2006 Fiscal Year Final Research Report Summary
Molecular and cellular approaches to the treatment of degenerative lumbar disc disease
| Project/Area Number |
17591595
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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, School of Medicine, Associate Professor, 医学部, 助教授 (80179952)
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| Co-Investigator(Kenkyū-buntansha) |
TAKAISHI Hironari Keio University, School of Medicine, Research Associate, 医学部, 助手 (60236180)
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| Project Period (FY) |
2005 – 2006
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| Keywords | cell and tissue / intervertebral disc / bioactive molecules / degeneration / low back pain |
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| Research Abstract |
There are several avascular tissues such as intervertebral disc, cartilage and lens. However, how these tissues are maintained without blood flow is poorly understood. Among the avascular tissues, we focused on nucleus pulposus (NP), avascular component of intervertebral disc. To explore what molecules are expressed in NP, microarray analysis was performed in NP and other eleven different tissues. Interestingly, we found that Vascular Endothelial Growth Factor (VEGF) was highly expressed in NP when compared with other tissues
To analyse role of VEGF in NP, VEGF expression in NP was confirmed by western blotting and RT-PCR analysis. All splice variants of VEGF were detected in NP. -Expressions of hypoxic response genes such as GLUT-1 and PGK-1 as well as VEGF were higher in NP cells than other tissues, and NP was hypoxic marker, pimonidazole, positive tissues. Moreover, VEGF expression in NP cells was up-regulated under hypoxic conditions and not in normoxic conditions in vitro suggestin
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g that VEGF expression in NP is promoted by hypoxia. Among VEGF receptors, the expression of Flt-1 but not Flk-1 was detected in NP by RT-PCR analysis, and this finding was confirmed by LacZ staining of NP in Flt-1-lacZ and Flk-1-lacZ knock-in mice. These results suggest that VEGF may function as an anti-apoptotic factor in NP cells through Flt-1 as autocrine or paracrine loop. In in vitro, numbers of apoptotic cells was increased by addition of Flt-1-Fc but not by CD4-Fc. Thus, anti-apoptosis may be one of functions of VEGF in NP cells. In MRI analysis, T2 high signal intensity of intervertebral disc, which indicate a healthy NP, decreased with aging in rat as seen in human. As T2 high signal decreased with aging, the VEGF mRNA expression in NP was down-regulated, which also correlated with down-regulation of expression of chondrogenic markers such as aggrecan and type II collagen.
Taken together, our results demonstrate that VEGF-Flt-1 signal may play role in NP survival in autocrine/paracrine manner. Now, we have started analysis on function of VEGF in NP cells using Flt-1-TK/TK mice, which has Flt-1 signaling deficiency because of disruption of cytoplasmic domain of Flt-1. Less
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Research Products
(8 results)
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[Journal Article] Association study of COL9A2 with lumbar disc disease in the Japanese population.2006
Author(s)
Seki S, Kawaguchi Y, Mori M, Mio F, Chiba K, Mikami Y, Tsunoda T, Kubo T, Toyama Y, Kimura T, Ikegawa S.
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Journal Title
J Hum Genet. 51(12)
Pages: 1063-7
Description
「研究成果報告書概要(欧文)」より
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