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

目标。我们研究了IVD中TIMP-3和TGF-β1表达的年龄相关变化，以阐明TIMP-3以及脊索NP在IVD稳态维持中的可能作用。背景资料摘要。在这四种timp中，TIMP-3具有许多独特的性质，其中最有趣的性质是除了抑制基质金属蛋白酶外，还能抑制聚合酶。目前还没有研究在IVD中发现TIMP-3，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免疫组化和TGF-β1、TIMP-3半定量基因表达分析。在TGF-β1和IL-1β存在下体外培养NP组织，检测TIMP-3 mRNA表达水平。免疫组化结果显示，TIMP-3仅在4周龄家兔中呈阳性。半定量RT-PCR结果显示TGF-β1和TIMP-3 mRNA的表达水平在未成熟家兔体内显著升高，随年龄增长而降低。TGF-β1可上调NP组织中timp - 3mrna的表达，并呈剂量依赖性，而il -1β对timp - 3mrna的表达无影响。TIMP-3的表达随着年龄的增长而下降，可能部分是由TGF-β1的下调介导的，发生在椎间盘退变的早期。Notochordal NP可能通过表达TGF-β1和TIMP-3参与IVD代谢的稳态。

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.