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DEVELOPMENT OF A NEW THERAPEUTC APPROCH TO BONE REGENERATION FOR GENE THERAPY

Research Project

Project/Area Number 12557153
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Morphological basic dentistry
Research InstitutionNAGASAKI UNIVERSITY

Principal Investigator

YAMAGUCHI Akira  Nagasaki University, Professor, 歯学部, 教授 (00142430)

Co-Investigator(Kenkyū-buntansha) NOJI Sumihare  Tokushima University, Professor, 工学部, 教授 (40156211)
SHIBATA Yasuaki  Nagasaki University, Research Associate, 歯学部, 助手 (80253673)
FUJITA Shuichi  Nagasaki University, Research Associate, 歯学部, 助教授 (00181355)
TANAKA Sakae  Tokyo University, Research Associate, 医学部, 助手 (50282661)
高橋 弘  長崎大学, 歯学部, 助教授 (20124597)
Project Period (FY) 2000 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥13,300,000 (Direct Cost: ¥13,300,000)
Fiscal Year 2001: ¥4,500,000 (Direct Cost: ¥4,500,000)
Fiscal Year 2000: ¥8,800,000 (Direct Cost: ¥8,800,000)
KeywordsBone / Regeneration / Mesenchymal stem cells / BMP / Cbfal
Research Abstract

We conducted the following experiments.
1. Characterization of mesenchymal stem cells during bone regeneration
We first made a round hole, 2.2 mm in a diameter, at diaphysis offemurs of growing mice. To investigate the proliferation activity of mesenchymal cells during the bone repair, we explored incorporation of BrdU. These studies demonstrated that proliferating mesenchymal cells incorporating BrdU increased 3 days after injury in our experimental system.
2. Changes in gene expression during bone regeneration
Using above described experimental model, we investigated the changes in expression patterns of bone-related genes by Northern blot analysis. ALP mRNA increased on day 4 and osteocalcin mRNA increased on day 5 after bone injury. Histochemical and immunohistochemical studies indicated similar expression patterns of these molecules.
3. Above experiments suggested that mesenchymal stem cells appeared during days 4 and 5 after injury in our experimental model. We are now exploring the genes related to mesenchymal stem cells by CDNA chips.
4. To develop new therapeutic method, we transplanted skin fibroblasts in bone defects (2.2 mm in a diameter) in calvariae of growing mice with carrier (PGS). Transplantation of the fibroblasts over-expressing BMP-2 CDNA induced more accelerated bone regeneration than that transplanted with the fibroblasts expression empty vector. In contrast, the fibroblasts over-expressing Cbfa l gene failed to stimulate bone regeneration, compared with that transplanted with the fibroblasts expression empty vector.

Report

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

    (22 results)

All Other

All Publications (22 results)

  • [Publications] Kusafuka K, et al.: "Cartilage-specific matrix protein chondromodulin-I is associated with chondroid formation in salivary pleomorphic adenomas : immunohistochemical analysis"Am.J.Pathol.. 158. 1465-1472 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kusafuka K, et al.: "Ossification of tracheal cartilage in aged humans : a histological and immunohistochemical analysis"J.Bone Miner.Metab.. 19. 168-174 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Tamura T, et al.: "The effects of transplantation of osteoblastic cells with BMP/carrier complex on bone repair"BONE. 29. 169-175 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Liu W, et al.: "Overexpression of Cbfa 1 in osteoblasts inhibits osteoblast maturation and causes osteopenia with multiple fractures"J.Cell Biol.. 155. 157-166 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Merida LM, et al.: "Effects of vitamin D analog, 22-oxa-1,25 dihydroxyvitamin D3, on bone reconstruction by vascularized bone allograft"BONE. 30. 422-427 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kusafuka K, Hiraki Y, Shukunami C, Yamaguchi A, Kayano T, Takemura T: "Cartilage-specific matrix protein chondromodulin-I is associated with chondroid formation in salivary pleomorphic adenomas : immunohistochemical analysis"Am. J. Pathl.. 158. 1465-1472 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kusafuka K, Yamaguchi A, Kayano T, and Takemura T: "Ossification of tracheal cartilage in aged humans : a histological and immunohistochemical analysis"J. Bone Miner. Metab. 19. 168-174 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Tamura T, Kataoka H, Matsui Y, Shionoya Y, Ohno K, Michi K, Takahashi K, and Yamaguchi A: "The effects of transplantation of osteoblastic cells with BMP/carrier complex on bone repair"BONE. 29. 169-175 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Liu W, Toyosawa S, Furuichi T, Kanatani N, Yoshida C, Liu Y, Himeno M, Narai S, Yamaguchi A, and Komori T: "Overexpression of Cbfal in osteoblasts inhibits osteoblast maturation and causes osteopenia with multiple fractures"J. Cell Biol.. 155. 157-166 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Merida LM, Shigetomi M, Ihara K, Tsubone T, Ikeda K, Yamaguchi A, Sugiyama T, and Kawai S: "Effects of vitamin D analog, 22-oxa-1, 25 dihydroxy vitamin D3, on bone reconstruction by vascularized bone allograft"BONE. 30. 422-427 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kusafuka K, et al.: "Cartilage-specific matrix protein chondromodulin-I is associated with chondroid formation in salivary pleomorphic adenomas : immunohistochemical analysis"Am. J. Pathol.. 158. 1465-1472 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kusafuka K, et al.: "Ossification of tracheal cartilage in aged humans : a histological and immunohistochemical analyssis"J. Bone Miner. Metab. 19. 168-174 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Tamura T, et al.: "The effects of transplantation of osteoblastic cells with BMP/carrier complex on bone repair"BONE. 29. 169-175 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Liu W, et al.: "Overexpression of Cbfa1 in osteoblasts inhibits osteoblast maturation and causes osteopenia with multiple fractures"J. Cell Biol.. 155. 157-166 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Merida LM, et al.: "Effects of vitamin D analog, 22-oxa-1, 25 dihydroxyvitamin D3, on bone reconstruction by vascularized bone allograft"BONE. 30. 422-427 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Shibata S,Fujita S,Takahashi H,Yamaguchi A,Koji T: "Assessment of decalcifying protocols for detection of specific RNA by nonradioactive in situ hybridization in calcified tissues."Histochem.Cell Biol.. 113. 153-159 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kobayashi H,Gao Y-H,Ueta C,Yamaguchi A,Komori T: "Multilineage differentiation of Cbfa1-deficient calvarial cells in vitro."Biochem.Biophys.Res.Commun.. 273. 630-636 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Enomoto-Iwamoto M,Nakamura T,Aikawa T,Higuchi Y,Yuasa T,Yamaguchi A,Nohno T,Noji S,Matsuya T,Kurisu K,Koyama E,Pacifici M,Iwamoto M: "Hedgehog proteins induce chondrogenic cell differentiation and cartilage formation."J.Bone Miner.Res.. 15. 1659-1668 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kataoka H,Ochi M,Enomoto K,Yamaguchi A: "Cloning and embryonic expression patterns of the zebrafish Runt domain genes, runxa and runxb."Mech Dev. 98. 139-143 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Yamaguchi A,Komori T,Suda T: "Regulation of Osteoblast Differentiation Mediated by BMPs, Hedgehogs and Cbfa1"Endocrine Reviews. 21. 393-411 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 山口朗(分担執筆): "骨形成と骨再生.先端医療シリーズ・歯科医学2:「歯周病-新しい治療を求めて」"岡田宏,石川烈,村山洋二 監修. 1-7 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Yamaguchi A(分担執筆): "Regulatory mechanism of osteoblast differentiation. In : Tissue Engineering for Therapeutic Use 4"Y.Ikada and Y.Shimizu (eds). 75-81 (2000)

    • Related Report
      2000 Annual Research Report

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

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