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Structure-function analysis of bacterial toxins in tissue destruction to apply their functional domains to regenerative medicine

Research Project

Project/Area Number 26460527
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Bacteriology (including mycology)
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) 内田 健太郎  北里大学, 医学部, 講師 (50547578)
美間 健彦  岡山大学, 医歯薬学総合研究科, 助教 (80596437)
Research Collaborator SAKON Joshua  University of Arkansas・Fulbright college of Arts and Sciences, Chemistry and Biochemistry Department, Professor
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords細菌毒素 / コラーゲン結合ドメイン / 細胞外マトリックス / 膠原線維 / アンカリング / 再生医療 / 骨新生 / 技術移転 / アンカーリング
Outline of Final Research Achievements

Flesh-eating bacteria produce collagenases to degrade collagen fibrils and to destruct the host tissue. The enzymes consist of a catalytic domain, PKD domain(s) (PKD), and collagen-binding domain(s) (CBD). Since PKD enhanced the binding of CBD to insoluble collagen, PKD-CBD region derived from a collagenase was used to anchor growth factors to collagenous matrix, e.g. high-density collagen sheet or demineralized bone matrix. These composite materials were utilized to induce osteogenesis at bone defect sites. 3D-structure of PKD was determined by X-ray crystallography, which gave an insight into the molecular basis of the collagen anchoring. Furthermore, dimeric CBD was shown to be an appropriate anchor for a synthetic collagenous matrix.

Report

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

    (24 results)

All 2017 2016 2015 2014 2013 Other

All Int'l Joint Research (2 results) Journal Article (9 results) (of which Peer Reviewed: 9 results,  Acknowledgement Compliant: 6 results,  Open Access: 2 results) Presentation (5 results) (of which Invited: 1 results) Remarks (3 results) Patent(Industrial Property Rights) (5 results) (of which Overseas: 3 results)

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

    • Related Report
      2016 Annual Research Report
  • [Int'l Joint Research] アーカンソー大学(米国)

    • Related Report
      2015 Research-status Report
  • [Journal Article] Oriented collagen tubes combined with basic fibroblast growth factor promote peripheral nerve regeneration in a 15 mm sciatic nerve defect rat model2017

    • Author(s)
      Fujimaki H, Uchida K, Inoue G, Miyagi M, Nemoto N, Saku T, Isobe Y, Inage K, Matsushita O, Yagishita S, Sato J, Takano S, Sakuma Y, Ohtori S, Takahashi K, Takaso M.
    • Journal Title

      J Biomed Mater Res A

      Volume: 105 Issue: 1 Pages: 8-14

    • DOI

      10.1002/jbm.a.35866

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Effect of Freeze-Dried Allograft Bone with Human Basic Fibroblast Growth Factor Containing a Collagen-Binding Domain From Clostridium Histolyticum Collagenase on Bone Formation After Lumbar Posterolateral Fusion Surgery in Rats2017

    • Author(s)
      Inoue G, Uchida K, Matsushita O, Fujimaki H, Saito W, Miyagi M, Sekiguchi H, Nishi N, Ohtori S, Yogoro M, Takaso M.
    • Journal Title

      Spine

      Volume: 印刷中 Issue: 17 Pages: 995-1001

    • DOI

      10.1097/brs.0000000000002074

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Acceleration of bone formation during fracture healing by poly(pro-hyp-gly)10 and basic fibroblast growth factor containing polycystic kidney disease and collagen-binding domains from Clostridium histolyticum collagenase2016

    • Author(s)
      Sekiguchi H, Uchida K, Inoue G, Matsushita O, Saito W, Aikawa J, Tanaka K, Fujimaki H, Miyagi M, Takaso M.
    • Journal Title

      J Biomed Mater Res A

      Volume: 104 Issue: 6 Pages: 1372-1378

    • DOI

      10.1002/jbm.a.35670

    • Related Report
      2016 Annual Research Report 2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Acceleration of callus formation during fracture healing using basic fibroblast growth factor-kidney disease domain-collagen-binding domain fusion protein combined with allogenic demineralized bone powder.2015

    • Author(s)
      Saito W, Uchida K, Matsushita O, Inoue G, Sekiguchi H, Aikawa J, Fujimaki H, Takaso M.
    • Journal Title

      J Orthop Surg Res.

      Volume: 10 Issue: 1 Pages: 59-59

    • DOI

      10.1186/s13018-015-0201-0

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Structures of three polycystic kidney disease-like domains from Clostridium histolyticum collagenases ColG and ColH.2015

    • Author(s)
      Bauer R, Janowska K, Taylor K, Jordan B, Gann S, Janowski T, Latimer EC, Matsushita O, Sakon J.
    • Journal Title

      Acta Crystallogr D Biol Crystallogr.

      Volume: 71 Issue: 3 Pages: 565-577

    • DOI

      10.1107/s1399004714027722

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Acceleration of periosteal bone formation by human basic fibroblast growth factor containing a collagen-binding domain from Clostridium histolyticum collagenase.2014

    • Author(s)
      Uchida K, Matsushita O, Naruse K, Mima T, Nishi N, Hattori S, Ogura T, Inoue G, Tanaka K, Takaso M.
    • Journal Title

      J Biomed Mater Res A.

      Volume: 102 Issue: 6 Pages: 1737-1743

    • DOI

      10.1002/jbm.a.34841

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Acceleration of bone union after structural bone grafts with a collagen-binding basic fibroblast growth factor anchored-collagen sheet for critical-size bone defects.2014

    • Author(s)
      Ueno M, Uchida K, Saito W, Matsushita O, Yogoro M, Nishi N, Ogura T, Hattori S, Inoue G, Tanaka K, Takahira N, Takaso M.
    • Journal Title

      Biomed Mater.

      Volume: 9 Issue: 3 Pages: 035014-035014

    • DOI

      10.1088/1748-6041/9/3/035014

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Direct cytocidal effect of galectin-9 localized on collagen matrices on human immune cell lines.2014

    • Author(s)
      Fukata Y, Itoh A, Nonaka Y, Ogawa T, Nakamura T, Matsushita O, Nishi N.
    • Journal Title

      Biochim Biophys Acta

      Volume: 1840 Issue: 6 Pages: 1892-1901

    • DOI

      10.1016/j.bbagen.2014.01.019

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Acceleration of bone formation during fracture healing by injectable collagen powder and human basic fibroblast growth factor containing a collagen-binding domain from Clostridium histolyticum collagenase2013

    • Author(s)
      Saito W, Uchida K, Ueno M, MatsushitaO, Inoue G, Nishi N, Ogura T, Hattori S, Fujimaki H, Tanaka K, Takaso M
    • Journal Title

      J Biomed Mater Res A

      Volume: in press Issue: 9 Pages: 3049-3055

    • DOI

      10.1002/jbm.a.34974

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Presentation] Structural analysis of a matrix anchor in bacterial collagenase to develop a therapeutic to induce osteogenesis.2017

    • Author(s)
      Osamu Matsushita, Kentaro Uchida, Hiroyuki Sekiguchi, Takehiko Mima, Kazuyoshi Goto, Yumiko Yamamoto, Kenji Yokota, Masashi Takaso, Ryan Bauer, Joshua Sakon
    • Organizer
      第90回日本細菌学会総会
    • Place of Presentation
      仙台国際センター(宮城県仙台市)
    • Year and Date
      2017-03-19
    • Related Report
      2016 Annual Research Report
  • [Presentation] 合成コラーゲン様基剤とコラーゲン結合型線維芽細胞増殖因子を用いた複合剤による骨形成促進法の開発2016

    • Author(s)
      濱本奈々,内田健太郎,関口裕之,美間健彦,後藤和義,山本由弥子,横田健治,高相晶士,松下 治
    • Organizer
      第89回日本細菌学会総会
    • Place of Presentation
      大阪府大阪市
    • Year and Date
      2016-03-23
    • Related Report
      2015 Research-status Report
  • [Presentation] 細菌毒素の機能性ドメインを用いた新規再生医療用複合材料2015

    • Author(s)
      松下 治,内田健太郎,西 望,小出隆規,Joshua Sakon
    • Organizer
      第15回日本蛋白質科学会年会
    • Place of Presentation
      徳島県徳島市
    • Year and Date
      2015-06-24
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] Growth factor delivery based on substrate-binding domains derived from a clostridial collagenase.2015

    • Author(s)
      松下 治、美間健彦、後藤和義、山本由弥子、横田憲治、内田健太郎
    • Organizer
      第88回日本細菌学会総会
    • Place of Presentation
      岐阜県岐阜市
    • Year and Date
      2015-03-26 – 2015-03-28
    • Related Report
      2014 Research-status Report
  • [Presentation] ガス壊疽菌コラゲナーゼの基質結合ドメインと再生医療への応用(第2報)2014

    • Author(s)
      松下 治、美間健彦、山本由弥子、後藤和義、西 望、小出隆規、内田健太郎、高相晶士、他5名
    • Organizer
      第61回トキシンシンポジウム
    • Place of Presentation
      徳島県鳴門市
    • Year and Date
      2014-09-03 – 2014-09-05
    • Related Report
      2014 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

    • Related Report
      2016 Annual Research Report 2014 Research-status Report
  • [Remarks] Okayama U. Grad. School of Med., Dept. Overview

    • URL

      http://www.hsc.okayama-u.ac.jp/mdps/e_side_552.html

    • Related Report
      2016 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

    • Related Report
      2015 Research-status Report
  • [Patent(Industrial Property Rights)] Collagen-binding agent compositions and methods of using same2017

    • Inventor(s)
      O Matsushita, K Uchida, J Sakon他
    • Industrial Property Rights Holder
      U Arkansas, Kitasato U.
    • Industrial Property Rights Type
      特許
    • Filing Date
      2017-02-10
    • Related Report
      2016 Annual Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] コラーゲン結合領域と副甲状腺ホルモンとの融合タンパク2015

    • Inventor(s)
      松下 治、サコン ジョシュア他
    • Industrial Property Rights Holder
      アーカンソー大学、香川大学、オクスナー クリニック
    • Industrial Property Rights Type
      特許
    • Filing Date
      2015-09-03
    • Acquisition Date
      2016-09-07
    • Related Report
      2016 Annual Research Report
  • [Patent(Industrial Property Rights)] Fusion proteins of collagen-binding domain and parathyroid hormone2015

    • Inventor(s)
      J Sakon, O Matsushita他
    • Industrial Property Rights Holder
      Ochsner, Kagawa U, U Arkansas
    • Industrial Property Rights Type
      特許
    • Filing Date
      2015-06-18
    • Acquisition Date
      2016-12-27
    • Related Report
      2016 Annual Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] 神経再生用移植材料、神経再生用移植材料の製造方法、及び神経再生用移植材料製造用キット2015

    • Inventor(s)
      内田,井上,藤巻,高相,佐久,礒部,松下,美間,西,服部,田中他
    • Industrial Property Rights Holder
      北里研究所、香川大学、株)アトリー、株)ニッピ
    • Industrial Property Rights Type
      特許
    • Filing Date
      2015-10-16
    • Related Report
      2015 Research-status Report
    • Overseas
  • [Patent(Industrial Property Rights)] 神経再生用移植材料、神経再生用移植材料の製造方法、及び神経再生用移植材料製造用キット2014

    • Inventor(s)
      内田健太郎、井上玄、藤巻寿子、高相晶士、佐久太郎、礒部仁博、他
    • Industrial Property Rights Holder
      北里研究所、香川大学、岡山大学、株)アトリー、株)ニッピ
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2014-212085
    • Filing Date
      2014-10-16
    • Related Report
      2014 Research-status Report

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Published: 2014-04-04   Modified: 2018-03-22  

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