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骨再生過程におけるOsteocrine factorの同定

Research Project

Project/Area Number 21659420
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeSingle-year Grants
Research Field Morphological basic dentistry
Research InstitutionTokyo Medical and Dental University

Principal Investigator

山口 朗  東京医科歯科大学, 大学院・医歯学総合研究科, 教授 (00142430)

Project Period (FY) 2009 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2010: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2009: ¥1,500,000 (Direct Cost: ¥1,500,000)
Keywords骨再生 / 骨形成 / 骨リモデリング / 骨吸収 / 全身性因子
Research Abstract

近年の骨生物学の飛躍的進歩により、骨格が骨外組織の機能を制御する内分泌器官であることが示唆されている。我々は、骨格で産生され、骨格のみならず生体全体の機能を制御する因子をOsteocrine factor、その制御機構をOsteocrine Systemという新しい概念で捉えることを提唱している。本研究では、骨再生過程で産生されるOsteocrine factorを同定することを目的とする。その成果により、内分泌器官としての骨格の理解をさらに深めることができる。
本研究では、8週齢のC57BL6マウスの頭蓋骨に直径1mmの円形骨欠損を作成し、骨再生1,2,3週後に骨再生部と周囲2mmを含む組織を歯科用ダイアモンドディスクで無菌的に切断し、これらの組織を器官培養し、in vitroでも骨再生が起こっていることを確認した。また、これらの培養上清をMI3T3-E1細胞に添加し、細胞増殖に与える作用を検討し、わずかな細胞増殖作を認した。また、培養上清を添加したMI3T3-E1細胞のアルカリフォスファターゼ活性の上昇作用も確認できたので、本実験系により骨再生過程におけるautocrine的な骨芽細胞刺激因子が産生されていることが示唆された。また、骨組織特異的な遺伝子改変マウスを用いて骨細胞が産生するOsteocrine factorであるFGF23の発現を制御すると思われる遺伝子を同定し、現在、さらに検討中である。

Report

(2 results)
  • 2010 Annual Research Report
  • 2009 Annual Research Report
  • Research Products

    (29 results)

All 2011 2010 2009

All Journal Article (15 results) (of which Peer Reviewed: 15 results) Presentation (14 results)

  • [Journal Article] Concurrent downregulation of keratin 4 and keratin 13 expression defines the neoplastic lesion of oral epithelium and serves as an ideal marker for oral squamous cell carcinoma and oral epithelial dysplasia.2011

    • Author(s)
      Sakamoto K, Aragaki T, Kawachi H, Katsube K, Miki Y, Takizawa T, Omura K, MoritaK, Okada N, Yamaguchi A
    • Journal Title

      Histopathology

      Volume: 58 Pages: 531-542

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Acerogenin A, a natural compound isolated from Acer nikoense Maxim, stimulates osteoblast differentiation through bone morphogenetic protem action.2011

    • Author(s)
      Kihara K, Ichikawa S, Yonezawa T, Lee JW, Akihisa T, Woo JT, Michi Y, Amagasa T, Yamaguchi A
    • Journal Title

      Biochem Bioph Res Commun

      Volume: 406 Pages: 211-217

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Comparative morphology of osteocytes in aquatic and land vertebrates.2011

    • Author(s)
      Cao L, Moriishi T, Miyazaki T Iimura T Tamamura S, Komori T, Yamaguchi A
    • Journal Title

      J Bone Miner Met

      Volume: In press

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Maf mediates the age-related switch in mesenchymal cell.2010

    • Author(s)
      Nishikawa K, Isogai M, Nakashima T, Takeda S, Michito, Hamada M, Kimura A, KodamaT, Yama uchi A, Owen MJ, Takahashi, Takayanagi H
    • Journal Title

      J Clin Invest

      Volume: 120 Pages: 3455-3465

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Repetition of continuous PTH treatments followed by periodic withdrawals exerts anabolic effects on rat bone.2010

    • Author(s)
      Etoh M, Yamaguchi A
    • Journal Title

      J Bone Miner Metab

      Volume: 28 Pages: 641-649

    • NAID

      10027845856

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Roles of IL-6 and PTHrP in osteoclast formation associated with oralcancers : The significance of IL-6 synthesized by stromal cells in response to cancer cells.2010

    • Author(s)
      Kayamori K, Sakamoto K Nakashima T, Takayanagi T, MoritaK Omura K N guyen ST, Miki, Iimura T, Himeno A, Akashi T, Yamada-Okabe H, Ogata E, Yamaguchi A
    • Journal Title

      Amer J Pathol

      Volume: 176 Pages: 968-980

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Deficiency of chemokine receptor CCRI causes osteopenia due to impaired functions of osteoclasts and osteoblasts.2010

    • Author(s)
      Hoshino A, limura T Ueha S, Hanada S, Maruoka 'Y, Mayahara M, Suzuki K, Imai T, Ito M, Manome Y, Yasuhara M, Kirino T, Yamaguchi A, Matsushima K, Yamamoto K
    • Journal Title

      J Biol Chem

      Volume: 285 Pages: 28826-28837

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Comprehensive keratin profiling reveals distinctions between keratocystic odontogenic tumor and orthokeratinized odontogenic cyst.2010

    • Author(s)
      Aragaki T, Michi Y, Katsube K, Uzawa N, Okada NAkashi T, Amagasa T Yamaguchi A, Sakamoto I
    • Journal Title

      Human Pathol

      Volume: 42 Pages: 1718-1725

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The significance of IL-6 synthesized by stromal cells in response to cancer cells2010

    • Author(s)
      Kayamori K, Sakamoto K, Nakashima T, Takayanagi T, Morita K, Omura K, Nguyen ST, Miki Y, Iimura T, Himeno A, Akashi T, Yamada-Okabe H, Ogata E, Yamaguchi A
    • Journal Title

      Am J Patholo 176

      Pages: 968-980

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Repetition of continuous PTH treatments followed by periodic withdrawals exerts anabolic effects on rat bone.2010

    • Author(s)
      Etoh M, Yamaguchi A
    • Journal Title

      J Bone Miner Metab (In press)

    • NAID

      10027845856

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Hox genes, a molecular constraint for development and evolution of vertebrate body plan.2010

    • Author(s)
      Iimura T, Himeno A, Nakane A, Yamaguchi A
    • Journal Title

      J Oral Biosci (In press)

    • NAID

      10027105813

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Role of CCN, a vertebrate specific gene family, in development.2009

    • Author(s)
      Katsube K, Sakamoto K, Tamamura Y, Yamaguchi A
    • Journal Title

      Dev Growth Differ 51

      Pages: 55-67

    • NAID

      10023963730

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Bone morphogenetic proteins are involved in the pathobiology of synovial chondromatosis.2009

    • Author(s)
      Nakanishi S, Sakamoto K, Yoshitake H, Kino K, Amagasa T, Yamaguchi A
    • Journal Title

      Biochem Biophys Res Commun 379

      Pages: 914-919

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] CCN3 and bone marrow cells.2009

    • Author(s)
      Katsube K, Ichikawa S, Katsuki Y, Kihara T, Terai M, Lau LF, Tamamura Y, Takeda S, Umezawa A, Sakamoto K, Yamaguchi A
    • Journal Title

      J Cell Commun Signal. 3

      Pages: 135-145

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Latexin is involved in bone morphogenetic protein-2-induced chondrocyte differentiation.2009

    • Author(s)
      Kadouchi I, Sakamoto K, Liu T, Murakami T, Kobayashi E, Hoshino Y, Yamaguchi A
    • Journal Title

      Biochem Biophys Res Commun 387

      Pages: 6000-6004

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Presentation] 骨再生のメカニズムと骨再生療法2010

    • Author(s)
      山口朗
    • Organizer
      DENTISTRY, QUO VADIS?
    • Place of Presentation
      東京都
    • Year and Date
      2010-12-05
    • Related Report
      2010 Annual Research Report
  • [Presentation] 骨代謝の基礎と骨再生2010

    • Author(s)
      山口朗
    • Organizer
      平成22年度日本小児歯科学会秋期大会
    • Place of Presentation
      郡山市
    • Year and Date
      2010-12-02
    • Related Report
      2010 Annual Research Report
  • [Presentation] オステオネットワークの維持と破綻:顎顔面骨疾患の病態解明を目指して2010

    • Author(s)
      山口朗
    • Organizer
      第58回NPO法人日本口腔科学会中国・四国地方部会
    • Place of Presentation
      広島市 招待講演
    • Year and Date
      2010-11-16
    • Related Report
      2010 Annual Research Report
  • [Presentation] 骨形成と血管石灰化の共通点と相違点2010

    • Author(s)
      山口朗
    • Organizer
      第28回日本骨代謝学会学術集会
    • Place of Presentation
      東京都
    • Year and Date
      2010-07-21
    • Related Report
      2010 Annual Research Report
  • [Presentation] 再生医療「骨再生」-そのメカニズムと応用-2010

    • Author(s)
      山口朗
    • Organizer
      平成22年日本歯科医師会生涯研修セミナー
    • Place of Presentation
      津市
    • Year and Date
      2010-06-27
    • Related Report
      2010 Annual Research Report
  • [Presentation] ビスフォスフォネート関連顎骨壊死(骨髄炎)の病理2010

    • Author(s)
      山口朗
    • Organizer
      第64回日本口腔科学会学術集会共催
    • Place of Presentation
      札幌市
    • Year and Date
      2010-06-25
    • Related Report
      2010 Annual Research Report
  • [Presentation] 再生医療「骨再生」-そのメカニズムと応用-2010

    • Author(s)
      山口朗
    • Organizer
      平成22年日本歯科医師会生涯研修セミナー
    • Place of Presentation
      水戸市
    • Year and Date
      2010-05-23
    • Related Report
      2010 Annual Research Report
  • [Presentation] ビスフォスフォネート関連顎骨壊死の病理2010

    • Author(s)
      山口朗
    • Organizer
      東京都臨床整形外科医会統合研修会
    • Place of Presentation
      東京
    • Year and Date
      2010-05-15
    • Related Report
      2010 Annual Research Report
  • [Presentation] 蛍光イメージングによる骨細胞の形態・機能分化の計測2010

    • Author(s)
      姫野彰子、仲根綾子、和泉雄一、山口朗、飯村忠浩
    • Organizer
      第30回日本骨形態計測学会
    • Place of Presentation
      米子市
    • Year and Date
      2010-05-14
    • Related Report
      2010 Annual Research Report
  • [Presentation] 口腔扁平上皮癌による骨破壊メカニズム2009

    • Author(s)
      栢森高、姫野彰子、飯村忠浩、山口朗
    • Organizer
      第12回癌と骨病変研究会
    • Place of Presentation
      大阪
    • Year and Date
      2009-11-20
    • Related Report
      2009 Annual Research Report
  • [Presentation] ビスフォスフォネート関連顎骨壊死の病理学的特徴.2009

    • Author(s)
      山口朗
    • Organizer
      第34回日本外科系連合学会学術集会
    • Place of Presentation
      東京
    • Year and Date
      2009-06-19
    • Related Report
      2009 Annual Research Report
  • [Presentation] 脊椎動物における骨格形成の変遷2009

    • Author(s)
      山口朗
    • Organizer
      第52回日本骨粗鬆症財団教育ゼミナール
    • Place of Presentation
      東京
    • Year and Date
      2009-06-05
    • Related Report
      2009 Annual Research Report
  • [Presentation] 水棲動物と陸棲動物における骨の形態と機能の相違2009

    • Author(s)
      山口朗
    • Organizer
      第114回日本解剖学会
    • Place of Presentation
      岡山
    • Year and Date
      2009-03-28
    • Related Report
      2009 Annual Research Report
  • [Presentation] 骨再生の分子メカニズムの解析とその応用.2009

    • Author(s)
      山口朗
    • Organizer
      第22回日本創外固定・骨延長学会
    • Place of Presentation
      京都
    • Year and Date
      2009-03-06
    • Related Report
      2009 Annual Research Report

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Published: 2009-04-01   Modified: 2016-04-21  

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