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The role of ets related gene (erg) in cartilage development

Research Project

Project/Area Number 12470384
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Morphological basic dentistry
Research InstitutionOsaka University

Principal Investigator

OGAWA Yuzo (2002)  Graduate School of Dentistry, Associate Professor, 大学院・歯学研究科, 助教授 (10135725)

岩本 容泰 (2000-2001)  大阪大学, 大学院・歯学研究科, 講師 (30223431)

Co-Investigator(Kenkyū-buntansha) IWAMOTO Masahiro  Graduate School of Dentistry, Assistant Professor, 大学院・歯学研究科, 助教授 (30223431)
HIGUCHI Yoshinobu  Chugal Pharmaceutical, Reseach Laboratory, Chairman, 創薬研, 主査(研究職)
TOYOSAW Satoru  Graduate School of Dentistry, Assistant Professor, 大学院・歯学研究科, 講師 (30243249)
IWAMOTO Motomi  Grsduate School of Dentistry, Associate Profeasor, 大学院・歯学研究科, 講師 (80203644)
小川 裕三  大阪大学, 大学院・歯学研究科, 助教授 (10135725)
Project Period (FY) 2000 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥10,000,000 (Direct Cost: ¥10,000,000)
Fiscal Year 2002: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 2001: ¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 2000: ¥6,300,000 (Direct Cost: ¥6,300,000)
Keywordschondrogenesis / growing cartilage / endochondral ossification / permanent cartilage / erg / transcription factor
Research Abstract

During limb development, limb long bones are initially formed as histologically homegenous cartflagenous tissues. Later, chondroeytes in these tissues take two distinct developmental fates. Most of chondrocytes consist of bone shaft proliferate, synthesize cartilage-matrix, mature into hypertrophic cells, and finally disappear through the procese of endochondral ossification. However, chondrocytes present in longitudinal ends show relatively stable phenotype. These cells persist throughout life as permanent articular chondroeytes. Although maturation of trangient chondrocytes has been extensively studied, it is poorly understood how articular chondrocytes acquire/maintain stable phenotype and avoid maturation. We have previously identified C-1-1, a novel isoform of chick ets-related gene and showed that C-1-1 is preferentially expressed in developing articular cartilage. C-1-1 inhibits maturation and induced tenascin-C, a marker of immature/ articular cartilage in trangient chondrocytes. We next examined whether C-1-1 like +lecule is expressed and suppresses maturation in mammalian articular chondrocyte. Three mouse erg isoforms and 2 human erg isoforms were obtainsd by combination of RACE technique and cDNA library scleening. Each isoform was subuloned into RCASBP retrovirus vector and then introduced in primary chick embryo chondrocytes.
All of these isoforms suppressed chondrocytes maturation from moderate to severe extent. We also generated transgenic mice which over-express human ERG3(-81), possibiy orthologue of C-1-1, under the control of type II collagen promoter/enhancar. Chondrocytes maturation and endochondral bone formation was severely impaired in the transgenic mice. These findings strongly suggest that erg is involved not only in maintenance of articular chondrocytes phenotype but also regulates endochondral ossification by its anti-maturation activity.

Report

(4 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • 2000 Annual Research Report
  • Research Products

    (33 results)

All Other

All Publications (33 results)

  • [Publications] Enomoto, H.: "Cbfal is a positive regulatory factor in chondrocyte maturation"J Biol Chem. 275. 8695-8702 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Iwamoto, M.: "transcription factor ERG variants and functional diversification of chondrocytes during limb long bone development"J Cell Biol. 150. 27-40 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Enomoto-Iwamoto, M.: "Hedgehog proteins stimulate chondrogenic cell differentiation and cartilage formation"J Bone Miner Res. 15. 1659-1668 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 岩本資己: "軟骨の発生と再生"実験医学. 18. 1325-1332 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ueta, C.: "Skeletal malformations caused by overexpression of Cbfa-1 or its dominant negative form in chondrocytes"J Cell Biol. 153. 87-99 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Enomoto-Iwamoto, M.: "Participation of cbfa-I in regulation of chondrocyte differentiation"Osteoarthritis Cartilage. 9. S76-S84 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Enomoto H et al.: "Cbfal is a positive regulatory pactor in chondrocyte maturation"J Biol Chem. 275. 8695-8702 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Iwamoto M et al.: "transcription factor ERG varianta and functional diversification of chondrocytas during limb long bone development"J Biol Chem. 150. 27-40 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Enomoto-Iwamoto M et al.: "Hedgehog proteins stimulate chondrogenic cell differentiation and cartilage formation"J Bone Miner Res. 15. 1659-1668 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ueta C et al.: "Skeletal malformations caused by overxpression of Cbfa-1 or its domlnant negetive form in chondrocytes"J Cell Biol. 153. 87-99 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Enomoto-Iwamoto M et al.: "Participation of cbfa-1 in regulation of chondracyte differentiation"Osteoarthritis Cartilage. 9. S76-84 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Iwamoto M et al.: "The role of erg ( ets related gene) in cartilage development"Osteoarthritis Cartilage. 9. S41-47 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Enomoto-Iwamoto M et al.: "The Wnt antagonist Frzb-1 regulates chondrocyte maturation and long bone development during limb skeletogenesis"Dev Biol. 251. 142-156 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tabata MJ et al.: "Bone morphogenetic protain 4 is involved in cusp formation in nolar tooth germ of mice"Eur J Oral Sci. 110. 114-120 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yuasa T et al.: "Sonic hedgehog is involved in osteoblast differentiation by cooperating with BNP-2"J Cell Physiol. 193. 225-232 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kitagaki J et al.: "Activation of beta-catenin-LEF/TCF signal pathway in chondrocytes stimulates sctopic endochondral ossification"Osteoarthritis Cartilage. 11. 36-43 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Iwamoto M et al.: "Runx2 expression and action in chondrocytes are regulated by retinoid signaling and parathyroid hormone-related peptide (PTHrP)"Osteoarthritis Cartilage. 11. 6-15 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Enomoto-Iwamoto, M.: "The Wnt antagonist Frzb-1 regulates chondrocyte maturation and long bone development during limb skeletogenesis"Dev.Biol.. 251. 142-156 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Tabata, M.J.: "Bone morphogenetic protein 4 is involved in cusp formation in molar tooth germ of mice"Eur.J.Oral Sci.. 110. 114-120 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yuasa, T.: "Sonic hedgehog is involved in osteoblast differentiation by cooperating with BMP-2"J.Cell Physiol.. 193. 225-232 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kitagaki, J.: "Activation of beta-catenin-LEF/TCF signal pathway in chondrocytes stimulates ectopic endochondral ossification"Osteoarthritis Cartilage. 11. 36-43 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Iwamoto, M.: "Runx2 expression and action in chondrocytes are regulated by retinoid signaling and parathyroid hormone-related peptide (PTHrP)"Osteoarthritis Cartilage. 11. 6-15 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ueta, C. et al.: "Sekeletal malformations Caused by overexpression of Cbfa1 or its dominant negative form in chondrocytes"J.Cell Biol.. 153. 87-99 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Enomoto-Iwamoto, M.et al.: "Participation of Cbfa1 in regulation of chondrocyte maturation"Osteoarthritis Cartilage. 9. S76-S84 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Iwamoto, M.: "Ther role of ERG (ets related gene) in cartilage development"Osateoarthiritis Cartilage. 9. S41-S47 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 岩本容泰: "関節発生と関節軟骨分化制御"現代医療. 33. 37-42 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 岩本資己: "Wnt可溶型受容体Frzb-1による軟骨細胞の分化制御"実験医学. 19. 1210-1214 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Enomoto,H. et al.: "Cbfal is a positive regulatory factor in chondrocyte maturation."J.Biol.Chem.. 275. 8695-8702 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Iwamoto,M.: "Transcription factor ERG variants and functional diversification of chondrocytes during limb long bone development."J.Cell Biol.. 150. 27-40 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Ueta,C. et al.: "Skeletal malformations caused by overexpression of Cbfa1 or its dominant negative form in chondrocytes."J.Cell Biol.. (In press).

    • Related Report
      2000 Annual Research Report
  • [Publications] Enomoto-Iwamoto,M. et al.: "Hedgehog proteins stimulate chondrogenic cell differentiation and cartilage formation"J.Bone Miner.Res.. 15. 1695-1688 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 岩本資己 ほか: "軟骨の発生と再生"実験医学. 18. 1325-1332 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 岩本資己 ほか: "新・分子骨代謝学と骨粗鬆症"メディカル・ビュー社(印刷中).

    • Related Report
      2000 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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