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Elucidation of substrate recognition mechanism of bacterial collagenases to develop angiogenic drug seeds

Research Project

Project/Area Number 18K07111
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 49050:Bacteriology-related
Research InstitutionOkayama University

Principal Investigator

Matsushita Osamu  岡山大学, 医歯薬学総合研究科, 教授 (00209537)

Co-Investigator(Kenkyū-buntansha) 美間 健彦  愛媛県立医療技術大学, 保健科学部, 教授 (80596437)
内田 健太郎  北里大学, 医学部, 講師 (50547578)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywordsガス壊疽菌群 / 細菌性コラゲナーゼ / 基質アンカー・モジュール / 構造活性相関 / 歯槽骨再生 / 神経再生 / 歯周病 / 組織学的解析 / 行動学的解析 / 基質アンカー / 多発性嚢胞腎(PKD) / 構造生物学 / 歯槽骨 / 骨新生 / バイオマーカー / 細菌毒素 / 細胞外マトリックス / アンカリング / 再生医療 / 薬物シーズ
Outline of Final Research Achievements

Bacterial collagenases are composed of a catalytic module and an anchor module. Fibroblast growth factor (CB-bFGF) was fused with the anchor module to exert local tissue regeneration, e.g. osteogenesis, by binding to collagen matrix or tissue collagen fibrils. In this study, we successfully 1) showed how the multi-domain anchor module binds to collagen fibrils, 2) demonstrated that CB-bFGF- collagen matrix can induce osteogenesis using an alveolar horizontal bone defect model simulating periodontal disease, 3) showed that CB-bFGF can induce nerve regeneration by anchoring CB-FGF and medical device filled with collagen in the lumen of a biodegradable outer sheath using a nerve defect model.

Academic Significance and Societal Importance of the Research Achievements

細菌は様々な機能性ドメインを進化させ、時には真核細胞から遺伝子の水平伝播により機能性ドメインを獲得して、多様な環境で生存してきた。細菌性コラゲナーゼに着目し、2種類の機能性ドメインよりなる基質アンカーの構造と機能の関係を明らかにした。また、細菌の機能性ドメインを生理活性物質と融合することで、歯科領域の歯槽骨や歯周組織の欠損や整形・形成外科領域の神経欠損に対する組織再生用複合材を創出した。

Report

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

    (17 results)

All 2021 2020 2019 2018 Other

All Int'l Joint Research (3 results) Journal Article (3 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 3 results,  Open Access: 2 results) Presentation (5 results) (of which Invited: 1 results) Remarks (3 results) Patent(Industrial Property Rights) (3 results) (of which Overseas: 2 results)

  • [Int'l Joint Research] アーカンソー大学(米国)

    • Related Report
      2020 Annual Research Report
  • [Int'l Joint Research] アーカンソー大学(米国)

    • Related Report
      2019 Research-status Report
  • [Int'l Joint Research] University of Arkansas(米国)

    • Related Report
      2018 Research-status Report
  • [Journal Article] Polyglycolic acid‐collagen tube combined with collagen‐binding basic fibroblast growth factor accelerates gait recovery in a rat sciatic nerve critical‐size defect model2019

    • Author(s)
      Fujimaki Hisako、Uchida Kentaro、Inoue Gen、Matsushita Osamu、Nemoto Noriko、Miyagi Masayuki、Inage Kazuhide、Takano Shotaro、Orita Sumihisa、Ohtori Seiji、Tanaka Keisuke、Sekiguchi Hiroyuki、Takaso Masashi
    • Journal Title

      Journal of Biomedical Materials Research Part B: Applied Biomaterials

      Volume: 108 Issue: 2 Pages: 326-332

    • DOI

      10.1002/jbm.b.34391

    • Related Report
      2020 Annual Research Report 2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Acceleration of bone regeneration of horizontal bone defect in rats using collagen‐binding basic fibroblast growth factor combined with collagen scaffolds2019

    • Author(s)
      Nakamura Shin、Ito Takashi、Okamoto Kentaro、Mima Takehiko、Uchida Kentaro、Siddiqui Yasir D.、Ito Masahiro、Tai Masako、Okubo Keisuke、Yamashiro Keisuke、Omori Kazuhiro、Yamamoto Tadashi、Matsushita Osamu、Takashiba Shogo
    • Journal Title

      Journal of Periodontology

      Volume: - Issue: 9 Pages: 1-10

    • DOI

      10.1002/jper.18-0674

    • NAID

      120006860089

    • Related Report
      2019 Research-status Report 2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Ca2+-induced orientation of tandem collagen binding domains from clostridial collagenase ColG permits two opposing functions of collagen fibril formation and retardation.2018

    • Author(s)
      Caviness P, Bauer R, Tanaka K, Janowska K, Roeser JR, Harter D, Sanders J, Ruth C, Matsushita O, Sakon J.
    • Journal Title

      FEBS J.

      Volume: 285 Issue: 17 Pages: 3254-3269

    • DOI

      10.1111/febs.14611

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] 細菌性コラゲナーゼ由来コラーゲン・アンカーの構造活性相関と神経再生への応用2021

    • Author(s)
      松下 治、美間健彦、後藤和義、山本由弥子、Perry Caviness、Joshua Sakon、内田健太郎、藤巻寿子、井上 玄、高相晶士
    • Organizer
      第94回日本細菌学会総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 細菌性コラゲナーゼのコラーゲン・アンカーと歯周組織治療への応用2020

    • Author(s)
      松下 治、美間健彦、後藤和義、山本由弥子、Perry Caviness、Joshua Sakon、中村 心、岡本健太郎、高柴正悟
    • Organizer
      第93回日本細菌学会総会
    • Related Report
      2019 Research-status Report
  • [Presentation] 細菌性コラゲナーゼのコラーゲン・アンカーと歯周組織再生への応用2019

    • Author(s)
      松下 治、美間健彦、後藤和義、山本由弥子、Perry Caviness、Joshua Sakon、小出隆規、内田健太郎、中村 心、高柴正悟
    • Organizer
      第92回日本細菌学会総会
    • Related Report
      2019 Research-status Report
  • [Presentation] 悪玉クロストリジウムの毒素を薬に2019

    • Author(s)
      松下 治
    • Organizer
      第2回岡山消化器学術講演会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] コラーゲン結合型塩基性線維芽細胞成長因子とコラーゲン基剤を用いた複合剤の歯周組織再生への応用2018

    • Author(s)
      中村 心、伊東 孝、松下 治、岡本 憲太郎、美間 健彦、内田 健太郎、高柴 正悟、他7名
    • Organizer
      第61回秋季日本歯周病学会学術大会
    • Related Report
      2018 Research-status Report
  • [Remarks] 岡山大学 大学院医歯薬学総合研究科 病原細菌学分野

    • URL

      http://www.okayama-u.ac.jp/user/saikin/Bacteriology/Welcome.html

    • Related Report
      2020 Annual Research Report
  • [Remarks] 岡山大学 大学院医歯薬学総合研究科 病原細菌学分野

    • URL

      http://www.okayama-u.ac.jp/user/saikin/Bacteriology/Welcome.html

    • Related Report
      2019 Research-status Report
  • [Remarks] 岡山大学大学院医歯薬学総合研究科病原細菌学分野

    • URL

      http://www.okayama-u.ac.jp/user/saikin/Bacteriology/Welcome.html

    • Related Report
      2018 Research-status Report
  • [Patent(Industrial Property Rights)] Release of Growth Factors at Wound Healing Stages2021

    • Inventor(s)
      J Sakon, O Matsushita, 他3名
    • Industrial Property Rights Holder
      アーカンソー大学、岡山大学
    • Industrial Property Rights Type
      特許
    • Filing Date
      2021
    • Related Report
      2020 Annual Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] コラーゲン結合タンパク質による治療剤の送達2020

    • Inventor(s)
      サコン ジョシュア、松下 治、他6名
    • Industrial Property Rights Holder
      アーカンソー大学、北里研究所、他2法人
    • Industrial Property Rights Type
      特許
    • Patent Publication Number
      2020-073554
    • Filing Date
      2020
    • Related Report
      2020 Annual Research Report
  • [Patent(Industrial Property Rights)] FUSION PROTEINS OF COLLAGEN-BINDING DOMAIN AND PARATHYROID HORMONE2019

    • Inventor(s)
      Gensure, Sakon, 松下, Ponnapakkam
    • Industrial Property Rights Holder
      U Ark, Ochsner Clinic, Kagawa U
    • Industrial Property Rights Type
      特許
    • Filing Date
      2019
    • Acquisition Date
      2019
    • Related Report
      2019 Research-status Report
    • Overseas

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Published: 2018-04-23   Modified: 2022-01-27  

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