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Mechanisms of the transition from hematopoietic cells to bone-resorbing osteoclasts

Planned Research

Project AreaMolecular mechanisms of cell fate determination in the cells that undergo stepwise differentiation to multiple pathways
Project/Area Number 22118007
Research Category

Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionNational Center for Geriatrics and Gerontology

Principal Investigator

IKEDA Kyoji  独立行政法人国立長寿医療研究センター, 運動器疾患研究部, 部長 (00222878)

Co-Investigator(Renkei-kenkyūsha) TAKESHITA Sunao  国立長寿医療研究センター, 運動器疾患研究部, 室長 (50263009)
Project Period (FY) 2010-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥105,820,000 (Direct Cost: ¥81,400,000、Indirect Cost: ¥24,420,000)
Fiscal Year 2014: ¥15,210,000 (Direct Cost: ¥11,700,000、Indirect Cost: ¥3,510,000)
Fiscal Year 2013: ¥15,600,000 (Direct Cost: ¥12,000,000、Indirect Cost: ¥3,600,000)
Fiscal Year 2012: ¥21,320,000 (Direct Cost: ¥16,400,000、Indirect Cost: ¥4,920,000)
Fiscal Year 2011: ¥21,060,000 (Direct Cost: ¥16,200,000、Indirect Cost: ¥4,860,000)
Fiscal Year 2010: ¥32,630,000 (Direct Cost: ¥25,100,000、Indirect Cost: ¥7,530,000)
Keywords破骨細胞 / 分化 / 骨リモデリング / RANKL / 細胞周期 / 細胞分化 / 転写制御 / 栄養 / エネルギー / ヒストン修飾
Outline of Final Research Achievements

Bone destruction precedes subsequent bone formation and is performed by multi-nuclear osteoclasts that differentiate from hematopoietic cells in the bone marrow. Excessive osteoclastic activity underlies osteoporosis and joint destruction associated with RA. In this study we have clarified metabolic adaptations and cell-cycle dynamics that take place during the transition from hematopoietic cells to bone-resorbing osteoclasts, and the transcriptional network involved. Further, we have identified by gene expression profiling and biochemical techniques secretory products that are released at distinct stages of osteoclastogenesis and send coupling signals to the subsequent bone formation by osteoblasts.

Report

(6 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Annual Research Report
  • 2012 Annual Research Report
  • 2011 Annual Research Report
  • 2010 Annual Research Report
  • Research Products

    (46 results)

All 2015 2014 2013 2012 2011 2010 Other

All Journal Article (19 results) (of which Peer Reviewed: 17 results,  Open Access: 4 results,  Acknowledgement Compliant: 10 results) Presentation (22 results) (of which Invited: 3 results) Book (3 results) Remarks (2 results)

  • [Journal Article] Secretion of PDGF isoforms during osteoclastogenesis and its modulation by anti-osteoclast drugs2015

    • Author(s)
      Rahman MM, Matsuoka K, Takeshita S, Ikeda K
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 460 Issue: 2 Pages: 159-164

    • DOI

      10.1016/j.bbrc.2015.04.115

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Physiological functions of osteoblast lineage and T cell–derived RANKL in bone homeostasis2014

    • Author(s)
      Fumoto T, Takeshita S, Ito M, Ikeda K
    • Journal Title

      J Bone Miner Res

      Volume: 29 Issue: 4 Pages: 830-842

    • DOI

      10.1002/jbmr.2096

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Integrin αv in the mechanical response of osteoblast lineage cells2014

    • Author(s)
      Kaneko K, Ito M, Naoe Y, Lacy-Hulbert A, Ikeda K
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 447 Issue: 2 Pages: 352-357

    • DOI

      10.1016/j.bbrc.2014.04.006

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Age-related marrow adipogenesis is linked to increased expression of RANKL2014

    • Author(s)
      Takeshita S, Fumoto T, Naoe Y, Ikeda K
    • Journal Title

      J Biol Chem

      Volume: 289 Issue: 24 Pages: 16699-16710

    • DOI

      10.1074/jbc.m114.547919

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Mineralocorticoid receptor function in bone metabolism and its role in glucocorticoid-induced osteopenia2014

    • Author(s)
      Fumoto T, Ishii K, Ito M, Berger S, Schutz G, Ikeda K
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 457 Issue: 3 Pages: 407-412

    • DOI

      10.1016/j.bbrc.2014.03.149

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Osteoclast-derived complement component 3a stimulates osteoblast differentiation2014

    • Author(s)
      Matsuoka K, Park K, Ito M, Ikeda K, Takeshita S
    • Journal Title

      J Bone Miner Res

      Volume: 29 Issue: 7 Pages: 1522-1530

    • DOI

      10.1002/jbmr.2187

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Lanthanum carbonate stimulates bone formation in a rat model of renal insufficiency with low bone turnover2014

    • Author(s)
      Fumoto T, Ito M, Ikeda K
    • Journal Title

      J Bone Miner Metab

      Volume: 32 Issue: 5 Pages: 484-493

    • DOI

      10.1007/s00774-013-0521-2

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Factors and mechanisms involved in the coupling from bone resorption to formation: how osteoclasts talk to osteoblasts2014

    • Author(s)
      Ikeda K, Takeshita S
    • Journal Title

      J Bone Metab

      Volume: 21 Issue: 3 Pages: 163-167

    • DOI

      10.11005/jbm.2014.21.3.163

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Metabolic regulation of osteoclast differentiation and function2013

    • Author(s)
      Indo Y, Takeshita S, Ishii K, Hoshii T, Aburatani H, Hirao A, Ikeda K
    • Journal Title

      J Bone Miner Res

      Volume: 28 Issue: 11 Pages: 2392-2399

    • DOI

      10.1002/jbmr.1976

    • Related Report
      2013 Annual Research Report 2012 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Osteoclast-secreted Cthrc1 in the coupling of bone resorption to formation2013

    • Author(s)
      Takeshita S, Fumoto T, Matsuoka K, Park K, Aburatani H, Kato S, Ito M, Ikeda K
    • Journal Title

      J Clin Invest

      Volume: 123 Issue: 9 Pages: 3914-3924

    • DOI

      10.1172/jci69493

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Bone-buried osteocytes regulate primary lymphoid organs and fat metabolism2013

    • Author(s)
      Sato M, Asada N, Kawano Y, Minagawa K, Kawano H, Wakahashi K, Sada A, Ikeda K, Matsui T, Katayama Y
    • Journal Title

      Cell Metab

      Volume: 18 Issue: 5 Pages: 749-758

    • DOI

      10.1016/j.cmet.2013.09.014

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Matrix-embedded osteocytes regulate mobilization of hematopoietic stem/progenitor cells2013

    • Author(s)
      Asada N, Katayama Y, Sato M, Minagawa K, Wakahashi K, Kawano H, Kawano Y, Sada A, Ikeda K, Matsui T, Tanimoto M
    • Journal Title

      Cell Stem Cell

      Volume: 12 Pages: 737-747

    • NAID

      120005359102

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Histological examination on osteoblastic activities in the alveolar bone of transgenic mice with induced ablation of osteocytes2013

    • Author(s)
      Li M, Hasegawa T, Hogo H, Tatsumi S, Liu Z, Guo Y, Sasaki M, Tabata C, Yamamoto T, Ikeda K, Amizuka N
    • Journal Title

      Histol Histopathol

      Volume: 28 Pages: 327-335

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 骨代謝制御における骨細胞の役割2012

    • Author(s)
      池田恭治
    • Journal Title

      アンチ・エイジング医学

      Volume: 8 Pages: 26-28

    • Related Report
      2012 Annual Research Report
  • [Journal Article] Physiological function of the angiotensin AT1a receptor in bone remodeling2011

    • Author(s)
      Kaneko K, Ito M, Fumoto T, Fukuhara R, Ishida J, Fukamizu A, Ikeda K
    • Journal Title

      J Bone Miner Res

      Volume: 26 Issue: 12 Pages: 2959-2966

    • DOI

      10.1002/jbmr.501

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Retroperitoneal liposarcoma with lamellar bone inside2011

    • Author(s)
      Yamauchi J, Ubara Y, Ikeda K, Takaichi K
    • Journal Title

      Lancet

      Volume: 377 Pages: 941-941

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Increased osteocyte death and mineralization inside bone after parathyroidectomy in patients with secondary hyperparathyroidism2010

    • Author(s)
      Yajima A, Inaba M, Tominaga Y, Nishizawa Y, Ikeda K, Ito A
    • Journal Title

      J Bone Miner Res

      Volume: 25 Pages: 2374-2381

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] SIRT1 Regulates Thyroid-Stimulating Hormone Release by Enhancing PIP5Kγ Activity through Deacetylation of Specific Lysine Residues in Mammals2010

    • Author(s)
      Akieda-Asai S, Zaima N, Ikegami K, Kahyo T, Yao I, Hatanaka T, Iemura S-i, Sugiyama R, Yokozeki T, Eishi Y, Koike M, Ikeda K, Chiba T, Yamaza H, Shimokawa I, Song Si-Y, Matsuno A, Mizutani A, Sawabe M, Chao MV, Tanaka M, Kanaho Y, Natsume T, Sugimura H, Date Y, McBurney MW, Guarente L, Setou M
    • Journal Title

      PLoS ONE

      Volume: 5

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Osteocytes in normal physiology and osteoporosis2010

    • Author(s)
      Watanabe K, Ikeda K
    • Journal Title

      Clinic Rev Bone Miner Metab

      Volume: 8 Pages: 224-232

    • Related Report
      2010 Annual Research Report
  • [Presentation] Osteoclast-derived coupling factor Cthrc1 stimulates osteoblast differentiation through Rac1/PKC/ERK2014

    • Author(s)
      Matsuoka K, Ikeda K, Takeshita S
    • Organizer
      The 36th Annual Meeting of the American Society for Bone & Mineral Research
    • Place of Presentation
      Houston、アメリカ
    • Year and Date
      2014-09-15
    • Related Report
      2014 Annual Research Report
  • [Presentation] How osteoclasts talk to osteoblasts2014

    • Author(s)
      Ikeda K
    • Organizer
      Second Asia-Pacific Bone and Mineral Research Meeting
    • Place of Presentation
      Seol、韓国
    • Year and Date
      2014-05-31
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Osteoclast-secreted complement component 3a stimulates osteoblast differentiation.2013

    • Author(s)
      Matsuoka K, Ito M, Ikeda K, Takeshita S
    • Organizer
      The 35th Annual Meeting of the American Society for Bone & Mineral Research
    • Place of Presentation
      ボルチモア、アメリカ
    • Year and Date
      2013-10-06
    • Related Report
      2013 Annual Research Report
  • [Presentation] Integrin αv in the Mechanical Response of Osteoblast Lineage Cells.2013

    • Author(s)
      Kaneko K, Ito M, Lacy-Hulbert A, Ikeda K
    • Organizer
      The 35th Annual Meeting of the American Society for Bone & Mineral Research
    • Place of Presentation
      ボルチモア、アメリカ
    • Year and Date
      2013-10-06
    • Related Report
      2013 Annual Research Report
  • [Presentation] Metabolic Adaptation during Osteoclastogenesis2013

    • Author(s)
      Indo Y, Takeshita S, Aburatani H, Ikeda K
    • Organizer
      The 35th Annual Meeting of the American Society for Bone & Mineral Research
    • Place of Presentation
      ボルチモア、アメリカ
    • Year and Date
      2013-10-06
    • Related Report
      2013 Annual Research Report
  • [Presentation] Osteoblastic and T Cell-derived RANKL in Bone Remodeling and Modeling2013

    • Author(s)
      Fumoto T, Takeshita S, Ito M, Ikeda K
    • Organizer
      The 35th Annual Meeting of the American Society for Bone & Mineral Research
    • Place of Presentation
      ボルチモア、アメリカ
    • Year and Date
      2013-10-05
    • Related Report
      2013 Annual Research Report
  • [Presentation] Integrin v and mechano signal transduction in osteoblast lineage cells.2013

    • Author(s)
      Kaneko K, Ito M, lacey-Hulbert A, Ikeda K
    • Organizer
      第86回日本生化学会大会
    • Place of Presentation
      横浜
    • Year and Date
      2013-09-11
    • Related Report
      2013 Annual Research Report
  • [Presentation] 骨リモデリングの制御機構2013

    • Author(s)
      池田恭治
    • Organizer
      第57回日本リウマチ学会学術集会
    • Place of Presentation
      京都
    • Year and Date
      2013-04-19
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] 骨粗鬆症の動物モデル2012

    • Author(s)
      池田恭治
    • 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
      2012-10-27
    • Related Report
      2012 Annual Research Report
  • [Presentation] Pre-adipocytes Support Osteoclastogenesis through RANKL Expression2012

    • Author(s)
      Takeshita S, Fumoto T, Ikeda K
    • Organizer
      The 34th Annual Meeting of the American Society for Bone Mineral Research
    • Place of Presentation
      アメリカ
    • Year and Date
      2012-10-15
    • Related Report
      2012 Annual Research Report
  • [Presentation] リモデリングと骨質2012

    • Author(s)
      池田恭治
    • Organizer
      第30回日本骨代謝学会学術集会
    • Place of Presentation
      東京
    • Year and Date
      2012-07-19
    • Related Report
      2012 Annual Research Report
  • [Presentation] 骨の代謝と老化2012

    • Author(s)
      池田恭治
    • Organizer
      第54回日本老年医学会学術集会
    • Place of Presentation
      東京
    • Year and Date
      2012-06-29
    • Related Report
      2012 Annual Research Report
  • [Presentation] Signaling between osteoclasts and osteoblasts2012

    • Author(s)
      池田恭治
    • Organizer
      4th International Conference on Osteoimmunology
    • Place of Presentation
      ギリシャ
    • Year and Date
      2012-06-20
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] アンジオテンシン受容体の骨代謝における生理機能2011

    • Author(s)
      兼子佳子、伊東昌子、石田純治、深水昭吉、池田恭治
    • Organizer
      第84回日本生化学会大会
    • Place of Presentation
      横浜
    • Year and Date
      2011-09-24
    • Related Report
      2011 Annual Research Report
  • [Presentation] An In Vitro Model for Osteocyte Differentiation2011

    • Author(s)
      Watanabe K, Ikeda K
    • Organizer
      The 33rd Annual Meeting of the American Society for Bone & Mineral Research
    • Place of Presentation
      San Diego, USA
    • Year and Date
      2011-09-18
    • Related Report
      2011 Annual Research Report
  • [Presentation] Between bone resorption and formation2011

    • Author(s)
      池田恭治
    • Organizer
      第8回Bone Biology Forum
    • Place of Presentation
      三島
    • Year and Date
      2011-08-19
    • Related Report
      2011 Annual Research Report
  • [Presentation] 骨粗鬆症の病因と治療をめぐる最近のトピックス2011

    • Author(s)
      池田恭治
    • Organizer
      第9回名城倶楽部
    • Place of Presentation
      名古屋市(特別講演)
    • Year and Date
      2011-03-05
    • Related Report
      2010 Annual Research Report
  • [Presentation] 鉄と破骨細胞2010

    • Author(s)
      池田恭治
    • Organizer
      第34回日本鉄バイオサイエンス学会
    • Place of Presentation
      東京
    • Year and Date
      2010-09-12
    • Related Report
      2010 Annual Research Report
  • [Presentation] アレンドロネート投与による皮質骨と海綿骨の代謝変化2010

    • Author(s)
      伊藤明美、杵鞭あゆみ、兼子佳子、池田恭治
    • Organizer
      第28回日本骨代謝学会
    • Place of Presentation
      東京
    • Year and Date
      2010-07-21
    • Related Report
      2010 Annual Research Report
  • [Presentation] 骨の細胞機能と情報伝達網2010

    • Author(s)
      池田恭治
    • Organizer
      山形大学大学院講義
    • Place of Presentation
      山形市
    • Year and Date
      2010-06-29
    • Related Report
      2010 Annual Research Report
  • [Presentation] 骨折は忘れたころにやってくる2010

    • Author(s)
      池田恭治
    • Organizer
      第11回知多北東部整形リハビリ病診連携会
    • Place of Presentation
      大府市(特別講演)
    • Year and Date
      2010-05-22
    • Related Report
      2010 Annual Research Report
  • [Presentation] Bone-resorbing osteoclasts secrete a factor that stimulates osteoblastic differentiation2010

    • Author(s)
      Takeshita S, Fumoto T, Park K-a, Aburatani H, Kato S, Ito M, Ikeda K
    • Organizer
      The 32nd Annual Meeting of the American Society for Bone & Mineral Research
    • Place of Presentation
      Toronto, Canada
    • Related Report
      2010 Annual Research Report
  • [Book] 運動器疾患の予防と治療2011

    • Author(s)
      池田恭治
    • Total Pages
      231
    • Publisher
      長寿科学振興財団
    • Related Report
      2011 Annual Research Report
  • [Book] Mechanosensing Biology (Chapter 9. Osteocytes in Mechanosensing : insights from mouse models and human patients)2011

    • Author(s)
      Watanabe K, Ikeda K
    • Total Pages
      219
    • Publisher
      Springer
    • Related Report
      2010 Annual Research Report
  • [Book] 図解 わかる骨形態計測~骨のなかをのぞいてみよう~2010

    • Author(s)
      伊藤明美、池田恭治
    • Total Pages
      71
    • Publisher
      医薬ジャーナル社
    • Related Report
      2010 Annual Research Report
  • [Remarks]

    • URL

      http://www.ncgg.go.jp/department/bjd/bjd/index.htm

    • Related Report
      2012 Annual Research Report
  • [Remarks]

    • URL

      http://www.mdlinx.com/rheumatology/news-article.cfm/4615532

    • Related Report
      2012 Annual Research Report

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Published: 2010-08-23   Modified: 2018-03-28  

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