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Investigation of stress response mechanism of chondrocytes by reproduction of physiological hypoxic environment

Research Project

Project/Area Number 26462312
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Orthopaedic surgery
Research InstitutionKyoto Prefectural University of Medicine

Principal Investigator

Arai Yuji  京都府立医科大学, 医学(系)研究科(研究院), 准教授 (50347449)

Co-Investigator(Kenkyū-buntansha) 久保 俊一  京都府立医科大学, 医学(系)研究科(研究院), 教授 (20178031)
中川 周士  京都府立医科大学, 医学(系)研究科(研究院), 助教 (30643382)
土田 真嗣  京都府立医科大学, 医学(系)研究科(研究院), 助教 (10719834)
Project Period (FY) 2014-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
KeywordsHIF-1α / hyaluronic acid / CD44 / articular cartilage / extracellular matrix / hypoxia / 軟骨 / 低酸素 / ヒアルロン酸 / 変形性関節症 / 低酸素環境 / 細胞外マトリックス / 高分子ヒアルロン酸 / HSP70
Outline of Final Research Achievements

High molecular weight hyaluronic acid (HA) is widely used clinically as an intra-articular injection for osteoarthritis, but the pharmacological effect under hypoxic condition is not clear. The purpose of this study is to clarify the effect of HA on articular cartilage under hypoxia. It was revealed that the cartilage assimilatory pharmacological action of the exogenous macromolecule HA on articular cartilage is promoted in hypoxic condition. As a mechanism, it was shown that the expression of CD44 was enhanced by the HIF-1α pathway and the binding affinity to the exogenous polymer HA was improved. Maintaining the hypoxic environment around chondrocytes is important for exerting the anabolic effect of exogenous high molecular weight HA.

Report

(5 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (11 results)

All 2017 2016 2015 2014

All Journal Article (2 results) (of which Peer Reviewed: 2 results,  Open Access: 2 results) Presentation (9 results) (of which Int'l Joint Research: 4 results)

  • [Journal Article] Hypoxia Potentiates Anabolic Effects of Exogenous Hyaluronic Acid in Rat Articular Cartilage2016

    • Author(s)
      Ichimaru S. et al.
    • Journal Title

      Int J Mol Sci.

      Volume: 17 Issue: 7 Pages: 1013-1013

    • DOI

      10.3390/ijms17071013

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] HIF-1α-induced HSP70 regulates anabolic responses in articular chondrocytes under hypoxic conditions2014

    • Author(s)
      Tsuchida S, Arai Y, Takahashi KA, Kishida T, Terauchi R, Honjo K, Nakagawa S, Inoue H, Ikoma K, Ueshima K, Matsuki T, Mazda O, Kubo T
    • Journal Title

      J Orthop Res

      Volume: (Epub ahead of print) Issue: 8 Pages: 975-980

    • DOI

      10.1002/jor.22623

    • URL

      http://www.ncbi.nlm.nih.gov/pubmed/24677016

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] The effect of treadmill running on knee articular cartilage in rats2017

    • Author(s)
      Seiji Shimomura, Hiroaki Inoue, Yuji Arai, Shuji Nakagawa, Shinji Tsuchida, Shohei Ichimaru, Osam Mazda, Toshikazu Kubo
    • Organizer
      20th World Congress of the Osteoarthritis Research Society International (OARSI)
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Regulation of inflammatory cytokine expression and osteoclastgenesis by gap junctional protein in vitro and in vivo.2017

    • Author(s)
      Seiji Shimomura, Shinji Tsuchida, Yuji Arai, Shuji Nakagawa, Hiroaki Inoue, Shohei Ichimaru, Yuta Fujii, Osam Mazda, Toshikazu Kubo
    • Organizer
      The 5th annual meeting of the international cytokine and interferon society
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] トレッドミル走行がラット膝関節軟骨に与える影響2016

    • Author(s)
      下村征史,井上裕章,新井祐志,中川周士,土田真嗣,市丸昌平,松田 修,久保俊一
    • 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 Research-status Report
  • [Presentation] 低酸素環境下における外因性ヒアルロン酸の薬理効果の変化2016

    • Author(s)
      市丸昌平,中川周士,新井祐志,土田真嗣,井上裕章,下村征史,松田 修,久保俊一
    • 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 Research-status Report
  • [Presentation] Pharmacological effects of exogenous hyaluronan in articular cartilage under hypoxia2016

    • Author(s)
      Ichimaru S, Nakagawa S, Arai Y, Tsuchida S, Inoue H, Shimomura S, Mazda O, Kubo T
    • Organizer
      19th World Congress of the Osteoarthritis Research Society International (OARSI)
    • Place of Presentation
      Amsterdam, Netherlands
    • Year and Date
      2016-04-01
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Pharmacological effects of exogenous hyaluronic acid in articular cartilage under hypoxia2016

    • Author(s)
      Ichimaru S, Nakagawa S, Arai Y, Tsuchida S, Inoue H, Shimomura S, Mazda O, Kubo T
    • Organizer
      第29回日本軟骨代謝学会
    • Place of Presentation
      広島
    • Year and Date
      2016-02-19
    • Related Report
      2015 Research-status Report
  • [Presentation] 低酸素環境下にある軟骨細胞に対する外因性ヒアルロン酸の薬理効果2015

    • Author(s)
      市丸昌平,中川周士,新井祐志,土田真嗣,井上裕章,本城邦晃,白井寿治,寺内 竜,松田 修,久保俊一
    • Organizer
      第30回日本整形外科学会基礎学術集会
    • Place of Presentation
      富山
    • Year and Date
      2015-10-22
    • Related Report
      2015 Research-status Report
  • [Presentation] HSP70 induced by HIF-1α regulates anabolic responses in chondrocytes under hypoxic conditions2015

    • Author(s)
      Kuniaki Honjo, Shinji Tsuchida, Shuji Nakagawa, Hiroaki Inoue, Masazumi Saito, Shohei Ichimaru, Seiji Shimomura, Atsuo Inoue, Ryu Terauchi, Osam Mazda, Yoshikazu Kubo
    • Organizer
      World Congress of the Osteoarthritis Research Society International (OARSI) annual meeting 2015
    • Place of Presentation
      Seattle, USA
    • Year and Date
      2015-04-30
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] The anabolic effects of HIF-1α-induced HSP70 in rabbit articular chondrocyte under hypoxic conditions2015

    • Author(s)
      Shohei Ichimaru, Shinji Tsuchida, Yuji Arai, Shuji Nakagawa, Hiroaki Inoue, Tomohiro Matsuki, Kuniaki Honjo, Keiichiro Ueshima, Osam Mazda, Toshikazu Kubo
    • Organizer
      Orthopaedic Research Society 2015 annual meeting
    • Place of Presentation
      Las Vegas
    • Year and Date
      2015-03-28 – 2015-03-31
    • Related Report
      2014 Research-status Report

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Published: 2014-04-04   Modified: 2019-03-29  

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