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The relationship between cell proliferation and RANKL-induced osteoclastogenesis

Research Project

Project/Area Number 18390495
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Functional basic dentistry
Research InstitutionMatsumoto Dental University

Principal Investigator

TAKAHASHI Naoyuki  Matsumoto Dental University, Graduate School of Oral Science, Hard Tissue Research, Professor (90119222)

Co-Investigator(Kenkyū-buntansha) MIZOGUCHI Toshihide  Matsumoto Dental University, Institute for Oral Science, Lecturer (90329475)
KOIDE Masanori  Matsumoto Dental University, Institute for Oral Science, Lecturer (10367617)
NAKAMURA Akihiro  Matsumoto Dental University, Second Department of Anatomy, Professor (50227930)
NINOMIYA Tadshi  Matsumoto Dental University, Institute for Oral Science, Assistant Professor (00360222)
細矢 明宏  松本歯科大学, 歯学部, 助手 (70350824)
Project Period (FY) 2006 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥17,420,000 (Direct Cost: ¥15,200,000、Indirect Cost: ¥2,220,000)
Fiscal Year 2007: ¥9,620,000 (Direct Cost: ¥7,400,000、Indirect Cost: ¥2,220,000)
Fiscal Year 2006: ¥7,800,000 (Direct Cost: ¥7,800,000)
KeywordsOsteoclasts / RANKL / M-CSF / Osteoblasts / Cell cycle-arrested quiescent osteoclast precursor / OPG / Osteoclast niche / Fos deficient mice / 骨髄細胞マクロファージ / RANK-Cre / 骨髄マクロファージ / プロモデオキシウリジン
Research Abstract

(1) In vitro analysis of the cell cycle in osteoclast progenitors : We have shown that cell cycle progression and withdrawal after the progression in osteoclast precursors are the two sequential events essential for RANKL-induced osteoclastogenesis.
(2) The isolation and the analysis of QOPs: Cell cycle-arrested quiescent osteoclast precursors (QOPs) were identified as the committed osteoclast precursors in vitro. In vivo experiments showed that mononuclear cells expressing c-Fms and RANK but not Ki67 were detected along bone surfaces in the vicinity of osteoblasts in RANKL-deficient mice. They were identified as QOPs.
(3) BMP transplantation experiments using RANKL(-/-) mice and OPG(-/-) mice : We examined the requirements for osteoclastogenesis using OPG(-/-) mice, RANKL(-/-) mice and a system involving BMP-induced ectopic bone formation. We have shown that osteoblasts also play important roles in osteoclastogenesis through offering the critical microenvironment for the action of RANKL.
(4) Establishment of the Cre-lox P system for osteoclast specific deletion of target genes : We have succeeded to establish RANK Cre mice. We are now analyzing the Cre recombinase expression in osteoclastss.
(5) Transgenic mice of cell cycle regulatory genes : We are advancing experiments on osteoclast niche, in stead of the production of the cycle regulatory gene transgenic mice.
(6) Clinical application of anti-cancer drugs in bone diseases : We have shown that that taxanes have beneficial effects on the treatment of bone metastatic cancers. Administration of an anti-cancer drug, 5-fluorouracil, to mice induced myelosuppression, but QOPs survived and differentiated into osteoclasts in response to an active vitamin D_3 analog given to those mice. We have shown that QOPs pre-exist at the site of osteoclastogenesis and that osteoblasts play roles in the maintenance of QuOPs in the undifferentiated state. We found that c-Fos(-/-) mice have not osteoclast niche.

Report

(3 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • Research Products

    (45 results)

All 2008 2007 2006 Other

All Journal Article (35 results) (of which Peer Reviewed: 17 results) Presentation (7 results) Book (3 results)

  • [Journal Article] MKK6-p38 MAPK signaling pathway enhances survival but not bone-resorbing activity of osteoclasts2008

    • Author(s)
      Yamashita T, et. al.
    • Journal Title

      Biochem Biophys Res Commun 365

      Pages: 252-257

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Docetaxel inhibits bone resorption through suppression of osteoclast formation and function in different manners2008

    • Author(s)
      Takahashi M, et. al.
    • Journal Title

      J Bone Miner Metab (In press)

    • NAID

      10025336084

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] The action of RANKL and OPG for osteoclastogenesis2008

    • Author(s)
      Kobayashi Y, et. al.
    • Journal Title

      Critical Reviews in Eukaryotic Gene Expression (In press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Roles of Wnt in bone formation and resorption2008

    • Author(s)
      Kobayashi Y, et. al.
    • Journal Title

      Japanese Dental Science Review (In press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Current paradigms of osteoblast-osteoclast interactions and bacterial pathogen-induced bone resorption.2008

    • Author(s)
      Takahashi N, et. al.
    • Journal Title

      Periodontal Medicine and Systems Biology, Blackwell Publishing, Oxford (In press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Osteoclast generation2008

    • Author(s)
      Takahashi N, et. al.
    • Journal Title

      Principles of bone biology Third edition, Academic Press, San Diego (In press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] The action of RANKL and OPG for osteoclastogenesis.2008

    • Author(s)
      Kobayashi Y, et. al.
    • Journal Title

      Critical Reviews in Eukaryotic Gene Expression (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Roles of Wnt in bone formation and resorption.2008

    • Author(s)
      Kobayashi Y, et. al.
    • Journal Title

      Japanese Dental Science Review (In press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Generation of osteoclasts in vitro,and assay of osteoclast activity2007

    • Author(s)
      Takahashi N, et. al.
    • Journal Title

      Methods Mol Med 135

      Pages: 285-301

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] New 19-(20S)-1・25-dihydroxyvitamin D_3 analogs strongly stimulate osteoclast formation in both in vivo and in vitro2007

    • Author(s)
      Sato M, et. al.
    • Journal Title

      Bone 40

      Pages: 293-304

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Osteoprotegerin suppresses the circulation of RANKL derived from osteoblasts2007

    • Author(s)
      Nakamichi Y, et. al.
    • Journal Title

      J Immunol 178

      Pages: 192-200

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Regulation of osteoclast polarization2007

    • Author(s)
      Takahashi N, et. al.
    • Journal Title

      Odontology 95

      Pages: 1-9

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Generation of osteoclasts in vitro, and assay of osteoclast activity.2007

    • Author(s)
      Takahashi N, et. al.
    • Journal Title

      Methods Mol Med 135

      Pages: 285-301

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] New 19-(20S)-1α, 25-dihydroxyvitamin D_3 analogs strongly stimulate osteoclast formation in both in vivo and in vitro.2007

    • Author(s)
      Sato M, et. al.
    • Journal Title

      Bone 40

      Pages: 293-304

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Regulation of osteoclast polarization.2007

    • Author(s)
      Takahashi N, et. al.
    • Journal Title

      Odontology 95

      Pages: 1-9

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Osteoprotegerin reduces the serum level of receptor activator of NF-KB ligand derived from osteoblasts.2007

    • Author(s)
      Nakamichi Y
    • Journal Title

      J Immunol 178

      Pages: 192-200

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] New 19-(20S)-1α, 25-dihydroxyvitamin D_3 analogs strongly stimulate osteoclast formation in both in vivo and in vitro2007

    • Author(s)
      Sato M
    • Journal Title

      Bone 40

      Pages: 293-304

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Regulation of osteoclast polarization2007

    • Author(s)
      Takahashi N
    • Journal Title

      Odontology 95

      Pages: 252-257

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Osteoblasts play important roles in osteoclastogenesis through offering the critical microenvironment for the action of RANKL.2007

    • Author(s)
      Udagawa N
    • Journal Title

      Dentistry in Japan 43

      Pages: 195-200

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Generation of osteoclasts in vitro, and assay of osteoclast activity2007

    • Author(s)
      Takahashi N
    • Journal Title

      Methods Mol Med 135

      Pages: 285-301

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 破骨細胞の形成部位を決める破骨細胞ニッチ2007

    • Author(s)
      高橋直之
    • Journal Title

      医学の歩み 221

      Pages: 285-301

    • Related Report
      2007 Annual Research Report
  • [Journal Article] 破骨細胞分化を調節する骨芽細胞の新しい役割2007

    • Author(s)
      小出雅則
    • Journal Title

      生体の科学 135

      Pages: 285-301

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Osteoblasts provide a suitable microenvironment for the action of receptor activator of NF-κB ligand2006

    • Author(s)
      Yamamoto Y, et. al.
    • Journal Title

      Endocrinology 147

      Pages: 3366-3374

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Coordination of microtubules and the actin cytoskeleton is important in osteoclast function,but calcitonin selectively disrupts actin rings without affecting microtubule networks2006

    • Author(s)
      Okumura S, et. al.
    • Journal Title

      Bone 39

      Pages: 684-693

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Effects of calcitonin on the function of human osteoclast-like cells formed from CD14-positive monocytes2006

    • Author(s)
      Yamamoto Y, et. al.
    • Journal Title

      Cell Mol Biol 52

      Pages: 25-31

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Osteoblasts provide a suitable microenvironment for the action of receptor activator of NF-κ ligand.2006

    • Author(s)
      Yamamoto Y, et. al.
    • Journal Title

      Endocrinology 147

      Pages: 3366-3374

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Coordination of microtubules and the actin cytoskeleton is important in osteoclast function, but calcitonin selectively disrupts actin rings without affecting microtubule networks. Submitted for publication.2006

    • Author(s)
      Okumura S, et. al.
    • Journal Title

      Bone 39

      Pages: 684-693

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Effects of calcitonin on the function of human osteoclast-like cells formed from CD14-positive monocytes.2006

    • Author(s)
      Yamamoto Y, et. al.
    • Journal Title

      Cell Mol Biol 52

      Pages: 25-31

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Establishment of primary cultures for mouse ameloblasts as a model of the life time.2006

    • Author(s)
      Suzawa T et al.
    • Journal Title

      Biochem Biophys Res Commun 345・(3)

      Pages: 1247-1253

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Gastric inhibitory polypeptide as an endogenous factor promoting new bone formation following food ingestion.2006

    • Author(s)
      Tsukiyama K et al.
    • Journal Title

      Mol Endocrinol 20・(7)

      Pages: 1644-1651

    • Related Report
      2006 Annual Research Report
  • [Journal Article] A critical role for interleukin-6 family-mediated Stat3 activation in osteoblast differentiation and bone formation.2006

    • Author(s)
      Itoh S et al.
    • Journal Title

      Bone 39・(3)

      Pages: 502-512

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Osteoblasts provide a suitable microenvironment for the action of receptor activator of NF-κB ligand.2006

    • Author(s)
      Yamamoto Y et al.
    • Journal Title

      Endocrinology 147・(7)

      Pages: 3366-3374

    • Related Report
      2006 Annual Research Report
  • [Journal Article] The mechanism of coupling between bone resorption and bone formation.2006

    • Author(s)
      Udagawa N et al.
    • Journal Title

      J Oral Biosciences 48・(3)

      Pages: 185-197

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Coordination of microtubules and the actin cytoskeleton is important in osteoclast function, but calcitonin selectively disrupts actin rings without affecting microtubule networks. Submitted for publication.2006

    • Author(s)
      Okumura S et al.
    • Journal Title

      Bone 39・(4)

      Pages: 684-693

    • Related Report
      2006 Annual Research Report
  • [Journal Article] MKK6-p38 MAPK signaling pathway enhances survival but not bone-resorbing activity of osteoclasts.

    • Author(s)
      Yamashita T, et. al.
    • Journal Title

      Biochem Biophys Res Commun 365

      Pages: 252-257

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] The RANK ligand-OPG system and a new role of osteoblasts in osteoclastogenesis2007

    • Author(s)
      Takahashi N
    • Organizer
      ASBMR Meeting of Targeting Bone Remodeling for the Treatment of Osteoporosis.
    • Place of Presentation
      Washington DC,USA
    • Year and Date
      2007-12-06
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] The RANK ligand-OPG system and a new role of osteoblasts in osteoclastogenesis.2007

    • Author(s)
      Takahashi N
    • Organizer
      ASBMR Meeting of Targeting Bone Remodeling for the Treatment of Osteoporosis
    • Place of Presentation
      Washington DC, USA
    • Year and Date
      2007-12-06
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] The RANK ligand-OPG system and a new role of osteoblasts in osteoclastogenesis2007

    • Author(s)
      Naoyuki Takahashi
    • Organizer
      米国骨代謝学会(ASBMR)Meeting of Targeting Bone Remodeling for the Treatment of Osteoporosis
    • Place of Presentation
      Washington DC
    • Year and Date
      2007-12-06
    • Related Report
      2007 Annual Research Report
  • [Presentation] 骨吸収を調節する骨芽細胞の新しい役割2007

    • Author(s)
      高橋 直之
    • Organizer
      第22回日本整形外科学会基礎学術集会
    • Place of Presentation
      浜松市
    • Year and Date
      2007-10-25
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] A new role of osteoblasts in osteoclastogenesis.2007

    • Author(s)
      Takahashi N
    • Organizer
      The 22nd annual Research Meeting of the Japanese Orthopaedic Association
    • Place of Presentation
      Hamamatsu
    • Year and Date
      2007-10-25
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] 骨吸収を調節する骨芽細胞の新しい役割2007

    • Author(s)
      高橋直之
    • Organizer
      第22回日本整形外科学会基礎学術集会教育講演
    • Place of Presentation
      浜松市
    • Year and Date
      2007-10-25
    • Related Report
      2007 Annual Research Report
  • [Presentation] 骨芽細胞による骨吸収調節機構-新しい考え方-2007

    • Author(s)
      高橋直之
    • Organizer
      第2回信州骨粗鬆症セミナー
    • Place of Presentation
      松本市
    • Year and Date
      2007-09-22
    • Related Report
      2007 Annual Research Report
  • [Book] Current paradigms of osteoblast-osteoclast interactions and bacterial pathogen-induced bone resorption. In Periodontal Medicine and Systems Biology2008

    • Author(s)
      Takahashi N
    • Publisher
      Blackwell Publishing,Oxford(In press)
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Book] Current paradigms of osteoblast-osteoclast interactions and bacterial pathogen-induced bone resorption.In Periodontal Medicine and Systems Biology2008

    • Author(s)
      Takahashi N
    • Publisher
      Academic Press,San Diego(In press)
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Book] Arthritis Research, Methods and Protocols Volume 1 "Generation of osteoclasts in vitro, and assay of osteoclast activity"2006

    • Author(s)
      Takahashi N et al.
    • Publisher
      Humana Press
    • Related Report
      2006 Annual Research Report

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Published: 2006-04-01   Modified: 2016-04-21  

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