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Comprehensive gene expression analysis during chondrogenesis from progenitor cells, ,and application of this technique to tissue repair

Research Project

Project/Area Number 16390436
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Orthopaedic surgery
Research InstitutionOsaka City University (2006-2007)
Shinshu University (2004-2005)

Principal Investigator

WAKITANI Shigeyuki  Osaka City University, Graduate School of Medicine, Associate Professor (70243243)

Co-Investigator(Kenkyū-buntansha) TAKAHASHI Jun  Shinshu University, Medical School, Lecturer (60345741)
清水 富永  信州大学, 医学部, 講師 (40283270)
谷上 信  藤井記念研究所, 所長
Project Period (FY) 2004 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥12,740,000 (Direct Cost: ¥12,200,000、Indirect Cost: ¥540,000)
Fiscal Year 2007: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2006: ¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 2005: ¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 2004: ¥5,600,000 (Direct Cost: ¥5,600,000)
Keywordsundifferentiated mesenchymal cells / chondrocyte differentiation factor / KLF9 / articular cartilage repair / 軟骨分化促進 / 転写因子 / 遺伝子解析 / 軟骨分化 / 遺伝子発現 / 超音波遺伝子導入 / 骨形成因子
Research Abstract

Articular cartilage defects are a major clinical problem for orthopaedic surgeons. Autologous chondrocyte implantation (ACI) was explored, and performed in more than 20,000 patients worldwide. However, the effectiveness of ACI remains controversial due to a lack of evidence of efficacy from randomized controlled trials. There is currently no satisfactory clinical technique that is widely accepted for the regenerative repair of these lesions.
We have been interested in the use of bone marrow mesenchymal cells (BMMC) because they have a number of suitable properties Therefore, this procedure can be performed clinically with relative ease. Thus, we performed BMMC transplantation in human articular cartilage defects in knee joints. Although the clinical results was good, the repair tissue was not hyaline cartilage, but fibrous cartilage. We thought that promotion of chondrogenic differentiation is very important not only in science but also in clinical practice.
We have reported that recombi … More nant human Bmp2 (rhBMP-2) could induce the differentiation of muscle-derived mesenchymal cells into chondrocytes and form cartilage tissue in a diffusion chamber. Since this diffusion chamber system can separate transplanted cells from host tissue and prevent host cell contamination (neovascularization and immune system infiltration), we attempted to identify the genes that regulate chondrocyte differentiation in this system by gene expression profile using GeneChip. Although gene expression profiles of chondrocyte differentiation were reported, the combination with a diffusion chamber system can be more powerful tool for the detailed analysis of the chondrocyte .differentiation. We identified many up-regulated genes in this chondrogenic system. We selected 20 transcriptional factor and within them 10 genes were up-regulated in the early phase of chondrogenesis and the suppression of some genes using RNA interference (RNAi) revealed the association of these genes with chondrogenesis. KLF9, which suppressed most, was transfected into undifferentiated mesenchymal cells, but the chondrogenic differentiation was not promoted. It is suggested that KLF9 needed co-factors. Less

Report

(5 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • 2005 Annual Research Report
  • 2004 Annual Research Report
  • Research Products

    (22 results)

All 2007 2006 2005 Other

All Journal Article (19 results) (of which Peer Reviewed: 8 results) Presentation (2 results) Book (1 results)

  • [Journal Article] Repair of articular cartilage defects in the patello-femoral joint with autologous bone marrow mesenchymal cell transplantation:three case reports involving 9 defects in 5 knees2007

    • Author(s)
      Wakitani S, et. al.
    • Journal Title

      J Tissue Engineering Regenerative Medicine 1

      Pages: 74-79

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] High inoculation cell density could accelerate the different iation of human bone marrow mesenchymal stem cells to chondrocyte cells2007

    • Author(s)
      Takagi M, Wakitani S, et. al.
    • Journal Title

      J Biosci Bioeng 103

      Pages: 98-100

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Detection of gene expression in synovirm of patients with osteoarthritis using a random sequencing method2007

    • Author(s)
      Okabe T, Wakitani S, et. al.
    • Journal Title

      Acta Orthop 78

      Pages: 687-692

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Serum keratan sulfate is a promising marker of early articular cartilage breakdown2007

    • Author(s)
      Wakitani S, et. al.
    • Journal Title

      Rheumatology(Oxford) 46

      Pages: 1652-1656

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Repair of articular cartilage defects in the patello-femoral joint with autologous bone marrow mesenchymal cell transplantation: three case reports involving 9 defects in 5 knees2007

    • Author(s)
      Wakitani, S., et. al.
    • Journal Title

      J Tissue Engineering Regenerative Medicine 1

      Pages: 74-79

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] High inoculation cell density could accelerate the differentiation of human bone marrow mesenchymal stem cells to chondrocyte cells.2007

    • Author(s)
      Takagi, M., et. al.
    • Journal Title

      J Biosci Bioeng 103

      Pages: 98-100

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Detection of gene expression in synovium of patients with osteoarth!itis using a random sequencing method2007

    • Author(s)
      Okabe, T., et. al.
    • Journal Title

      Acta Orthop 78

      Pages: 687-692

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Serum keratan sulfate is a promising marker of early articular cartilage breakdown2007

    • Author(s)
      Wakitani, S., et. al.
    • Journal Title

      Rheumatology (Oxford) 46

      Pages: 1652-1656

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Repair of articular cartilage defects in the patello-femoral joint with autologous bone marrow mesenchymal cell transplantation:three case reports involving 9 defects in 5 knees.2007

    • Author(s)
      Wakitani S, et. al.
    • Journal Title

      J Tissue Engineering Regenerative Medicine 1

      Pages: 74-79

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] High inoculation cell density could accelerate the differentiation of human bone marrow mesenchymal stem cells to chondr ocyte cells.2007

    • Author(s)
      Takagi M, Wakitani S, et. al.
    • Journal Title

      J Biosci Bioeng 103

      Pages: 98-100

    • NAID

      110006164023

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Detection of gene expression in synovium of patients with osteoarthritis using a random sequencing method.2007

    • Author(s)
      Okabe T, Wakitani S, et. al.
    • Journal Title

      Acta Orthop 78

      Pages: 687-692

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Serum keratan sulfate is a promising marker of early articular cartilage breakdown.2007

    • Author(s)
      Wakitani S, et. al.
    • Journal Title

      Rheumatology(Oxford) 46

      Pages: 1652-1656

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Co-ordinate expression of BMP-2, BMP receptors and Noggin in normal mouse spine.2006

    • Author(s)
      Nakamura Y, Nakaya H, Saito N, Wakitani S
    • Journal Title

      J Clinical Neuroscience 13

      Pages: 250-256

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Microbubble-enhanced ultrasound exposure promotes uptake of methotrexate into synovial cells and enhanced anti-inflammatory effects in rabbit antigen-induced arthritic knees.2005

    • Author(s)
      Nakaya H, et al.
    • Journal Title

      Arthritis Rheum 52

      Pages: 2559-2566

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Low dose fibroblast growth factor-2 (FGF-2) enhanced bone morphogenetic protein (BMP-2) induced ectopic bone formation in mice.2005

    • Author(s)
      Nakamura Y, et al.
    • Journal Title

      Bone 36

      Pages: 399-407

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Expression profiles and functional analyses of Wnt-related genes in human joint disorders.2005

    • Author(s)
      Nakamura Y, et al.
    • Journal Title

      Am J Pathol 167

      Pages: 97-105

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Use of bone morphogenetic protein-2 and diffusion chambers to engineer cartilage tissue for the repair of defects in articular cartilage.2005

    • Author(s)
      Nawata S, et al.
    • Journal Title

      Arthritis and Rheumatism 52

      Pages: 155-163

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Gene expression in synovium of patients with osteoarthritis using random sequencing method.

    • Author(s)
      Okabe T, Ohmori Y, Tanigami A, Hishigaki H, Suzuki Y, Sugano S, Kawaguchi A, Nakaya H, Wakitani S
    • Journal Title

      Acta Orthop In press

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Repair of articular cartilage defects in the patello-femoral joint with autologous bone marrow mesenchymal cell transplantation : three case reports involving 9 defects in 5 knees.

    • Author(s)
      Wakitani S, Nawata M, Tensho K, Okabe Y, Machida H, Ohgushi H
    • Journal Title

      J Tissue Engineering Regenerative Medicine In press

    • Related Report
      2006 Annual Research Report
  • [Presentation] Cartilage repair with bone marrow mesenchymal cells-its preparation and clinical use2007

    • Author(s)
      Wakitani S.
    • Organizer
      2007 Bioengineering for Cell Therapy. Ajou Cell Therapy Center
    • Place of Presentation
      Ajjou University,in Suwan,Korea
    • Year and Date
      2007-03-22
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Cartilage repair with bone marrow mesenchymal cells -its preparation and clinical use-2007

    • Author(s)
      Wakitani, S
    • Organizer
      2007 Bioengineering for Cell Therapy. Ajou Cell Therapy Center
    • Place of Presentation
      Suwan, Korea
    • Year and Date
      2007-03-22
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Book] Bone marrow transplantation2006

    • Author(s)
      Wakitani S, Ohgushi H, Machida H, Nakaya H, Murakami N, Yamasaki H, Kato H, Kawaguchi A, Okabe T, Tensho K
    • Publisher
      Autologous culture expanded bone marrow stromal cell transplantation for cartilage repair.
    • Related Report
      2006 Annual Research Report

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Published: 2004-04-01   Modified: 2016-04-21  

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