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Molecular Mechanisms of How Mechanical Stress Regulates Inflammation of Locomotive Organs

Research Project

Project/Area Number 18H04088
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Review Section Medium-sized Section 59:Sports sciences, physical education, health sciences, and related fields
Research InstitutionNational Rehabilitation Center for Persons with Disabilities

Principal Investigator

Sawada Yasuhiro  国立障害者リハビリテーションセンター(研究所), 病院 臨床研究開発部(研究所併任), 臨床研究開発部長 (50313135)

Co-Investigator(Kenkyū-buntansha) 今村 武史  鳥取大学, 医学部, 教授 (00552093)
齋藤 琢  東京大学, 医学部附属病院, 准教授 (30456107)
篠原 正浩  国立障害者リハビリテーションセンター(研究所), 研究所 運動機能系障害研究部, 研究室長 (60345733)
吉野 大輔  東京農工大学, 工学(系)研究科(研究院), 准教授 (80624816)
原田 伊知郎  社会医療法人社団蛍水会名戸ヶ谷病院(名戸ヶ谷研究所メカノメディスン部門), メカノメディスン部門, 主任研究員 (00361759)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥44,850,000 (Direct Cost: ¥34,500,000、Indirect Cost: ¥10,350,000)
Fiscal Year 2020: ¥12,480,000 (Direct Cost: ¥9,600,000、Indirect Cost: ¥2,880,000)
Fiscal Year 2019: ¥12,480,000 (Direct Cost: ¥9,600,000、Indirect Cost: ¥2,880,000)
Fiscal Year 2018: ¥19,890,000 (Direct Cost: ¥15,300,000、Indirect Cost: ¥4,590,000)
Keywords適度な運動 / リハビリテーション / メカニカルストレス / 生体恒常性 / 恒常性維持 / 抗炎症 / 身体不活動 / 運動器 / 炎症 / 抗老化 / 筋萎縮
Outline of Final Research Achievements

(1) We observed that mechanical stress generated during muscle contraction contributes to muscle homeostasis by modulating the function of macrophages in situ. (2) We found that Cas translocates into the nucleus upon fluid shear stress application, alleviates the activity of NF-κB by interfering with its acetylation in the nucleus, and decreases RANKL expression in osteocytes, thereby suppressing the subsequent osteoclastogenesis and maintaining bone homeostasis. (3) We demonstrated that mechanical stimulation to the head recapitulates the effect of exercise on serotonin-induced signaling in the prefrontal cortex neurons through interstitial fluid shear stress.

Academic Significance and Societal Importance of the Research Achievements

運動の健康維持・増進効果を利用した介入法の開発により、社会を健康で元気にするという本研究の着想の起点となった細胞へのメカニカルストレス による(慢性)炎症抑制作用のメカニズムを、分子・細胞レベル及び個体レベルで明らかにした。このような、メカニカルストレスによる生体恒常性維持効果に関する基礎研究で得られる知見の蓄積は、安全で安価で、運動ができない障害者にも適用可能な治療法の開発につながる。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • Research Products

    (16 results)

All 2021 2020 2019 2018

All Journal Article (8 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 7 results,  Open Access: 5 results) Presentation (5 results) (of which Invited: 3 results) Book (2 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Mechanical load regulates bone growth via periosteal Osteocrin2021

    • Author(s)
      Watanabe-Takano H, Ochi H, Chiba A, Matsuo A, Kanai Y, Fukuhara S, Ito N, Sako K, Miyazaki T, Tainaka K, Harada I, Sato S, Sawada Y, Minamino N, Takeda S, Ueda HR, Yasoda A, Mochizuki N.
    • Journal Title

      Cell Reports

      Volume: 36 Pages: 109380-109380

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Early escitalopram administration as a preemptive treatment strategy against spasticity after contusive spinal cord injury in rats2021

    • Author(s)
      Ryu Y, Ogata T, Nagao M, Sawada Y, Nishimura R, Fujita N
    • Journal Title

      Scientific Reports

      Volume: 11 Issue: 1 Pages: 7120-7120

    • DOI

      10.1038/s41598-021-85961-5

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Mechanical regulation underlies effects of exercise on serotonin-induced signaling in the prefrontal cortex neurons.2020

    • Author(s)
      Ryu Y, Maekawa T, Yoshino D, Sakitani N, Takashima A, Inoue T, Suzurikawa J, Toyohara J, Tago T, Fujita N, Sawada K, Murase S, Watanave M, Sakai T, Yoshikawa Y, Ogata T, Shinohara M, Nagao M, Sawada Y
    • Journal Title

      iScience

      Volume: 23 Issue: 2 Pages: 100874-100874

    • DOI

      10.1016/j.isci.2020.100874

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Mechanical regulation of bone homeostasis through p130Cas-mediated alleviation of NF-κB activity.2019

    • Author(s)
      Miyazaki T, Zhao Z, Ichihara Y, Yoshino D, Imamura T, Sawada K, Hayano S, Kamioka H, Mori S, Hirata H, Araki K, Kawauchi K, Shigemoto K, Tanaka S, Bonewald LF, Honda H, Shinohara M, Nagao M, Ogata T, Harada I, Sawada Y
    • Journal Title

      Sci Adv

      Volume: 5 Issue: 9 Pages: 7802-7802

    • DOI

      10.1126/sciadv.aau7802

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Application of Consistent Massage-Like Perturbations on Mouse Calves and Monitoring the Resulting Intramuscular Pressure Changes2019

    • Author(s)
      Sakitani Naoyoshi、Maekawa Takahiro、Saitou Kumiko、Suzuki Katsuhiko、Murase Shuhei、Tokunaga Masakuni、Yoshino Daisuke、Sawada Keisuke、Takashima Atsushi、Nagao Motoshi、Ogata Toru、Sawada Yasuhiro
    • Journal Title

      Journal of Visualized Experiments

      Volume: 151 Issue: 151

    • DOI

      10.3791/59475

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 運動ってなんだ?~“Exercise is Medicine”を支えるサイエンスを拓く2019

    • Author(s)
      澤田泰宏
    • Journal Title

      実験医学

      Volume: 37 Pages: 1220-1224

    • Related Report
      2019 Annual Research Report
  • [Journal Article] Local cyclical compression modulates macrophage function in situ and alleviates immobilization-induced muscle atrophy2018

    • Author(s)
      1.Saitou K, Tokunaga M, Yoshino D, Sakitani N, Maekawa T, Ryu Y, Nagao M, Nakamoto H, Saito T, Kawanishi N, Suzuki K, Ogata T, Makuuchi M, Takashima A, Sawada K, Kawamura S, Nakazato K, Kouzaki K, Harada I, Ichihara Y, Sawada Y
    • Journal Title

      Clinical Science

      Volume: 132 Issue: 19 Pages: 2147-2161

    • DOI

      10.1042/cs20180432

    • NAID

      40021950316

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Effects of treadmill training combined with serotonergic interventions on spasticity after contusive spinal cord injury2018

    • Author(s)
      Ryu Y, Ogata T, Nishimura R. Sawada Y, Nagao M, Fujita N
    • Journal Title

      J Neurotrauma

      Volume: Epub ahead of print Issue: 12 Pages: 1358-1366

    • DOI

      10.1089/neu.2017.5400

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Presentation] Exercise is Mechanical Stress2019

    • Author(s)
      澤田泰宏
    • Organizer
      日本分子生物学会年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 細胞のメカニカルストレス応答を介する生体恒常性維持2019

    • Author(s)
      澤田泰宏、前川貴郊、﨑谷直義
    • Organizer
      日本生化学会年会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 体表からの局所的反復性圧迫は身体不活動により促進される単球/マクロファージの活性を抑制し骨格筋の萎縮を緩和する2018

    • Author(s)
      澤田泰宏、斎藤久美子、徳永正邦、市原克則、吉野大輔、前川貴郊、緒方徹、長尾元史
    • Organizer
      第91回日本生化学会大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 身体へのメカニカルストレスとしての運動の抗炎症作用2018

    • Author(s)
      澤田泰宏
    • Organizer
      第39回日本肥満学会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Local Cyclical Compression Modulates Macrophage Function In Situ and Alleviates Immobilization-Induced Muscle Atrophy. 10th Anniversary Symposium, Mechanobiology Institute.2018

    • Author(s)
      Yasuhiro Sawada
    • Organizer
      10th Anniversary Symposium, Mechanobiology Institute of Singapore
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Book] カレントテラピー2018

    • Author(s)
      澤田泰宏, 﨑谷直義
    • Total Pages
      2
    • Publisher
      ライフメディコム
    • Related Report
      2018 Annual Research Report
  • [Book] 別冊BIO Clinica2018

    • Author(s)
      澤田泰宏
    • Total Pages
      4
    • Publisher
      北隆館
    • Related Report
      2018 Annual Research Report
  • [Patent(Industrial Property Rights)] 健康促進装置2018

    • Inventor(s)
      小西あおい, 秋下雅弘, 澤田泰宏他
    • Industrial Property Rights Holder
      小西あおい, 秋下雅弘, 澤田泰宏他
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2017-104095
    • Filing Date
      2018
    • Acquisition Date
      2019
    • Related Report
      2019 Annual Research Report

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Published: 2018-04-23   Modified: 2022-01-27  

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