Matrix metalloproteinase-1,-3,-13 and aggrecanase-1 and-2 are differentially expressed in experimental osteoarthritis

Matrix metalloproteinase-1,-3,-13 and aggrecanase-1 and-2 are differentially expressed in experimental osteoarthritis
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DOI:
10.1016/s0304-4165(01)00122-2
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发表时间:
2001-05-03
影响因子:
3
通讯作者:
Mallein-Gerin, F
Mallein-Gerin, F
中科院分区:
生物学3区
文献类型:
--
作者:
Bluteau, G;Conrozier, T;Mallein-Gerin, F

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本研究的目的是用组织学和分子生物学技术研究实验性骨关节炎(OA)兔关节软骨和半月板的细胞表型。采用切断膝关节前交叉韧带的方法诱导兔膝前交叉韧带骨性关节炎,术后2、4、9周处死动物。我们的组织学观察显示,两种组织的细胞外基质都有进行性破坏。为了确定这些形态变化是否与相关分子亚群基因表达调控的变化有关,采用逆转录-聚合酶链式反应(RT-PCR)检测了蛋白水解酶和一种抑制物(MMP1、-3和-13,聚合酶-1和-2以及TIMP-1)、基质分子和一种伴侣蛋白(II型和X型胶原、聚集素、骨结素、β-igh3和Bip)的mRNA水平。我们的结果表明,对于大多数标记,两种组织的表达谱是相似的。尤其是。在骨性关节炎进展过程中,基质蛋白基因表达保持稳定或变化不大,提示组织修复能力较差。基质金属蛋白酶基因的表达迅速增加,而聚集聚糖酶基因的表达保持稳定。这些发现表明,在骨性关节炎过程中,基质金属蛋白酶-1、-3和-13以及聚集酶-1和-2的mRNA水平发生了不同的调节。(C)2001 Elsevier Science B.V.保留所有权利。
The aim of this study was to characterize the cellular phenotypes of articular cartilage and meniscus in rabbits with experimentally induced osteoarthritis (OA), by histological and molecular biological techniques. OA was induced by severing the anterior cruciate ligament of the knee and rabbits were killed 2, 4 or 9 weeks following surgery. Our histological observations show a progressive destruction of extracellular matrix in both tissues. To determine whether these morphological changes could be related to alterations in the regulation of gene expression for a subset of relevant molecules, levels of mRNA for proteinases and one inhibitor (MMP-1, -3 and -13, aggrecanase-1 and -2 and TIMP-1), matrix molecules and one chaperone (type II and X collagens, aggrecan, osteonectin, beta ig-h3 and BiP) were assessed by reverse transcription-polymerase chain reaction. Our results indicate that for most markers expression profiles were similar in both tissues. In particular. matrix protein gene expression remained stable or varied little during progression of OA, suggesting a poor repair capacity of the tissues. MMP gene expression increased rapidly whereas aggrecanase gene expression remained stable. These findings suggest that differential regulation of mRNA levels of MMP-1, -3 and -13 on the one hand and aggrecanase-1 and -2 on the other, occurs during OA. (C) 2001 Elsevier Science B.V. All rights reserved.