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Basic approach for investigating epigenetic therapeutic strategies for bone and joint diseases

Research Project

Project/Area Number 23689066
Research Category

Grant-in-Aid for Young Scientists (A)

Allocation TypeSingle-year Grants
Research Field Orthopaedic surgery
Research InstitutionEhime University (2012-2013)
The University of Tokyo (2011)

Principal Investigator

IMAI YUUKI  愛媛大学, プロテオサイエンスセンター, 教授 (10423873)

Project Period (FY) 2011-11-18 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥13,390,000 (Direct Cost: ¥10,300,000、Indirect Cost: ¥3,090,000)
Fiscal Year 2013: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
Fiscal Year 2012: ¥7,280,000 (Direct Cost: ¥5,600,000、Indirect Cost: ¥1,680,000)
Keywords骨関節疾患 / エピゲノム / 軟骨細胞 / 破骨細胞 / クロマチン / Aire / 関節リウマチ
Research Abstract

To clarify regulatory mechanism on epigenetics in bone and joint diseases, we identified Aire as a novel regulator in chondrocyte differentiation using gene expression microarray. Aire possesses PHD domain, which recognizes hypomethylated lysine residues of histone proteins. As the results of analyses of molecular function, Aire can facilitate chondrocyte differentiation through regulating status of histone H3K4me2 in promoter region of Bmp-2 (Si et al BBRC 2013).
In terms of osteoclasts, which resorb bone matrix, we tried to figure out dynamic chromatin remodeling during osteoclastogenesis using DNase-seq. Based on the combined information from gene expression and DNase-seq, we successfully identified novel transcription factors in osteoclastogenesis (Inoue et al. JBMR 2014 in press).

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Annual Research Report
  • 2011 Annual Research Report
  • Research Products

    (34 results)

All 2014 2013 2012 2011 Other

All Journal Article (16 results) (of which Peer Reviewed: 16 results) Presentation (15 results) (of which Invited: 4 results) Remarks (3 results)

  • [Journal Article] Identification of Novel Transcription Factors in Osteoclast Differentiation using Genome–wide Analysis of Open Chromatin Determined by DNase-seq2014

    • Author(s)
      Inoue K and Imai Y
    • Journal Title

      J Bone Miner Res

      Volume: (Epub ahead of print) Issue: 8 Pages: 1823-1832

    • DOI

      10.1002/jbmr.2229

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Estrogen receptor a in osteocytes regulates trabecular bone fo rmation in female mice.2014

    • Author(s)
      Kondoh S, Inoue K, Igaras hi K, Sugizaki H, Shirode-Fukuda Y, Inoue E, Yu T, Takeuchi JK, Kanno J, Bonewald LF, Imai Y.
    • Journal Title

      Bone

      Volume: 60 Pages: 68-77

    • DOI

      10.1016/j.bone.2013.12.005

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Novel insights into histone modifiers in Adipogenesis2013

    • Author(s)
      Okuno Y, Inoue K, Imai Y
    • Journal Title

      Adipocyte

      Volume: 2(4) Issue: 4 Pages: 285-8

    • DOI

      10.4161/adip.25731

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Autoimmune regulator, Aire, is a novel regulator of chondrocyte differentiation2013

    • Author(s)
      Si Y, Inoue K, Igarashi K, Kanno J, Imai Y
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 437(4) Issue: 4 Pages: 579-84

    • DOI

      10.1016/j.bbrc.2013.07.001

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Nuclear Receptors in Bone Physiology and Diseases2013

    • Author(s)
      Imai Y, Youn MY, Inoue K, Takada I, Kouzmenko A, Kato S
    • Journal Title

      Physiol Rev

      Volume: 93(2) Issue: 2 Pages: 481-523

    • DOI

      10.1152/physrev.00008.2012

    • Related Report
      2013 Final Research Report 2012 Annual Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Female sex hormones ameliorate arthritis in SKG mice2013

    • Author(s)
      Inoue K, Inoue E, Imai Y
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 434(4) Issue: 4 Pages: 740-5

    • DOI

      10.1016/j.bbrc.2013.03.111

    • Related Report
      2013 Final Research Report 2012 Annual Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Vitamin D receptor in osteoblasts is a negative regulator of bone mass control2013

    • Author(s)
      Yamamoto Y, Yoshizawa T, Fukuda T, Shirode-Fukuda Y, Yu T, Sekine K, Sato T, Kawano H, Aihara K, Naka michi Y, Watanabe T, Shindo M, Inoue K, Inoue E, Tsuji N, Hoshino M, Karsenty G, Metzger D, Chambon P, Kato S, Imai Y.
    • Journal Title

      Endocrinology.

      Volume: 154 Issue: 3 Pages: 1008-20

    • DOI

      10.1210/en.2012-1542

    • Related Report
      2013 Final Research Report 2012 Annual Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Epigenetic Regulation of Adipogenesis by PHF2 Histone Demethylase2013

    • Author(s)
      Okuno Y
    • Journal Title

      Diabetes

      Volume: in press Issue: 5 Pages: 1426-34

    • DOI

      10.2337/db12-0628

    • Related Report
      2013 Final Research Report 2012 Annual Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] JMJD5, a Jumonji C(JmjC) domain-containing protein, negatively regulates osteoclastogenesis by facilitating NFATc1 protein degradation2012

    • Author(s)
      Youn, M.-Y., Imai, Y., et al.
    • Journal Title

      J Biol Chem

      Volume: 287 Issue: 16 Pages: 12994-13004

    • DOI

      10.1074/jbc.m111.323105

    • Related Report
      2013 Final Research Report 2012 Annual Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] GlcNAcylation of histone H2B facilitates its monoubiquitination2011

    • Author(s)
      Fujiki R, Hashiba W, Sekine H, Yokoyama A, Chikanishi T, Ito S, Imai Y, Kim J, He HH, Igarashi K, Kanno J, Ohtake F, Kitagawa H, Roeder RG, Brown M, Kato S
    • Journal Title

      Nature

      Volume: 480(7378) Issue: 7378 Pages: 557-560

    • DOI

      10.1038/nature10656

    • Related Report
      2013 Final Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Local delivery of siRNA using a biodegradable polymer application to enhance BMP-induced bone formation.2011

    • Author(s)
      Manaka T
    • Journal Title

      Biomaterials.

      Volume: 32 Issue: 36 Pages: 9642-8

    • DOI

      10.1016/j.biomaterials.2011.08.026

    • Related Report
      2013 Final Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Conditional deletionof Bmpr1ab in differentiatedosteoclasts increases osteoblastic boneformation,increasing volume ofremodeling bone in mice.2011

    • Author(s)
      Okamoto,M.,Murai,J.,Imai,Y.,Ikegami,D.,Kamiya,N.,Kato,S.,Mishita,Y.,Yoshikawa,H.and Tsumaki,N
    • Journal Title

      J.BoneMiner.Res.

      Volume: 26巻 Issue: 10 Pages: 2511-22

    • DOI

      10.1002/jbmr.477

    • Related Report
      2013 Final Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Targeting Fas/FasL signaling, a new strategy for maintaining bone health2011

    • Author(s)
      Imai Y
    • Journal Title

      Expert Opin Ther Targets

      Volume: 15 Issue: 10 Pages: 1143-5

    • DOI

      10.1517/14728222.2011.600690

    • Related Report
      2013 Final Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Targeting Androgen Receptor in Estrogen Receptor-Negative Breast Cancer2011

    • Author(s)
      Ni M
    • Journal Title

      Cancer Cell

      Volume: 20 Issue: 1 Pages: 119-31

    • DOI

      10.1016/j.ccr.2011.05.026

    • Related Report
      2013 Final Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Signal-sensing activation of a histone lysine demethylase complex2011

    • Author(s)
      Baba A
    • Journal Title

      Nat Cell Biol.

      Volume: 13 Issue: 6 Pages: 669-76

    • DOI

      10.1038/ncb2228

    • Related Report
      2013 Final Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] ERKs induce expression of the transcriptional repressor Blimp-1 and subsequent plasma cell differentiation2011

    • Author(s)
      Yasuda T., Kometani, K., Takahashi, N., Imai, Y., Aiba, Y. and Kurosaki, T
    • Journal Title

      Sci. Signal

      Volume: 4, (169) Issue: 169 Pages: 104-16

    • DOI

      10.1126/scisignal.2001592

    • Related Report
      2013 Final Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Presentation] Identification of Novel Transcription Factors in Osteoclast differentiation using DNase­‐seq2014

    • Author(s)
      Kazuki Inoue and Yuuki Imai
    • Organizer
      IBMS Herbert Fleisch Workshop
    • Place of Presentation
      ベルギー
    • Related Report
      2013 Annual Research Report
  • [Presentation] 骨疾患におけるエピジェネティック制御2013

    • Author(s)
      今井祐記、井上和樹
    • Organizer
      第40回日本毒性学会学術年会
    • Place of Presentation
      千葉
    • Year and Date
      2013-06-17
    • Related Report
      2013 Annual Research Report 2013 Final Research Report
  • [Presentation] SERMによる骨代謝制御2013

    • Author(s)
      今井祐記
    • Organizer
      第31回日本骨代謝学会学術集会
    • Place of Presentation
      神戸
    • Year and Date
      2013-05-30
    • Related Report
      2013 Annual Research Report 2013 Final Research Report
  • [Presentation] 骨代謝制御における性ホルモン受容体の生体内機能解明2012

    • Author(s)
      今井祐記
    • Organizer
      第85回日本生化学会
    • Place of Presentation
      福岡
    • Year and Date
      2012-12-16
    • Related Report
      2013 Final Research Report 2012 Annual Research Report 2011 Annual Research Report
  • [Presentation] Estrogen Exerts Osteoprotective Function through Facilitating Bone Formation via ERαin Osteocytes2012

    • Author(s)
      今井祐記
    • Organizer
      15th International Congress on Hormonal Steroids and Hormones & Cancer
    • Place of Presentation
      金沢
    • Year and Date
      2012-11-16
    • Related Report
      2013 Final Research Report
  • [Presentation] 軟骨代謝制御における性ホルモン受容体の機能解析2012

    • Author(s)
      今井祐記
    • Organizer
      第27回日本整形外科学会基礎学術集会
    • Place of Presentation
      名古屋
    • Year and Date
      2012-10-26
    • Related Report
      2013 Final Research Report 2012 Annual Research Report 2011 Annual Research Report
  • [Presentation] 破骨細胞分化におけるエピジェネティック制御2012

    • Author(s)
      今井祐記
    • Organizer
      第39回日本毒性学会学術年会
    • Place of Presentation
      仙台
    • Year and Date
      2012-07-17
    • Related Report
      2013 Final Research Report 2012 Annual Research Report 2011 Annual Research Report
  • [Presentation] 性ホルモン受容体による骨代謝調節2012

    • Author(s)
      今井祐記
    • Organizer
      第54回日本老年医学会学術集会
    • Place of Presentation
      東京
    • Year and Date
      2012-06-27
    • Related Report
      2013 Final Research Report 2012 Annual Research Report 2011 Annual Research Report
  • [Presentation] 性ホルモン欠乏による骨粗鬆症の分子基盤2012

    • Author(s)
      今井祐記
    • Organizer
      第12回日本抗加齢医学会総会
    • Place of Presentation
      横浜
    • Year and Date
      2012-06-23
    • Related Report
      2013 Final Research Report 2012 Annual Research Report 2011 Annual Research Report
  • [Presentation] Osteoblastic Androgen Receptor mediates androgenic anabolic actions in Bone remodeling、骨細胞におけるERaの高次機能解析2012

    • Author(s)
      今井祐記
    • Organizer
      第30回日本骨代謝学会学術集会
    • Place of Presentation
      東京
    • Related Report
      2013 Final Research Report
  • [Presentation] Osteoblastic Androgen Receptor mediates androgenic anabolic actions in Bone remodeling2012

    • Author(s)
      Yuuki Imai
    • Organizer
      Keystone Symposia
    • Place of Presentation
      Whistler, British Columbia, Canada
    • Related Report
      2012 Annual Research Report 2011 Annual Research Report
  • [Presentation] 性ホルモンによる骨代謝調節機構の新知見と骨再生医療への展開

    • Author(s)
      今井祐記
    • Organizer
      第55回歯科基礎医学会学術大会・総会
    • Place of Presentation
      岡山
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] 骨細胞におけるERaの高次機能解析

    • Author(s)
      今井祐記
    • Organizer
      第30回日本骨代謝学会学術集会
    • Place of Presentation
      東京
    • Related Report
      2012 Annual Research Report 2011 Annual Research Report
    • Invited
  • [Presentation] Osteoblastic Androgen Receptor mediates androgenic anabolic actions in Bone remodeling

    • Author(s)
      Yuuki Imai
    • Organizer
      第30回日本骨代謝学会学術集会
    • Place of Presentation
      東京
    • Related Report
      2012 Annual Research Report 2011 Annual Research Report
    • Invited
  • [Presentation] Estrogen Exerts Osteoprotective Function through Facilitating Bone Formation via ERα in Osteocytes

    • Author(s)
      Yuuki Imai
    • Organizer
      15th International Congress on Hormonal Steroids and Hormones & Cancer
    • Place of Presentation
      金沢
    • Related Report
      2012 Annual Research Report 2011 Annual Research Report
    • Invited
  • [Remarks] 愛媛大学 プロテオサイエンスセンター病 態生理解析部門/大学院医学系研究科病態 生理学講座ホームページ

    • URL

      http://www.m.ehime-u.ac.jp/school/imailab

    • Related Report
      2013 Final Research Report
  • [Remarks] 愛媛大学 今井研究室ウェブサイト

    • URL

      http://www.m.ehime-u.ac.jp/school/imailab

    • Related Report
      2013 Annual Research Report
  • [Remarks] 愛媛大学 今井研究室ウェブサイト

    • URL

      http://www.m.ehime-u.ac.jp/school/imailab

    • Related Report
      2012 Annual Research Report

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Published: 2013-05-15   Modified: 2019-07-29  

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