Gene expression of matrix metalloproteinases 1, 3, and 9 by chondrocytes in osteoarthritic human knee articular cartilage is zone and grade specific
Gene expression of matrix metalloproteinases 1, 3, and 9 by chondrocytes in osteoarthritic human knee articular cartilage is zone and grade specific
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DOI：
10.1136/ard.56.9.542
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发表时间：
1997-09-01
影响因子：
27.4
通讯作者：
Hoyland, JA
中科院分区：
文献类型：
--
作者：
Freemont, AJ;Hampson, V;Hoyland, JA
基质金属蛋白酶（MMPs）被认为是软骨破坏的主要介质。骨关节炎（OA）的特征在于软骨降解。本研究探讨了三种MMPs在关节软骨细胞中的基因表达对OA软骨病变的组织学发展的治疗作用。方法采用S-35标记的cDNA探针，使用自动图像分析仪在四个不同深度（区域）测量信号，并与来自用λ DNA探测的切片的信号进行比较。类风湿性关节炎滑膜用作MMP基因表达的阳性对照。结果-类风湿性关节炎组织含有所有三种MMP的mRNA。在软骨细胞中的表达随着软骨细胞在软骨中的深度和OA的组织形态学改变程度而变化。在正常软骨中没有检测到这三种MMPs的mRNA信号。一般而言，在OA中，MMP-1基因表达在已建立疾病的浅表软骨中最大。相比之下，MMP-3和9的mRNA在软骨中表达更深，MMP-9在疾病早期表达，MMP-3在早期和晚期疾病中具有双相模式，在后者中最明显。这是一个结果的差异表达在单细胞和软骨细胞集群在晚期diseases. Conclusion的数据表明，MMPs 1，3和9的基因的表达差异调节在人关节软骨细胞，在个别细胞，是有关的软骨细胞的深度低于软骨表面和软骨病变的性质和程度。
Objectives-Matrix metalloproteinases (MMPs) are thought to be major mediators of cartilage destruction. Osteoarthritis (OA) is characterised by cartilage degradation. This study explores gene expression of three MMPs in articullar chondrocytes curing the histological development of the cartilage lesion of OA.Methods-Biopsy specimens of human normal and OA cartilage, classified into four grades on the basis of histology, were probed for MMPs 1, 3, and 9 using S-35-labelled cDNA, probes, The signal was measured at four different depths (zones) using an automated image analyser and compared with signal from sections probed with lambda DNA. Rheumatoid synovium was used as a positive control for MMP gene expression.Results-Rheumatoid tissue contained mRNA for all three MMPs. Expression in chondrocytes varied with the depth of the chondrocyte in the cartilage and the histomorphological extent of the OA changes. There was no detectable mRNA signal for these three MMPs in normal cartilage. In general, in OA, MMP-1 gene expression was greatest in the superficial cartilage in established disease. By contrast mRNAs for MMP-3 and 9 were expressed deeper in the cartilage, MMP-9 early in disease and MMP-3 with a biphasic pattern in early and late stage disease, most pronounced in the latter. This was a consequence of differential expression in single cells and chondrocyte clusters in late disease.Conclusion-The data indicate that expression of genes for MMPs 1, 3, and 9 is differentially regulated in human articular chondrocytes and, in individual cells, is related to the depth of the chondrocyte below the cartilage surface and the nature and extent of the cartilage lesion.