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Elucidation of osteoclast differentiation by exosome isolated from mechanical stress-stimulated osteocyte.

Research Project

Project/Area Number 18K11019
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 59040:Nutrition science and health science-related
Research InstitutionMie University

Principal Investigator

ITOH Tomohiro  三重大学, 生物資源学研究科, 准教授 (30435854)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywordsメカニカルストレス / 骨細胞 / 破骨細胞分化 / 膜小胞 / 骨代謝 / マイクロRNA / CD9 / CD63 / ショットガンプロテオーム解析 / エクソソーム / 破骨細胞 / 分化 / 膜微小胞
Outline of Final Research Achievements

Osteocyte, which is the most abundant cell in bone tissues, is well known as a mechanical stress (MS) receiving cell. During bone remodelling, bone resorption by osteoclasts precedes bone formation by osteoblasts. However, its mechanism is still unknown. In this study, we examined whether exosome released from osteocyte by MS stimulation are involved in osteoclast differentiation.
Though the vesicles isolated from mechanical stress-loaded MLO-Y4 cells had no effect against osteoblast differentiation, these vesicles significantly induced osteoclast differentiation. To characterize the mechanisms by which mechanical stress-loaded MLO-Y4 cell vesicles induces osteoclast differentiation in murine macrophage RAW264.7 cells, we analysed vesicle membrane and vesicle internal proteins by nano-LC-MS/MS-based shotgun proteomics. As a result, Protein X , CD9 and CD63 were only detected in mechanical stress-loaded MLO-Y4 cell vesicles.

Academic Significance and Societal Importance of the Research Achievements

私たちが日常の生活活動する中で起きる骨代謝の基本機構である「まず骨が壊され,新しい骨が作られる」というホメオスタシス機構について様々な知見が報告されているが,未解明なところが多い。本研究では,成長期の体重増によるメカニカルストレスを受けた際の骨代謝時に骨細胞から分泌される膜小胞が深く関与していることを示すことができ,骨のホメオスタシス機構の一機構を明らかにできた点で学術的意義があった。また,骨代謝における膜小胞の役割(機能)を見出すことで,超高齢化社会の中で増える骨粗鬆症患者への治療薬への応用利用など発展性が期待できた点では社会的意義ある研究成果を導くことができたと考える。

Report

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

    (11 results)

All 2021 2020 2019 2018 Other

All Journal Article (5 results) (of which Peer Reviewed: 5 results,  Open Access: 2 results) Presentation (4 results) (of which Int'l Joint Research: 1 results) Remarks (2 results)

  • [Journal Article] Citrulluside H and citrulluside T from young watermelone (Citrullus lanatus) fruit attenuate ultraviolet B radiation-induced matrix metalloproteinase expression through the scavenging of generated reactive oxygen species in human dermal fibroblast.2021

    • Author(s)
      Tomohiro Itoh, Singo Fujita, Masayuki NInomiya, Mamoru Koketsu, Toshiharu Hashizume.
    • Journal Title

      Photodermatology, Photoimmunology & Photomedicine

      Volume: 00 Issue: 5 Pages: 1-9

    • DOI

      10.1111/phpp.12669

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Phenolic glycosides from young fruits of Citrullus lanatus.2020

    • Author(s)
      Masayuki Ninomiya, Tomohiro Itoh, Shingo Fujita, Toshiharu Hashizume, Mamoru Koketsu.
    • Journal Title

      Phytochemistry Letters

      Volume: 40 Pages: 135-138

    • DOI

      10.1016/j.phytol.2020.09.014

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Evaluation of the inhibition of mercury absorption by vegetable juices using a red sea bream intestine model2020

    • Author(s)
      Masashi Ando, Takahiro Yamada, Yoichiro Okinaga, Etsuko Taguchi, You Sugimoto,Akiko Takeuchi, Tomohiro Itoh, Takashi Fukuda, Yasuyuki Tsukamasa
    • Journal Title

      Food Chemistry

      Volume: 303 Pages: 12535-12535

    • DOI

      10.1016/j.foodchem.2019.125351

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] MicroRNA-141-3p and microRNA-200a-3p regulate α-melanocyte stimulating hormone-stimulated melanogenesis by directly targeting microphthalmia-associated transcription factor.2020

    • Author(s)
      Itoh T, Fukatani K, Nakashima A, Suzuki K.
    • Journal Title

      Sci. Rep.

      Volume: 10 Issue: 1 Pages: 2149-2149

    • DOI

      10.1038/s41598-020-58911-w

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Comparative analysis of stilbene and benzofuran neolignan derivatives as acetylcholinesterase inhibitors with neuroprotective and anti-inflammatory activities.2019

    • Author(s)
      Nagumo M, Ninomiya M, Oshima N, Itoh T, Tanaka K, Nishina A, Koketsu M.
    • Journal Title

      Bioorg. Med. Chem. Lett.

      Volume: 29 Issue: 17 Pages: 2475-2479

    • DOI

      10.1016/j.bmcl.2019.07.026

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Presentation] メカニカルストレス負荷骨目細胞が分泌する膜小胞による破骨細胞分化誘導2020

    • Author(s)
      伊藤智広,伊藤裕子,赤尾幸博
    • Organizer
      日本細胞外小胞学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] The exosome that are released from mechanical stress-loaded osteocyte induces osteoclastogenesis.2019

    • Author(s)
      Tomohiro ITOH
    • Organizer
      International society for extracellular vesicles annunal meeting ISEV2019
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] miRNA-294によるマウス骨芽細胞株MC3T3-E1細胞の分化制御機構2019

    • Author(s)
      伊藤智広,赤尾幸博
    • Organizer
      日本分子生物学会
    • Related Report
      2019 Research-status Report
  • [Presentation] メカニカルストレス負荷骨細胞から分泌されたexosomeは破骨細胞の分化を誘導する2018

    • Author(s)
      伊藤智広,赤尾幸博
    • Organizer
      2018年度日本分子生物学会(横浜市,パシフィコ横浜)
    • Related Report
      2018 Research-status Report
  • [Remarks] 三重大学大学院 生物資源学研究科 水圏材料分子化学教育研究分野ホームページ

    • URL

      http://www.bio.mie-u.ac.jp/seimei/marine/mcam

    • Related Report
      2020 Annual Research Report
  • [Remarks] 三重大学大学院生物資源学研究科 水圏材料分子化学研究分野ホームページ

    • URL

      https://tomo-itoh.wixsite.com/mie-uni-mcam

    • Related Report
      2019 Research-status Report

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Published: 2018-04-23   Modified: 2022-12-28  

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