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Chondrocyte glycome analysis reveals the pathogenesis of osteoarthritis

Research Project

Project/Area Number 19K18516
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 56020:Orthopedics-related
Research InstitutionHokkaido University

Principal Investigator

Homan Kentaro  北海道大学, 医学研究院, 博士研究員 (40823331)

Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2021: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2020: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywordsグライコーム / 変形性関節症 / 軟骨変性 / 糖鎖解析 / FUT8 / N-glycome / コアフコシル化 / 軟骨 / 関節軟骨 / 高マンノース型N型糖鎖 / 肥大化 / 糖鎖
Outline of Research at the Start

変形性関節症(OA)病変の首座である軟骨の変性は、プロテオグリカン中の糖鎖構造の破壊から始まる。これまでOAの発症に関する研究は軟骨細胞の肥大分化に着目したものが多く、複合糖質糖鎖の変化に言及したものはなかった。申請者らはこれまで軟骨基質の組織学的変化の出現前にN型糖鎖が変化することを明らかにするとともに、糖脂質が軟骨細胞肥大やOA進行に関わることを示してきた。そこで、軟骨組織変性および軟骨細胞の分化過程において相同的な糖鎖変動を検出するために、1種類の糖鎖クラスに限定せずに全クラスの糖鎖構造変化を定性・定量的に比較解析を行うことによりOA発症に中心的役割を果たす糖鎖を同定できると考えた。

Outline of Final Research Achievements

Degeneration of cartilage, the main component of osteoarthritis (OA) lesions, is believed to begin with the destruction of glycan structures in proteoglycans. Although many studies on the pathogenesis of OA have focused on the hypertrophic differentiation of chondrocytes, none have addressed changes in glycoconjugate sugar chains. We have shown that N-glycans are altered before the appearance of histological changes in the cartilage matrix and that glycosphingolipids are involved in chondrocyte hypertrophy and OA progression. Therefore, in order to detect homologous glycan variation during cartilage tissue degeneration and chondrocyte differentiation, we succeeded in identifying glycans that play a important role in the onset of OA by performing qualitative and quantitative comparative analysis of glycan structural changes in all classes of glycans without limiting to one glycan class.

Academic Significance and Societal Importance of the Research Achievements

糖鎖は同一のエピトープ構造にN-、O-結合型糖鎖、糖脂質などの異なるクラスの複合糖質を一塊として発現しており、あるクラスの糖鎖の合成不全が他の糖鎖で代償される可能性がある。軟骨変性や軟骨細胞の肥大分化の開始を理解するためには細胞全体が提示する糖鎖を網羅的に解析する必要がある。これまでグライコーム解析は時間や感度の問題から技術的に困難であったが、糖鎖の固相担体からの切断と同時に液体クロマトグラフィーや質量分析を用いて大規模かつ高速に糖鎖を解析できるグライコブロッティング法とピラゾロン試薬共存下にβ脱離反応を行う手法を確立することによってこの問題を克服した。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (12 results)

All 2022 2021 2020 2019

All Journal Article (4 results) (of which Peer Reviewed: 4 results,  Open Access: 3 results) Presentation (8 results) (of which Int'l Joint Research: 4 results)

  • [Journal Article] Optical coherence tomography evaluation of the spatiotemporal effects of 3D bone marrow stromal cell culture using a bioreactor2022

    • Author(s)
      Yamaguchi Jun、Onodera Tomohiro、Homan Kentaro、Liang Xu、Matsuoka Masatake、Miyazaki Takuji、Yoshiaki Hosokawa、Saito Mitsuru、Iwasaki Norimasa
    • Journal Title

      Journal of Biomedical Materials Research Part B: Applied Biomaterials

      Volume: - Issue: 8 Pages: 1-9

    • DOI

      10.1002/jbm.b.35043

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Flightless I is a catabolic factor of chondrocytes that promotes hypertrophy and cartilage degeneration in osteoarthritis2021

    • Author(s)
      Ebata Taku、Terkawi Mohamad Alaa、Hamasaki Masanari、Matsumae Gen、Onodera Tomohiro、Aly Mahmoud Khamis、Yokota Shunichi、Alhasan Hend、Shimizu Tomohiro、Takahashi Daisuke、Homan Kentaro、Kadoya Ken、Iwasaki Norimasa
    • Journal Title

      iScience

      Volume: 24 Issue: 6 Pages: 102643-102643

    • DOI

      10.1016/j.isci.2021.102643

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Quantification of Cartilage Surface Degeneration by Curvature Analysis Using 3D Scanning in a Rabbit Model2021

    • Author(s)
      Liang Dawei、Onodera Tomohiro、Hamasaki Masanari、Hishimura Ryosuke、Homan Kentaro、Xu Liang、Tian Yuan、Kanai Satoshi、Iwasaki Norimasa
    • Journal Title

      CARTILAGE

      Volume: 13 Issue: 2_suppl Pages: 1734S-1741S

    • DOI

      10.1177/19476035211059597

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Alteration of the Total Cellular Glycome during Late Differentiation of Chondrocytes2019

    • Author(s)
      Homan Kentaro、Hanamatsu Hisatoshi、Furukawa Jun-ichi、Okada Kazue、Yokota Ikuko、Onodera Tomohiro、Iwasaki Norimasa
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 20 Issue: 14 Pages: 3546-3546

    • DOI

      10.3390/ijms20143546

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 関節軟骨におけるフコシル化糖鎖の欠失は不可逆的な軟骨変性を惹起する2022

    • Author(s)
      宝満 健太郎, 小野寺 智洋, 花松 久寿, 古川 潤一, 宮崎 拓自, 山口 純, 細川 吉暁, 梁 大偉, 金 佑泳, 江畑 拓, 木村 洋介, 松岡 正剛, 岩崎 倫政
    • Organizer
      第34回日本軟骨代謝学会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Core-fucosylation deficiency inhibits recovery in early degenerative cartilage.2022

    • Author(s)
      K. Homan, T. Onodera, H. Hanamatsu, J. Furukawa, T. Miyazaki, J. Yamaguchi, K. Y. Hosokawa, T. Ebata, D. Liang, W. Kim, M. Matsuoka, N. Iwasaki.
    • Organizer
      The16th World Congress of International Chemical Reference Substances (ICRS)
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Deficiency of core-fucosylated glycan in articular cartilage inhibits recovery from cartilage damage and promotes cartilage degeneration.2021

    • Author(s)
      Kentaro Homan, Tomohiro Onodera, Hisatoshi Hanamatsu, Jun-ichi Furukawa, Takuji Miyazaki, Jun Yamaguchi, Taku Ebata, Dawei Liang, WooYoung Kim, Masatake Matsuoka, Norimasa Iwasaki.
    • Organizer
      The 67th Annual Meeting of Orthopaedic Research Society (ORS)
    • Related Report
      2021 Annual Research Report 2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] 細胞特異的糖鎖解析による定量評価を応用した未分化iPS細胞除去条件の最適化2021

    • Author(s)
      宮崎 拓自, 小野寺 智洋, 花松 久寿, 古川 潤一, 宝満 健太郎, 川嵜 敏祐, 岩崎 倫政
    • Organizer
      第36回日本整形外科基礎学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 関節軟骨におけるフコシル化糖鎖の欠損は可逆的修復を阻害し軟骨変性を進行させる2020

    • Author(s)
      宝満健太郎、小野寺智洋、古川潤一、花松久寿、濱崎雅成、徐亮、宮崎拓自、細川吉暁、岩崎倫政.
    • Organizer
      第35回日本整形外科学会基礎学術集会
    • Related Report
      2020 Research-status Report
  • [Presentation] Identification of M9 high-mannose glycan regulating hypertrophy in articular cartilage.2020

    • Author(s)
      Kentaro Homan, Tomohiro Onodera, Jun-ichi Furukawa, Masanari Hamasaki, Liang Xu, Takuji Miyazaki, Norimasa Iwasaki.
    • Organizer
      The 66th Annual Meeting of Orthopaedic Research Society (ORS)
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Identification of M9 high-mannose glycan regulating hypertrophy in articular cartilage.2019

    • Author(s)
      Kentaro Homan, Tomohiro Onodera, Jun-ichi Furukawa, Hisatoshi Hanamatsu, Ryosuke Hishimura, WooYoung Kim, Masanari Hamasaki, Liang Xu, Norimasa Iwasaki.
    • Organizer
      The15th World Congress of International Chemical Reference Substances (ICRS)
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] M9高マンノース型糖鎖は関節軟骨における肥大化を制御する2019

    • Author(s)
      宝満健太郎, 小野寺智洋, 花松久寿, 古川潤一, 菱村亮介, 金佑泳, 濱崎雅成, 徐亮, 岩崎倫政
    • Organizer
      第34回日本整形外科学会基礎学術集会
    • Related Report
      2019 Research-status Report

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Published: 2019-04-18   Modified: 2023-01-30  

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