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髋关节继发骨关节炎关节软骨细胞的全基因组转录组分析。

A whole-genome transcriptome analysis of articular chondrocytes in secondary osteoarthritis of the hip.

机构信息

Department of Orthopaedic Surgery, Tohoku University Graduate School of Medicine, Sendai, Japan.

出版信息

PLoS One. 2018 Jun 26;13(6):e0199734. doi: 10.1371/journal.pone.0199734. eCollection 2018.

DOI:10.1371/journal.pone.0199734
PMID:29944724
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6019400/
Abstract

OBJECTIVE

To date, exhaustive gene expression analyses of chondrocytes in hip osteoarthritis (OA) have yielded specific gene expression patterns. No study has reported on the exhaustive transcriptome of secondary hip OA based on acetabular dysplasia in a Japanese population, while previous reports have focused on primary or idiopathic hip OA in Caucasian populations. This study aims to search for specific gene expression patterns of secondary hip OA chondrocytes by transcriptome analysis.

DESIGN

Human articular cartilage was obtained from femoral heads following hemiarthroplasty for femoral neck fracture (N = 8; non-OA) and total hip arthroplasty for secondary hip OA (N = 12). Total RNA was extracted from the articular cartilage and submitted for microarray analysis. The obtained data were used to perform gene expression analysis, GO enrichment analysis and pathway analysis and were compared with data from primary hip OA in Caucasian populations in the literature.

RESULTS

We identified 888 upregulated (fold change: FC ≥ 2) and 732 downregulated (FC ≤ 0.5) genes in hip OA versus non-OA chondrocytes, respectively. Only 10% of upregulated genes were common between the secondary and primary OA. The newly found genes prominently overexpressed in the secondary hip OA chondrocytes were DPT, IGFBP7, and KLF2. Pathway analysis revealed extracellular matrix (ECM)-receptor interaction as an OA-related pathway, which was similar to previous reports in primary hip OA.

CONCLUSIONS

This is the first study to report the genome-wide transcriptome of secondary hip OA chondrocytes and demonstrates new potential OA-related genes. Gene expression patterns were different between secondary and primary hip OA, although the results of pathway and functional analysis were similar.

摘要

目的

迄今为止,对髋骨关节炎(OA)软骨细胞的详尽基因表达分析已经产生了特定的基因表达模式。没有研究报告过基于日本人群髋臼发育不良的继发性髋 OA 的详尽转录组,而之前的报告则集中在白种人群的原发性或特发性髋 OA 上。本研究旨在通过转录组分析寻找继发性髋 OA 软骨细胞的特定基因表达模式。

设计

从股骨颈骨折半髋关节置换术(N=8;非 OA)和继发性髋 OA 全髋关节置换术(N=12)患者的股骨头中获取关节软骨。从关节软骨中提取总 RNA,并进行微阵列分析。所获得的数据用于进行基因表达分析、GO 富集分析和途径分析,并与文献中白种人群原发性髋 OA 的数据进行比较。

结果

我们分别鉴定出髋 OA 与非 OA 软骨细胞中 888 个上调(倍数变化:FC≥2)和 732 个下调(FC≤0.5)的基因。在继发性和原发性 OA 之间,仅有 10%的上调基因是共同的。在继发性髋 OA 软骨细胞中显著过表达的新发现基因包括 DPT、IGFBP7 和 KLF2。途径分析显示细胞外基质(ECM)-受体相互作用是一种与 OA 相关的途径,这与原发性髋 OA 的先前报告相似。

结论

这是第一项报告继发性髋 OA 软骨细胞全基因组转录组的研究,并展示了新的潜在与 OA 相关的基因。尽管在途径和功能分析的结果相似,但继发性和原发性髋 OA 的基因表达模式不同。

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