权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

The basic research of the mechanism and the treatment for intervertebral disc degeneration.

椎间盘退变机制及治疗的基础研究。

基本信息

批准号：
15591601
负责人：
CHIBA Kazuhiro
金额：
$ 2.24万
依托单位：
Keio University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2004
项目状态：
已结题

项目摘要

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.

目标.研究了IVD中TIMP-3和TGF-β 1表达的与血管紧张素Ⅱ相关的变化，以阐明TIMP-3的可能作用，从而阐明脊索NP在维持IVD稳态中的作用。在四种TIMP中，TIMP-3具有许多独特的性质，其中最令人感兴趣的性质是除了基质金属蛋白酶之外还抑制聚集蛋白聚糖酶。目前还没有研究确定TIMP-3在IVD中的表达并研究其表达的年龄相关变化以阐明TIMP-3在IVD代谢中的可能作用。对4周龄和160周龄家兔进行TIMP-3免疫组织化学染色及TGF-β 1和TIMP-3基因表达的半定量分析。在TGF-β 1和IL-1 β存在下体外培养NP组织，检测TIMP-3 mRNA的表达。免疫组化结果显示TIMP-3仅在4周龄的家兔中表达。半定量RT-PCR结果显示，TGF-β 1和TIMP-3mRNA在幼兔中的表达水平明显升高，随着年龄的增长表达水平逐渐降低。TGF-β 1可剂量依赖性地上调NP中TIMP-3mRNA的表达，而IL-1 β对TIMP-3mRNA的表达无影响。TIMP-3的表达随着年龄的增长而减少，可能部分由TGF-β 1的下调介导，发生在椎间盘退变的早期阶段。脊索NP可能通过表达TGF-β 1和TIMP-3在IVD代谢的稳态中发挥作用。