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Construction of therapeutic strategies for arthritis via ion channels in human synovial and chondrocytes.

Research Project

Project/Area Number 17K16690
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Orthopaedic surgery
Research InstitutionShiga University of Medical Science

Principal Investigator

Kumagai Kosuke  滋賀医科大学, 医学部, 助教 (50649366)

Project Period (FY) 2017-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2019: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2017: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywords変形性関節症 / 関節リウマチ / 滑膜細胞 / 炎症性サイトカイン / 細胞膜イオンチャネル / 軟骨変性疾患 / 軟骨細胞 / イオンチャネル / 再生医学 / シグナル伝達 / 関節変性疾患
Outline of Final Research Achievements

We have focused on the homeostasis maintenance mechanism of cells from the viewpoint of preventing the onset of joint degenerative diseases, and has conducted analysis centered on ion channels. Comprehensive miRNA expression profiling was performed from cultured synovial cells. From the results, disease-specific miRNAs were identified and verified, and related synovial proliferative potential was comprehensively analyzed for cytokines, growth factors, and transcription factors by the suspension array system. From the above, we were able to reach the point of narrowing down the target to some ion channels, but human cells have large individual differences and have not yet reached the point where reliable results can be obtained. Therefore, it is considered necessary to further increase the number of cases as a future research subject.

Academic Significance and Societal Importance of the Research Achievements

本研究の特色は、細胞の恒常性維持に関わるイオンチャネルを遺伝子レベルから網羅的に扱い、その分子機構・機能解析を客観的かつ定量的に行う点にある。今回の結果より細胞膜イオンチャネルを経路とした関節変性疾患の発症機序の解明、早期診断ならびにその予防といった臨床的応用、治療法の確立の一助となる知見を得ることが出来た。現時点でいくつかのイオンチャネルに標的候補を絞るところまでは到達することが出来たため、今後更なる解析が進めば、関節症発症のリスク管理や患者の訴えが関節変形を認めず疼痛のみの初期症状の際に、正確な診断を得ることが可能となると考えられる。

Report

(5 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (28 results)

All 2021 2020 2019 2018 2017

All Journal Article (6 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 6 results,  Open Access: 2 results) Presentation (22 results) (of which Int'l Joint Research: 14 results)

  • [Journal Article] Consideration of differences in drug usage between young-onset and elderly-onset rheumatoid arthritis with target of low disease activity2021

    • Author(s)
      Kumagai Kosuke、Okumura Noriaki、Amano Yasutaka、Yayama Takafumi、Mimura Tomohiro、Maeda Tsutomu、Kubo Mitsuhiko、Mori Kanji、Barrett-Jolley Richard、Imai Shinji
    • Journal Title

      Modern Rheumatology

      Volume: online Issue: 6 Pages: 1-10

    • DOI

      10.1080/14397595.2021.1883251

    • NAID

      120007009029

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effects of malalignment and disease activity on osteophyte formation in knees of rheumatoid arthritis patients2020

    • Author(s)
      Okumura Noriaki、Kawasaki Taku、Kubo Mitsuhiko、Yayama Takafumi、Mimura Tomohiro、Kumagai Kosuke、Maeda Tsutomu、Imai Shinji
    • Journal Title

      Journal of Orthopaedic Surgery

      Volume: 28 Issue: 1 Pages: 1-8

    • DOI

      10.1177/2309499020911852

    • NAID

      120006839259

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Pro-inflammatory Cytokines Drive Deregulation of Potassium Channel Expression in Primary Synovial Fibroblasts2020

    • Author(s)
      Haidar Omar、O’Neill Nathanael、Staunton Caroline A.、Bavan Selvan、O’Brien Fiona、Zouggari Sarah、Sharif Umar、Mobasheri Ali、Kumagai Kosuke、Barrett-Jolley Richard
    • Journal Title

      Frontiers in Physiology

      Volume: 11 Pages: 1-13

    • DOI

      10.3389/fphys.2020.00226

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Ischiofemoral impingement between the ischium and the posterior facet of the greater trochanter: A case report2018

    • Author(s)
      Mimura Tomohiro、Shibata Kohei、Tamura Sho、Okumura Noriaki、Kumagai Kosuke、Maeda Tsutomu、Mori Kanji、Imai Shinji
    • Journal Title

      Journal of Orthopaedic Science

      Volume: x Issue: 3 Pages: 500-504

    • DOI

      10.1016/j.jos.2018.08.029

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] P2X7 ionotropic receptor is functionally expressed in rabbit articular chondrocytes and mediates extracellular ATP cytotoxicity.2018

    • Author(s)
      Tanigawa H, Toyoda F, Kumagai K, Okumura N, Maeda T, Matsuura H, Imai S
    • Journal Title

      Purinergic Signal

      Volume: 14 Issue: 3 Pages: 245-258

    • DOI

      10.1007/s11302-018-9611-x

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Wnt signaling pathway correlates with ossification of the spinal ligament: A microRNA array and immunohistochemical study2018

    • Author(s)
      Yayama Takafumi、Mori Kanji、Okumura Noriaki、Nishizawa Kazuya、Kumagai Kosuke、Nakamura Akira、Imai Shinji
    • Journal Title

      Journal of Orthopaedic Science

      Volume: 23 Issue: 1 Pages: 26-31

    • DOI

      10.1016/j.jos.2017.09.024

    • Related Report
      2018 Research-status Report 2017 Research-status Report
    • Peer Reviewed
  • [Presentation] 変形性関節症および関節リウマチにおける膝関節滑膜線維芽細胞でのサイトカイン発現解析2020

    • Author(s)
      熊谷康佑, 奥村法昭, 豊田 太, 前田 勉, 谷川仁士, 彌山峰史, 久保充彦, 三村朋大, 斎藤英貴, 今井晋二
    • Organizer
      第35回日本整形外科学会基礎学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 術中Navigation使用下Journey II BCS症例における術後1年経過時の臨床成績2020

    • Author(s)
      熊谷康佑 久保充彦 前田勉 天野泰孝 上中一泰 荒木勧  藤川ひとみ 三村朋大 奥村法昭 川崎拓 松末吉隆 今井晋二
    • Organizer
      第50回日本人工関節学会
    • Related Report
      2019 Research-status Report
  • [Presentation] Differences in drug usage between EORA and YORA patients with target of low disease activity2019

    • Author(s)
      Kosuke Kumagai, Noriaki Okumura, Takafumi Yayama, Tomohiro Mimura, Yuki Furuya, Tsutomu Maeda, Mitsuhiko Kubo, Taku Kawasaki, Shinji Imai
    • Organizer
      EULAR 2019 Annual European Congress of Rheumatology coverage
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Anion channel activity in chondrocytes analyzed using in vitro osteoarthritis model.2019

    • Author(s)
      Kosuke Kumagai, Futoshi Toyoda, Caroline Staunton, Tsutomu Maeda, Hitoshi Tanigawa, Noriaki Okumura, Shinji Imai, Richard Barrett-Jolley
    • Organizer
      ICRS 2019 World Congress
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Cytokine-induced apoptosis in rabbit articular chondrocytes inhibited by COX-2 blocker via anion channel inactivation2019

    • Author(s)
      Kosuke Kumagai, Futoshi Toyoda, Mitsuhiko Kubo, Tsutomu Maeda, Hitoshi Tanigawa, Noriaki Okumura, Tomohiro Mimura, Takafumi Yayama, Hiroshi Matsuura, Shinji Imai
    • Organizer
      ICRS 2019 World Congress
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Navigation使用下Journey II BCSの術後短期臨床成績, 既存評価項目とキネマティクスの相関2019

    • Author(s)
      熊谷康佑 久保充彦 前田勉 上中一泰 荒木勧 藤川ひとみ 奥村法昭 三村朋大 川崎拓 松末吉隆 今井晋二
    • Organizer
      第92回日本整形外科学会学術総会
    • Related Report
      2019 Research-status Report
  • [Presentation] 家兎変形性関節症モデルにおける肉眼的軟骨病変形成以前の容積感受性Clーチャネルの役割とその分子実体の検討2019

    • Author(s)
      熊谷康佑 豊田太 前田勉 奥村法昭 谷川仁士 久保充彦 彌山峰史 松浦博 松末吉隆 今井晋二
    • 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] Reduction rate of rheumatoid factor reflects disease activity of rheumatoid arthritis2018

    • Author(s)
      N. Okumura, T. Kawasaki, T. Yayama, K. Kumagai, S. Imai
    • Organizer
      Annual European Congress of Rheumatology, EULAR 2018
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Efficacy of the Japanese forgotten joint score-12 as an outcome measure for total knee arthroplasty in a Japanese population2018

    • Author(s)
      T. Maeda, M. Kubo, K. Kumagai, K. Uenaka, S. Araki, H. Fujikawa, S. Imai, Y. Matsusue
    • Organizer
      OARSI 2018 World Congress in Osteoarthritis
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Analysis of anion channel activity in chondrocytes in vitro model of osteoarthritis2018

    • Author(s)
      K. Kumagai, F. Toyoda, C. Staunton, U. Sharif, R. Lewis, T. Maeda, H. Tanigawa, A. Mobasheri, R. Barrett-Jolley.
    • Organizer
      OARSI 2018 World Congress in Osteoarthritis
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] The COX-2 selective blocker inhibit cytokine-induced apoptosis in isolated articular chondrocytes2018

    • Author(s)
      K. Kumagai, F. Toyoda, M. Kubo, T. Maeda, H. Tanigawa, N. Okumura, T. Yayama, H. Matsuura, S. Imai
    • Organizer
      OARSI 2018 World Congress in Osteoarthritis
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Effect of denosumab on bone formation marker P1NP2018

    • Author(s)
      H. Tanigawa, T. Maeda, K. Kumagai, S. Imai
    • Organizer
      OARSI 2018 World Congress in Osteoarthritis
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] The effect of coronal alignment on the docotr-derived outcome, patient-reported outcome, and the patient satisfaction after total knee arthroplasty2018

    • Author(s)
      M. Kubo, T. Maeda, K. Kumagai, S. Imai
    • Organizer
      OARSI 2018 World Congress in Osteoarthritis
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] ウサギ軟骨細胞におけるATP受容体サブタイプP2X7の機能的発現 P2X7活性化を介したATP誘発性軟骨細胞障害の検討2018

    • Author(s)
      谷川 仁士, 熊谷 康佑, 前田 勉, 奥村 法昭, 豊田 太, 松浦 博, 今井 晋二
    • Organizer
      第33回 日本整形外科学会基礎学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] 変形性関節症モデルにおける疾患発症因子としての容積感受性Cl-チャネルの役割とその分子実体の検討2018

    • Author(s)
      熊谷 康佑, 豊田 太, 前田 勉, 奥村 法昭, 谷川 仁士, 久保 充彦, 彌山 峰史, 松浦 博, 松末 吉隆, 今井 晋二
    • Organizer
      第33回 日本整形外科学会基礎学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] ANALYSIS OF ANION CHANNEL ACTIVITY IN CHONDROCYTES IN VITRO MODEL OF OSTEOARTHRITIS.2018

    • Author(s)
      K. Kumagai, F. Toyoda, C. Staunton, U. Sharif, R. Lewis, T. Maeda, H. Tanigawa, A. Mobasheri, R. Barrett-Jolley.
    • Organizer
      OARSI 2018 World Congress in Osteoarthritis
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] THE COX-2 SELECTIVE BLOCKER INHIBIT CYTOKINE-INDUCED APOPTOSIS IN ISOLATED ARTICULAR CHONDROCYTES.2018

    • Author(s)
      K. Kumagai, F. Toyoda, M. Kubo, T. Maeda, H. Tanigawa, N. Okumura, T. Yayama, H. Matsuura, S. Imai
    • Organizer
      OARSI 2018 World Congress in Osteoarthritis
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] EFFICACY OF THE JAPANESE FORGOTTEN JOINT SCORE-12 AS AN OUTCOME MEASURE FOR TOTAL KNEE ARTHROPLASTY IN A JAPANESE POPULATION2018

    • Author(s)
      T. Maeda, M. Kubo, K. Kumagai, K. Uenaka, S. Araki, H. Fujikawa, S. Imai, Y. Matsusue
    • Organizer
      OARSI 2018 World Congress in Osteoarthritis
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] THE EFFECT OF CORONAL ALIGNMENT ON THE DOCOTR-DERIVED OUTCOME, PATIENT-REPORTED OUTCOME, AND THE PATIENT STISFACTION AFTER TOTAL KNEE ARTHROPLASTY2018

    • Author(s)
      M. Kubo, T. Maeda, K. Kumagai, S. Imai
    • Organizer
      OARSI 2018 World Congress in Osteoarthritis
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] EFFECT OF DENOSUMAB ON BONE FORMATION MARKER P1NP2018

    • Author(s)
      H. Tanigawa, T. Maeda, K. Kumagai, S. Imai
    • Organizer
      OARSI 2018 World Congress in Osteoarthritis
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Early activation of volume-sensitive Cl- current in the rabbit knee anterior cruciate ligament transection2018

    • Author(s)
      K. Kumagai, F. Toyoda, T. Maeda, H. Tanigawa, N. Okumura, H. Matsuura, S. Imai
    • Organizer
      第95回日本生理学会大会
    • Related Report
      2017 Research-status Report
  • [Presentation] ウサギ変形性関節症モデルにおける疾患発症因子としての容積感受性Cl-チャネルの役割の検討2017

    • Author(s)
      熊谷康佑 豊田太 前田勉 奥村法昭 谷川仁士 久保充彦 松浦博 松末吉隆 今井晋二
    • Organizer
      第32回日本整形外科学会基礎学術集会
    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2022-01-27  

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