalk between skeletal muscle and adipose tissue.2014

    • Author(s)
      Tsuchida K.
    • Journal Title

      Austin J Endo Metab

      Volume: 1 Pages: 2-2

    • Related Report
      2014 Annual Research Report 2013 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Identification and characterization of PDGFRα mesenchymal progenitors in human skeletal muscle.2014

    • Author(s)
      Uezumi A, Fukada S, Yamamoto N, Ikemoto-Uezumi M, Yamada H, Nishino I, Hamada Y, Tsuchida K.
    • Journal Title

      Cell Death Disease

      Volume: 5 Issue: 4 Pages: 1186-1186

    • DOI

      10.1038/cddis.2014.161

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Identification and characterization of PDGFRα + mesenchymal progenitors in human skeletal muscle.2014

    • Author(s)
      Uezumi A, Fukada S, Yamamoto N, Ikemoto-Uezumi M, Nakatani M, Morita M, Yamaguchi A, Yamada H, Nishino I, Y Hamada Y, Tsuchida K.
    • Journal Title

      Cell Death Disease

      Volume: 5 Issue: 4 Pages: e1184-e1184

    • DOI

      10.1038/cddis.2014.152

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] マイオスタチンの機能制御による骨格筋量増加と筋力増強2014

    • Author(s)
      土田邦博
    • Journal Title

      日本整形外科学会雑誌

      Volume: 88(1) Pages: 29-33

    • Related Report
      2013 Research-status Report
  • [Journal Article] サルコペニアの新規治療法2014

    • Author(s)
      土田邦博
    • Journal Title

      医学のあゆみ

      Volume: 248(9) Pages: 753-757

    • Related Report
      2013 Research-status Report
  • [Journal Article] Origin and therapeutic strategies for ectopic bone formation in skeletal muscle.2013

    • Author(s)
      Tsuchida K, Oishi T, Uezumi A, Yamada H.
    • Journal Title

      Human Genet Embryol

      Volume: 3(2) Issue: 02 Pages: 110-110

    • DOI

      10.4172/2161-0436.1000110

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] iTRAQ-based proteomics reveals novel biomarkers of osteoarthritis.2013

    • Author(s)
      Ikeda D, Ageta H, Tsuchida K, Yamada H.
    • Journal Title

      Biomarkers

      Volume: 18(7) Issue: 7 Pages: 565-572

    • DOI

      10.3109/1354750x.2013.810667

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] 幹細胞の動態から見た骨格筋の脂肪化と線維化の分子機構2013

    • Author(s)
      土田邦博, 上住聡芳.
    • Journal Title

      小児科診療

      Volume: 76(4) Pages: 670-670

    • Related Report
      2013 Research-status Report
  • [Journal Article] 再生医療の役者としての幹細胞 筋組織内間葉系幹細胞―その特徴と機能2013

    • Author(s)
      上住聡芳、土田邦博.
    • Journal Title

      整形・災害外科

      Volume: 56(5) Pages: 493-499

    • Related Report
      2013 Research-status Report
  • [Journal Article] Mechanism of cell interactions with water-dispersed carbon nanohorns.2013

    • Author(s)
      Murakami T
    • Journal Title

      Nanosci Nanotech Lett

      Volume: VOL.5 Issue: 3 Pages: 402-407

    • DOI

      10.1166/nnl.2013.1544

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Osteogenic differentiation capacity of human skeletal muscle-derived progenitor2013

    • Author(s)
      Oishi T, Uezumi A, Kanaji A, Yamamoto N, Yamaguchi A, Yamada H, Tsuchida K.
    • Journal Title

      PLoS One

      Volume: 8 Issue: 2 Pages: e56641-e56641

    • DOI

      10.1371/journal.pone.0056641

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] An inhibitor of transforming growth factor beta type I receptor ameliorates muscle atrophy in a mouse model of caveolin 3-deficient muscular dystrophy2012

    • Author(s)
      Ohsawa Y, Okada T, Nishimatsu SI, Ishizaki M, Suga T, Fujino M, Murakami T, Uchino M, Tsuchida K, Noji S, Hinohara A, Shimizu T, Shimizu K, Sunada Y
    • Journal Title

      Lab Invest

      Volume: 78 Issue: 8 Pages: 1100-1114

    • DOI

      10.1038/labinvest.2012.78

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Characterization of inorganic nanomaterials as therapeutic vehicles.2012

    • Author(s)
      Murakami T
    • Journal Title

      Recent Advances Medicinal Chemistry

      Volume: VOL.1 Pages: 165-188

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] ヒト筋幹細胞移植を目指した基礎的研究2015

    • Author(s)
      中村美紀, 村上聡, 上住聡芳, 佐藤貴彦, 土田邦博, 辻川和丈, 深田宗一朗
    • Organizer
      第14回日本再生医療学会総会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2015-03-19 – 2015-03-21
    • Related Report
      2014 Annual Research Report
  • [Presentation] 骨格筋の変性および再生そして恒常性維持に関わる間葉系前駆細胞の機能2015

    • Author(s)
      上住聡芳, 上住円, 深田宗一朗, 土田邦博
    • Organizer
      第14回日本再生医療学会総会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2015-03-19 – 2015-03-21
    • Related Report
      2014 Annual Research Report
  • [Presentation] Pro-IGF-II補充による老化骨格筋再生不良改善効果の検討2015

    • Author(s)
      上住円, 上住聡芳, 深田宗一朗, 土田邦博, 橋本有弘
    • Organizer
      第14回日本再生医療学会総会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2015-03-19 – 2015-03-21
    • Related Report
      2014 Annual Research Report
  • [Presentation] 筋ジストロフィー関連疾患におけるTGF-βシグナルの解明と標的医薬の開発2014

    • Author(s)
      大澤裕, 砂田芳秀, 深井雄太, 藤野雅広, 西松伸一郎, 高山健太郎,伊東史子, 林良雄,土田邦博
    • Organizer
      精神・神経疾患研究『筋ジストロフィー関連疾患の基盤的診断・治療開発研究』
    • Place of Presentation
      JA共済ビル,東京都
    • Year and Date
      2014-12-05 – 2014-12-06
    • Related Report
      2014 Annual Research Report
  • [Presentation] 難治性筋疾患の病態進行過程の解明と治療に関する基盤研究2014

    • Author(s)
      土田邦博, 中谷直史, 上田洋司,常陸圭介,上住聡芳,山田治基
    • Organizer
      精神・神経疾患研究『筋ジストロフィー関連疾患の基盤的診断・治療開発研究』
    • Place of Presentation
      JA共済ビル,東京都
    • Year and Date
      2014-12-05 – 2014-12-06
    • Related Report
      2014 Annual Research Report
  • [Presentation] BMP-3bの新たなアディポカインとしての脂肪細胞機能制御と抗肥満作用2014

    • Author(s)
      日野純,中谷直史,荒井勇二,土田邦博,宮里幹也,寒川賢治
    • Organizer
      第35回日本肥満学会
    • Place of Presentation
      宮崎
    • Year and Date
      2014-10-24 – 2014-10-25
    • Related Report
      2014 Annual Research Report
  • [Presentation] 骨格筋分泌因子の探索2014

    • Author(s)
      中谷直史, 上田洋司, 土田邦博
    • Organizer
      第35回日本肥満学会
    • Place of Presentation
      宮崎
    • Year and Date
      2014-10-24 – 2014-10-25
    • Related Report
      2014 Annual Research Report
  • [Presentation] 抗肥満作用を有するBMP-3b過剰発現マウスにおける脂肪細胞機能の解析2014

    • Author(s)
      日野純, 中谷直史, 荒井勇二, 土田邦博, 宮里幹也, 寒川賢治
    • Organizer
      第87回日本生化学会大会
    • Place of Presentation
      国立京都国際会館、京都
    • Year and Date
      2014-10-15 – 2014-10-18
    • Related Report
      2014 Annual Research Report
  • [Presentation] 筋疾患や筋再生における骨格筋内在性の間葉系前駆細胞の役割2014

    • Author(s)
      上住聡芳, 深田宗一朗, 上住円, 土田邦博
    • Organizer
      第87回日本生化学会大会
    • Place of Presentation
      国立京都国際会館、京都
    • Year and Date
      2014-10-15 – 2014-10-18
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Overexpression of BMP-3b in adipose tissue prevents high-fat diet induced obesity with alteration of energy metabolism.2014

    • Author(s)
      Hino J, Nakatani M, Arai Y, Tsuchida K, Miyazato M, Kangawa K.
    • Organizer
      10th International BMP Conference
    • Place of Presentation
      Berlin, Germany
    • Year and Date
      2014-09-16 – 2014-09-20
    • Related Report
      2014 Annual Research Report
  • [Presentation] miR-486 is the intermediary molecule connecting myostatin signaling and the IGF-1/Akt/mTOR pathway in skeletal muscle.2014

    • Author(s)
      Hitachi K, Tsuchida K.
    • Organizer
      FASEB Science Research Conferences, Skeletal Muscle Satellite and Stem Cells.
    • Place of Presentation
      Steamboat Springs, CO, U.S.A.
    • Year and Date
      2014-07-20 – 2014-07-25
    • Related Report
      2014 Annual Research Report
  • [Presentation] 骨格筋内在性間葉系前駆細胞による筋再生促進機構の解析.2014

    • Author(s)
      上住聡芳, 深田宗一郎, 土田邦博.
    • Organizer
      第13回日本再生医療学会総会
    • Place of Presentation
      京都
    • Related Report
      2013 Research-status Report
  • [Presentation] 老化骨格筋再生能力低下を引き起こす環境因子の同定.2014

    • Author(s)
      上住円, 上住聡芳, 土田邦博, 深田宗一郎, 橋本有弘.
    • Organizer
      第13回日本再生医療学会総会
    • Place of Presentation
      京都
    • Related Report
      2013 Research-status Report
  • [Presentation] iTRAQ-based proteomics reveals markers of osteoarthritis.2013

    • Author(s)
      Ikeda D, Ageta H, Tsuchida K, Yamada H.
    • Organizer
      Osteoarthritis Research Society International (OARSI2013)
    • Place of Presentation
      Philadelphia, USA.
    • Related Report
      2013 Research-status Report
  • [Presentation] 新しい躁鬱病モデルマウスに対する網羅的解析.2013

    • Author(s)
      上田洋司, 高崎昭彦, 井ノ口馨,土田邦博.
    • Organizer
      第5回日本RNAi研究会
    • Place of Presentation
      広島
    • Related Report
      2013 Research-status Report
  • [Presentation] 抗肥満作用を示すBMP-3b過剰発現マウスの機能解析及び脂肪細胞におけるBMP-3bの遺伝子発現調節.2013

    • Author(s)
      日野純,中谷直史,荒井勇二,宮澤崇,吉本光佐,白井幹康,土田邦博,宮里幹也,寒川賢治.
    • Organizer
      第86回日本生化学会大会
    • Place of Presentation
      横浜
    • Related Report
      2013 Research-status Report
  • [Presentation] BMP-3bの新規アディポカインとしての機能:過剰発現マウスによる抗肥満作用および代謝解析.2013

    • Author(s)
      日野純,中谷直史, 荒井勇二, 宮澤崇, 吉本光佐, 白井幹康, 土田邦博, 宮里幹也, 寒川賢治.
    • Organizer
      第34回日本肥満学会
    • Place of Presentation
      東京
    • Related Report
      2013 Research-status Report
  • [Presentation] The functional role of UBL3 in the brain.2013

    • Author(s)
      Ageta H, Kahyo T, Setou M, Tsuchida K.
    • Organizer
      Annual Meeting American Society for Cell Biology
    • Place of Presentation
      New Orleans, Louisiana, USA.
    • Related Report
      2013 Research-status Report
  • [Presentation] Prevention of fat mass increase and hepatic steatosis by myostatin inhibition.2012

    • Author(s)
      Tsuchida K
    • Organizer
      2nd World Congress of Endobolism
    • Place of Presentation
      Beijin, China
    • Related Report
      2012 Research-status Report
    • Invited
  • [Presentation] BMP-3b acts as a novel adipocytokine that inhibits adipogenesis and BMP-3b transgenic mice are resistant to high-fat diet induced obesity.2012

    • Author(s)
      Hino J
    • Organizer
      9th International Conference on Bone Morphogenetic Proteins
    • Place of Presentation
      California U.S.A.
    • Related Report
      2012 Research-status Report
  • [Presentation] 骨格筋(白筋)を増加させる方法.2012

    • Author(s)
      土田邦博
    • Organizer
      第12回日本抗加齢医学会
    • Place of Presentation
      パシフィコ横浜(神奈川県)
    • Related Report
      2012 Research-status Report
    • Invited
  • [Presentation] Roles for nonmyogenic mesenchymal progenitors in skeletal muscle regeneration.2012

    • Author(s)
      Uezumi A
    • Organizer
      FASEB SRC
    • Place of Presentation
      Lucca, Italy
    • Related Report
      2012 Research-status Report
  • [Presentation] 幹細胞の動態から見た骨格筋の脂肪化と線維化の分子機構.2012

    • Author(s)
      土田邦博
    • Organizer
      第29回小児神経筋疾患懇話会
    • Place of Presentation
      東京ステーションカンファレンス(東京都)
    • Related Report
      2012 Research-status Report
    • Invited
  • [Presentation] マイオスタチンの機能制御による骨格筋量増加と筋力増強.2012

    • Author(s)
      土田邦博
    • Organizer
      第27回日本整形外科学会基礎学術集会
    • Place of Presentation
      名古屋国際会議場(愛知県)
    • Related Report
      2012 Research-status Report
    • Invited
  • [Presentation] ナノテクノロジーとDDS.2012

    • Author(s)
      土田邦博
    • Organizer
      第14回snns研究会学術集会
    • Place of Presentation
      ウィンク愛知(愛知県)
    • Related Report
      2012 Research-status Report
    • Invited
  • [Presentation] マイオスタチン欠損骨格筋肥大とmicroRNAsの関係.2012

    • Author(s)
      常陸圭介
    • Organizer
      第35回日本分子生物学会年会
    • Place of Presentation
      福岡国際会議場・マリンメッセ福岡(福岡県)
    • Related Report
      2012 Research-status Report
  • [Presentation] BMP-3bの脂肪組織過剰発現マウスによる抗肥満作用及び細胞内情報伝達系の解明.2012

    • Author(s)
      日野純
    • Organizer
      第85回日本生化学会大会
    • Place of Presentation
      福岡国際会議場・マリンメッセ福岡(福岡県)
    • Related Report
      2012 Research-status Report
  • [Book] 最新医学, The Medical Frontline, サルコペニアの基礎と臨床2015

    • Author(s)
      土田邦博他
    • Total Pages
      174
    • Publisher
      最新医学社
    • Related Report
      2014 Annual Research Report
  • [Book] 整形・災害外科, サルコペニアの病態と治療2015

    • Author(s)
      土田邦博, 上住聡芳, 中谷直史, 上田洋司, 常陸圭介
    • Total Pages
      252
    • Publisher
      金原出版株式会社
    • Related Report
      2014 Annual Research Report
  • [Book] 膨大なデータを徹底整理する 『サイトカイン・増殖因子キーワード事典』2015

    • Author(s)
      土田邦博他
    • Total Pages
      420
    • Publisher
      羊土社
    • Related Report
      2014 Annual Research Report
  • [Book] 筋損傷を科学する2014

    • Author(s)
      土田邦博他
    • Total Pages
      202
    • Publisher
      日本整形外科学会雑誌
    • Related Report
      2014 Annual Research Report
  • [Book] 医学のあゆみ, サルコペニアー成因と対策2014

    • Author(s)
      土田邦博他
    • Total Pages
      757
    • Publisher
      医歯薬出版株式会社
    • Related Report
      2014 Annual Research Report
  • [Book] 生体の科学2013

    • Author(s)
      上住聡芳、土田邦博
    • Total Pages
      192
    • Publisher
      医学書院
    • Related Report
      2012 Research-status Report
  • [Remarks]

    • URL

      https://www.fujita-hu.ac.jp/facility/related-facilities/icms/index.html

    • Related Report
      2014 Annual Research Report
  • [Remarks]

    • URL

      http://www.fujita-hu.ac.jp/ICMS/

    • Related Report
      2014 Annual Research Report
  • [Remarks]

    • URL

      http://www.fujita-hu.ac.jp/ICMS/research_category/res04/index.html

    • Related Report
      2014 Annual Research Report
  • [Remarks]

    • URL

      http://info.fujita-hu.ac.jp/~nanbyou/

    • Related Report
      2014 Annual Research Report
  • [Remarks] 藤田保健衛生大学総合医科学研究所難病治療学研究部門

    • URL

      http://info.fujita-hu.ac.jp/~nanbyou/

    • Related Report
      2013 Research-status Report
  • [Remarks] 藤田保健衛生大学総合医科学研究所難病治療学研究部門

    • URL

      http://info.fujita-hu.ac.jp/~nanbyou/nanbyou/Top.html

    • Related Report
      2012 Research-status Report

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Published: 2013-05-31   Modified: 2019-07-29  

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