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Mechanisms underlying formation of tissue domains integrating the skeletal components

Research Project

Project/Area Number 26293395
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Functional basic dentistry
Research InstitutionHiroshima University

Principal Investigator

Shukunami Chisa  広島大学, 医歯薬保健学研究院, 教授 (60303905)

Co-Investigator(Kenkyū-buntansha) 滝本 晶  京都大学, 健康長寿社会の総合医療開発ユニット, 特定助教 (00378902)
秋山 治彦  岐阜大学, 医学(系)研究科(研究院), 教授 (60402830)
Research Collaborator GERD SCHERER  Freiburg University
RALF KIST  Newcastle University
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥16,250,000 (Direct Cost: ¥12,500,000、Indirect Cost: ¥3,750,000)
Fiscal Year 2016: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2015: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2014: ¥7,280,000 (Direct Cost: ¥5,600,000、Indirect Cost: ¥1,680,000)
Keywords発生・分化 / 腱 / 靭帯 / 硬組織 / 遺伝子改変動物 / ゲノム編集 / 靱帯 / 顎関節 / 発生・分化
Outline of Final Research Achievements

In this study, we generated and analyzed genetically modified mice to analyze the mechanisms underlying tendon/ligament and enthesis formation. We analyzed mice lacking Scleraxis (Scx), a basic helix-loop-helix transcription factor, to find that Scx is required for maturation of tissue domains for proper integration of the musculoskeletal system. Analysis of conditional knockout mice lacking Sox9 in the Scx-expressing region, we found that Sox9 is important for formation of the tenpolomandibular joint during development. Lineage analysis and double immunostaining revealed that cells expressing both Scx and Sox9 contribute to formation of the enthesis.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Annual Research Report
  • 2014 Annual Research Report
  • Research Products

    (46 results)

All 2017 2016 2015 2014

All Journal Article (17 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 11 results,  Open Access: 8 results,  Acknowledgement Compliant: 2 results) Presentation (29 results) (of which Int'l Joint Research: 3 results,  Invited: 21 results)

  • [Journal Article] Scleraxis is required for maturation of tissue domains for proper integration of the musculoskeletal system.2017

    • Author(s)
      Yoshimoto Y, Takimoto A, Watanabe H, Hiraki Y, Kondoh G, Shukunami C.
    • Journal Title

      Sci Rep

      Volume: 7 Issue: 1 Pages: 45010-45010

    • DOI

      10.1038/srep45010

    • NAID

      120005998026

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Tenomodulin is required for tendon endurance runnning and collagen I fibril adaptation to mechanical load.2017

    • Author(s)
      Dex S, Alberton P, Willkomm L, Soellradl T, Milz S, Shakivaei M, Ignatius A, Bloch W, Clausen-Schaumann H, Shukunami C, Schieker M, Docheva D.
    • Journal Title

      EbioMedicine

      Volume: - Pages: 240-254

    • DOI

      10.1016/j.ebiom.2017.05.003

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] TGF-β1 improves the biomechanical strength by extracellular matrix accumulation without increasing the number of tenogenic lineage cells in a rat rotator cuff repair model.2017

    • Author(s)
      Arimura H, Shukunami C, Tokunaga T, Karasugi T, Okamoto N, Taniwaki T, Sakamoto H, Mizuta H, Hiraki Y.
    • Journal Title

      Am J Sports Med

      Volume: -

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 腱・靱帯と骨格筋2017

    • Author(s)
      宿南 知佐
    • Journal Title

      CLINICAL CALCIUM

      Volume: 27 Pages: 43-49

    • Related Report
      2016 Annual Research Report
  • [Journal Article] 靱帯の形成と再生2016

    • Author(s)
      吉本 由紀,滝本晶,宿南 知佐
    • Journal Title

      Keynote RA

      Volume: 4 Pages: 20-25

    • Related Report
      2016 Annual Research Report
  • [Journal Article] TEnogenic modulating insider factor : Systematic assessment on the functions of TNMD gene.2016

    • Author(s)
      Dex S, LinD, Shukunami C, Docheva D.
    • Journal Title

      GENE

      Volume: in press Issue: 1 Pages: 1-17

    • DOI

      10.1016/j.gene.2016.04.051

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Molecular characterization and function of tenomodulin, a marker of tendons and ligaments that integrate musculoskeletal components.2016

    • Author(s)
      Shukunami C, Yoshimoto Y, Takimoto A, Yamashita H, Hiraki Y.
    • Journal Title

      Japanese Dental Science Review

      Volume: 164 Issue: 4 Pages: 1-9

    • DOI

      10.1016/j.jdsr.2016.04.003

    • NAID

      50010101372

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Functional Investigation of a Non-coding Variant Associated with Adolescent Idiopathic Scoliosis in Zebrafish: Elevated Expression of the Ladybird Homeobox Gene Causes Body Axis Deformation.2016

    • Author(s)
      Guo, L., Yamashita, H., Kou, I., Takimoto, A., Meguro-Horike, M., Horike, S., Adachi, T., Ikegawa, S., Hiraki, Y., Shukunami, C.
    • Journal Title

      Plos Genetics

      Volume: 12 Issue: 1 Pages: e1005802-e1005802

    • DOI

      10.1371/journal.pgen.1005802

    • NAID

      120005698038

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] FGF-2 stimulates the growth of tenogenic progenitor cells to facilitate the generation of Tenomodulin-positive tenocytes in a rat rotator cuff healing model.2015

    • Author(s)
      Tokunaga TS, Shukunami C. Okamoto, N. Okada, T. Taniwaki, T. Oka, K. Sakamoto H. Mizuta H. Hiraki Y.
    • Journal Title

      Am J Sports Med.

      Volume: 43 Issue: 10 Pages: 2411-2422

    • DOI

      10.1177/0363546515597488

    • NAID

      120005678196

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] OASIS modulates hypoxia pathway activity to regulate bone angiogenesis.2015

    • Author(s)
      Min Cui, Soshi Kanemoto, Xiang Cui, Masayuki Kaneko, Rie Asada, Koji Matsuhisa, Keiji Tanimoto, Yuki Yoshimoto, Chisa Shukunami, Kazunori Imaizumi.
    • Journal Title

      Scientific Reports

      Volume: 5 Issue: 1 Pages: 16455-16455

    • DOI

      10.1038/srep16455

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 骨の血管・神経2015

    • Author(s)
      宿南 知佐
    • Journal Title

      骨ペディア 骨疾患・骨代謝キーワード事典

      Volume: - Pages: 25-29

    • Related Report
      2015 Annual Research Report
  • [Journal Article] 筋と骨をつなぐ臓器:腱と筋膜2015

    • Author(s)
      吉本 由紀, 山下 寛、宿南 知佐
    • Journal Title

      THE BONE

      Volume: 29 Pages: 63-68

    • Related Report
      2015 Annual Research Report
  • [Journal Article] 腱・靱帯形成の制御2015

    • Author(s)
      滝本 晶、吉本 由紀、山下 寛、宿南 知佐
    • Journal Title

      整形・災害外科

      Volume: 58 Pages: 1373-1379

    • Related Report
      2015 Annual Research Report
  • [Journal Article] 腱・靱帯細胞、Chondromodulin-I 、Tenomodulin、Scleraxis2015

    • Author(s)
      宿南 知佐
    • Journal Title

      再生医療 用語ハンドブック (日本再生医療学会監修/メディカルトリビューン)

      Volume: なし Pages: 106-109

    • Related Report
      2015 Annual Research Report
  • [Journal Article] Loss of Tenomodulin Results in Reduced Self-Renewal and Augmented Senescence of Tendon Stem/Progenitor Cells.2015

    • Author(s)
      Alberton P, Dex S, Popov C, Shukunami C, Schieker M, Docheva D.
    • Journal Title

      Stem Cells Dev

      Volume: 24 Issue: 5 Pages: 597-609

    • DOI

      10.1089/scd.2014.0314

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Scleraxis and osterix antagonistically regulate tensile force-responsive remodeling of the periodontal ligament and alveolar bone.2015

    • Author(s)
      Takimoto A., Kawatsu M., Yoshimoto Y., Kawamoto T., Seiryu M., Takano-Yamamoto T., Hiraki Y., Shukunami C.
    • Journal Title

      Development.

      Volume: 142(4) Issue: 4 Pages: 787-796

    • DOI

      10.1242/dev.116228

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Sox9- and Scleraxis-Cre Lingeage Fate Mapping in Aortic and Mitral Valve Structures.2014

    • Author(s)
      Austin B, Yoshimoto Y, Shukunami C, Lincoln J.
    • Journal Title

      J. Cardiovasc. Dev. Dis.

      Volume: 1 Issue: 2 Pages: 163-176

    • DOI

      10.3390/jcdd1020163

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Presentation] Regulation of intervertebral disc development by Pax1 and Sox92017

    • Author(s)
      Chisa Shukunami
    • Organizer
      Gordon Research Conference (Cartilage Biology and Pathology)
    • Place of Presentation
      Lucca (Barga), Italy
    • Year and Date
      2017-04-04
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 腱・靱帯付着部形成のメカニズム2017

    • Author(s)
      宿南知佐
    • Organizer
      第24回母子医療センターシンポジウム
    • Place of Presentation
      和泉市
    • Year and Date
      2017-02-17
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 筋・骨格系を連結する腱・靱帯の形成におけるScleraxisの役割2016

    • Author(s)
      吉本 由紀、滝本 晶、渡邊 仁美、近藤 玄、開 祐司、宿南 知佐
    • Organizer
      第4回若手による骨格筋細胞研究会
    • Place of Presentation
      名古屋市
    • Year and Date
      2016-11-15
    • Related Report
      2016 Annual Research Report
  • [Presentation] 腱・靱帯付着部の形成メカニズム2016

    • Author(s)
      宿南知佐
    • Organizer
      第31回日本整形外科学会基礎学術集会
    • Place of Presentation
      福岡市
    • Year and Date
      2016-10-14
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Molecular characterization and function of tenomodulin, a marker of tendon/ligaments to integrate the musculoskeletal components2016

    • Author(s)
      Chisa Shukunami
    • Organizer
      The 13th Bone Biology Forum
    • Place of Presentation
      千葉市
    • Year and Date
      2016-08-19
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 筋/骨格系を連結する組織におけるScleraxisの機能解析2016

    • Author(s)
      吉本由紀、滝本 晶、佐久間哲史、渡邊仁美、近藤 玄、山本 卓、開 祐司、宿南知佐
    • Organizer
      日本ゲノム編集学会第1回大会
    • Place of Presentation
      広島市
    • Year and Date
      2016-08-06
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 新たに樹立した腱細胞株T2Sを用いた成熟腱分子マーカーTenomodulinの発現制御機構の解析2016

    • Author(s)
      山下 寛、吉本由紀、宿南知佐
    • Organizer
      第2回日本筋学会学術集会
    • Place of Presentation
      小平市
    • Year and Date
      2016-08-05
    • Related Report
      2016 Annual Research Report
  • [Presentation] 新たに樹立したマウス由来不死化腱細胞株T2Sを用いた成熟腱分子マーカーTenomodulinの発現制御に関わる細胞内シグナル伝達経路の解析2016

    • Author(s)
      山下 寛、吉本由紀、宿南知佐
    • Organizer
      第34回日本骨代謝学会学術集会・第3回アジア太平洋骨代謝学会議
    • Place of Presentation
      大阪市
    • Year and Date
      2016-07-22
    • Related Report
      2016 Annual Research Report
  • [Presentation] bHLH型転写因子Scleraxisによる腱・靱帯形成制御2016

    • Author(s)
      宿南知佐
    • Organizer
      第11回しまなみ骨・関節フォーラム
    • Place of Presentation
      愛媛県東温市
    • Year and Date
      2016-06-30
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 筋・骨格系を統合する腱・靱帯の形成・維持機構2016

    • Author(s)
      宿南知佐
    • Organizer
      第48回日本結合組織学会学術大会
    • Place of Presentation
      長崎市
    • Year and Date
      2016-06-25
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 新規マウス由来腱細胞株T2Sを用いた腱分化関連遺伝子の発現制御機構の解析2016

    • Author(s)
      山下 寛、吉本由紀、宿南知佐
    • Organizer
      第7回骨バイオサイエンス研究会
    • Place of Presentation
      岡山市
    • Year and Date
      2016-06-04
    • Related Report
      2016 Annual Research Report
  • [Presentation] In vivo screening of the element regulating cartilage-specific chm1 gene expression2016

    • Author(s)
      Hiroshi Yamashita, Long Guo, Chisa Shukunami, Yuji Hiraki
    • Organizer
      第29回日本軟骨代謝学会
    • Place of Presentation
      広島市、広島大学広仁会館
    • Year and Date
      2016-02-19
    • Related Report
      2015 Annual Research Report
  • [Presentation] Molecular mechanisms regulating tendon and ligament formation2016

    • Author(s)
      Chisa Shukunami
    • Organizer
      獣医科学グローバルリーダー育成プログラム」のThe 21st Leading Special Lecture
    • Place of Presentation
      札幌市、北海道大学大学院獣医学研究科講堂
    • Year and Date
      2016-01-22
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 腱・靱帯形成の分子メカニズム2016

    • Author(s)
      宿南 知佐
    • Organizer
      第37回北海道大学獣医学学術交流基金群講演会
    • Place of Presentation
      札幌市、北海道大学大学院獣医学研究科講堂
    • Year and Date
      2016-01-21
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] The anti-angiogenic action of Tenomodulin, a specific marker for tendons and ligaments2015

    • Author(s)
      Chisa Shukunami
    • Organizer
      6th Hiroshima Conference on Education and Science in Dentistry Symposium
    • Place of Presentation
      広島市、広島国際会議場
    • Year and Date
      2015-10-23
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Contribution of the Scx+/Sox9+ cell population to the establishment of the junction between tendons/ligaments and cartilage2015

    • Author(s)
      Chisa Shukunami
    • Organizer
      第57回歯科基礎医学会学術大会 日韓合同シンポジウム
    • Place of Presentation
      新潟市、朱鷺メッセ 新潟コンベンションセンター
    • Year and Date
      2015-09-13
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] In vivo screening of the element regulating cartilage-specific chm1 gene expression2015

    • Author(s)
      山下 寛、宿南知佐、開 祐司
    • Organizer
      第12回 Bone Biology Forum
    • Place of Presentation
      千葉市、セミナーハウス クロス・ウェーブ幕張
    • Year and Date
      2015-08-22
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 骨格と筋肉を連結する腱の形成2015

    • Author(s)
      宿南知佐
    • Organizer
      第1回日本筋学会
    • Place of Presentation
      小平市、国立研究開発法人 国立精神・神経医療センター
    • Year and Date
      2015-08-08
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 腱・靱帯の形成機構2015

    • Author(s)
      宿南 知佐
    • Organizer
      第26回Bone Research Joint Meeting
    • Place of Presentation
      吹田市、大阪大学銀杏会館
    • Year and Date
      2015-07-25
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Scxによる腱・靱帯付着部の形成の制御2015

    • Author(s)
      吉本 由紀、滝本 晶、開 祐司、宿南 知佐
    • Organizer
      第33回日本骨代謝学会学術集会
    • Place of Presentation
      東京都新宿区、京王プラザホテル
    • Year and Date
      2015-07-25
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Pax1とSox9による軟骨細胞の分化制御と脊柱の組織構築2015

    • Author(s)
      滝本 晶、開 祐司、宿南 知佐
    • Organizer
      第33回日本骨代謝学会学術集会
    • Place of Presentation
      東京都新宿区、京王プラザホテル
    • Year and Date
      2015-07-23
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] ゼブラフィッシュを用いたchm1遺伝子発現制御領域のin vivoスクリーニング2015

    • Author(s)
      山下 寛、宿南知佐、開 祐司
    • Organizer
      第6回骨バイオサイエンス研究会
    • Place of Presentation
      岡山市、岡山コンベンションセンター
    • Year and Date
      2015-07-04
    • Related Report
      2015 Annual Research Report
  • [Presentation] 歯周靱帯におけるメカニカルストレス応答2015

    • Author(s)
      宿南 知佐
    • Organizer
      日本組織培養学会第88回大会
    • Place of Presentation
      広島市、広島大学広仁会館
    • Year and Date
      2015-05-26
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 腱・靱帯付着部の形成機構2015

    • Author(s)
      宿南 知佐
    • Organizer
      第28回日本軟骨代謝学会
    • Place of Presentation
      東京都文京区 東京医科歯科大学 鈴木章夫記念講堂
    • Year and Date
      2015-03-07
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 歯周靱帯形成を解析するためのin vivoモデルの構築2014

    • Author(s)
      吉本由紀,宿南知佐
    • Organizer
      第56回歯科基礎医学会学術大会・総会
    • Place of Presentation
      福岡市、福岡国際会議場
    • Year and Date
      2014-09-26
    • Related Report
      2014 Annual Research Report
  • [Presentation] 腱・靭帯と骨格の付着部を形成する細胞の分化と系譜解析2014

    • Author(s)
      滝本晶,吉本由紀,秋山治彦,開祐司,宿南知佐
    • Organizer
      第15回運動器科学研究会
    • Place of Presentation
      東京都港区、ベルサール三田
    • Year and Date
      2014-09-05
    • Related Report
      2014 Annual Research Report
  • [Presentation] Molecular mechanisms regulating tendon and ligament formation2014

    • Author(s)
      Chisa Shukunami
    • Organizer
      The 11th Bone Biology Forum
    • Place of Presentation
      裾野市、富士教育研究所
    • Year and Date
      2014-08-23
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 腱と骨を連結する分子機構2014

    • Author(s)
      宿南 知佐
    • Organizer
      第32回日本骨代謝学会
    • Place of Presentation
      大阪市、大阪国際会議場
    • Year and Date
      2014-07-26
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 筋骨格系を連結する腱・靱帯形成の分子機構2014

    • Author(s)
      宿南 知佐
    • Organizer
      第27回骨代謝セミナー
    • Place of Presentation
      東京都文京区、ホテル椿山荘東京 アンフィシアター
    • Year and Date
      2014-06-06
    • Related Report
      2014 Annual Research Report
    • Invited

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Published: 2014-04-04   Modified: 2018-03-22  

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