| Project/Area Number |
18591626
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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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 | University of Yamanashi |
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Principal Investigator |
HARO Hirotaka University of Yamanashi, Department of Orthopaedic Surgery,Interdiatfinary, graduate school of Medicine and Engineering, Assistant Professor (10313264)
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| Co-Investigator(Kenkyū-buntansha) |
HAMADA Yoshiki University of Yamanashi, Department of Orthopaedic Surgery Interdisciplinary graduate school of Medicine and Engineering, Professor (80096544)
TAKEDA Shu Tokyo Medical and Dental University, Department of Orthopaedic Surgery, Visiting Associate Professor (30376727)
NAKAO Atuhito University of Yamanashi, Department of Immunology, Interdisciplinary graduate school of Medicine and Engineering, Professor (80317445)
HARA Yasushi Nippon Veterinary and Science University, Department of Surgery, Associate Professor (00228628)
ASOU Yoshinori Tokyo Medical and Dental University, Department of Orthopaedic Surgery, Assistant Professor (50345279)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,860,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥360,000)
Fiscal Year 2007: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2006: ¥2,300,000 (Direct Cost: ¥2,300,000)
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| Keywords | TEWAK / Degeneration of intervertebral disc / MMP-3 |
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| Research Abstract |
The goal of this research was to examine the role of TWEAK in normal disc cells and to investigate its potential role in disc degeneration. We performed histological examinations of disc tissues and assessed the role of the novel cytokine TWEAK using murine organ disc culture. The expression of both TWEAK and its receptor, Fn14, in discs was confirmed by immunohistochemistry and quantitative real time PCR. TWEAK induced disc cells to generate MMP-3 in a dose- and time-dependent manner. This induction was strongly inhibited in the presence of a neutralizing antibody to TWEAK or a chimeric Fn14/Fc fusion protein. In disc tissues derived from TNF-a receptor 1- or TNF-a receptor 2-deficient mice, recombinant TWEAK modestly induced MMP-3. In contrast, in disc cultures lacking TWEAK, tissues from wild type mice or receptor-deficient mice failed to express MMP-3. Furthermore, aggrecan expression was potently abrogated in a time-dependent manner in the presence of recombinant TWEAK. This is the first report to confirm expression of TWEAK and its receptor Fn14 in murine intervertebral disc tissues. The data suggest that TWEAK plays a role in MMP-3 up-regulation and aggrecan down-regulation in disc tissues, resulting in proteoglycan degradation and promotion of disc degeneration.
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