2007 Fiscal Year Final Research Report Summary
Comprehensive gene expression analysis during chondrogenesis from progenitor cells, ,and application of this technique to tissue repair
| Project/Area Number |
16390436
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Orthopaedic surgery
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| Research Institution | Osaka City University (2006-2007)
Shinshu University (2004-2005) |
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Principal Investigator |
WAKITANI Shigeyuki Osaka City University, Graduate School of Medicine, Associate Professor (70243243)
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| Co-Investigator(Kenkyū-buntansha) |
TAKAHASHI Jun Shinshu University, Medical School, Lecturer (60345741)
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| Project Period (FY) |
2004 – 2007
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| Keywords | undifferentiated mesenchymal cells / chondrocyte differentiation factor / KLF9 / articular cartilage repair |
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| 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
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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
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