| Project/Area Number |
11671431
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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 | Osaka University |
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Principal Investigator |
HOSONO Nobuko (2001) Osaka University Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (70238757)
米延 策雄 (1999-2000) 大阪大学, 医学系研究科, 助教授 (50127320)
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| Co-Investigator(Kenkyū-buntansha) |
NAKASE Takanobu Osaka University Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (00283755)
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| Project Period (FY) |
1999 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 2001: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2000: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1999: ¥900,000 (Direct Cost: ¥900,000)
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| Keywords | endochondral bone formation / hypertrophic chondrocyte / cellular senescence / Hic-5 / terminal differentiation / apoptosis / p16^<INK4a> / Hic-5 |
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| Research Abstract |
We have investigated the mechanisms of aging and degeneration of spinal structure using intervertebral disc cells and experimental spondylosis model in mice.
1. Analysis of gene expression in intervertebral disc cells using RT-PCR revealed the age-dependent decline in expression of TGF-b1, TGF-b1 receptor I, IGF-1 receptor mRNA. Consistent with the PCR results, stimulation of proteoglycan synthesis by TGF-b1 and IGF-1 decreased with age.
2. We analyzed the experimental spondylosis model comparing with normal aging with immunohistochemistry and in situ hybridization. The expression of growth factors such as GDF-5, BMP receptors and BMP-4, -6 mRNA was observed especially in the area of proliferation of chondrocytes in intervertebral discs of experimental spondylosis model. In this area, formation of osteophyte was observed in histology and PCNA positive cells, a marker of proliferating cells, were also observed by immunohistochemistry. On the other hand, p16^<INK4a> positive cells were observed in the area of hypertrophic chondrocytes in endochondral bone formation of growth cartilage and osteophyte. p16^<INK4a> may be involved in terminal differentiation of chondrocyte. However, we could not have evidence of involvement of cellular senescence in terminal differentiation of chondrocyte in endochondral bone formation.
3. We analyzed the experimental spondylosis model comparing with normal aging with TUNEL procedure. The occurrence of apoptosis was observed mainly in the cartilaginous endplate. The rate of occurrence of apoptosis increased with aging, and the vital cells in cartilaginous endplate decreased. The apoptotic rate was significantly higher in spondylosis model than in normal aging.
In conclusion, the occurrence of apoptosis and the change in expression of several growth factors were involved in the process of aging and degeneration of spinal structure.
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