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Fundamental Approach to Gene Therapy for Osteoarthritis

Research Project

Project/Area Number 06671465
Research Category

Grant-in-Aid for General Scientific Research (C)

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

Principal Investigator

TAKAHASHI Katsuro  Nagasaki University, School of Medicine, Assistant professor, 医学部, 助手 (00244046)

Co-Investigator(Kenkyū-buntansha) OOTSURU Akira  Nagasaki University, School of Medicine, Assistant professor, 医学部, 助手 (00233198)
IWASAKI Katsuro  Nagasaki University, School of Medicine, professor, 医学部, 教授 (60039542)
Project Period (FY) 1994 – 1995
Project Status Completed (Fiscal Year 1995)
Budget Amount *help
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1995: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1994: ¥1,300,000 (Direct Cost: ¥1,300,000)
KeywordsGene Therapy / Arthritis / Articular Cartilage / Transformong growth factor / Signal Transduction / gene therapy / arthritis / TGF-β / トランスホ-ミンググロースファクター / 細胞内情報伝達
Research Abstract

Transforming growth factor (TGF-b) has been found to be a powerful multipotential regulator of the cellular activity of chondrocytes, and it is assumed to play a role in the repair of cartilage tissue. Delivery of TGT-b to the articular space by gene transfer offers a potential therapeutic modality. To determine the feasibility of using rat as a gene transfer system, intraarticular injections of the rat knee were performed. The pSV-b Galactosidase vector was injected intraarticulaly using lipofectin to ascertain whether gene delivery was possible with this approach. Synovial membrane and cartilage tissue were examined for lac-z expression histologically. High efficiency expression was observed in these tissues. And transgene expression could still be detected after 14 days.
We also examined the signal transduction of TGF-b in chondrocytes and found that it was different from the other cells. TGF-b upregulated the induction of c-fos gene in chondrocytes. We are now determing the response element of c-fos gene for TGF-b by using a CAT assay method.
Although, the delivery of TGF-b has not been successful, these results suggest the feasibility of gene therapy for osteoarthritis.

Report

(3 results)
  • 1995 Annual Research Report   Final Research Report Summary
  • 1994 Annual Research Report
  • Research Products

    (13 results)

All Other

All Publications (13 results)

  • [Publications] T.Matsumoto: "Effects of interleukin-1b on insulin-like growth factor-I autocrine/paracrine axis in cultured rat articular chondrocytes." Annals of the Rheumatic Diseases. 53. 128-133 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] T.Tsukazaki: "Effect of transforming growth factor-b on the insuin-like growth factor-I autocrine/paracrine axis in cultured rat articular chondrocytes." Exp Cell Res. 215. 9-16 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] T.Tsukazaki: "Growth hormone directly and indirectly stimulates articular chondrocyte cell growth." Osteoarthritis Cartilage. 2. 258-267 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] T.Tsukazaki: "Expression of parathyroid hormone-related protein in rat aritcular cartilage." Calcif Tissue Int. 57. 196-200 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] T.Tsukazaki: "Parathyroid hormone-related protein (PTHrP) action in rat articular chondrocytes : comparison of PTH (1-34), PTHrP (1-34), (1-141), (100-114) and antisense oligonueleotides against PTHrP." Endocrinol. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] H.Yano,: "Evidence of c-fos expression implicating cell fate during palatal fusion in the rat." Develop Growth Different. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] T.Matsumoto: "Effects of interleukin-1b on insulin-like growth factor-I autocrine/paracrine axis in cultured rat articular chondrocytes." Annals of the Rheumatic Diseases. 53. 128-133 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] T.Tsukazaki: "Effect of transforming growth factor-b on the insuin-like growth factor-I autocrine/paracrine axis in cultured rat articular chondrocytes." Exp Cell Res. 215. 9-16 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Tsukazaki: "Growth hormone directly and indirectly stimulates articular chondrocyte cell growth." Osteoarthritis Cartilage. 2. 258-267 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] T.Tsukazaki: "Expression of parathyroid hormone-related protein in rat aritcular cartilage." Calcif Tissue Int. 57. 196-200 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] H.Yano: "Evidence of c-fos expression implicating cell fate during palatal fusion in the rat." Develop Growth Different. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] T.Tsukazaki: "Parathyroid hormone-related protein (PTHrP) action in rat articular chondrocytes : comparison of PTH (1-34), PTHrP (1-34), (1-141), (100-114) and antisense oligonucleotides against PTHrP." Endocrinol. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Tomoo Tsukazaki et al.: "Expression of parathyroidhormone-relatedpeptide in rat articular cartilage" Cal Tissue Int. (in presse). (1995)

    • Related Report
      1994 Annual Research Report

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Published: 1994-04-01   Modified: 2016-04-21  

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