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Physiologic functions of RANKL in bone metabolism

Research Project

Project/Area Number 22390064
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Pathological medical chemistry
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) FUMOTO Toshio  (独)国立長寿医療研究センター, 運動器疾患研究部, 研究員 (80463206)
Project Period (FY) 2010 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥18,590,000 (Direct Cost: ¥14,300,000、Indirect Cost: ¥4,290,000)
Fiscal Year 2012: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2011: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2010: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000)
Keywords分子病退学 / RANKL / 骨代謝 / 遺伝子 / 細胞・組織 / 生体分子 / 発生・分化 / 老化
Research Abstract

The cytokine RANKL is essential for osteoclast development in bone. The cellular sources of RANKL for support of osteoclast generation under various pathophysiological conditions have remained unclear, however. In this study we have shown that inactivation of Rankl specifically in osteoblast lineage cells with the use of an Osterix-Cre transgene results in typical osteopetrosis in the trabecular compartment of the tibia, with the phenotype being much less marked in the vertebrae. In contrast to its effects on trabecular bone, osteoblastic deficiency of RANKL resulted in thinning of the femoral cortex in association with suppression of bone formation during the modeling process. Ablation of RANKL specifically in T cells resulted in a moderate but significant increase in tibial trabecular bone. Mice with osteoblastic deficiency of RANKL were protected from bone loss induced by ovariectomy and also from joint destruction associated with arthritis, whereas loss of RANKL in T cells did not confer such protection. Finally, inducible deletion of Rankl selectively in the osteoblasts at 6 wk of age resulted in an increase in bone mass in association with reduced bone resorption and formation at 12 wk. Our results thus suggest that RANKL produced by osteoblasts contributes to osteoclast development in vivo.

Report

(4 results)
  • 2012 Annual Research Report   Final Research Report ( PDF )
  • 2011 Annual Research Report
  • 2010 Annual Research Report
  • Research Products

    (35 results)

All 2013 2012 2011 2010 Other

All Journal Article (10 results) (of which Peer Reviewed: 8 results,  Acknowledgement Compliant: 1 results) Presentation (20 results) (of which Invited: 1 results) Book (5 results)

  • [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
      2012 Final Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Osteoclast-secreted Cthrcl in the coupling of bone resorption to formation.2013

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

      J Clin Invest

      Volume: (in press)

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [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 Pages: 11755-11755

    • 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
  • [Journal Article] Physiological functions of osteoblast lineage and T cell-derived RANKL in bone homeostasis.

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

      J Bone Miner Res

      Volume: (revise中)

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Presentation] Osteoblast- and T cell-derived RANKL in osteoclasto-genesis.2012

    • Author(s)
      Fumoto T, Takeshita S, Ito M, Ikeda K
    • Organizer
      International Symposium on genetic and epigenetic control of cell fate
    • Place of Presentation
      Kyoto
    • Year and Date
      2012-11-06
    • Related Report
      2012 Final Research Report
  • [Presentation] 骨粗耘症の動物モデル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シンポジウム
    • Place of Presentation
      名古屋
    • Year and Date
      2012-10-27
    • Related Report
      2012 Final Research Report
  • [Presentation] Pre-adipocytes Support Osteoclastogenesis through RANKL Expression.2012

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

    • Author(s)
      池田恭治
    • Organizer
      シンポジウム"骨質"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 Final 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 若手企画シンポジウム"筋骨格系の老化とその制御について"
    • Place of Presentation
      東京
    • Year and Date
      2012-06-29
    • Related Report
      2012 Final Research Report
  • [Presentation] Signaling between osteoclasts and osteoblasts2012

    • Author(s)
      池田恭治
    • Organizer
      4^<th> International Conference on Osteoimmunology.
    • Place of Presentation
      Corfu, Greece
    • Year and Date
      2012-06-20
    • Related Report
      2012 Final Research Report
  • [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] 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
      2011-09-19
    • Related Report
      2012 Final Research 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] 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
  • [Presentation] リモデリングと骨質

    • 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
    • Related Report
      2012 Annual Research Report
  • [Presentation] 骨粗鬆症の動物モデル

    • 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
    • Related Report
      2012 Annual Research Report
  • [Presentation] 骨の代謝と老化

    • 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
    • Related Report
      2012 Annual Research Report
  • [Presentation] Signaling between osteoclasts and osteoblasts

    • Author(s)
      池田恭治
    • Organizer
      4th International Conference on Osteoimmunology
    • Place of Presentation
      ギリシャ
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] Pre-adipocytes Support Osteoclastogenesis through RANKL Expression

    • 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
    • Related Report
      2012 Annual Research Report
  • [Book] 破骨細胞分化のメカニズム。"運動器疾患の予防と治療"2011

    • Author(s)
      池田恭治
    • Publisher
      長寿科学振興財団
    • Related Report
      2012 Final 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
    • Publisher
      医薬ジャーナル社
    • Related Report
      2012 Final 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

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Published: 2010-08-23   Modified: 2019-07-29  

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