• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Mechanisms of the osteoblast-like phenotypic conversion and its application to regenerative therapy of bone diseases

Research Project

Project/Area Number 17H04316
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Orthopaedic surgery
Research InstitutionKyoto Prefectural University of Medicine

Principal Investigator

Mazda Osam  京都府立医科大学, 医学(系)研究科(研究院), 教授 (00271164)

Co-Investigator(Kenkyū-buntansha) 菅波 晃子  千葉大学, 大学院医学研究院, 助教 (10527922)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥17,030,000 (Direct Cost: ¥13,100,000、Indirect Cost: ¥3,930,000)
Fiscal Year 2019: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2018: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2017: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
Keywordsダイレクト・リプログラミング / 骨芽細胞 / 再生医学 / ダイレクト・コンヴァージョン / 再生医療
Outline of Final Research Achievements

Recently we established procedures to directly convert human fibroblasts into osteoblasts by transducing some transcription factor genes or by treating the cells with a chemical compound. To apply this technology to bone regenerative therapy, it should be important to determine optimal procedures of the reprogramming, to understand the mechanisms of reprogramming, and to create 3D bone tissue in culture that is suitable for tailor-made autologous transplantation. In this project we explored chemical compounds that inhibit the molecules involved in the direct reprogramming by means of AI-based combinatorial chemistry. We also developed 3D bone tissue in culture using the directly converted osteoblasts. The results offered valuable information to apply the direct reprogramming technology to bone regenerative medicine in the near future.

Academic Significance and Societal Importance of the Research Achievements

骨粗鬆症性骨折後の癒合不全などに対して骨再生医療が求められている。我々のダイレクト・リプログラミング法を用いれば、患者から極めて低侵襲に採取できる線維芽細胞から、高機能な移植用自家骨芽細胞を均質かつ無尽蔵に作出することができる。さらに、遺伝子導入が不要で化合物添加だけで誘導できること、効率が高く骨基質の産生能が高いこと、3Dスキャフォールド中で誘導することにより患者の病変部に合致した任意の形状にテーラーメイドで立体造形できることが必要とされる。本研究はこのような骨再生医療に適したケミカル・ダイレクト・リプログラミング技術につながる成果をもたらしたので、高い学術的および社会的意義を有する。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • Research Products

    (19 results)

All 2020 2019 2018 2017

All Journal Article (11 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 11 results,  Open Access: 5 results) Presentation (8 results) (of which Int'l Joint Research: 6 results,  Invited: 2 results)

  • [Journal Article] Fabrication of contractile skeletal muscle tissues using directly converted myoblasts from human fibroblasts2020

    • Author(s)
      Shimizu Kazunori、Ohsumi Saki、Kishida Tsunao、Mazda Osam、Honda Hiroyuki
    • Journal Title

      Journal of Bioscience and Bioengineering

      Volume: 129 Issue: 5 Pages: 632-637

    • DOI

      10.1016/j.jbiosc.2019.11.013

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 3D-additive deposition of an antibacterial and osteogenic silicon nitride coating on orthopaedic titanium substrate2020

    • Author(s)
      Zanocco Matteo、Boschetto Francesco、Zhu Wenliang、Marin Elia、McEntire Bryan J.、Bal B. Sonny、Adachi Tetsuya、Yamamoto Toshiro、Kanamura Narisato、Ohgitani Eriko、Yamamoto Kengo、Mazda Osam、Pezzotti Giuseppe
    • Journal Title

      Journal of the Mechanical Behavior of Biomedical Materials

      Volume: 103 Pages: 103557-103557

    • DOI

      10.1016/j.jmbbm.2019.103557

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Osteogenic response of mesenchymal progenitor cells to natural polysaccharide nanogel and atelocollagen scaffolds: A spectroscopic study2019

    • Author(s)
      Horiguchi Satoshi、Adachi Tetsuya、Rondinella Alfredo、Boschetto Francesco、Marin Elia、Zhu Wenliang、Tahara Yoshiro、Yamamoto Toshiro、Kanamura Narisato、Akiyoshi Kazunari、Pezzotti Giuseppe、Mazda Osam
    • Journal Title

      Materials Science and Engineering: C

      Volume: 99 Pages: 1325-1340

    • DOI

      10.1016/j.msec.2019.02.043

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The tetraspanin CD81 mediates the growth and metastases of human osteosarcoma2019

    • Author(s)
      Mizoshiri Naoki、Shirai Toshiharu、Terauchi Ryu、Tsuchida Shinji、Mori Yuki、Hayashi Daichi、Kishida Tsunao、Arai Yuji、Mazda Osam、Nakanishi Tohru、Kubo Toshikazu
    • Journal Title

      Cellular Oncology

      Volume: 42 Issue: 6 Pages: 861-871

    • DOI

      10.1007/s13402-019-00472-w

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Treadmill Running in Established Phase Arthritis Inhibits Joint Destruction in Rat Rheumatoid Arthritis Models2019

    • Author(s)
      Fujii Yuta、Inoue Hiroaki、Arai Yuji、Shimomura Seiji、Nakagawa Shuji、Kishida Tsunao、Tsuchida Shinji、Kamada Yoichiro、Kaihara Kenta、Shirai Toshiharu、Terauchi Ryu、Toyama Shogo、Ikoma Kazuya、Mazda Osam、Mikami Yasuo
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 20 Issue: 20 Pages: 5100-5100

    • DOI

      10.3390/ijms20205100

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Treadmill Running Ameliorates Destruction of Articular Cartilage and Subchondral Bone, Not Only Synovitis, in a Rheumatoid Arthritis Rat Model.2018

    • Author(s)
      Shimomura S, Inoue H, Arai Y, Nakagawa S, Fujii Y, Kishida T, Ichimaru S, Tsuchida S, Shirai T, Ikoma K, Mazda O, Kubo T.
    • Journal Title

      Int J Mol Sci

      Volume: 19 Issue: 6 Pages: 1653-1653

    • DOI

      10.3390/ijms19061653

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Nanogel tectonic porous 3D scaffold for direct reprogramming fibroblasts into osteoblasts and bone regeneration.2018

    • Author(s)
      Sato Y, Yamamoto K, Horiguchi S, Tahara Y, Nakai K, Kotani SI, Oseko F, Pezzotti G, Yamamoto T, Kishida T, Kanamura N, Akiyoshi K, Mazda O.
    • Journal Title

      Sci Rep

      Volume: 8 Issue: 1 Pages: 15824-15824

    • DOI

      10.1038/s41598-018-33892-z

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Incorporating Si3N4 into PEEK to Produce Antibacterial, Osteocondutive, and Radiolucent Spinal Implants2018

    • Author(s)
      Pezzotti Giuseppe、Marin Elia、Adachi Tetsuya、Lerussi Federica、Rondinella Alfredo、Boschetto Francesco、Zhu Wenliang、Kitajima Takashi、Inada Kosuke、McEntire Bryan J.、Bock Ryan M.、Bal B. Sonny、Mazda Osam
    • Journal Title

      Macromolecular Bioscience

      Volume: 18 Issue: 6 Pages: 1800033-1800033

    • DOI

      10.1002/mabi.201800033

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Evaluation of femoral perfusion using dynamic contrast-enhanced MRI after simultaneous initiation of electrical stimulation and steroid treatment in an osteonecrosis model2018

    • Author(s)
      Yamamoto Hiroki、Ueshima Keiichiro、Saito Masazumi、Ikoma Kazuya、Ishida Masashi、Goto Tsuyoshi、Hayashi Shigeki、Ikegami Akira、Fujioka Mikihiro、Mazda Osam、Kubo Toshikazu
    • Journal Title

      Electromagnetic Biology and Medicine

      Volume: Epub ahead of print Issue: 2 Pages: 1-11

    • DOI

      10.1080/15368378.2018.1466310

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Silicon nitride surface chemistry: A potent regulator of mesenchymal progenitor cell activity in bone formation2017

    • Author(s)
      G. Pezzotti, R. M. Bock, T. Adachi, A. Rondinella, F. Boschetto, W. Zhu, E. Marin, B. McEntire, B. S. Bal, O. Mazda
    • Journal Title

      Applied Materials Today

      Volume: 9 Pages: 82-95

    • DOI

      10.1016/j.apmt.2017.05.005

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] PGE1 and E3 show lower efficacies than E2 to β-catenin-mediated activity as biased ligands of EP4 prostanoid receptors2017

    • Author(s)
      Araki Yumi、Suganami Akiko、Endo Suzu、Masuda Yuta、Fukushima Keijo、Regan John W.、Murayama Toshihiko、Tamura Yutaka、Fujino Hiromichi
    • Journal Title

      FEBS Lett.

      Volume: 591 Issue: 22 Pages: 3771-3780

    • DOI

      10.1002/1873-3468.12878

    • NAID

      130007900719

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] HIF-1α in articular cartilage is up-regulated by treadmill running in vivo2019

    • Author(s)
      Y. Fujii, H. Inoue, Y. Arai, S. Shimomura, S. Nakagawa, S. Tsuchida, S. Ichimaru, O. Mazda, T. Kubo
    • Organizer
      Orthopaedic Research Society
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Hypoxic condition promotes differentiation from human iPSC to cartilage2019

    • Author(s)
      Shimomura S, Inoue H, Arai Y, Nakagawa S, Tsuchida S, Ichimaru S, Fujii Y, Mazda O, Kubo T.
    • Organizer
      65th Annual Meeting of Orthopaedic Research Society
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Direct reprogramming of fibroblasts into osteoblast-like cells having chemotaxis by defined factors2019

    • Author(s)
      Ohara M, Taniguchi D, Oda R, Fujiwara H, Kishida T, Mazda O and Kubo T.
    • Organizer
      65th Annual Meeting of Orthopaedic Research Society
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Regulation of inflammatory cytokine expression and osteoclastgenesis by gap junctional protein in vitro and in vivo.2017

    • Author(s)
      Shimomura S. et al.
    • Organizer
      The 5th annual meeting of the international cytokine and interferon society
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Effects of hypoxic conditions in differentiation of human iPSC to cartilage2017

    • Author(s)
      Shimomura S. et al.
    • Organizer
      64th Annual Meeting of Orthopaedic Research Society
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ダイレクト・リプログラミングの運動器再生医療への展開2017

    • Author(s)
      松田 修他
    • Organizer
      第36回日本運動器移植・再生医学研究会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Rewriting cell scenarios for regenerative medicine2017

    • Author(s)
      Mazda O. et al.
    • Organizer
      Italy meets Asia: Scientific Venue in Kyoto 2017
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Combination therapy of anti-cancer drugs with photo-induced immunotherapy2017

    • Author(s)
      Suganami A. et al.
    • Organizer
      第76回日本癌学会学術総会
    • Related Report
      2017 Annual Research Report

URL: 

Published: 2017-04-28   Modified: 2021-02-19  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi