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Analysis of osteoclast niche regulated by Wnt signals.

Research Project

Project/Area Number 22390351
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  松本歯科大学, 総合歯科医学研究所, 教授 (90119222)

Co-Investigator(Kenkyū-buntansha) KOBOYASHI Yasuhiro  松本歯科大学, 総合歯科医学研究所, 准教授 (20264252)
MIZOGUCHI Toshihide  松本歯科大学, 総合歯科医学研究所, 講師 (90329475)
NINOMIYA Tadashi  松本歯科大学, 総合歯科医学研究所, 講師 (00360222)
Co-Investigator(Renkei-kenkyūsha) UDAGAWA Nobuyuki  松本歯科大学, 歯学部, 教授 (70245801)
NAKAMURA Hiroaki  松本歯科大学, 歯学部, 教授 (50227930)
Project Period (FY) 2010 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥19,240,000 (Direct Cost: ¥14,800,000、Indirect Cost: ¥4,440,000)
Fiscal Year 2012: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2011: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000)
Fiscal Year 2010: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
Keywords口腔生化学 / 破骨細胞 / 骨芽細胞 / Wnt / IL-34 / 破骨細胞前駆細胞 / 破骨細胞ニッチ / Wnt5a / Ror2 / Wnt非古典経路 / OPG / RANKL / M-CSF
Research Abstract

We examined the role of Wnt signaling for the formation of osteoclast niche, and the results as follows. (1) The osteoclast niche was analyzed and characteristics of osteoclast precursors (quiescent osteoclast precursors, QOP) were clarified. (2) The role of noncanonical Wnt signaling in osteoclastogenesis was examined. Noncanonical Wnt signals (Wnt5a-Ror2 signals) were shown to play important roles in osteoclastogenesis. (3) Wnt5a-Ror2 signals enhanced RANKexpression in QOPs. Canonical Wnt signals did not appear to play a role in osteoclastogenesis. (4) GeneChip analysis was performed on QOPs to identify specific markers of QOPs. But we failed to isolate specific markers of QOPs. However, we found that osteoclasts specifically express Wnt5a.(5) IL-34 was identified as an important cytokine for generation of QOP in hematopoietic tissues. (6) Alveolar bone loss was examined in OPG-deficient (OPG?/?) mice and RANKL-overexpressing transgenic mice. OPG?/? mice were shown to be a use l model of periodontitis. (7) Administration of soluble form of Ror2 into collagen-induced arthritis mice effectively suppressed bone destruction.

Report

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

    (44 results)

All 2013 2012 2011 2010 Other

All Journal Article (21 results) (of which Peer Reviewed: 21 results,  Open Access: 1 results) Presentation (22 results) (of which Invited: 1 results) Remarks (1 results)

  • [Journal Article] Osteoprotegerin-deficient male mice as a model for severe alveolar bone loss: Comparison with RANKL-overexpressing transgenic male mice.2013

    • Author(s)
      Koide M et al.
    • Journal Title

      Endocrinology

      Volume: 190 Issue: 2 Pages: 773-782

    • DOI

      10.1210/en.2012-1928

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] an active vitamin D analog, on bone resorption in vivo2012

    • Author(s)
      Takahashi N: Mechanism of inhibitory action of Eldecalcitol
    • Journal Title

      J Steroid Biochem Mol Biol

      Pages: 960-760

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] New roles of osteoblasts involved in osteoclast differentiation.2012

    • Author(s)
      Yamashita T, Takahashi N, Udagawa N
    • Journal Title

      World J Osteoarthritis

      Volume: 3 Issue: 11 Pages: 175-181

    • DOI

      10.5312/wjo.v3.i11.175

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Spleen serves as a reservoir of osteoclast precursors through vitamin D-induced IL-34 expression in osteopetrotic op/op mice.2012

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

      Proc Natl Acad Sci USA

      Volume: 109 Issue: 25 Pages: 10006-10011

    • DOI

      10.1073/pnas.1207361109

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] c-Fos plays an essential role in the up-regulation of RANK expression in osteoclast precursors within the bone microenvironment2012

    • Author(s)
      Arai A, et al
    • Journal Title

      J Cell Sci

      Volume: (印刷中) Pages: 2910-2917

    • DOI

      10.1242/jcs.099986

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Regulation of Osteoclast Function. Mod Rheumatol, 22:167-177, 2012.Suda T, Takahashi F, Takahashi N Bone Effects of vitamin D-Discrepancies between in vivo and in vitro studies -2012

    • Author(s)
      Nakamura I, Takahashi N, Jimi E, Udagawa N, Suda T
    • Journal Title

      Arch Biochem Biophys

      Volume: 523 Issue: 2 Pages: 22-29

    • DOI

      10.1007/s10165-011-0530-8

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Wnt5a-Ror2 signaling between osteoblasts and osteoclast precursors enhances osteoclastogenesis2012

    • Author(s)
      Maeda, K., Kobayashi, Y., Udagawa, N., Uehara, S., Ishihara, A., Mizoguchi, T., Kikuchi, Y., Takada, I., Kato, S., Kani, S., Nishita, M., Marumo, K., Martin, T.J., Minami, Y., Takahashi, N.
    • Journal Title

      Nat.Med.

      Volume: (印刷中) Issue: 3 Pages: 405-12

    • DOI

      10.1038/nm.2653

    • Related Report
      2012 Annual Research Report 2012 Final Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Daily administration of Eldecalcitol (ED-71), an active vitamin Danalog, increases bone mineral density by suppressing RANKL expression in mouse trabecular bone2012

    • Author(s)
      Harada S, et al
    • Journal Title

      J Bone Miner Res

      Volume: 27 Issue: 2 Pages: 461-473

    • DOI

      10.1002/jbmr.555

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Tetracyclines convert the osteoclastic-differentiation pathway of orogenitor cells to produce dendritic cell-like cells2012

    • Author(s)
      Kinugawa S, et al
    • Journal Title

      J Immunol

      Volume: 188 Issue: 4 Pages: 1772-1781

    • DOI

      10.4049/jimmunol.1101174

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Polarized osteoclasts put marks of tartate-resistant acid phosphatase on dentine slices-a simple method for identifying polarized osteoclasts2012

    • Author(s)
      Nakayama T, et al
    • Journal Title

      Bone

      Volume: 49 Issue: 6 Pages: 1331-1339

    • DOI

      10.1016/j.bone.2011.09.045

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Bone Effects of vitamin D -Discrepancies between in vivo and in vitro studies -.2012

    • Author(s)
      Suda T
    • Journal Title

      Arch Biochem Biophys

      Volume: 523 Issue: 1 Pages: 22-29

    • DOI

      10.1016/j.abb.2011.11.011

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mechanism of inhibitory action of Eldecalcitol, an active vitamin D analog, on bone resorption in vivo.2012

    • Author(s)
      Takahashi N
    • Journal Title

      J Steroid Biochem Mol Biol

      Volume: 12 Pages: 243-249

    • DOI

      10.1016/j.jsbmb.2012.11.010

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] c-Fos plays an essential role in the up-regulation of RANK expression in osteoclast precursors within the bone microenvironment2012

    • Author(s)
      Arai A, et al
    • Journal Title

      J Cell Sci

      Volume: (in press)

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Lineage-Committed Osteoclast Precursors Circulate in Blood and Settle Down Into Bone2011

    • Author(s)
      Muto, A, Mizoguchi, T, Udagawa, N., Ito, S, Kawahara, I, Abiko, Y, Arai, A., Harada, S., Kobayashi, Y., Nakamichi, Y, Penninger, JM, Noguchi, T, Takahashi, N.
    • Journal Title

      Journal of Bone and Mineral Research

      Volume: 26 Issue: 12 Pages: 2978-2990

    • DOI

      10.1002/jbmr.490

    • Related Report
      2012 Final Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Identification of osteoclasts in culture2011

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

      Methods Mol Biol

      Volume: 690 Pages: 273-284

    • DOI

      10.1007/978-1-60761-962-8_18

    • ISBN
      9781607619611, 9781607619628
    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Regulatory mechanism of osteoclastogenesis by RANKL and Wnt signals.2011

    • Author(s)
      Takahashi N, Maeda K, Ishihara A, Uehara S, Kobayashi Y
    • Journal Title

      Front Biosci

      Volume: 16 Pages: 21-30

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Osteoclastic bone resorption induced by innate immune responses.2010

    • Author(s)
      Koide M, Kinugawa S, Takahashi N, UdagawaN.
    • Journal Title

      Perriodontol

      Volume: 54 Issue: 1 Pages: 235-46

    • DOI

      10.1111/j.1600-0757.2010.00355.x

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Identification of cell cycle-arrested quiescent osteoclast precursors in vivo.2010

    • Author(s)
      Takahashi N, Muto A, Arai A, Mizoguchi T
    • Journal Title

      Adv Exp Med Biol

      Volume: 658 Pages: 21-30

    • DOI

      10.1007/978-1-4419-1050-9_3

    • ISBN
      9781441910493, 9781441910509
    • Related Report
      2012 Final Research Report 2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Osteoclastic bone resorption induced by innate immune responses.2010

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

      Periodontol 2000

      Volume: 54 Pages: 235-246

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Function of OPG as a traffic regulator for RANKL is crucial for controlled osteoclastogenesis.2010

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

      J Bone Miner Res

      Volume: 25 Pages: 1907-1921

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Regulatory mechanism of osteoclastogenesis by Wnt signaling.

    • Author(s)
      Kobayashi Y, Maeda K, Uehara S, Yamashita T, Takahashi N
    • Journal Title

      Inflammation and Regeneration

      Volume: (In press)

    • NAID

      130004943807

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Presentation] チタンインプラント埋入における生体側のイベントII2012

    • Author(s)
      高橋直之
    • Place of Presentation
      東京
    • Year and Date
      2012-12-08
    • Related Report
      2012 Final Research Report
  • [Presentation] 破骨細胞の分化を調節する骨芽 細胞の新しい役割2012

    • Author(s)
      高橋直之
    • Organizer
      創価大学セミナー
    • Place of Presentation
      東京
    • Year and Date
      2012-11-16
    • Related Report
      2012 Final Research Report
  • [Presentation] 破骨細胞の分化と機能の調節機構2012

    • Author(s)
      高橋直之
    • Organizer
      九州大学大学院セミナー
    • Place of Presentation
      福岡
    • Year and Date
      2012-10-25
    • Related Report
      2012 Annual Research Report 2012 Final Research Report
  • [Presentation] 破骨細胞はどのように骨を認識し 極性化するか日本歯科理工学会・2012

    • Author(s)
      高橋直之
    • Organizer
      中部支部夏季セミナー
    • Place of Presentation
      妙高高原
    • Year and Date
      2012-08-23
    • Related Report
      2012 Final Research Report
  • [Presentation] Mechanism of inhibitory action of eldecalcitol an active vitamin D analog, on bone resorption in vivo.2012

    • Author(s)
      Naoyuki Takahashi
    • Organizer
      Invited lecture, 5th Workshop on Vitamin D
    • Place of Presentation
      Huston
    • Year and Date
      2012-06-22
    • Related Report
      2012 Final Research Report
  • [Presentation] Osteoclast precursors in vivo2012

    • Author(s)
      Naoyuki Takahashi
    • Organizer
      東京医科歯科大学 GCOE
    • Year and Date
      2012-01-24
    • Related Report
      2012 Final Research Report
  • [Presentation] 骨吸収の調節機構2012

    • Author(s)
      高橋直之
    • Organizer
      鹿児島大学歯学部セミナー
    • Place of Presentation
      鹿児島
    • Year and Date
      2012-01-16
    • Related Report
      2012 Final Research Report
  • [Presentation] 分子メカニズムを知る意味とは2011

    • Author(s)
      高橋直之
    • Organizer
      Dentistry Quo Vadis
    • Place of Presentation
      東京
    • Year and Date
      2011-12-11
    • Related Report
      2012 Final Research Report
  • [Presentation] チタンインプラント埋入における生 体側のイベント2011

    • Author(s)
      高橋直之
    • Organizer
      Dentistry Quo Vadis
    • Place of Presentation
      東京
    • Year and Date
      2011-12-10
    • Related Report
      2012 Final Research Report
  • [Presentation] 骨吸収を調節する骨芽細胞の新 しい役割2011

    • Author(s)
      高橋直之
    • Organizer
      第26回長崎骨粗鬆症研究会
    • Year and Date
      2011-11-30
    • Related Report
      2012 Final Research Report
  • [Presentation] 骨吸収を調節する骨芽細胞の新しい役割2011

    • Author(s)
      高橋直之
    • Organizer
      第26回長崎骨粗鬆症研究会
    • Place of Presentation
      長崎県医師会館(長崎)(招待講演)
    • Year and Date
      2011-11-30
    • Related Report
      2011 Annual Research Report
  • [Presentation] Quiescent Osteoclast Precursors.2011

    • Author(s)
      Naoyuki Takahashi
    • Organizer
      Invited lecture 2nd Asia-Pacific Osteoporosis and Bone Meeting
    • Year and Date
      2011-09-07
    • Related Report
      2012 Final Research Report
  • [Presentation] Quiescent Osteoclast Precursors2011

    • Author(s)
      Naoyuki Takahashi
    • Organizer
      2nd Asia-Pacific Osteoporosis and Bone Meeting
    • Place of Presentation
      Gold Coast Convention Center Gold Coast, Autraria(招待講演)
    • Year and Date
      2011-09-07
    • Related Report
      2011 Annual Research Report
  • [Presentation] 破骨細胞を制御する骨芽細胞の新しい役割2011

    • Author(s)
      高橋直之
    • Organizer
      九州大学大学院講義
    • Place of Presentation
      福岡
    • Year and Date
      2011-05-12
    • Related Report
      2012 Final Research Report
  • [Presentation] 破骨細胞形成を調節する骨芽細 胞の新しい役割2010

    • Author(s)
      高橋直之
    • Organizer
      第10回徳島 Bone Forum
    • Place of Presentation
      徳島
    • Year and Date
      2010-12-02
    • Related Report
      2012 Final Research Report
  • [Presentation] Noncanonical Wnt signaling and osteoclastogenesis. Invited lecture2010

    • Author(s)
      Naoyuki Takahashi
    • Organizer
      Satellite Symposium) 22nd Meeting of Korean Society of Bone Metabolism
    • Place of Presentation
      Seoul, Korea
    • Year and Date
      2010-11-13
    • Related Report
      2012 Final Research Report
  • [Presentation] Noncanonical Wnt signaling and osteoclastogenesis2010

    • Author(s)
      Naoyuki Takahashi
    • Organizer
      22nd Meeting of Korean Society of Bone Metabolism
    • Place of Presentation
      Sheraton Grande Walkerhill, 韓国
    • Year and Date
      2010-11-13
    • Related Report
      2010 Annual Research Report
  • [Presentation] Characteristics of osteoclast precursors in vivo.2010

    • Author(s)
      Naoyuki Takahashi
    • Organizer
      7th Meeting of Bone Biology Forum
    • Place of Presentation
      Susono,Japan
    • Year and Date
      2010-08-20
    • Related Report
      2012 Final Research Report
  • [Presentation] 破骨細胞前駆細胞の起源と動態.2010

    • Author(s)
      高橋直之
    • Organizer
      第31回に本炎症・再生学会ミニシンポジウム
    • Place of Presentation
      東京
    • Year and Date
      2010-08-06
    • Related Report
      2012 Final Research Report
  • [Presentation] 骨吸収を調節するRANKL-RANK 系. ランチョンセミナー2010

    • Author(s)
      高橋直之
    • Organizer
      第28回日本骨代謝会学術集会
    • Place of Presentation
      東京
    • Year and Date
      2010-07-21
    • Related Report
      2012 Final Research Report
  • [Presentation] 骨吸収を調節するRANKL-RANK系2010

    • Author(s)
      高橋直之
    • Organizer
      第28回日本骨代謝会学術集会,ランチョンセミナー
    • Place of Presentation
      京王プラザホテル、東京
    • Year and Date
      2010-07-21
    • Related Report
      2010 Annual Research Report
  • [Presentation] Mechanism of inhibitory action of eldecalcitol, an active vitamin D analog, on bone resorption in vivo.

    • Author(s)
      Takahashi naoyuki
    • Organizer
      5th Workshop on Vitamin D
    • Place of Presentation
      Huston、米国
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Remarks] 松本歯科大学大学院ホームページ

    • URL

      http://www.mdu.ac.jp/graduate/index.html

    • Related Report
      2012 Annual Research Report

URL: 

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

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