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Molecular Mechanisms of How Mechanical Stress Regulates Inflammation of Locomotive Organs

Research Project

Project/Area Number 15H01820
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Rehabilitation science/Welfare engineering
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), その他部局等, 臨床研究開発部長 (50313135)

Co-Investigator(Kenkyū-buntansha) 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)
本田 浩章  東京女子医科大学, 医学部, 教授 (40245064)
江面 陽一  東京医科歯科大学, 難治疾患研究所, 准教授 (50333456)
宮崎 剛  地方独立行政法人東京都健康長寿医療センター(東京都健康長寿医療センター研究所), 東京都健康長寿医療センター研究所, 研究員 (50376480)
矢野 文子  東京大学, 医学部附属病院, 特任講師 (80529040)
中田 雄一郎  広島大学, 原爆放射線医科学研究所, 助教 (90793430)
Co-Investigator(Renkei-kenkyūsha) TAKEDA Shin'ichi  独立行政法人国立精神・神経医療研究センター, 神経研究所遺伝子疾患治療研究部, 部長 (90171644)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥39,390,000 (Direct Cost: ¥30,300,000、Indirect Cost: ¥9,090,000)
Fiscal Year 2017: ¥10,140,000 (Direct Cost: ¥7,800,000、Indirect Cost: ¥2,340,000)
Fiscal Year 2016: ¥14,040,000 (Direct Cost: ¥10,800,000、Indirect Cost: ¥3,240,000)
Fiscal Year 2015: ¥15,210,000 (Direct Cost: ¥11,700,000、Indirect Cost: ¥3,510,000)
Keywordsメカニカルストレス / 適度な運動 / 抗炎症・抗老化 / 不動性筋萎縮 / 炎症 / マクロファージ / リハビリテーション / メカノバイオロジー / 骨代謝
Outline of Final Research Achievements

We investigated molecular mechanisms underlying the beneficial effects of physical exercise on our health. To this end, we generated genetically modified mice in which the expression of a protein called Cas was deleted in osteocytes, the mechanosensory cells in bones. This Cas KO mice exhibited severe osteoporosis caused by excessive bone resorption with hyperactivation of inflammatory proteins. When we applied mechanical stress on cultured osteocytes, Cas translocated into the nucleus, leading to inactivation of an inflammatory protein and decreased expression of a bone resorption-enhancing protein. These results suggest that Cas is responsible for mediating‘optimal exercise’effects.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Annual Research Report
  • 2015 Annual Research Report
  • Research Products

    (18 results)

All 2018 2017 2016 2015 Other

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

  • [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
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Chd7 collaborates with Sox2 to regulate activation of oligodendrocyte precursor cells after spinal cord injury2017

    • Author(s)
      Doi T, Ogata T, Yamauchi J, Sawada Y, Tanaka S, Nagao M
    • Journal Title

      J Neurosci

      Volume: 37(43) Issue: 43 Pages: 10290-10309

    • DOI

      10.1523/jneurosci.1109-17.2017

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Oligodendrocyte progenitor cells directly utilize lactate for promoting cell cycling and differentiation.2017

    • Author(s)
      Ichihara Y, Doi T, Ryu Y, Nagao M, Sawada Y, Ogata T
    • Journal Title

      J Cell Physiol

      Volume: 232 Pages: 986-995

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] New mouse model of skeletal muscle atrophy using spiral wire immobilization2016

    • Author(s)
      Onda A, Kono H, Jiao Q, Akimoto T, Miyamoto T, Sawada Y, Suzuki K, Kusakari Y, Minamisawa S, Fukubayashi T
    • Journal Title

      Muscle Nerve

      Volume: 54 Issue: 4 Pages: 788

    • DOI

      10.1002/mus.25202

    • URL

      https://localhost/en/publications/92025944-65a3-40ea-ad02-6849e98f15cd

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] MEKK1-dependent phosphorylation of calponin-3 tunes cell contractility2016

    • Author(s)
      Hirata H, Ku WC, Yip AK, Ursekar CP, Kawauchi K, Roy A, Guo AK, Vedula SR, Harada I, Chiam KH, Ishihama Y, Lim CT, Sawada Y, Sokabe M
    • Journal Title

      J Cell Sci

      Volume: 129(19) Issue: 19 Pages: 3574-3582

    • DOI

      10.1242/jcs.189415

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Zbtb20 promotes astrocytogenesis during neocortical development2016

    • Author(s)
      Nagao, M., Ogata, T., Sawada, Y., Gotoh, Y.
    • Journal Title

      Nature Communications

      Volume: 7 Issue: 1 Pages: 11102-11102

    • DOI

      10.1038/ncomms11102

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Association between tensin 1 and p130Cas at focal adhesions links actin inward flux to cell migration2016

    • Author(s)
      Zhao Z, Tan SH, Machiyama H, Kawauchi K, Araki K, Hirata H, Sawada Y
    • Journal Title

      Biology Open

      Volume: 5 Issue: 4 Pages: 1-8

    • DOI

      10.1242/bio.016428

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Mechanical Regulation and Maintenance of Organismal Homeostasis – Scientific Basis for Health Promotion by Physical Motility and Exercise.2016

    • Author(s)
      Sawada Y, Ichihara Y, Harada I.
    • Journal Title

      Juntendo Medical Journal

      Volume: 5 Pages: 5-12

    • NAID

      130005865705

    • Related Report
      2015 Annual Research Report
  • [Presentation] 1生体へのメカニカルストレスとしての身体運動・スポーツ・理学療法2017

    • Author(s)
      澤田泰宏
    • Organizer
      第39回日本分子生物学会年会 第90回日本生化学会大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] メカニカルストレス応答を介する生体恒常性維持 ― 障害性メカニカルストレスと治療的メカニカルストレス2016

    • Author(s)
      澤田泰宏
    • Organizer
      第39回日本分子生物学会年会
    • Place of Presentation
      横浜
    • Year and Date
      2016-11-30
    • Related Report
      2016 Annual Research Report
  • [Presentation] 「治療型」メカニカルストレスと「障害型」メカニカルストレス.2016

    • Author(s)
      澤田泰宏
    • Organizer
      第31回日本整形外科学会基礎学術集会
    • Place of Presentation
      福岡
    • Year and Date
      2016-10-13
    • Related Report
      2016 Annual Research Report
  • [Presentation] 1生体のメカノセンシングを介する恒常性維持 -「善玉」メカニカルストレスと「悪玉」メカニカルストレス2016

    • Author(s)
      澤田泰宏
    • Organizer
      第43回日本生体電気・物理刺激研究会
    • Place of Presentation
      和歌山
    • Year and Date
      2016-03-05
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 「緊張型」と「緩和型」のメカニカルストレスによる生体恒常性維持2015

    • Author(s)
      澤田泰宏
    • Organizer
      第42 回日本臨床バイオメカニクス学会シンポジウム
    • Place of Presentation
      東京
    • Year and Date
      2015-11-26
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 4メカニカルストレスによる生体機能制御 ― 恒常性維持に「善玉」あるいは「悪玉」として作用するメカニカルストレス2015

    • Author(s)
      澤田泰宏
    • Organizer
      第15回日本Men's Health医学会
    • Place of Presentation
      越谷
    • Year and Date
      2015-09-04
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 生体恒常性維持における「善玉」メカニカルストレスと「悪玉」メカニカルストレス2015

    • Author(s)
      澤田泰宏
    • Organizer
      第1回日本筋学会学術集会
    • Place of Presentation
      国立精神・神経医療研究センター
    • Year and Date
      2015-08-08
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Cell mechano-sensing and organismal homeostasis - Exploration of optimal exercise based on mechanobiology2015

    • Author(s)
      Sawada Y.
    • Organizer
      International Symposium on Nanoarchitectonics for Mechanobiology
    • Place of Presentation
      筑波
    • Year and Date
      2015-07-29
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Remarks]

    • URL

      http://www.rehab.go.jp/ri/undou/2014Oct-J/141204SY.pdf

    • Related Report
      2016 Annual Research Report
  • [Patent(Industrial Property Rights)] 健康促進装置2017

    • Inventor(s)
      小西あおい, 秋下雅弘, 澤田泰宏, 柳泳在 他
    • Industrial Property Rights Holder
      株式会社甦蓑家
    • Industrial Property Rights Type
      特許
    • Filing Date
      2017
    • Related Report
      2017 Annual Research Report

URL: 

Published: 2015-04-16   Modified: 2019-03-29  

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