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全基因组表达谱分析揭示与骨关节炎相关的新候选基因。

Genome-wide expression profiling reveals new candidate genes associated with osteoarthritis.

机构信息

Institute of Laboratory Medicine, Department of Clinical Chemistry and Transfusion Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden. v

出版信息

Osteoarthritis Cartilage. 2010 Apr;18(4):581-92. doi: 10.1016/j.joca.2009.12.002. Epub 2010 Jan 4.

DOI:10.1016/j.joca.2009.12.002
PMID:20060954
Abstract

INTRODUCTION

Although the extracellular matrix (ECM) is the functional element in articular cartilage and its degradation is central in the pathogenetic process in osteoarthritis (OA), increasing the knowledge about the cellular OA phenotype is essential. The aim of this study is therefore to provide a more complete picture of the cellular and molecular alterations detected in OA cartilage.

MATERIAL AND METHODS

Human articular cartilage biopsies were collected from donors with macroscopical and microscopical signs of OA as well as donors with no previous history of OA and with microscopically intact cartilage. RNA was isolated from the biopsies and subjected to whole genome microarray analysis. Important results from the microarray analysis were verified using real-time PCR and immunohistochemistry.

RESULTS

Our results reveal several new candidate genes not previously associated with OA to display significantly higher expression in OA cartilage than in normal donor cartilage, including genes involved in bone formation (CLEC3B, CDH11, GPNMB, CLEC3A, CHST11, MSX1, MSX2) and genes encoding collagens (COL13A1, COL14A1, COL15A1, COL8A2).

DISCUSSION

This study is the first to report a comprehensive gene expression analysis of human OA cartilage compared to control cartilage from donors lacking macroscopical and microscopical signs of OA using recently developed microarrays containing the whole human genome. Our results could broadly confirm previously published data on many characteristic features of OA as well as adding a panel of genes to the list of genes known to be differentially expressed in OA. Elucidation of the phenotypical alterations occurring in OA chondrocytes is important for the development of effective treatments for OA.

摘要

简介

尽管细胞外基质(ECM)是关节软骨的功能元素,其降解是骨关节炎(OA)发病过程的核心,但增加对 OA 软骨中细胞表型的了解是至关重要的。因此,本研究的目的是提供一个更完整的 OA 软骨中细胞和分子变化的图片。

材料和方法

从有宏观和微观 OA 迹象的供体以及没有 OA 既往病史且微观上软骨完整的供体中收集关节软骨活检。从活检中分离 RNA,并进行全基因组微阵列分析。使用实时 PCR 和免疫组织化学验证微阵列分析的重要结果。

结果

我们的结果揭示了一些以前与 OA 无关的新候选基因,这些基因在 OA 软骨中的表达明显高于正常供体软骨中的表达,包括参与骨形成的基因(CLEC3B、CDH11、GPNMB、CLEC3A、CHST11、MSX1、MSX2)和编码胶原的基因(COL13A1、COL14A1、COL15A1、COL8A2)。

讨论

这是第一项使用最近开发的包含全人类基因组的微阵列,对与缺乏宏观和微观 OA 迹象的供体的正常软骨相比,对人 OA 软骨进行全面基因表达分析的研究。我们的结果可以广泛证实以前发表的关于 OA 许多特征的许多数据,并且还将一组基因添加到已知在 OA 中差异表达的基因列表中。阐明 OA 软骨细胞中发生的表型变化对于开发 OA 的有效治疗方法非常重要。

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