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Mechanisms of Rho family proteins during cartolage and bone formation

Research Project

Project/Area Number 15K11051
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

Atsushi Yamada  昭和大学, 歯学部, 講師 (50407558)

Project Period (FY) 2015-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords細胞内シグナル伝達 / 細胞内シグナル伝達因子 / 遺伝子改変動物
Outline of Final Research Achievements

We created mice with double deletion of Rac1 and Cdc42. We aimed to study the functional duplication of Rac1 and Cdc42 genes by comparing their phenotypes with those of mice. In order to specifically delete the Rac1 and Cdc42 genes in cartilage tissue, Rac1 flox mice Cdc42 flox mice and Col2 Cre transgenic mice were mated. The mice in which the Rac1 and Cdc42 genes were double deleted became lethal soon after birth, as in the case where the Cdc42 gene was single deleted. The long bones were shorter compared to the single deletion of the Rac1 and Cdc42 genes. In addition, the mice in which the Rac1 and Cdc42 genes were double deleted were found to have abnormal formation in skeletal organs. Stronger abnormalities were observed in cell composition and columnar formation in the growth plate than those of Rac1 and Cdc42 single knockout mice.

Academic Significance and Societal Importance of the Research Achievements

Rhoファミリー低分子量Gタンパク質Rac1およびCdc42は細胞外からの様々な情報を細胞内に伝達する細胞内シグナル伝達因子である。主にアクチン細胞骨格制御を介した様々な生物活性、例えば細胞の増殖、分化、細胞死等を制御していることが知られている。Rac1およびCdc42の硬組織形成における機能を、組織および時期特異的に欠損させたコンディショナルノックアウトマウスを作製したところ、それぞれ共通した表現型と異なる表現型を呈した。Rac1およびCdc42をダブル欠損させたマウスを作製し、シングル欠損させたマウスと表現型を比較することによりRac1およびCdc42遺伝子の機能重複性が明らかとなった。

Report

(5 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (30 results)

All 2018 2017 2016 2015

All Journal Article (16 results) (of which Int'l Joint Research: 7 results,  Peer Reviewed: 16 results,  Open Access: 12 results,  Acknowledgement Compliant: 10 results) Presentation (14 results) (of which Int'l Joint Research: 2 results)

  • [Journal Article] Nephronectin Expression is Inhibited by Inorganic Phosphate in Osteoblasts2018

    • Author(s)
      Kato Tadashi、Yamada Atsushi、Sasa Kiyohito、Yoshimura Kentaro、Morimura Naoko、Ogata Hiroaki、Sakashita Akiko、Kamijo Ryutaro
    • Journal Title

      Calcified Tissue International

      Volume: 104 Issue: 2 Pages: 201-206

    • DOI

      10.1007/s00223-018-0484-3

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Monocarboxylate transporter-1 promotes osteoblast differentiation via suppression of p53, a negative regulator of osteoblast differentiation.2018

    • Author(s)
      Sasa K, Yoshimura K, Yamada A, Suzuki D, Miyamoto Y, Imai H, Nagayama K, Maki K, Yamamoto M, Kamijo R
    • Journal Title

      Sci. Rep.

      Volume: 8(1) Issue: 1 Pages: 10579-10579

    • DOI

      10.1038/s41598-018-28605-5

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Cooperation of Rho family proteins Rac1 and Cdc42 in cartilage development and calcified tissue formation2018

    • Author(s)
      Ikehata M, Yamada A, Fujita K, Yoshida Y, Kato T, Sakashita A, Ogata H, Iijima T, Kuroda M, Chikazu D, Kamijo R.
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 印刷中 Issue: 3 Pages: 525-529

    • DOI

      10.1016/j.bbrc.2018.04.032

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] IL-1β suppresses nephronectin expression in osteoblasts via ERK1/2 and JNK2017

    • Author(s)
      Iezumi Yuka、Yamada Atsushi、Minami Erika、Ikehata Mikiko、Yoshida Yuko、Kato Tadashi、Morimura Naoko、Ogata Hiroaki、Sakashita Akiko、Iijima Takehiko、Chikazu Daichi、Kamijo Ryutaro
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 493 Issue: 1 Pages: 773-775

    • DOI

      10.1016/j.bbrc.2017.08.104

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Comprehensive genetic exploration of selective tooth agenesis of mandibular incisors by exome sequencing2017

    • Author(s)
      Yamaguchi T, Hosomichi K, Yano K, Kim Y, Nakaoka H, Kimura R, Otsuka H, Nonaka N, Haga S, Takahashi M, Shirota T, Kikkawa Y, Yamada A, Kamijo R, Park SB, Nakamura M, Maki K, Inoue I
    • Journal Title

      Hum Genome Variation

      Volume: 印刷中 Issue: 1 Pages: 17005-17005

    • DOI

      10.1038/hgv.2017.5

    • NAID

      120006891152

    • Related Report
      2017 Research-status Report 2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Wnt/β-catenin signaling activates nephronectin expression in osteoblasts.2017

    • Author(s)
      Ikehata M, Yamada A, Morimura N, Itose M, Suzawa T, Shirota T, Chikazu D, Kamijo R
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 484 Issue: 2 Pages: 231-234

    • DOI

      10.1016/j.bbrc.2017.01.053

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Continuous monitoring of caspase-3 activation induced by propofol in developing mouse brain.2016

    • Author(s)
      Konno A, Nishimura A, Nakayama S, Mochizuki A, Yamada A, Kamijo R, Inoue T, Iijima T
    • Journal Title

      Int J Dev Neurosci

      Volume: 51 Issue: 1 Pages: 42-49

    • DOI

      10.1016/j.ijdevneu.2016.04.007

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Expression of nephronectin is enhanced by α,25-dihydroxyvitamin D3.2016

    • Author(s)
      Hiranuma K, Yamada A, Kurosawa T, Aizawa R, Suzuki D, Saito Y, Nagahama R, Ikehata M, Tsukasaki M, Morimura N, Chikazu D, Maki K, Shirota T, Takami M, Yamamoto M, Iijima T, Kamijo R
    • Journal Title

      FEBS Open Bio

      Volume: 6 Issue: 9 Pages: 914-918

    • DOI

      10.1002/2211-5463.12085

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Nephronectin Expression Is Up-Regulated by BMP-22016

    • Author(s)
      Kurosawa T, Yamada A, Suzuki D, Morimura N, Sasagane Y, Itabe H, Kamijo R
    • Journal Title

      Biological and Pharmaceutical Bulletin

      Volume: 39 Issue: 7 Pages: 1211-1215

    • DOI

      10.1248/bpb.b15-00941

    • NAID

      130005160772

    • ISSN
      0918-6158, 1347-5215
    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Rho GTPase protein Cdc42 is critical for postnatal cartilage development.2016

    • Author(s)
      Nagahama R, Yamada A, Tanaka J, Aizawa R, Suzuki D, Kassai H, Yamamoto M, Mishima K, Aiba A, Maki K, Kamijo R.
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 470 Issue: 4 Pages: 813-817

    • DOI

      10.1016/j.bbrc.2016.01.111

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Cdc42 is crucial for facial and palatal formation during craniofacial development.2016

    • Author(s)
      Oshima-Nakayama M
    • Journal Title

      Bone Reports

      Volume: 5 Pages: 1-6

    • DOI

      10.1016/j.bonr.2016.01.001

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Localization and osteoblastic differentiation potential of neural crest-derived cells in oral tissues of adult mice.2015

    • Author(s)
      Ono M
    • Journal Title

      Biochem. Biophys. Res. Commun.

      Volume: 464 Issue: 4 Pages: 1209-1214

    • DOI

      10.1016/j.bbrc.2015.07.106

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Association of aging with gene expression profiling in mouse submandibular glands.2015

    • Author(s)
      Saito Y
    • Journal Title

      Genomics Data

      Volume: 5 Pages: 115-119

    • DOI

      10.1016/j.gdata.2015.05.012

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Enhanced in vitro biological activity generated by surface characteristics of anodically oxidized titanium ― the contribution of the oxidation effect.2015

    • Author(s)
      Wurihan
    • Journal Title

      European Cells & Materials

      Volume: 29 Pages: 290-302

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Expression of nephronectin is inhibited by oncostatin M via both JAK/STAT and MAPK pathways2015

    • Author(s)
      Kurosawa T, Yamada A, Takami M, Suzuki D, Saito Y, Hiranuma K, Enomoto T, Morimura N, Yamamoto M, Iijima T, Shirota T, Itabe H, Kamijo R.
    • Journal Title

      FEBS Open Bio

      Volume: 5 Issue: 1 Pages: 303-307

    • DOI

      10.1016/j.fob.2015.04.001

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Bone micro-fragility caused by the mimetic aging processes in α-klotho deficient mice: in situ nanoindentation assessment of dilatational bands2015

    • Author(s)
      Maruyama N., Shibata Y., Mochizuki A., Yamada A., Maki K., Inoue T., Kamijo R., Miyazaki T.
    • Journal Title

      Biomaterials

      Volume: 47 Pages: 62-71

    • DOI

      10.1016/j.biomaterials.2015.01.004

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] Cdc42は出生後の血管形成および血管を介した骨形成に重要な役割を果たしている。2018

    • Author(s)
      吉田優子、山田篤、上條竜太郎
    • Organizer
      第55回日本口腔組織培養学会学術大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 骨軟骨形成におけるRhoファミリー低分子量Gタンパク質Rac1とCdc42の機能解析2018

    • Author(s)
      池畑美紀子、山田篤、吉田優子、加藤憲、近津大地、上條竜太郎
    • Organizer
      第36回日本骨代謝学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Cdc42は出生後の血管形成および血管を介した骨形成に重要な役割を果たしている。2018

    • Author(s)
      吉田優子、山田篤、池畑美紀子、加藤憲、上條竜太郎
    • Organizer
      第36回日本骨代謝学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 細胞外リン濃度の上昇はFGFシグナルを介し、細胞外マトリックスタンパク質Nephronectinの発現を抑制する。2018

    • Author(s)
      加藤憲、山田篤、吉田優子、池畑美紀子、緒方浩顕、上條竜太郎
    • Organizer
      第36回日本骨代謝学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Molecular mechanisms of palatal development controlled by Cdc42.2017

    • Author(s)
      Erika Minami, Atsushi Yamada, Ryutaro Kamijo
    • Organizer
      The 65 th Annual Meeting of Japanese Association for Dental Research (JADR 2017)
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] FGF-2による細胞外マトリックスタンパク質Nephronectinの発現制御機構の解明2017

    • Author(s)
      加藤憲、山田篤、上條竜太郎
    • Organizer
      第54回日本口腔組織培養学会学術大会
    • Related Report
      2017 Research-status Report
  • [Presentation] Cdc42はPTHシグナルを介し骨軟骨形成を制御している2016

    • Author(s)
      長濱諒、山田篤、上條竜太郎、槇宏太郎
    • Organizer
      第75回日本矯正歯科学会大会
    • Place of Presentation
      徳島
    • Year and Date
      2016-11-08
    • Related Report
      2016 Research-status Report
  • [Presentation] 低分子量Gタンパク質Cdc42はPTHシグナルを介し胎生期および生後成長期の軟骨形成を制御している2016

    • Author(s)
      長濱諒、山田篤、槇宏太郎、上條竜太郎
    • Organizer
      第58回歯科基礎医学会学術集会
    • Place of Presentation
      札幌
    • Year and Date
      2016-08-25
    • Related Report
      2016 Research-status Report
  • [Presentation] 低分子量Gタンパク質Cdc42は生後成長期の軟骨形成において重要である2016

    • Author(s)
      長濱諒、山田篤、鈴木大、槇宏太郎、上條竜太郎
    • Organizer
      第34回日本骨代謝学会学術集会
    • Place of Presentation
      大阪
    • Year and Date
      2016-07-23
    • Related Report
      2016 Research-status Report
  • [Presentation] Cdc42 is critical for cartilage development during endochondral ossification at postnatal stage2015

    • Author(s)
      Nagahama R
    • Organizer
      2015 cell biology ascb annual meeting
    • Place of Presentation
      Sandiego
    • Year and Date
      2015-12-12
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Cdc42 is critical for postnatal cartilage development.2015

    • Author(s)
      長濱諒
    • Organizer
      第63回国際歯科研究学会
    • Place of Presentation
      福岡
    • Year and Date
      2015-10-30
    • Related Report
      2015 Research-status Report
  • [Presentation] 神経堤由来細胞に発現するRhoファミリー低分子量Gタンパク質Cdc42は口蓋形成に必須である2015

    • Author(s)
      大島睦子
    • Organizer
      第57回歯科基礎医学会学術大会・総会
    • Place of Presentation
      新潟
    • Year and Date
      2015-09-14
    • Related Report
      2015 Research-status Report
  • [Presentation] 低分子量Gタンパク質Cdc42は口蓋形成において重要な遺伝子である2015

    • Author(s)
      大島睦子
    • Organizer
      第33回日本骨代謝学会学術集会
    • Place of Presentation
      東京
    • Year and Date
      2015-07-22
    • Related Report
      2015 Research-status Report
  • [Presentation] Rhoファミリー低分子量Gタンパク質Rac1およびCdc42の骨・軟骨形成における機能解析2015

    • Author(s)
      山田篤
    • Organizer
      第1回日本骨免疫学会
    • Place of Presentation
      宮古島
    • Year and Date
      2015-06-30
    • Related Report
      2015 Research-status Report

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Published: 2015-04-16   Modified: 2020-03-30  

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