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Implications for novel drug development in bone metabolism: Beyond the dentin extracellular matrix.

Research Project

Project/Area Number 22792040
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeSingle-year Grants
Research Field Orthodontic/Pediatric dentistry
Research InstitutionTokyo Medical and Dental University

Principal Investigator

HARUYAMA Naoto  東京医科歯科大学, 歯と骨のGCOE拠点, GCOE拠点形成特任教員 (70359529)

Project Period (FY) 2010 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2011: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2010: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords細胞外マトリクス / 象牙質シアロリン酸化タンパク / 骨代謝 / 間葉系幹細胞 / 歯学 / 細胞外マトリックス / 破骨細胞 / 骨芽細胞 / 歯科矯正学 / 象牙シアロリン酸化タンパク
Research Abstract

In this study, we examined the effects of dentin sialophosphoprotein (DSPP), one of the major extracellular matrix proteins in dentin, on bone turnover in vivo and in vitro. According to micro CT analysis, DSPP knock out (KO) mouse femora showed significantly decreased bone mineral density as compared to those in DSPP wild type (WT) mice. However, calvarial organ culture analysis revealed that the decreased osteoclastogenesis in DSPP KO as compared to WT calvaria. Using bone marrow stromal cells (BMSCs) isolated from both WT and KO mice, we found that under the osteogenic media,ALP activity and in vitro mineralization were higher in BMSCs derived from WT mice as compared to those from KO mice. On the other hand, the KO derived BMSCs showed increased differentiation into adipocytes as compared to those from WT mice. Thus, the DSPP may be a positive regulator for the bone mineral density, promoting the bone formation but not suppressing the bone resorption.

Report

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

    (29 results)

All 2013 2012 2011 2010 Other

All Journal Article (16 results) (of which Peer Reviewed: 16 results) Presentation (10 results) (of which Invited: 1 results) Book (1 results) Remarks (2 results)

  • [Journal Article] Amelogenin splice isoforms stimulate chondrogenic differentiation of ATDC5 cells2013

    • Author(s)
      Mitani K, Haruyama N, Hatakeyama J, Igarashi K
    • Journal Title

      Oral Dis

      Volume: 19(2) Pages: 169-79

    • URL

      http://dx.doi.org/10.1111/j.1601-0825.2012.01967.x

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Amelogenin splice isoforms stimulate chondrogenic differentiation of ATDC5 cells.2013

    • Author(s)
      Mitani K, Haruyama N, Hatakeyama J, Igarashi K.
    • Journal Title

      Oral Dis.

      Volume: 19(2) Issue: 2 Pages: 169-179

    • DOI

      10.1111/j.1601-0825.2012.01967.x

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Dentin sialophosphoprotein and dentin matrix protein-1: Two highly phosphorylated proteins in mineralized tissues2012

    • Author(s)
      Suzuki S, Haruyama N, Nishimura F, Kulkarni AB
    • Journal Title

      Arch Oral Biol

      Volume: 57(9) Pages: 1165-75

    • URL

      http://dx.doi.org/10.1016/j.archoralbio.2012.03.005

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Bone regeneration of canine artificial alveolar clefts using bone-marrow-derived mesenchymal stromal cells and β-tricalciumphosphate: A preliminary study2012

    • Author(s)
      Tokugawa Y, Kubota M, Nishimura M, Haruyama N, Igarashi K
    • Journal Title

      Orthod Waves

      Volume: 71(2) Pages: 51-58

    • URL

      http://dx.doi.org/10.1016/j.odw.2012.01.003

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Accuracy of orthodontic miniscrew implantation guided by stereolithographic surgical stent based on cone-beam CT derived 3D images2012

    • Author(s)
      Qiu L, Haruyama N, Suzuki S, Yamada D, Obayashi N, Kurabayashi T, Moriyama K
    • Journal Title

      Angle Orthod

      Volume: 82(2) Pages: 284-93

    • URL

      http://dx.doi.org/10.2319/033111-231.1

    • Related Report
      2012 Final Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Dentin sialophosphoprotein and dentin matrix protein-1: Two highly phosphorylated proteins in mineralized tissues.2012

    • Author(s)
      Suzuki S, Haruyama N, Nishimura F, Kulkarni AB.
    • Journal Title

      Arch Oral Biol.

      Volume: 57(9) Issue: 9 Pages: 165-175

    • DOI

      10.1016/j.archoralbio.2012.03.005

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Bone regeneration of canine artificial alveolar clefts using bone-marrow-derived mesenchymal stromal cells and β-tricalcium phosphate: A preliminary study.2012

    • Author(s)
      Tokugawa Y, Kubota M, Nishimura M, Haruyama N, Igarashi K
    • Journal Title

      Orthod Waves.

      Volume: 71(2) Issue: 2 Pages: 51-58

    • DOI

      10.1016/j.odw.2012.01.003

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Multi-functional enamel matrix proteins and their binding partners2011

    • Author(s)
      Haruyama N, Hatakeyama J, Moriyama K, Kulkarni AB. Amelogenins
    • Journal Title

      J Oral Biosci

      Volume: 53(3) Pages: 257-66

    • URL

      http://dx.doi.org/10.2330/joralbiosci.53.257

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] A novel role of Periostin in postnatal tooth formation and mineralization2011

    • Author(s)
      Ma D, Zhang R, Rios HF, Haruyama N, Sun Y, Xie Y, Kulkarni AB, Qin C, Feng JQ
    • Journal Title

      J Biol Chem

      Volume: 286(6) Pages: 4302-9

    • URL

      http://dx.doi.org/10.1074/jbc.M110.140202

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Amelogenins: Multi-Functional Enamel Matrix Proteins and Their Binding Partners2011

    • Author(s)
      Haruyama N, Hatakeyama J, Moriyama K, Kulkarni AB
    • Journal Title

      Journal of Oral Biosciences

      Volume: 53 Issue: 3 Pages: 257-266

    • DOI

      10.2330/joralbiosci.53.257

    • NAID

      130004475745

    • ISSN
      1349-0079, 1880-3865
    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A novel role of Periostin in postnatal tooth formation and mineralization.2011

    • Author(s)
      Ma D, Zhang R, Rios HF, Haruyama N, Sun Y, Xie Y, Kulkarni AB, Qin C, Feng JQ
    • Journal Title

      J Biol Chem

      Volume: 286(6) Pages: 4302-9

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A Method for Rapid Demineralization of Teeth and Bones2010

    • Author(s)
      Cho A, Suzuki S, Hatakeyama J, Haruyama N, Kulkarni AB
    • Journal Title

      Open Dent J

      Volume: 4 Pages: 223-229

    • URL

      http://dx.doi.org/10.2174/1874210601004010223

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Mutant DLX 3 disrupts odontoblast polarization and dentin formation2010

    • Author(s)
      Choi SJ, Song IS, Feng JQ, Gao T, Haruyama N, Gautam P, Robey PG, Hart TC
    • Journal Title

      Dev Biol

      Volume: 344(2) Pages: 682-92

    • URL

      http://dx.doi.org/10.1016/j.ydbio.2010.05.499

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] A Method for Rapid Demineralization of Teeth and Bones.2010

    • Author(s)
      Cho A, Suzuki S, Hatakeyama J, Haruyama N, Kulkarni AB
    • Journal Title

      Open Dent J

      Volume: 4 Pages: 223-229

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mutant DLX 3 disrupts odontoblast polarization and dentin formation.2010

    • Author(s)
      Choi SJ, Song IS, Feng JQ, Gao T, Haruyama N, Gautam P, Robey PG, Hart TC.
    • Journal Title

      Dev Biol

      Volume: 344(2) Pages: 682-92

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Dentin sialophosphoprotein and dentin matrix protein-1 : Two highly phosphorylated proteins in mineralized tissues

    • Author(s)
      Suzuki S, Haruyama N, Nishimura F, Kulkarni AB
    • Journal Title

      Arch Oral Biol

      Volume: (未定)(in press)

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Presentation] Amelogenins : Multifaceted enamel matrix proteins in hard tissue biolog2012

    • Author(s)
      Haruyama N
    • Organizer
      the 7th Global COE International Symposium
    • Place of Presentation
      Tokyo, Japan
    • Related Report
      2012 Final Research Report
  • [Presentation] ペリオスチンはヒト歯根膜細胞における低酸素誘導性アポトーシスを抑制する2012

    • Author(s)
      アッカラソンサップ パビーナラット,春山直人,松本力,志賀百年,森山啓司
    • Organizer
      第71回日本矯正歯科学会
    • Place of Presentation
      盛岡
    • Related Report
      2012 Final Research Report
  • [Presentation] 創内型装置を用いて上顎骨延長法を行った口唇裂・口蓋裂症例における術後変化2012

    • Author(s)
      片岡恵一,小川卓也,春山直人,小林起穂,阿彦希,大宅彩,東堀紀尚,森山啓司
    • Organizer
      第36回日本口蓋裂学会総会
    • Place of Presentation
      京都
    • Related Report
      2012 Final Research Report
  • [Presentation] Amelogenins: Multifaceted enamel matrix proteins in hard tissue biology.2012

    • Author(s)
      Haruyama N
    • Organizer
      Molecular Science in Oral-Systemic Medicine - Autumn Seminar -, The 7th Global COE International Symposium
    • Place of Presentation
      Tokyo, Japan
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] ペリオスチンはヒト歯根膜細胞における低酸素誘導性アポトーシスを抑制する.2012

    • Author(s)
      アッカラソンサップ パビーナラット, 春山直人, 松本力, 志賀百年, 森山啓司.
    • Organizer
      第71回日本矯正歯科学会
    • Place of Presentation
      盛岡
    • Related Report
      2012 Annual Research Report
  • [Presentation] 創内型装置を用いて上顎骨延長法を行った口唇裂・口蓋裂症例における術後変化.2012

    • Author(s)
      片岡恵一, 小川卓也, 春山直人, 小林起穂, 阿彦希, 大宅彩, 東堀紀尚, 森山啓司.
    • Organizer
      第36回日本口蓋裂学会総会・学術集会
    • Place of Presentation
      京都
    • Related Report
      2012 Annual Research Report
  • [Presentation] Accuracy of miniscrew implantation guided by cone-beam CT based stereolithographic stent2011

    • Author(s)
      Haruyama N, Qiu L, Suzuki S, Yamada D, Obayashi N, Kurabayashi T, Moriyama K
    • Organizer
      The4th International Congress and the70th Annual Meeting of the Japanese Orthodontic Society
    • Place of Presentation
      Nagoya, Japan
    • Related Report
      2012 Final Research Report
  • [Presentation] Accuracy of miniscrew implantation guided by cone-beam CT based stereolithographic stent2011

    • Author(s)
      Haruyama N, Qiu L, Suzuki S, Yamada D, Obayashi N, Kurabayashi T, Moriyama K
    • Organizer
      The 4^<th> International Congress and the 70^<th> Annual Meeting of the Japanese Orthodontic Society
    • Place of Presentation
      Nagoya, Japan
    • Related Report
      2011 Annual Research Report
  • [Presentation] メインシンポジウム「エナメルタンパク「アメロジェニン」の新規機能について-from bench to clinics and from clinics to bench-」Amelogenins : Multi-functional enamel matrix proteins.2010

    • Author(s)
      春山直人
    • Organizer
      第52回歯科基礎医学会学術大会・総会
    • Place of Presentation
      タワーホール船堀(東京都)
    • Year and Date
      2010-09-21
    • Related Report
      2010 Annual Research Report
  • [Presentation] Amelogenins: Multi-functional enamel matrix proteins. メインシンポジウム「エナメルタンパク「アメロジェニン」の新規機能について-from bench to clinics and from clinics to bench-」2010

    • Author(s)
      春山直人
    • Organizer
      第52回歯科基礎医学会学術大会・総会
    • Place of Presentation
      東京
    • Related Report
      2012 Final Research Report
  • [Book] Lessons from the amelogenin knockout mice. In: Amelogenins: multifaceted proteins for dental and bone formation and repair2011

    • Author(s)
      Haruyama N, Hatakeyama J, Hatakeyama Y, Gibson CW, Kulkarni AB
    • Publisher
      Bentham Science Publishers Ltd. Chapter 3
    • Related Report
      2012 Final Research Report
  • [Remarks]

    • URL

      http://www.tmd.ac.jp/cmn/gcoe/reports/index.html

    • Related Report
      2012 Final Research Report
  • [Remarks] 東京医科歯科大学 歯と骨のGCOE成果公開

    • URL

      http://www.tmd.ac.jp/cmn/gcoe/reports/index.html

    • Related Report
      2012 Annual Research Report

URL: 

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

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