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Study of a key factor in chondrogenic differentiation for craniofacial skeletal regeneration

Research Project

Project/Area Number 14207092
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field 矯正・小児・社会系歯学
Research InstitutionOKAYAMA UNIVERSITY

Principal Investigator

YANMAMOTO Teruko  Okayama University, Graduate school of Medicine and Dentistry, Professor, 大学院・医歯学総合研究科, 教授 (00127250)

Co-Investigator(Kenkyū-buntansha) TAKIGAWA Masaharu  Okayama University, Graduate School of Medicine and Dentistry, Professor, 大学院・医歯学総合研究科, 教授 (20112063)
YAMASHIRO Takashi  Osaka University, Graduate School of Dentistry, Associate professor, 大学院・歯学研究科, 助教授 (70294428)
KURODA Shingo  Okayama University, Graduate School of Medicine and Dentistry, Research assistant, 大学院・医歯学総合研究科, 助手 (40332796)
FUKUNAGA Tomohiro  Okayama University, Graduate School of Medicine and Dentistry, Research assistant, 大学院・医歯学総合研究科, 助手 (70362994)
宮本 学  岡山大学, 大学院・医歯学総合研究科, 助手 (40252978)
Project Period (FY) 2002 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥49,660,000 (Direct Cost: ¥38,200,000、Indirect Cost: ¥11,460,000)
Fiscal Year 2004: ¥9,880,000 (Direct Cost: ¥7,600,000、Indirect Cost: ¥2,280,000)
Fiscal Year 2003: ¥11,570,000 (Direct Cost: ¥8,900,000、Indirect Cost: ¥2,670,000)
Fiscal Year 2002: ¥28,210,000 (Direct Cost: ¥21,700,000、Indirect Cost: ¥6,510,000)
Keywordslaser microdissection / chondrocyte / in situ hybridization / differentiation / regeneration / 新生仔マウス下顎頭軟骨 / 未固定非脱灰切片 / collagen type I / collagen type II / collagen type IX / 新生児マウス下顎頭軟骨 / ラット顎頭骨折 / in situ hybridization / Sox-9
Research Abstract

The purpose of the present study was to investigate a key factor in chondrogenic differentiation that play a role in craniofacial skeletal development.
1.We evaluated the expression of CTGF, type I, type II, and type X collagen in chondrocytes of different types of cartilages, including mandibular condylar cartilage, cartilage formed during the healing of mandibular ramus factures, femoral growth plate cartilage, and femoral articular cartilage revealed by in situ hybridization. Among these different types of cartilages we found distinct patterns of CTGF expression. Growth plate cartilage showed localization of CTGF in the hypertrophic chondrocytes that expressed type X collagen with less expression in proliferating chondrocytes that expressed type II collagen, whereas it was also expressed in the proliferating chondrocytes that expressed type I collagen in the condylar cartilage, the articular cartilage, and the cartilage appearing during fracture healing. In contrast, the growth plate … More cartilage were negative for type I collagen and showed sparse expression of CTGF in the proliferating chondrocytes. The spatial distribution of CTGF in the cartilages with type I collagen suggested its role in the early differentiation of those cartilages.
2.Runx1,Runx2, and Sox9 expression was evaluated by in situ hybridization in the growing craniofacial bones of embryonic day (E)12-16 mice. In addition, we evaluated Runx2 expression in the growing face of Runxl knockout mice at E12.5 and Runx1 expression in Runx2 knockout mice at E14.5. Runx1 and Sox9 were expressed in cartilage, and the regions of expression expanded to the neighboring Runx2-expressing osteogenic regions. Expression of both Runx1 and Sox9 was markedly downregulated on ossification. Runx1 and Sox9 expression was absent in actively modeling or remodeling bone tissues in ossified craniofacial bones. Runx2 expression was not affected by gene disruption of Runx1, whereas the expression domains of Runx1 were extended in Runx2^<-/-> mice compared with wildtype mice. These results suggest that Runx1 may play a role in incipient intramembranous bone formation.
3.We investigated that the function of Zac1 in endochondral bone formation. Chondrocytes were isolated from the 17-day embryonic chick sterna. RT-PCR analysis revealed that Zac1 expression was decreased during 3-week culture. To examine the effect of Zac1 on chondrocyte differentiation, we characterized chondrocytes transfected Zac1 gene by chick retrovirus compared to mock transfected group. After retinoic acid(RA) treatment, type IX collagen expression was decreased, and MMP-13 and ADAM-TS5 expression were increased in mock transfected group. In contrast, these changes in Zac1-infected chondrocytes treated with RA were markedly inhibited. These results suggest that Zac1 may play a role in the metabolism of the cartilage.
4.Normal newborn mice mandibular condylar chondrocytes from type I collagen-expressing cells and non-type I collagen-expressing cells were isolated by laser capture microdissection(LCM) and then subjected to microarray analysis. LCM allows isolation of chondrocytes from individual zones of mandibular condylar cartilage for comparative analysis. These techniques will hopefully serve as a guide for the further analysis. Less

Report

(4 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • 2002 Annual Research Report
  • Research Products

    (31 results)

All 2005 2004 2003 2002 Other

All Journal Article (19 results) Book (1 results) Publications (11 results)

  • [Journal Article] Effect of transcription factor Zac1 on metabolism of cartilage extracellular matrix2005

    • Author(s)
      N.Takeshita
    • Journal Title

      岡山歯学会雑誌(Thesis) 24

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Possible roles of Runx1 and Sox9 in incipient intramembranous ossification2004

    • Author(s)
      Yamashiro, T.
    • Journal Title

      J Bone Miner Res 19

      Pages: 1671-1677

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Denervation resulting in dento-alveolar ankylosis associated with decreased Malassez epithelium2004

    • Author(s)
      Fujiyama, K.
    • Journal Title

      J Dent Res 83

      Pages: 625-629

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Possible roles of Runx1 and Sox9 in incipient intramembranous ossification.2004

    • Author(s)
      Yamashiro, T.
    • Journal Title

      J Bone Miner Res. 19

      Pages: 1671-1677

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Denervation resulting in dento-alveolar ankylosis associated with decreased Malassez epithelium.2004

    • Author(s)
      Fujiyama, K.
    • Journal Title

      J Dent Res. 83

      Pages: 625-6259

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Runx2 mediates FGF signaling from epithelium to mesenchyme during tooth morphogenesis2004

    • Author(s)
      Thomas Aberg
    • Journal Title

      Developmental Biology 270

      Pages: 76-93

    • Related Report
      2004 Annual Research Report
  • [Journal Article] VR1-, VRL-1- and P2X3 receptor-immunoreactive innervation of the rat temporomandibular joint2004

    • Author(s)
      H.Ichikawa
    • Journal Title

      Brain Research 1008

      Pages: 131-136

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Induction of activated caspase-3-immunoreactivity and apoptosis in the trigeminal ganglion neurons by neonatal peripheral nerve injury2004

    • Author(s)
      T.Sugimoto
    • Journal Title

      Brain Research 1017

      Pages: 238-243

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Possible roles of Runxl and Sox9 in incipient intramembranous ossification2004

    • Author(s)
      T.Yamashiro
    • Journal Title

      J.Bone Miner.Res. 19

      Pages: 1671-1677

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Denervation resulting in dento-alveolar ankylosis associated with decreased Malassez epithelium2004

    • Author(s)
      K.Fujiyama
    • Journal Title

      J.Dent.Res. 83

      Pages: 625-629

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Connective tissue growth factor mRNA expression pattern in cartilages is associated with their type I collagen expression2003

    • Author(s)
      Fukunaga, T.
    • Journal Title

      Bone 33

      Pages: 911-918

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Galanin-immunoreactive nerve fibers in the periodontal ligament during experimental tooth movement2003

    • Author(s)
      Deguchi, T.
    • Journal Title

      J Dent Res 82

      Pages: 677-681

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] CTGF/Hcs24, hypertrophic chondrocyte-specific gene product, interacts with perlecan in regulating the proliferation and differentiation of chondrocytes2003

    • Author(s)
      Nishida, T.
    • Journal Title

      J Cell Physiol 196

      Pages: 265-275

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Interaction of AP-1 and the ctgf gene : a possible driver of chondrocyte hypertrophy in growth cartilage2003

    • Author(s)
      Moritani, NH.
    • Journal Title

      J Bone Miner Metab 21

      Pages: 205-210

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Connective tissue growth factor mRNA expression pattern in cartilages is associated with their type I collagen expression.2003

    • Author(s)
      Fukunaga, T.
    • Journal Title

      Bone. 33

      Pages: 911-918

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Galanin-immunoreactive nerve fibers in the periodontal ligament during experimental tooth movement.2003

    • Author(s)
      Deguchi, T.
    • Journal Title

      J Dent Res. 82

      Pages: 677-681

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] CTGF/Hcs24, hypertrophic chondrocyte-specific gene product, interacts with perlecan in regulating the proliferation and differentiation of chondrocytes.2003

    • Author(s)
      Nishida, T.
    • Journal Title

      J Cell Physiol. 196

      Pages: 265-275

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Interaction of AP-1 and the ctgf gene : a possible driver of chondrocyte hypertrophy in growth cartilage.2003

    • Author(s)
      Moritani, NH.
    • Journal Title

      J Bone Miner Metab. 21

      Pages: 205-210

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Introductory Remarks : Current views of Molecular biology in Orthodontics.2002

    • Author(s)
      Takano-Yamamoto T
    • Journal Title

      Orthodontics in the 21^<st> Century-Where are We Now? Where Are We Going? (Ed.Kenji Takada and William R.Proffit)(Osaka University Press)

      Pages: 81-88

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Book] Orthodontics in the 21^<st> Century-Where are We Now? Where Are We Going?2002

    • Author(s)
      T.Takano-Yamamoto (Ed.K.Takada, William R.Proffit)
    • Total Pages
      216
    • Publisher
      Osaka University Press
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Publications] Hiroshi Kamioka: "Terminal differentiation of osteoblasts to osteocytes is accompanied by dramatic changes in the distribution of actin-binding proteins"Journal of bone and mineral research. 19. 471-478 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Tomohiro Fukunaga: "Connective tissue growth factor mRNA expression pattern in cartilages is associated with their type I collagen expression"Bone. 33. 911-918 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] T.Nishida: "CTGF/Hcs24,hypertrophic chondrocyte-specific gene product, interacts with perlecan in regulating the proliferation and differentiation of chondrocytes"J cell physiol.. 196. 265-275 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] NH.Moritani: "Interaction of AP-l and the ctgf gene : a possible driver of chondrocyte hypertrophy in growth cartilage"Journal of bone and mineral metabolism. 21. 205-210 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Miyatake, E.: "Mandibular prognathism with transverse maxillary deficiency and skeletal asymmetry treated by segmental high LeFoft I osteotomy and IVRO"Orthodontic Waves. 61(3). 184-190 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yosimichi G: "CTGF/Hcs24 interacts with the cytoskeletal protein actin in chondrocytes"Biochem Biophys Res Commun. 299(5). 755-761 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Deguchi, T.: "Miniature implants for orthodontic anchorage"J Dent Res. (in press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Eri MIYATAKE: "Angle Class III case with severe facial asymmetry, unilateral posterior crossbite and temporamandibular disorders treated by LeFort I osteotomy and IVRO"American Journal of Orthodontics and Dentofacial Orthodontics. (in press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Deguchi, T.: "Increase in number of Galanin-immunoreactive nerve fibers in the periodontal ligament during experimental tooth movement in rats"J Dent Res. (in press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] N.H Moritani: "Interaction of AP-1 and the ctgf gene"JBMM. (in press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] T.Takano-Yamamoto (Ed.K.Takada, William R Proffit): "Orthodontics in the 21^<st> Century-Where are We Now? Where Are We Going?"Osaka University Press. 216 (2002)

    • Related Report
      2002 Annual Research Report

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

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