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Novel function of osteoclastogenesis and bone resorption by membrane trafficking regulatory molecule

Research Project

Project/Area Number 15K11046
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Functional basic dentistry
Research InstitutionSaga University

Principal Investigator

Kukita Akiko  佐賀大学, 医学部, 准教授 (30153266)

Co-Investigator(Kenkyū-buntansha) 久木田 敏夫  九州大学, 歯学研究院, 教授 (70150464)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords破骨細胞分化 / 小胞輸送 / 骨吸収 / 破骨細胞 / 分化 / 酸分泌 / 膜トラフィッキング / 膜タンパク質
Outline of Final Research Achievements

Regulator of membrane trafficking play an important role in osteoclastogenesis and bone resorption. We analyzed expression and role of Nedd4 adaptor protein in differentiation and function of osteoclast. Nedd4 adaptor protein was induced in mononuclear osteoclast precursor cells by RANKL via p38MAPK pathway. Nedd4 adaptor protein was also expressed in osteoclasts formed on dentin slices. In addition, expression of the protein was detected in osteoclasts of bone tissues of adjuvant-induced arthritis rat. Knockdown experiment with shRNA lentivirus revealed that Nedd4 adaptor protein regulates transport of RANK to cell surface in osteoclast precursor cells. In addition, analysis of osteoclasts derived from knockout mice which were prepared using the CRISPR/Cas9 system showed that Nedd4 adaptor protein regulates bone resorption of osteoclasts.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (26 results)

All 2018 2017 2016 2015 Other

All Journal Article (7 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 7 results,  Open Access: 4 results,  Acknowledgement Compliant: 1 results) Presentation (18 results) (of which Int'l Joint Research: 2 results,  Invited: 1 results) Remarks (1 results)

  • [Journal Article] IL-1β induce pathologically activated osteoclasts bearing extremely high level of resorption activity imaged by pH-sensitive fluorescence probes: A possible pathological subpopulation of osteoclasts, accompanied with suppressed expression of integrin regulating molecule kindling-3 and talin-1.2018

    • Author(s)
      Shiratori T., Kyumoto-Nakamura Y., Kukita A., Uehara N., Zhang J., Koda K., Kamiya M., Badawy T., Tomoda E., Xu X., Yamaza T., Urano Y., Koyano K., Kukita T.
    • Journal Title

      J. Immunology

      Volume: 200 Issue: 4 Pages: 218-228

    • DOI

      10.1002/jcp.26147

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] IL-1beta induce pathologically activated osteoclasts bearing extremely high level of resorption activity imaged by pH-sensitive fluorescence probes: A possible pathological subpopulation of osteoclasts, accompanied with suppressed expression of integrin regulating molecule kindling-3 and talin-1.2018

    • Author(s)
      Shiratori T., Kyumoto-Nakamura Y., Kukita A., Uehara N., Zhang J., Koda K., Kamiya M., Badawy T., Tomoda E., Xu X., Yamaza T., Urano Y., Koyano K., Kukita T.
    • Journal Title

      J. Immunology

      Volume: 200 Issue: 1 Pages: 218-228

    • DOI

      10.4049/jimmunol.1602035

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Osteoblast-derived Laminin-332 is a novel negative regulator of osteoclastogenesis in bone microenvironments.2017

    • Author(s)
      Uehara N, Kukita A, Kyumoto-Nakamura Y, Yamaza T, Yasuda H, Kukita T.
    • Journal Title

      Lab Invest.

      Volume: 97 Issue: 10 Pages: 1235-1244

    • DOI

      10.1038/labinvest.2017.55

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Extremely high expression of antisense RNA for Wilms’ Tumor 1 in active osteoclasts: Suppression of Wilms’ Tumor 1 protein expression during osteoclastogenesis.2016

    • Author(s)
      Li YJ, Kukita A, Kyumoto-Nakamura Y, Kukita T.
    • Journal Title

      American Journal of Pathology

      Volume: 186(9) Issue: 9 Pages: 2317-2325

    • DOI

      10.1016/j.ajpath.2016.05.005

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Generation mechanism of RANKL+ effector memory B cells: its relevance to the pathogenesis of rheumatoid arthritis2016

    • Author(s)
      Ota Y., Niiro H., Ota S., Ueki N., Tsuzuki H., Nakayama T., Mishima K., Higashioka K., Jabbarzadeh-Tabrizi S., Mitoma H., Akahoshi M., Arinobu Y., Kukita A., Yamada H., Tsukamoto H., Akashi K.
    • Journal Title

      Arthritis Reseach & Therapy

      Volume: 印刷中

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Interferon-gamma improves impaired dentinogenic and immunosuppressive functions of irreversible pulpitis-derived human dental pulp stem cells.2016

    • Author(s)
      Sonoda S, Yamaza H, Ma L, Tanaka Y, Tomoda E, Aijima R, Nonaka K, Kukita T, Shi S, Nishimura F, Yamaza T.
    • Journal Title

      Sci Rep.

      Volume: 6 Issue: 1 Pages: 19286-19286

    • DOI

      10.1038/srep19286

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Membrane Nanotube Formation in Osteoclastogenesis.2015

    • Author(s)
      Kukita T., Takahahsi A., Zhang J-Q., Kukita A.
    • Journal Title

      Kurt Pfannkuche (ed), Cell Fusion: Overviews and Methods, Methods in Molecular Biology

      Volume: 1313 Pages: 193-202

    • DOI

      10.1007/978-1-4939-2703-6_14

    • ISBN
      9781493927029, 9781493927036
    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] zBTBタンパク質LRF/OCZFのBcl-Xのスプライシング制御因子Sam68を介した破骨細胞の生存調節2017

    • Author(s)
      久木田明子、徐祥赫、白木誠、蒲原麻菜、菖蒲池健夫、久木田敏夫
    • Organizer
      第3回日本骨免疫学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] IL1beta刺激下に形成される破骨細胞は高度のプロトン産生能と吸収活性を持つ2017

    • Author(s)
      久木田敏夫、白鳥卓麻、久本由香里、上原範久、久木田明子
    • Organizer
      第3回 骨免疫学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Nedd4 adaptor protein Pmepa1 is induced by bone components and involved in bone resorption2017

    • Author(s)
      Xu X., Shiraki M., Kamohara A., Kukita T., Kukita A.
    • Organizer
      第35回 日本骨代謝学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 黄色ブドウ球菌はプロテインAによるIgG複合体形成を介して破骨細胞の分化を亢進する2017

    • Author(s)
      蒲原 麻菜,徐 祥赫,白木 誠,久木田明子
    • Organizer
      第35回 日本骨代謝学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Pmepa1 is Specifically Induced by Bone Components in Osteoclasts and Regulates Bone Resorption2017

    • Author(s)
      Xu X., Shiraki M., Kamohara A., Nishioka K., Matsuhisa F., Kitajima S., Kukita T., Kukita A.
    • Organizer
      Annual Meeting of American Society for Bone and Mineral Research
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] LRF/OCZF regulates Survival of Osteoclasts via Sam68, a Splicing Regulator of Bcl-x.2017

    • Author(s)
      Xu X, Shiraki M., Kamohara A., Shobuike T., Kukita T., Kukita A
    • Organizer
      Annual Meeting of American Society for Bone and Mineral Research
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Pmepa1は骨基質成分によって破骨細胞で発現が誘導され、骨吸収を制御する2017

    • Author(s)
      徐祥赫、蒲原麻菜、久木田敏夫、久木田明子
    • Organizer
      第59 回歯科基礎医学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 黄色ブドウ球菌はプロテインAによるIgG複合体形成を介して破骨細胞の分化を亢進する2017

    • Author(s)
      蒲原 麻菜,徐 祥赫, 久木田明子
    • Organizer
      第59 回歯科基礎医学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 病的に活性化された破骨細胞:形成条件の検討と蛍光プローブを用いた骨吸収イメージング2016

    • Author(s)
      白鳥卓麻、久木田明子、上原範久、久本由香里、張旌旗、山座孝義、古谷野潔、久木田敏夫
    • Organizer
      第58回歯科基礎医学会
    • Place of Presentation
      札幌コンベンションセンター
    • Year and Date
      2016-08-24
    • Related Report
      2016 Research-status Report
  • [Presentation] 久本由香里、上原範久、久木田明子、山座孝義、久木田敏夫2016

    • Author(s)
      Galectin-9による破骨細胞分化抑制と転写因子MafBの発現制御
    • Organizer
      第58回歯科基礎医学会
    • Place of Presentation
      札幌コンベンションセンター
    • Year and Date
      2016-08-24
    • Related Report
      2016 Research-status Report
  • [Presentation] ストレス応答タンパク質Nuclear protein 1/p8の破骨細胞における新たな機能2016

    • Author(s)
      白木誠、徐祥赫、蒲原麻菜、馬渡正明、久木田明子
    • Organizer
      第34回 日本骨代謝学会
    • Place of Presentation
      大阪国際会議場
    • Year and Date
      2016-07-20
    • Related Report
      2016 Research-status Report
  • [Presentation] zBTBタンパク質LRF/OCZFの破骨細胞分化における機能と骨吸収中の破骨細胞における発現の解析2016

    • Author(s)
      徐祥赫、白木誠、蒲原麻菜、菖蒲池健夫、久木田敏夫、久木田明子
    • Organizer
      第34回 日本骨代謝学会
    • Place of Presentation
      大阪国際会議場
    • Year and Date
      2016-07-20
    • Related Report
      2016 Research-status Report
  • [Presentation] 骨転移性乳癌細胞由来エクソソームは破骨細胞分化を促進する2016

    • Author(s)
      上原範久、久本由香里、久木田明子、久木田敏夫
    • Organizer
      第34回 日本骨代謝学会
    • Place of Presentation
      大阪国際会議場
    • Year and Date
      2016-07-20
    • Related Report
      2016 Research-status Report
  • [Presentation] POZ-ZF転写制御因子LRF/OCZFの破骨細胞の分化と機能における役割2015

    • Author(s)
      久木田 明子, 徐 祥赫, 菖蒲池 健夫, 武智 香織, 古賀 貴子, 白木 誠, 蒲原 麻菜, 久木田 敏夫, 高柳 広
    • Organizer
      第38回日本分子生物学会年会 第88回日本生化学会大会 合同大会(ワークショップ)
    • Place of Presentation
      神戸ポートピアホテル(兵庫県神戸市)
    • Year and Date
      2015-12-01
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] OCZF(Zbtb7a)タンパク質の破骨細胞分化における発現誘導とその機能の解析2015

    • Author(s)
      久木田明子、徐祥赫、久木田敏夫
    • Organizer
      第57回歯科基礎医学会
    • Place of Presentation
      朱鷺メッセ(新潟県新潟市)
    • Year and Date
      2015-09-11
    • Related Report
      2015 Research-status Report
  • [Presentation] Galectin-9による破骨細胞形成抑制機構:MafB制御関与の可能性2015

    • Author(s)
      久本由香里、上原範久、久木田明子、久木田敏夫
    • Organizer
      第57回歯科基礎医学会
    • Place of Presentation
      朱鷺メッセ(新潟県新潟市)
    • Year and Date
      2015-09-11
    • Related Report
      2015 Research-status Report
  • [Presentation] ラミニン332によるRANK発現調節とマクロファージ-破骨細胞分化転換の制御2015

    • Author(s)
      上原範久、久木田明子、久本由香里、保田尚孝、久木田敏夫
    • Organizer
      第33回日本骨代謝学会
    • Place of Presentation
      京王プラザホテル(東京都)
    • Year and Date
      2015-07-23
    • Related Report
      2015 Research-status Report
  • [Presentation] Novel Role of Nedd4 adaptor protein, Pmepa1 in the differentiation and function of osteoclasts.2015

    • Author(s)
      Xu Xianghe, Noboru Funakubo, Makoto Shiraki, Toshio Kukita, Akiko Kukita
    • Organizer
      第33回日本骨代謝学会
    • Place of Presentation
      京王プラザホテル(新宿)
    • Year and Date
      2015-07-23
    • Related Report
      2015 Research-status Report
  • [Remarks]

    • URL

      http://www.microbio.med.saga-u.ac.jp/biodefense/per-kuki.html

    • Related Report
      2015 Research-status Report

URL: 

Published: 2015-04-16   Modified: 2019-03-29  

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