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Basic research to clarify the mechanism of delayed tooth eruption in cleidocranial dysplasia

Research Project

Project/Area Number 14370690
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field 矯正・小児・社会系歯学
Research InstitutionTokyo Medical and Dental University

Principal Investigator

SUDA Naoto  Graduate School, Tokyo Medical and Dental University, Assistant Professor, 大学院・医歯学総合研究科, 助手 (90302885)

Co-Investigator(Kenkyū-buntansha) OHYAMA Kimie  Graduate School, Tokyo Medical and Dental University, Professor, 大学院・医歯学総合研究科, 教授 (90014216)
KOMORI Toshihisa  Osaka University Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (00252677)
Project Period (FY) 2002 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥12,100,000 (Direct Cost: ¥12,100,000)
Fiscal Year 2003: ¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 2002: ¥8,100,000 (Direct Cost: ¥8,100,000)
Keywordstooth / eruption / cleidocranial dysplasia / Runx2 / runx2
Research Abstract

1) The cause of the Cleidocranial dysplasia (CCD), characterized by hypoplastic clavicle and cranial bones, is known as a gene mutation of RUNX2/CBFA1. Runx2/Cbfal is a mouse homolog of RUNX2/CBFA1 and heterozygous Runx2/Cbfa1 gene-deficient mice of this gene resembles to the bone abnormalities in CCD. CCD frequently accompanies supernumerary teeth and impaction and delayed eruption of teeth, however, these causes are yet not known. To clarify these points, teeth and periodontal tissues were examined in heterozygous mice. The number of teeth or the formation of cementum and periodontal ligament did not show difference between heterozygous and normal mice. However, the timing of tooth eruption into the oral cavity was significantly delayed in the former than in the latter. The osteoclast number located in the eruption pathway was significantly lower in the former., These observations suggest that impaired osteoclast recruitment due to the haploinsufficiency of RUNX2/CBFA1 as one of the cause of the delayed tooth eruption in CCD.
2) The process of tooth eruption is divided into the eruption 'pathway formation and vertical tooth movement. We reported the contribution and function of parathyroid hormone-related protein (PTHrP) and RANKL in the former process. We also developed a novel culture system to assay the osteoclast formation and activation using the erupting teeth and periodontal tissues.
3) Since the periodontal ligament (PDL) is known to play an important role during the tooth eruption, DNA microarray was carried out to compare the gene expression of PDL isolated from erupting and non-erupting teeth. Interestingly, the expression of CALBINDINi, which is also known to show high expression in the compression side of the PDL during the experimental tooth movement in rats, was dramatically higher in PDLs from erupting teeth than non-erupting teeth.

Report

(3 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • Research Products

    (22 results)

All Other

All Publications (22 results)

  • [Publications] Suda, N: "Development of a novel mouse osteoclast culture system using mandibular body and erupting teeth"Bone. 33・1. 38-45 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Shibata, S: "Mandibular coronoid process in parathyroid hormone-related protein (PTHrP) deficient mice shows ectopic cartilage formation accompanied by abnormal bone modeling."Anat.Embyrol.. 207・1. 35-44 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Suzuki T: "Osteoclastogenesis during mouse tooth germ development is mediated by receptor activator of NF-κB ligand (RANKL)."J.Bone Miner.Metab.. (印刷中).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Takeshima T: "Relation between formation and eruption of permanent mandibularbuccal dentition and vertical height of the mandibular body."World of Journal of Orthodontics. (印刷中).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yoda, S: "Delayed tooth eruption and suppressed osteoclast number in the eruption pathway of heterozygous Runx2/Cbfa1 knockout mice."Archs.Oral Biol. (印刷中).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Suda N.: "Development of a novel mouse Osteoclast culture system using mandibular body and erupting teeth."Bone. 33(1). 38-45 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Shibata S.: "Mandibular coronoid process in parathyroid hormone-related protein (PTHrP) deficient mice shows ectopic cartilage formation accompanied by abnormal bone modeling."Anat.Embryol.. 207(1). 35-44 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Suzuki T.: "Osteoclastogenesis during mouse tooth germ development is mediated by receptor activator of NF K-B ligand (RANKL)."J Bone Miner Metab.. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Takeshima T.: "Relation between formation and eruption of permanent mandibular buccal dentit ion and vertical height of the mandibular body.-Longitudinal, study of Japanese boys from four to nine years old-."World Journal of Orthodontics. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yoda S.: "Delayed tooth eruption and suppressed osteoclast number in the eruption pathway of heterozygous Runx2/Cbfa1 knockout mice."Archs Oral Biol. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Suda, N: "Development of a novel mouse osteoclast culture system using mandibular body and erupting teeth."Bone. 33・1. 38-45 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Shibata, S: "Mandibular coronoid process in parathyroid hormone-related protein (PTHrP) deficient mice shows ectopic cartilage formation accompanied by abnormal bone modeling."Anat.Embryol.. 207・1. 35-44 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 須田 直人: "膜性骨形成と歯の発生・萌出における副甲状ホルモン関連ペプチド(PTHrP)のはたらき"歯科基礎医師. 45・3. 103-112 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Suzuki, T: "Osteoclastogenesis during mouse tooth germ development is mediated by receptor activator of NF K-B ligand (RANKL)."J.Bone Miner.Metab.. 印刷中.

    • Related Report
      2003 Annual Research Report
  • [Publications] Takeshima, T: "Relation between formation and eruption of permanent mandibular buccal dentition and vertical height of the mandibular body."World Journal of Orthodontics. 印刷中.

    • Related Report
      2003 Annual Research Report
  • [Publications] Yoda, S: "Delayed tooth eruption and suppressed osteoclast number in the eruption pathway of heterozygous Runx2/Cbfal knockout mice."Archs.Oral Biol.. 印刷中.

    • Related Report
      2003 Annual Research Report
  • [Publications] Y.Kitahara: "Disturbed tooth development in Parathyroid hormone-related protein (PYHrP) gene-knockout mice"Bone. vol.30 no.1. 48-56 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] N.SUDA: "Relationship between upper tooth formation/eruption and skeletal pattern of maxilla"Am. J. Orthod. Dentfacial Orthop. vol.121 no.1. 46-52 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] K.Mekaapiruk: "The influence of parathyroid hormone-related protein (PTHrP) on tooth-germ development and osteoclastogenesis in alveolar bone of PTHrP-knock out and wild-type mice in vitro"Archs Oral Biol. vol.47 no.9. 665-672 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] N.Suda: "Three cases of anterior maxillary osteotomy under onotracheal intubation"Int. J. Orthod. Prthognath. Surg. vol.17 no.4. (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] S.Hiyama: "Effects of maxillary protractio on craniofacial structures and upper-airway dimension"Angle Orthod. vol.72 no.1. 43-47 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 黒田敬之: "アトラス顎顔面矯正"医歯薬出版. 201 (2002)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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