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Development of isolation method of musculoskeletal system-derived exosomes and elucidation of the mechanism of individual functional decline caused by decreased physical activity

Research Project

Project/Area Number 19K22680
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 56:Surgery related to the biological and sensory functions and related fields
Research InstitutionTokyo Medical and Dental University

Principal Investigator

Sato Shingo  東京医科歯科大学, 医学部附属病院, 講師 (40462220)

Project Period (FY) 2019-06-28 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2020: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2019: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Keywords整形外科 / エクソソーム / 非コードRNA / 臓器間ネットワーク / メカニカルストレス
Outline of Research at the Start

本研究では、まず、血液中を循環しているエクソソームから、筋骨格系組織由来のエクソソームのみを単離・抽出する技術の開発を目指す。続いて、臓器間の情報伝達因子として作用しうる非コードRNA(以下ncRNA)に着目し、筋骨格系の機能低下に伴って血液中への分泌が変動する筋骨格系由来ncRNAの同定と、同定したncRNAが他臓器の機能低下に与える影響の解明を目指す。さらに、宇宙航空研究開発機構(JAXA)と共同で、宇宙微小重力空間で飼育されたマウスの血中ncRNA解析も実施し、究極の非荷重状態において血液中への分泌が変化する筋骨格系由来ncRNAの同定も目指す。

Outline of Final Research Achievements

In this study, we proceeded with the development of isolation method of musculoskeletal tissue-derived exosomes circulating in blood. In addition, we focused on non-coding RNA (ncRNA), which is known as a signal transduction factor between organs, and identified several ncRNAs whose expression in blood fluctuates with changes in mechanical stress or gravity. We also investigated the effect of identified ncRNAs on the functional decline of other organs. Furthermore, in collaboration with the Japan Aerospace Exploration Agency (JAXA), we plan to carry out a comprehensive expression analysis of ncRNA in the blood of mice bred in space microgravity environment, and various preliminary preparations were performed for space experiments.

Academic Significance and Societal Importance of the Research Achievements

寝たきりや加齢による筋骨格系の機能低下(骨密度低下、筋力低下)は、個体全体の機能低下を引き起こすため、社会的にも医学的にも大きな問題となっている。本研究にて同定したメカニカルストレス応答ncRNAは、個体の機能低下を予測する新規バイオマーカーとなる可能性を秘めており、また、このncRNAを標的とすることで、新たな抗加齢治療薬の開発も期待できる。筋骨格系ならびに個体の機能低下を抑制することができれば、国民の健康寿命は飛躍的に延伸し、一方で医療費・介護費の抑制が期待できる。

Report

(3 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • Research Products

    (19 results)

All 2021 2020 2019

All Journal Article (11 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 8 results,  Open Access: 7 results) Presentation (8 results) (of which Invited: 3 results)

  • [Journal Article] A novel PAI-1 inhibitor prevents ageing-related muscle fiber atrophy.2021

    • Author(s)
      Aihemaiti A, Yamamoto N, Piao J, Oyaizu T, Ochi H, Sato S, Okawa A, Miyata T, Tsuji K, Ezura Y, Asou Y.
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 534 Pages: 849-856

    • DOI

      10.1016/j.bbrc.2020.10.089

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Cyclin-Dependent Kinase 1 Is Essential for Muscle Regeneration and Overload Muscle Fiber Hypertrophy2020

    • Author(s)
      Kobayashi Yutaka、Tanaka Tomoyuki、Mulati Mieradilli、Ochi Hiroki、Sato Shingo、Kaldis Philipp、Yoshii Toshitaka、Okawa Atsushi、Inose Hiroyuki
    • Journal Title

      Frontiers in Cell and Developmental Biology

      Volume: 8 Pages: 1-14

    • DOI

      10.3389/fcell.2020.564581

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Identification of a Novel MAN1A1-ROS1 Fusion Gene Through mRNA-based Screening for Tyrosine Kinase Gene Aberrations in a Patient with Leiomyosarcoma2020

    • Author(s)
      Suehara Y, Kohsaka S, Hayashi T, Akaike K, Kurisaki-Arakawa A, Sato S, Kobayashi E, Mizuno S, Ueno T, Morii T, Okuma T, Kurihara T, Hasegawa N, Sano K, Sasa K, Okubo T, Kim Y, Mano H, Saito T
    • Journal Title

      Clin Orthop Relat Res

      Volume: - Issue: 4 Pages: 838-852

    • DOI

      10.1097/corr.0000000000001548

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Incidence of atypical femoral fractures in the treatment of bone metastasis: An alert report2020

    • Author(s)
      Kaku Takumi、Oh Yoto、Sato Shingo、Koyanagi Hirotaka、Hirai Takashi、Yuasa Masato、Yoshii Toshitaka、Nakagawa Tsuyoshi、Miyake Satoshi、Okawa Atsushi
    • Journal Title

      Journal of Bone Oncology

      Volume: 23 Pages: 100301-100301

    • DOI

      10.1016/j.jbo.2020.100301

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Surgical stabilization of spinal metastasis in diffuse idiopathic skeletal hyperostosis (“Mets-on-DISH”)2020

    • Author(s)
      Kawabata Atsuyuki、Hirai Takashi、Tohara Ryo、Yuasa Masato、Inose Hiroyuki、Koyanagi Hirotaka、Sato Shingo、Utagawa Kurando、Hashimoto Jun、Okawa Atsushi、Yoshii Toshitaka
    • Journal Title

      Medicine

      Volume: 99 Issue: 22 Pages: e20397-e20397

    • DOI

      10.1097/md.0000000000020397

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] ひとりじゃない、チームで行う骨転移診療2020

    • Author(s)
      佐藤信吾
    • Journal Title

      Bone Joint Nerve

      Volume: 10 Pages: 397-403

    • Related Report
      2020 Annual Research Report
  • [Journal Article] The long noncoding RNA Crnde regulates osteoblast proliferation through the Wnt/β-catenin signaling pathway in mice.2020

    • Author(s)
      Mieradili Mulati,Toshitaka Yoshii, Atsushi Okawa, Hiroyuki Inose
    • Journal Title

      Bone

      Volume: 130 Pages: 115076-115076

    • DOI

      10.1016/j.bone.2019.115076

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] The L-type amino acid transporter LAT1 inhibits osteoclastogenesis and maintains bone homeostasis through the mTORC1 pathway2019

    • Author(s)
      Ozaki Kakeru、Yamada Takanori、Horie Tetsuhiro、Ishizaki Atsushi、Hiraiwa Manami、Iezaki Takashi、Park Gyujin、Fukasawa Kazuya、Kamada Hikari、Tokumura Kazuya、Motono Mei、Kaneda Katsuyuki、Ogawa Kazuma、Ochi Hiroki、Sato Shingo、Kobayashi Yasuhiro、Shi Yun-Bo、Taylor Peter M.、Hinoi Eiichi
    • Journal Title

      Science Signaling

      Volume: 12 Issue: 589 Pages: 589-589

    • DOI

      10.1126/scisignal.aaw3921

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Pericytes as a Source of Osteogenic Cells in Bone Fracture Healing2019

    • Author(s)
      Supakul Sopak、Yao Kenta、Ochi Hiroki、Shimada Tomohito、Hashimoto Kyoko、Sunamura Satoko、Mabuchi Yo、Tanaka Miwa、Akazawa Chihiro、Nakamura Takuro、Okawa Atsushi、Takeda Shu、Sato Shingo
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 20 Issue: 5 Pages: 1079-1079

    • DOI

      10.3390/ijms20051079

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] 骨転移とマイクロRNA2019

    • Author(s)
      佐藤信吾
    • Journal Title

      BIO Clinica

      Volume: 34 Pages: 28-32

    • Related Report
      2019 Research-status Report
  • [Journal Article] ペリサイト(血管周皮細胞)は多分化能を有し骨折治癒に貢献する2019

    • Author(s)
      佐藤信吾
    • Journal Title

      臨床雑誌整形外科

      Volume: 70 Pages: 788-788

    • Related Report
      2019 Research-status Report
  • [Presentation] 多職種協働でがんロコモを防ぐ ~がん患者が最後まで「動ける」を目指した緩和ケアの実践~.2020

    • Author(s)
      佐藤信吾、酒井朋子、岡安健、野里洵子、入山哲次、高橋萌々子、岡梨津子、本松裕子、三宅智
    • Organizer
      緩和・支持・心のケア合同学術大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] デノスマブが支える運動器の健康 ~直ちに骨を守る行動を!~2020

    • Author(s)
      佐藤信吾
    • Organizer
      第60回関東整形災害外科学会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] TES施行後、隣接椎体の骨転移による歩行障害が出現し、その治療に難渋した症例2020

    • Author(s)
      佐藤信吾、平井高志、吉井俊貴、小柳広高、阿江啓介、湯浅将人、三宅智、大川淳
    • Organizer
      第53回日本整形外科学会骨軟部腫瘍学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 緩和ケアにおける整形外科医の意義を考える ~がん患者が最後まで「動ける」を目指した緩和ケアの実践~2020

    • Author(s)
      佐藤信吾、小柳広高、平井高志、湯浅将人、酒井朋子、三宅智、大川淳
    • Organizer
      第53回日本整形外科学会骨軟部腫瘍学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 骨転移キャンサーボードで示すがん診療における整形外科医の存在意義2020

    • Author(s)
      佐藤信吾、小柳広高、平井高志、湯浅将人、本橋正隆、大川淳
    • Organizer
      第69回東日本整形災害外科学会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 骨転移におけるがん細胞と骨の細胞とのコミュニケーション2020

    • Author(s)
      佐藤信吾、橋本恭子、越智広樹、大川淳、三宅智
    • Organizer
      第125回日本解剖学会総会・全国学術集会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] 骨細胞の長鎖ノンコーディングRNAによる骨代謝制御機構の解明2019

    • Author(s)
      佐藤信吾、荒井誠、越智広樹、砂村聡子、竹田秀、大川淳
    • Organizer
      第34回日本整形外科学会基礎学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] ペリサイト(血管周皮細胞)は多分化能を有し骨折治癒に貢献する2019

    • Author(s)
      佐藤信吾、Supakul Sopak、八尾健太、越智広樹、橋本恭子、砂村聡子、竹田秀、大川淳
    • Organizer
      第37回日本骨代謝学会学術集会
    • Related Report
      2019 Research-status Report

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Published: 2019-07-04   Modified: 2022-01-27  

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