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生物信息学分析揭示了椎间盘退变过程中纤维环和髓核不同的基因表达模式。

Bioinformatics analysis reveals different gene expression patterns in the annulus fibrosis and nucleus pulpous during intervertebral disc degeneration.

作者信息

Wang Yi, Jiang Ling, Dai Guogang, Li Shengwu, Mu Xiaoyuan

机构信息

Cervicodynia/Omalgia/Lumbago/Sciatica Department 2, Sichuan Provincial Orthopedic Hospital, Chengdu, Sichuan 610041, P.R. China.

College Hospital, Sichuan Agricultural University, Chengdu, Sichuan 611130, P.R. China.

出版信息

Exp Ther Med. 2018 Dec;16(6):5031-5040. doi: 10.3892/etm.2018.6884. Epub 2018 Oct 19.

Abstract

Degeneration of the intervertebral disc (IVD), which consists of the annulus fibrosus (AF) and nucleus pulposus (NP), is a multifactorial physiological process associated with lower back pain. Despite decades of research, the knowledge of the underlying molecular mechanisms of IVD degeneration (IDD) has remained limited. The present study aimed to reveal the differential gene expression patterns in AF and NP during the process of IDD and to identify key biomarkers contributing to these differences. The microarray dataset GSE70362 containing 24 AF and 24 NP samples was retrieved from the Gene Expression Omnibus database. Of these, 8 healthy samples were discarded. GeneSpring11.5 software was employed to identify differentially expressed genes (DEGs). Metascape online tools were used to perform enrichment analyses. Finally, the DEGs were mapped with the Search Tool for the Retrieval of Interacting Genes, and a protein-protein interaction (PPI) network was constructed in Cytoscape software. A total of 87 DEGs were identified. Gene ontology enrichment revealed that these DEGs were mainly involved in the inflammatory response, the extracellular matrix and RNA polymerase II transcription factor activity. Pathway enrichment revealed that the DEGs were mainly involved in the transforming growth factor (TGF-β) and estrogen signaling pathways. Matrix metalloproteinase (MMP)1 and interleukin (IL)6 were included in the genes enriched in rheumatoid arthritis, whereas bone morphogenetic protein (BMP)2 and thrombospondin 1 (THBS1) were among the genes enriched in the TGF-β signaling pathway. In the PPI network, IL6 was identified as the central gene. In conclusion, as MMP1 has been demonstrated degrade collagen III at higher rates compared with other types of collagen (which is at a higher quantity in AF than NP), collagen types may be in different distribution patterns, which may contribute to the upregulation of MMP1 in AF. Differences in the expression of BMP2, ESR1 and THBS1 may explain for the pathological differences between AF and NP. IL6 may have a key role in different degeneration processes in AF and NP.

摘要

椎间盘(IVD)退变是一个与下背痛相关的多因素生理过程,IVD由纤维环(AF)和髓核(NP)组成。尽管经过数十年研究,但对IVD退变(IDD)潜在分子机制的了解仍然有限。本研究旨在揭示IDD过程中AF和NP的差异基因表达模式,并确定导致这些差异的关键生物标志物。从基因表达综合数据库中检索了包含24个AF样本和24个NP样本的微阵列数据集GSE70362。其中,8个健康样本被剔除。使用GeneSpring11.5软件鉴定差异表达基因(DEG)。利用Metascape在线工具进行富集分析。最后,将DEG与检索相互作用基因的搜索工具进行映射,并在Cytoscape软件中构建蛋白质-蛋白质相互作用(PPI)网络。共鉴定出87个DEG。基因本体富集显示,这些DEG主要参与炎症反应、细胞外基质和RNA聚合酶II转录因子活性。通路富集显示,DEG主要参与转化生长因子(TGF-β)和雌激素信号通路。基质金属蛋白酶(MMP)1和白细胞介素(IL)6包含在类风湿性关节炎富集的基因中,而骨形态发生蛋白(BMP)2和血小板反应蛋白1(THBS1)属于TGF-β信号通路富集的基因。在PPI网络中,IL6被确定为中心基因。总之,由于已证明MMP1降解III型胶原的速率高于其他类型的胶原(III型胶原在AF中的含量高于NP),胶原类型可能存在不同的分布模式,这可能导致AF中MMP1的上调。BMP2、ESR1和THBS1表达的差异可能解释了AF和NP之间的病理差异。IL6可能在AF和NP的不同退变过程中起关键作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a90e/6257805/e3a6e200814a/etm-16-06-5031-g00.jpg

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