Research for angiogenesis mechanism in hemialed disc (HD) resorption process and development of new therapies for HD using the resorption process
| Project/Area Number |
13671494
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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 | Tokyo Medical and Dental University |
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Principal Investigator |
HARO Hirotaka Graduated school, assistant professor, 大学院・医歯学総合研究科, 助手 (10313264)
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| Co-Investigator(Kenkyū-buntansha) |
KOMORI Hiromichi Graduated school, associate professor, 大学院・医歯学総合研究科, 助教授 (60262169)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥4,200,000 (Direct Cost: ¥4,200,000)
Fiscal Year 2002: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2001: ¥3,100,000 (Direct Cost: ¥3,100,000)
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| Keywords | herniated disc / spontaneous resorption / inflammatory cytokine / angiogenesis inducing factor / matrix degradation / cascade / TNF-alpha / MMPs / VEGF / sequential expressions / 血行新生 / 血管内皮細胞増殖因子(VEGF) / Matrix Metalloproteinase(MMP) / 生理的椎間板ヘルニア治療 |
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| Research Abstract |
MRI analysis of herniated discs(HP)has revealed a spontaneous resorption mechanism related with neo-vascnlarization. It appears that interaction of activated macrophages with disc tissues leads to the generation of inflammnatory cytokines. Moreover, inflammatory cytokines such as tumor necrosis factor-α(TNF-α)is required for the induction of angiogenesis inducing factors such as vascular endothelial growth factor((VEGF) or matrix degrading enzymes such as MMP-3, MMP-7 and Plasmin.
We hypothesized that these molecules play a crucial role during spontaneous HD resorption. In the study we have examined the sequential expression of these molecules using a co-culture system as a model of the acute phase of disc herniation. Our results indicate that upregulation of TNF-α expression occurs first in the inflammation induced by disc herniation. VEGF upregluation follows flie increased level of TNF-α expression. Both plasmin and MMP-3 are upregulated at later time points.
Our previous work has demonstrated that TNF-α can upregulate the expression of VEGF, MMP-3 and MMP-7 under the co-culture system. Therefore, we propose that TNF-α acts as the initiator of inflammation following contact between macrophages and disc chondrocytes. TNF-α could also act to accelerate the cascade of both angiogenesis and matrix degradation thereby facilitating HD resorption. Further understanding of the resorption process may provide future novel therapies for HD.
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Report
(3 results)
Research Products
(3 results)
