| Project/Area Number |
15591601
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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 | Keio University |
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Principal Investigator |
CHIBA Kazuhiro Keio University, Department of Orthopaedic Surgery, Associate Professor, 医学部, 助教授 (80179952)
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| Co-Investigator(Kenkyū-buntansha) |
TAKAISHI Hironari Keio University, Department of Orthopaedic Surgery, Instructor, 医学部, 助手 (60236180)
三尾 太 慶應義塾大学, 医学部, 助手
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2004: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2003: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | intervertebral disc / nucleus pulposus / annulus fibrosus / degeneration / matrix / TIMP-3 / Aggrecan / collagen / 組織培養 / プロテオグリカン |
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| Research Abstract |
Objectives. Age-related changes in the expressions of TIMP-3 and TGF-β1 in the IVD were investigated to elucidate possible roles of TIMP-3 and, thereby, the notochordal NP in the maintenance of IVD homeostasis.
Summary of Background Data. Among the four TIMPs, TIMP-3 has a number of unique properties, the most interesting properties of which is to inhibit aggrecanases in addition to matrix metalloproteinases. There has been no study that identified TIMP-3 in the IVD and investigated the age-related changes in its expression to elucidate possible roles of TIMP-3 in the IVD metabolism.
Methods. Immunohistochemistry of TIMP-3 and semi-quantitative gene expression analysis of TGF-β1 and TIMP-3 were conducted using 4-week-old and 160-week-old rabbits. NP tissues were cultured in vitro in the presence of TGF-β1 and IL-1β and the levels of TIMP-3 mRNA were assessed.
Results. Immunohistochemistry revealed that TIMP-3 was positive in 4-week-old rabbits only. Semi-quantitative RT-PCR revealed that the levels of expressions of TGF-β1 and TIMP-3 mRNA were significantly higher in the immature rabbit and decreased with aging in vivo. The expression of TIMP-3 mRNA in the NP was upregulated by TGF-β1 in a dose dependent manner, but was not affected by IL-1β.
Conclusions. Decrease in the expression of TIMP-3 with aging, possibly mediated in part by the downregulation of TGF-β1, occurs in the early stage of disc degeneration. Notochordal NP may play a role in the homeostasis of IVD metabolism, by expressing TGF-β1 and TIMP-3.
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