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Functional analyses of chondroitin sulfate chains in bone remodeling and skeletal muscle plasticity

Research Project

Project/Area Number 20K06551
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 43030:Functional biochemistry-related
Research InstitutionKobe Pharmaceutical University

Principal Investigator

Mikami Tadahisa  神戸薬科大学, 薬学部, 講師 (20330425)

Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywordsコンドロイチン硫酸 / 組織リモデリング / 骨粗鬆症 / サルコペニア / 筋サテライト細胞 / 筋萎縮症
Outline of Research at the Start

超高齢化社会を迎えた本邦において、健康寿命の延伸を達成するためには運動器症候群の克服が不可欠である。その代表疾患である骨粗鬆症およびサルコペニアの発症要因は、加齢に伴う組織リモデリング機構の破綻であると捉えることができるが、その分子基盤の実体は不明である。本研究では、コンドロイチン硫酸(CS)鎖が加齢に伴い減少することを踏まえ、「運動器全般の正常な組織リモデリング機構が機能的CS鎖の発現により担保されている」という仮説の実証を試みる。

Outline of Final Research Achievements

Chondroitin sulfate (CS) chains are representative sulfated glycosaminoglycan polysaccharides covalently attached to distinct protein cores to form proteoglycans (CSPGs). CSPGs are ubiquitous extra/pericellular matrix components that contribute to creating microenvironmental niches to support diverse cellular processes, including cell adhesion, proliferation, differentiation, and regeneration. These multiple actions of CSPGs are largely exerted through the CS moieties with structural heterogeneity.
In this study, we focused on functional roles of CS chains in bone remodeling and skeletal muscle plasticity. We found the potential sites of action for CS chains to inhibit osteoclastogenesis, and the structural and functional characteristics of age-related CS chains in skeletal muscles.

Academic Significance and Societal Importance of the Research Achievements

本研究結果から、細胞周囲の微細環境を形づくるCS鎖が、骨や骨格筋といった運動器を支える構成要素の分化・再生過程を調節する多機能糖鎖であることを裏付けることができた。CS鎖の質的・量的な発現制御に主眼を置いた本研究の成果は、運動器症候群の原因疾患である骨粗鬆症やサルコペニアに対する新たな治療戦略の基盤構築に大きく貢献するものと期待される。

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (14 results)

All 2023 2022 2021 2020 Other

All Journal Article (7 results) (of which Peer Reviewed: 7 results,  Open Access: 3 results) Presentation (5 results) Remarks (2 results)

  • [Journal Article] Chondroitin sulfate glycosaminoglycans function as extra/pericellular ligands for cell surface receptors.2023

    • Author(s)
      Mikami, T., and Kitagawa, H.
    • Journal Title

      J. Biochem.

      Volume: 173 Issue: 5 Pages: 329-332

    • DOI

      10.1093/jb/mvac110

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Immunochemical detection and glycosaminoglycan disaccharide-based characterization of chondroitin sulfate proteoglycans.2023

    • Author(s)
      Mikami, T., and Kitagawa, H.
    • Journal Title

      Proteoglycans. Methods in Molecular Biology (ed. Karamanos, N.K.), Springer

      Volume: 2619 Pages: 25-38

    • DOI

      10.1007/978-1-0716-2946-8_2

    • ISBN
      9781071629451, 9781071629468
    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Genome-wide CRISPR screen for HSV-1 host factors reveals PAPSS1 contributes to heparan sulfate synthesis2022

    • Author(s)
      Suzuki Takeshi、Sato Yoshitaka、Okuno Yusuke、Goshima Fumi、Mikami Tadahisa、Umeda Miki、Murata Takayuki、Watanabe Takahiro、Watashi Koichi、Wakita Takaji、Kitagawa Hiroshi、Kimura Hiroshi
    • Journal Title

      Communications Biology

      Volume: 5 Issue: 1 Pages: 694-694

    • DOI

      10.1038/s42003-022-03581-9

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Altered sulfation status of FAM20C-dependent chondroitin sulfate is associated with osteosclerotic bone dysplasia.2022

    • Author(s)
      Koike, T., Mikami, T., Tamura, J., and Kitagawa, H.
    • Journal Title

      Nat. Commun.

      Volume: 13 Issue: 1 Pages: 7952-7952

    • DOI

      10.1038/s41467-022-35687-3

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Chondroitin Sulfate Glycosaminoglycans Regulate Distinct Cell Surface Receptor-Mediated Neuronal Functions2021

    • Author(s)
      Mikami Tadahisa、Kitagawa Hiroshi
    • Journal Title

      Trends in Glycoscience and Glycotechnology

      Volume: 33 Issue: 191 Pages: E11-E16

    • DOI

      10.4052/tigg.2004.1E

    • NAID

      130007974651

    • ISSN
      0915-7352, 1883-2113
    • Year and Date
      2021-01-25
    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Biosynthesis and Degradation of Glycans of the Extracellular Matrix: Sulfated Glycosaminoglycans, Hyaluronan, and Matriglycan2021

    • Author(s)
      Mikami Tadahisa、Kitagawa Hiroshi
    • Journal Title

      Comprehensive Glycoscience, 2nd edition (ed. Joe Barchi), Elsevier

      Volume: 3 Pages: 29-62

    • DOI

      10.1016/b978-0-12-819475-1.00018-3

    • ISBN
      9780128222447
    • Related Report
      2021 Research-status Report 2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Distinct effects of chondroitin sulfate on hematopoietic cells and the stromal microenvironment in bone marrow hematopoiesis.2021

    • Author(s)
      Takayuki Katagiri, Shun Uemura, Takashi Ushiki, Yaeko Nakajima-Takagi, Motohiko Oshima, Tadahisa Mikami, Asami Kawasaki, Hajime Ishiguro, Tomoyuki Tanaka, Hirohito Sone, Hiroshi Kitagawa, Michihiro Igarashi, Atsushi Iwama, Masayoshi Masuko
    • Journal Title

      Experimental hematology

      Volume: 96 Pages: 52-62

    • DOI

      10.1016/j.exphem.2021.02.003

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Presentation] 骨格筋におけるコンドロチン硫酸の加齢性構造変化と再生・維持機能に与える影響2022

    • Author(s)
      三上 雅久、北川 裕之
    • Organizer
      第41回日本糖質学会年会
    • Related Report
      2022 Annual Research Report
  • [Presentation] コンドロイチン硫酸の骨格筋維持機構における役割と加齢性構造変化2021

    • Author(s)
      三上雅久, 北川裕之
    • Organizer
      第44回日本分子生物学会年会
    • Related Report
      2021 Research-status Report
  • [Presentation] コンドロイチン硫酸-DによるインテグリンαVβ3の活性化は神経突起伸長や神経分化を制御する2021

    • Author(s)
      森下 雅子, 藤本 卓也, 志田 美春, 三上 雅久, 北川 裕之
    • Organizer
      日本薬学会141年会
    • Related Report
      2020 Research-status Report
  • [Presentation] コンドロイチン硫酸の骨格筋可塑性における役割と加齢性変化2020

    • Author(s)
      三上雅久, 北川裕之
    • Organizer
      第93回日本生化学会大会
    • Related Report
      2020 Research-status Report
  • [Presentation] 骨格筋内コンドロイチン硫酸鎖の加齢性構造変化とサルコペニア発症との関連2020

    • Author(s)
      井村 朱里, 藤本 麻里, 香川 倫乃, 伊藤 宜広, 三上 雅久, 北川 裕之
    • Organizer
      第70回日本薬学会関西支部大会
    • Related Report
      2020 Research-status Report
  • [Remarks] 神戸薬科大学生化学研究室ホームページ

    • URL

      https://www.kobepharma-u.ac.jp/biochem/

    • Related Report
      2022 Annual Research Report
  • [Remarks] 神戸薬科大学生化学研究室ホームページ

    • URL

      http://www.kobepharma-u.ac.jp/biochem/

    • Related Report
      2021 Research-status Report 2020 Research-status Report

URL: 

Published: 2020-04-28   Modified: 2024-01-30  

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