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Analysis of cartilage protection by mechanical stress -miRNA and extracellular vesicles functions in osteoarthritis-

Research Project

Project/Area Number 16K10905
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Orthopaedic surgery
Research InstitutionOkayama University

Principal Investigator

Ohtsuki Takashi  岡山大学, 保健学研究科, 非常勤研究員 (10534802)

Co-Investigator(Kenkyū-buntansha) 古松 毅之  岡山大学, 大学病院, 講師 (20432651)
西田 圭一郎  岡山大学, 医歯薬学総合研究科, 准教授 (80284058)
廣畑 聡  岡山大学, 保健学研究科, 教授 (90332791)
品岡 玲  岡山大学, 医歯薬学総合研究科, 助教 (90724500)
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywordsエクソソーム / miRNA / マトリックス / ADAMTS / アグリカン / ヒアルロン酸 / コラーゲン / 変形性関節症 / micro RNA / メカニカルストレス
Outline of Final Research Achievements

We established the method how to purify Extracellular vesicles (EVs) from synovial fluid. Furthermore, we analyzed the effects of adding EVs in culture medium in mRNA expressions (matrix components and matrix degradative enzymes) by RT-PCR method. Using fluorescence labelled EVs and some inhibitors, we revealed EVs were up-taken by clathrin mediated endocytosis in chondrocyte.
We isolated several miRNAs that reduced inflammatory cytokine induced matrix degradative enzyme protein expression.

Academic Significance and Societal Importance of the Research Achievements

関節液からエクソソーム(EVs)の精製する方法を確立し、軟骨細胞へのEVs添加試験系を用いて滑液中EVsが周辺組織に作用するかを解析可能にした。また軟骨細胞のEVs取り込み機構を解明したことでEVs が変形性関節症(OA)にどのように関与するか、EVsの内包するどの成分(mRNA、miRNA、タンパク)が作用するのかという解析を行うことができるようになった。また、本研究でマトリックス分解酵素発現を抑制する可能性のあるmiRNAを同定し、これらmiRNAのタンパクレベルでのマトリックス分解因子産生抑制を確認した。OA治療薬としてのmiRNAの可能性が示された。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (22 results)

All 2019 2018 2017 2016

All Journal Article (5 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 5 results,  Open Access: 4 results) Presentation (17 results) (of which Int'l Joint Research: 3 results)

  • [Journal Article] A High-Fat and High-Cholesterol Diet Induces Cardiac Fibrosis, Vascular Endothelial, and Left Ventricular Diastolic Dysfunction in SHRSP5/Dmcr Rats2018

    • Author(s)
      Watanabe S, Kumazaki S, Kusunoki K, Inoue T, Maeda Y, Usui S, Shinohata R, Ohtsuki T, Hirohata S, Kusachi S, Kitamori K, Mori M, Yamori Y, Oka H.
    • Journal Title

      Journal of Atherosclerosis and Thrombosis

      Volume: 25 Issue: 5 Pages: 439-453

    • DOI

      10.5551/jat.40956

    • NAID

      130006729837

    • ISSN
      1340-3478, 1880-3873
    • Year and Date
      2018-05-01
    • Related Report
      2018 Annual Research Report 2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Host-produced ADAMTS4 inhibited early stage of tumor growth.2018

    • Author(s)
      Asano K, Edamatsu M, Hatipoglu O F, Cilek M Z, Inagaki J, Ohtsuki T, Oohashi T, Hirohata S.
    • Journal Title

      Acta Med Okayama.

      Volume: 2018 Pages: 257-266

    • NAID

      120006482820

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] High molecular weight hyaluronan protects cartilage from degradation by inhibiting aggrecanase expression.2018

    • Author(s)
      Ohtsuki T, Asano K, Inagaki J, Shinaoka A, Kumagishi-Shinaoka K, Cilek MZ, Hatipoglu OF, Oohashi T, Nishida K, Komatsubara I, Hirohata S.
    • Journal Title

      J Orthop Res.

      Volume: 36 Pages: 3247-3255

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Diverse Functions of a Disintegrin and Metalloproteinase with Thrombospondin Motif-12017

    • Author(s)
      廣畑 聡、稲垣 純子、大月 孝志
    • Journal Title

      YAKUGAKU ZASSHI

      Volume: 137 Issue: 7 Pages: 811-814

    • DOI

      10.1248/yakushi.16-00236-4

    • NAID

      130007287836

    • ISSN
      0031-6903, 1347-5231
    • Year and Date
      2017-07-01
    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Stromal Versican Regulates Tumor Growth by Promoting Angiogenesis2017

    • Author(s)
      Asano Keiichi、Nelson Courtney M.、Nandadasa Sumeda、Aramaki-Hattori Noriko、Lindner Daniel J.、Alban Tyler、Inagaki Junko、Ohtsuki Takashi、Oohashi Toshitaka、Apte Suneel S.、Hirohata Satoshi
    • Journal Title

      Scientific Reports

      Volume: 7 Issue: 1 Pages: 1-11

    • DOI

      10.1038/s41598-017-17613-6

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Isolation and characterization of extracellular microvesicles in osteoarthritis2019

    • Author(s)
      Liu Guole, Takashi Ohtsuki, Akira Shinaoka, Kana Komatsu, Yurika Notsu, Omer Faruk Hatipoglu, Takuto Nishimur, Miho Tatii, Junko Inagaki, Hiroshi Yamada, Keiichiro Nishida, Sun Liankun, Satoshi Hirohata
    • Organizer
      The 32th Annual meeting of the Japanese Society of Cartilage metabolism
    • Related Report
      2018 Annual Research Report
  • [Presentation] Isolation and characterization of Osteoarthritis concerning microRNA2018

    • Author(s)
      Takashi Ohtsuki, Omer Faruk Hatipoglu, Akira Shinaoka, Mehmet Zeynel Cilek, Takuto Nishimura, Keiichi Asano, Junko Inagaki, Toshitaka Oohashi, Keiichiro Nishida, Yasunori Okada, Satoshi Hirohata
    • Organizer
      Joint Conference of 50th Annual Meeting of the Japanese Society of Connective Tissue Research (JSCTR)
    • Related Report
      2018 Annual Research Report
  • [Presentation] Silencing of Important Molecules in Pathogenesis of Idiopathic Pulmonary Fibrosis via RNA interference2018

    • Author(s)
      OF Hatipoglu, E Uctepe, E. Gunduz, M. Gunduz, M. Aca, T Ohtsuki, J Inagaki, S Hirohata
    • Organizer
      Joint Conference of 50th Annual Meeting of the Japanese Society of Connective Tissue Research (JSCTR)
    • Related Report
      2018 Annual Research Report
  • [Presentation] Eosinophyl derived cationic protein purification and cardiomyoblast protection activity2018

    • Author(s)
      Takuto Nishimura, Miho Tachiki, Junko Inagaki, Omer faruk Hatipogl, Takashi Ohtsuki, Kentaro Ikemura, Liu Guole, Satoshi Hirohata
    • Organizer
      The 13th JAPANESE ASSOCIATION OF MEDICAL TECHONOLOGY EDUCATION
    • Related Report
      2018 Annual Research Report
  • [Presentation] Isolation and characterization of matrix degradative microRNA2018

    • Author(s)
      Takashi Ohtsuki, Omer Faruk Hatipoglu, Akira Shinaoka, Mehmet Zeynel Cilek, Takuto Nishimura, Keiichi Asano, Junko Inagaki, Toshitaka Oohashi, Keiichiro Nishida, Yasunori Okada, Satoshi Hirohata
    • Organizer
      10th Annual Meeting of the Japan CCN family study group
    • Related Report
      2018 Annual Research Report
  • [Presentation] Analysis of cartilage matrix degradation and regeneration mechanism2018

    • Author(s)
      Takashi Ohtsuki, Liu Guole, Omer Faruk Hatipoglu, Akira Shinaoka, Junko Inagaki, Ken Takahashi, Hiroshi Yamada, Toshitaka Ohashi, Keiichiro Nishida, Yasunori Okada, Suneel S, Apte, Satoshi Hirohata
    • Organizer
      Brainstorming 2018
    • Related Report
      2018 Annual Research Report
  • [Presentation] Purification and characterization of exosome from chondrocyte conditioned medium and analysis of exosome up-taking mechanism in chondrocyte2018

    • Author(s)
      Liu Guole, Takashi Ohtsuki, Akira Shinaoka, Kana Komatsu, Yurika Notsu, Omer Faruk Hatipoglu, Takuto Nishimura1, Miho Tatiki, Junko Inagaki, Hiroshi Yamada, Keiichiro Nishida, Sun Liankun, Satoshi Hirohata
    • Organizer
      Brainstorming 2018
    • Related Report
      2018 Annual Research Report
  • [Presentation] Mechanical stress attenuated inflammatory cytokines induced matrix degradative enzymes expression in chondrocyte by inhibition of NF-kB translocation2018

    • Author(s)
      Takashi Ohtsuki, Omer Faruk Hatipoglu, Guole Liu, Akira Shinaoka, Keiichi Asano, Takuto Nishimura, Junko Inagaki, Keiichiro Nishida, Toshitaka Oohashi, Satoshi Hirohata
    • Organizer
      American Society for Matrix Biology Biennial Meeting 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Isolation and characterization of extracellular microvesicles in osteoarthritis2018

    • Author(s)
      Liu Guole, Takashi Ohtsuki, Akira Shinaoka, Kana Komatsu, Yurika Notsu, Omer Faruk Hatipoglu, Takuto Nishimur, Miho Tatii, Junko Inagaki, Hiroshi Yamada, Keiichiro Nishida, Sun Liankun, Satoshi Hirohata
    • Organizer
      The 41st Annual Meeting of the molecular Biology Society of Japan
    • Related Report
      2018 Annual Research Report
  • [Presentation] HYBID (HYaluronan-Binding protein Involved in hyaluronan Depolymerization) 遺伝子の炎症性サイトカインによる発現機構解析2017

    • Author(s)
      大月孝志、吉田浩之、品岡玲、熊岸-品岡加苗、メフメット・ゼイネル・チレッキ、オメル・ファルク・ハティポール、稲垣純子、西田圭一郎、岡田保典 、廣畑聡 "
    • Organizer
      第30回日本軟骨代謝学会
    • Place of Presentation
      京都
    • Year and Date
      2017-03-03
    • Related Report
      2016 Research-status Report
  • [Presentation] INFLAMMATORY CYTOKINE INDUCED HYBID (HYALURONAN-BINDING PROTEIN INVOLVED IN HYALURONAN DEPOLYMERAZATION) -EXPRESSION MECHANISM-2017

    • Author(s)
      Takashi Ohtsuki, Lyu Chen, Hiroyuki Yoshida, Akira Shinaoka, Kanae Kumagishi-Shinaoka, Mehmet Zeynel Cilek, Omer Faruk Hatipoglu, Junko Inagaki, Keiichiro Nishida, Yasunori Okada, Satoshi Hirohata
    • Organizer
      HYALRONAN 2017
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] メカニカルストレスの軟骨細胞に及ぼす多彩な作用-マトリックス合成促進と炎症性サイトカイン誘導性マトリックス分解活性抑制2017

    • Author(s)
      大月孝志、品岡玲、熊岸-品岡加苗、メフメット・ゼイネル・チレッ、オメル・ファルク・ハティポール、稲垣純子、西田圭一郎、廣畑聡
    • Organizer
      第49回日本結合組織学会学術大会
    • Related Report
      2017 Research-status Report
  • [Presentation] がん微小環境におけるバーシカン分解酵素ADAMTSの局在と血管新生におけるバーシカンの意義2017

    • Author(s)
      浅野恵一、廣畑 聡、大月孝志、オメル・ファルク・ハティポール、稲垣純子、大橋俊孝
    • Organizer
      第49回日本結合組織学会学術大会
    • Related Report
      2017 Research-status Report
  • [Presentation] 炎症性サイトカイン誘導性マトリックス分解酵素発現のイオンチャネルを介した抑制機構解析2017

    • Author(s)
      大月孝志、品岡玲、熊岸-品岡加苗、オメル・ファルク・ハティポール、山之口奈保、岡田真澄、西村拓人、稲垣純子、西田圭一郎、廣畑聡
    • Organizer
      第40回日本分子生物学会年会 第90回日本生化学会大会 合同大会
    • Related Report
      2017 Research-status Report
  • [Presentation] Expression and proteolysis of the proteoglycan versican in the tumor microenvironment2016

    • Author(s)
      Keiichi Asano, Tyler Alban, Courtney Nelson, Junko Inagaki, Takashi Ohtsuki, Shozo Kusachi, Yoshifumi Ninomiya, Toshitaka Oohashi, Suneel Apte, Satoshi Hirohata
    • Organizer
      American Society for Matrix Biology Biennial Meeting 2016
    • Place of Presentation
      Florida, USA
    • Year and Date
      2016-11-13
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] 変形性膝関節症の治療効果に関する組織学的解析-ラットモデルを用いての検討-2016

    • Author(s)
      熊岸-品岡 加苗、大月孝志、廣畑聡、河村顕治、大塚愛二 、坂田賢一郎、坂田俊輔
    • Organizer
      第29回日本臨床整形外科学会学術集会
    • Place of Presentation
      札幌
    • Year and Date
      2016-08-31
    • Related Report
      2016 Research-status Report
  • [Presentation] 変形性関節症へのヒアルロン酸投与、いつ投与すべきか?~動物モデルからの知見~2016

    • Author(s)
      大月孝志、品岡玲、熊岸加苗、河野真優美、篠原真歩、浅野恵一、稲垣純子、大橋俊孝、西田圭一郎、廣畑聡
    • Organizer
      第48回日本結合組織学会学術大会
    • Place of Presentation
      長崎
    • Year and Date
      2016-06-24
    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2020-03-30  

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