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2002 Fiscal Year Final Research Report Summary

Identification of novel genes regulating fracture healing and their functional analyzes

Research Project

Project/Area Number 13671490
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Orthopaedic surgery
Research InstitutionChiba University

Principal Investigator

YAMAZAKI Masashi  Chiba University, University Hospital, Assistant, 医学部附属病院, 助手 (50281712)

Co-Investigator(Kenkyū-buntansha) SEKI Naohiko  Chiba University, Graduate School of Medicine, Associate Professor, 大学院・医学研究院, 助教授 (50345013)
OKAWA Akihiko  Chiba University, Graduate School of Medicine, Assistant, 大学院・医学研究院, 助手 (30312945)
Project Period (FY) 2001 – 2002
KeywordscDNA microarray / gene expression / mouse / bone formation / fracture repair / periostin / knock-out mouse / TNF-alpha
Research Abstract

To comprehensively evaluate gene expression in the early stage of fracture healing, we used a cDNA microarray with 2304 cDNA clones derived from an oligo-capped mouse embryo library. Closed middiaphyseal fractures were created in mouse tibiae and expression profiles were analyzed 3 days after fracture. The expression levels of six genes were up-regulated in comparison to those in unfractured bones, and 3 of 6 were identified as novel candidate genes involved in fracture repair. These are periostin, calumenin, and FHL-1, for which cloning has been already completed, but their function during bone formation remains to be elucidated. We also found that the expression of 11 genes was down-regulated. The up-regulation of the 6 genes was reconfirmed by semi-quantitative RT-PCR analysis. Furthermore, among the 6 genes, we analyzed the spatial and temporal expression of periostin by means of in situ hybridization and Northern blot analysis since it displayed the highest up-regulation ratio. A strong signal for periostin was detected in undifferentiated mesenchymal cells and immature osteoblastic cells in the periosteum between days 3 and 7, but the signal rapidly decreased by day 14. The temporal expression pattern exhibited a peak in expression on day 3, followed by a rapid decrease in expression on day 14. These findings suggest that periostin is a specific marker for preosteoblasts and plays an important role in callus formation during the early stage of fracture healing.

  • Research Products

    (11 results)

All Other

All Publications (11 results)

  • [Publications] Nakazawa, T: "Spatial and temporal expression of periostin, a novel gene detected by complementary DNA microarray during fracture healing"Transactions of the 49th annual meeting, Orthopaedic Research Society. 296 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nakajima, A: "Mechanism for the enhancement of fracture healing treated with low dose human parathyroid hormon (1-34)"J Bone Miner Res. 17. 2038-2047 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kon, T.: "Expression of osteoprotegerin, RANK-L (osteoprotegerin ligand) and related pro-inflammatory cytokines during fracture healing"J. Bone Miner. Res.. 16. 1004-1014 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nakajima, F.: "Spatial and temporal gene expression for chondrogenesis during fracture healing and the effects of basic fibroblast growth factor"J. Orthop. Res.. 19. 935-944 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nakajima, A: "Spatial and temporal gene expression for fibroblast growth factor type I receptor (FGFR1) during fracture healing in the rat"Bone. 29. 458-466 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nakazawa, T.: "Spatial and temporal expression of periostin, a novel gene detected by complementary DNA microarray during fracture healing"Transactions of the 49th annual meeting, Orthopaedic Research Society. 296 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nakajima, A.: "Mechanism for the enhancement of fracture healing treated with low dose human parathyroid hormon (1-34)"J. Bone. Miner. Res.. 17. 2038-2047 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kon, T.: "Expression of osteoprotegerin, RANK-L (osteoprotegerin ligand) and related pro-inflammatory cytokines during fracture healing"J. Bone Miner. Res.. 16. 1004-1014 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nakajima, F.: "Spatial and temporal gene expression in chondrogenesis during fracture healing and the effects of basic fibroblast growth factor"J. Orthop. Res.. 19. 935-944 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nakajima, A.: "Spatial and temporal gene expression for fibroblast growth factor type I receptor (FGFR1) during fracture healing in the rat"Bone. 29. 458-466 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kon, T.: "Inhibition of intramembranous bone formation during fracture healing in tumor necrosis factor receptors deficient mice"Transactions of the 46th annual meeting, Orthopaedic Research Society. 298 (2000)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2004-04-14  

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