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Functional analysis of TNF signaling in bone metabolism using knocked-out mice of type I and II TNF receptors.

Research Project

Project/Area Number 14571385
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

ENOMOTO Hiroshi  Nagasaki University, Graduate School of Biomedical Science, Assistant Professor, 大学院・医歯薬学総合研究科, 助手 (90284679)

Co-Investigator(Kenkyū-buntansha) YAMAGUCHI Akira  Nagasaki University, Graduate School of Biomedical Science, Professor, 大学院・医歯薬学総合研究科, 教授 (00142430)
OKANO Kunihiko  Nagasaki University, Hospital of Medicine & Dentistry, Assistant Professor, 医学部・歯学部附属病院, 助手 (70325645)
SHINDO Hiroyuki  Nagasaki University, Graduate School of Biomedical Science, Professor, 大学院・医歯薬学総合研究科, 教授 (30107677)
ITO Masako  Nagasaki University, Hospital of Medicine & Dentistry, Lecturer, 医学部・歯学部附属病院, 講師 (10193517)
TSUKAZAKI Tomoo  Nagasaki University, Graduate School of Biomedical Science, Assistant Professor, 大学院・医歯薬学総合研究科, 助教授 (50315230)
Project Period (FY) 2002 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2003: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2002: ¥1,900,000 (Direct Cost: ¥1,900,000)
KeywordsTNF receptor / knock-out mice / osteoclasts / 破骨細胞 / 骨形態計測 / pQCT
Research Abstract

TNF signaling is known to play a crucial role in bone absorption under inflammatory condition. To distinguish the functional role of type I and type II TNF receptor, knock-out mice of each receptor were subjected to histological and bone morphometric analysis. In 12 wks old femurs, bone volume, thickness and mineral content in both cortical and cancellous bone were decreased in type I (-/-) mice, whereas these parameters were increased in type II (-/) mice. To investigate a molecular mechanism of TNF receptor involved bone metabolism, osteoblasts and osteoclasts were cultured from calvariae and macrophage from bone marrow, respectively. Treatment of osteoblasts with BMP-2 or Dexamethasone, however, did not alter their ALP expression as well as cell proliferation. In contrast, osteoclast formation was only induced in type II (-/-) macrophage by treating with M-CSF and RANKL, indicating that certain molecules secreted of exposed on cell surface could be important for osteoclasts formation. To identify these molecules, we applied DNA tip analysis to each cultured cell and found three novel and 5 known genes that could be target or down-stream signaling for TNF receptor activation. We are now analyzing the functional role and expression pattern of these genes.

Report

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

    (15 results)

All Other

All Publications (15 results)

  • [Publications] Iioka et al.: "p300/CBP Acts as a Coactivator to Cartilage Homeoorotein-1(Cart1),Paired-Like Homeoprotein, via Acetylation of the Conserved Lysine Residue Adjacent to the Homeodomain"J Bone Miner Res. 18・8. 1419-1429 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hirata et al.: "Transnlantation of skin fibroblasts expressing BMP-2 promotes Bone repair more effectively than those expressing Runx2"BONE. 32・5. 502-512 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Takahara et al.: "Autocrine/paracrine role of the angiopoietin-1 and -2/Tie2 system in cell proliferation and chemotaxis of cultured fibroblastic synoviocytes in rheumatoid arthritis"Hum Pathoi. 35・2. 150-158 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kadowaki et al.: "Isolation and characterization of a raesenchymal cell line that differentiates in to osteoblasts in response to BMP-2 from calvariae of GFP transgenic mice"BONE. In press. (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Iioka et al.: "p300/CBP Acts as a Coactivator to Cartilage Homeoprotein-l (Cart 1), Paired-Like Homeoprotein, via Acetylation of the Conserved Lysine Residue Adjacent to the Homeodomain"J Bone Miner Res. 18(8). 1419-1429 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hirata et al.: "Transplantation of skin fibroblasts expressing BMP-2 promotes Bone repair more Effectively than those expressing Runx2"BONE. 32(5). 502-512 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Takahara et al.: "Autocrine/paracrine role of the angiopoietin-1 and -2/Tie2 system in cell proliferation and chemotaxis of cultured fibroblastic synoviocytes in rheumatoid arthritis"Hum Pathol. 35(2). 150-158 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kadowaki et al.: "Isolation and characterization of a mesenchymal cell line that differentiates into osteoblasts in response to BMP-2 from calvariae of GFP transgenic mice"BONE. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Iioka et al.: "p300/CBP Acts as a Coactivator to Cartilage Homeoprotein-1 (Cart1), Paired-Like Homeoprotein, via Acetylation of the Conserved Lysine Residue Adjacent to the Homeodomain"J Bone Miner Res. 18・8. 1419-1429 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Hirata et al.: "Transplantation of skin fibroblasts expressing BMP-2 promotes Bone repair more effectively than those expressing Runx2"BONE. 32・5. 502-512 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Takahara et al.: "Autocrine/paracrine role of the angiopoietin-1 and -2/Tie2 system in cell proliferation and chemotaxis of cultured fibroblastic synoviocytes in rheumatoid arthritis"Hum Pathol. 35・2. 150-158 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kadowaki et al.: "Isolation and characterization of a mesenchymal cell line that differentiates in to osteoblasts in response to BMP-2 from calvariae of GFP transgenic mice"BONE. (In press). (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Furukawa et al.: "Functional domains of paired-like homeoprotein Cart1 and the relationship between dimerization and transcription activity"Genes to Cells. 7. 1135-1147 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Iioka et al.: "p300/CBP Acts as a Coactivator to Cartilage Homeoprotein-1 (Cart1), Paired-Like Homeoprotein, via Acetylation of the Conserved Lysine Residue Adjacent to the Homeodomain"J Bone Miner Res. (In press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Hirata et al.: "Transplantation of skin fibroblasts expressing BMP-2 promotes Bone repair more effectively than those expressing Runx2"BONE. (In press). (2003)

    • Related Report
      2002 Annual Research Report

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

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