scholarly journals Identification of Key Modules and Hub Genes of Annulus Fibrosus in Intervertebral Disc Degeneration

2021 ◽  
Vol 11 ◽  
Author(s):  
Hantao Wang ◽  
Wenhui Liu ◽  
Bo Yu ◽  
Xiaosheng Yu ◽  
Bin Chen

Background: Intervertebral disc degeneration impairs the quality of patients lives. Even though there has been development of many therapeutic strategies, most of them remain unsatisfactory due to the limited understanding of the mechanisms that underlie the intervertebral disc degeneration.Questions/purposes: This study is meant to identify the key modules and hub genes related to the annulus fibrosus in intervertebral disc degeneration (IDD) through: (1) constructing a weighted gene co-expression network; (2) identifying key modules and hub genes; (3) verifying the relationships of key modules and hub genes with IDD; and (4) confirming the expression pattern of hub genes in clinical samples.Methods: The Gene Expression Omnibus provided 24 sets of annulus fibrosus microarray data. Differentially expressed genes between the annulus fibrosus of degenerative and non-degenerative intervertebral disc samples have gone through the Gene Ontology (GO) and pathway analysis. The construction of a gene network and classification of genes into different modules were conducted through performing Weighted Gene Co-expression Network Analysis. The identification of modules and hub genes that were most related to intervertebral disc degeneration was proceeded. In order to verify the relationships of the module and hub genes with intervertebral disc degeneration, Ingenuity Pathway Analysis was operated. Clinical samples were adopted to help verify the hub gene expression profile.Results: One thousand one hundred ninety differentially expressed genes were identified. Terms and pathways associated with intervertebral disc degeneration were presented by GO and pathway analysis. The construction of a Weighted Gene Coexpression Network was completed and clustering differentially expressed genes into four modules was also achieved. The module with the lowest P-value and the highest absolute correlation coefficient was selected and its relationship with intervertebral disc degeneration was confirmed by Ingenuity Pathway Analysis. The identification of hub genes and the confirmation of their expression profile were also realized.Conclusions: This study generated a comprehensive overview of the gene networks underlying annulus fibrosus in intervertebral disc degeneration.Clinical Relevance: Modules and hub genes identified in this study are highly associated with intervertebral disc degeneration, and may serve as potential therapeutic targets for intervertebral disc degeneration.

2021 ◽  
Author(s):  
Ning Fan ◽  
Shuo Yuan ◽  
Yong Hai ◽  
Peng Du ◽  
Jian Li ◽  
...  

Abstract BackgroundInflammatory processes exacerbated by IL-1β are believed to be key mediators of disc degeneration and low back pain. However, the underlying mechanism remains unclear. We performed a bioinformatics analysis to identify the key genes that were differentially expressed between degenerative intervertebral disc cells with and without exposure to interleukin (IL)-1β, and explore the related signaling pathways and interaction networks.MethodsThe microarray data were downloaded from the Gene Expression Omnibus (GSE 27494). Then, analyses of the gene ontology, signaling pathways, and interaction networks for the differentially expressed genes (DEGs) were conducted using tools including the Database for Annotation, Visualization, and Integrated Discovery (DAVID), Metascape, Gene Set Enrichment Analysis (GSEA), Search Tool for the Retrieval of Interacting Genes (STRING), Cytoscape, the Venn method, and packages of the R computing language.ResultsA total of 260 DEGs were identified, including 161 upregulated genes and 99 down-regulated genes. Gene Ontology (GO) annotation analysis showed that these DEGs were mainly associated with the extracellular region, chemotaxis, taxis, cytokine activity, and cytokine receptor binding. A Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway analysis showed that these DEGs were mainly involved in the interactions of cytokine-cytokine receptor interaction, rheumatoid arthritis, tumor necrosis factor (TNF) signaling pathway, salmonella infection, and chemokine signaling pathway. The interaction network analysis indicated that 10 hub genes, including CXCL8, CXCL1, CCL20, CXCL2, CXCL5, CXCL3, CXCL6, C3, PF4, and GPER1 may play key roles in intervertebral disc degeneration.ConclusionsBioinformatic analysis showed that CXCL8 and other 9 key genes may play a role in the development of disc degeneration induced by inflammatory reactions, and can be used to identify the potential therapeutic target genes.


Author(s):  
John McMorran ◽  
Diane Gregory

Abstract In light of the correlation between chronic back pain and intervertebral disc degeneration, this literature review seeks to illustrate the importance of the hydraulic response across the nucleus pulposus- annulus fibrosus interface, by synthesizing current information regarding injurious biomechanics of the spine, stemming from axial compression. Damage to vertebrae, endplates, the nucleus pulposus, and the annulus fibrosus, can all arise from axial compression, depending on the segment's posture, the manner in which it is loaded, and the physiological state of tissue. Therefore, this movement pattern was selected to illustrate the importance of the bracing effect of a pressurized nucleus pulposus on the annulus fibrosus, and how injuries interrupting support to the annulus fibrosus may contribute to intervertebral disc degeneration.


2021 ◽  
Author(s):  
Li Guoquan ◽  
Du Junwei ◽  
He Qi ◽  
Fu Xinghao ◽  
Ji Feihong ◽  
...  

Abstract BackgroundHashimoto's thyroiditis (HT), also known as chronic lymphocytic thyroiditis, is a common autoimmune disease, which mainly occurs in women. The early manifestation was hyperthyroidism, however, hypothyroidism may occur if HT was not controlled for a long time. Numerous studies have shown that multiple factors, including genetic, environmental, and autoimmune factors, were involved in the pathogenesis of the disease, but the exact mechanisms were not yet clear. The aim of this study was to identify differentially expressed genes (DEGs) by comprehensive analysis and to provide specific insights into HT. MethodsTwo gene expression profiles (GSE6339, GSE138198) about HT were downloaded from the Gene Expression Omnibus (GEO) database. The DEGs were assessed between the HT and normal groups using the GEO2R. The DEGs were then sent to the Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. The hub genes were discovered using Cytoscape and CytoHubba. Finally, NetworkAnalyst was utilized to create the hub genes' targeted microRNAs (miRNAs). ResultsA total of 62 DEGs were discovered, including 60 up-regulated and 2 down-regulated DEGs. The signaling pathways were mainly engaged in cytokine interaction and cytotoxicity, and the DEGs were mostly enriched in immunological and inflammatory responses. IL2RA, CXCL9, IL10RA, CCL3, CCL4, CCL2, STAT1, CD4, CSF1R, and ITGAX were chosen as hub genes based on the results of the protein-protein interaction (PPI) network and CytoHubba. Five miRNAs, including mir-24-3p, mir-223-3p, mir-155-5p, mir-34a-5p, mir-26b-5p, and mir-6499-3p, were suggested as likely important miRNAs in HT. ConclusionsThese hub genes, pathways and miRNAs contribute to a better understanding of the pathophysiology of HT and offer potential treatment options for HT.


2019 ◽  
Vol 51 (6) ◽  
pp. 571-579 ◽  
Author(s):  
Shunmin Wang ◽  
Jingchuan Sun ◽  
Haisong Yang ◽  
Weiguo Zou ◽  
Bing Zheng ◽  
...  

AbstractThe functional changes of nucleus pulposus (NP) cells are considered to be the initiating factors of intervertebral disc degeneration (IDD), and the differentially expressed circRNAs in NP cells may play an important role in the process of IDD. To identify circular RNAs (circRNAs) associated with human IDD, we isolated the NP cells from human degenerated and non-degenerated intervertebral disc and identified NP cells by microscopy and cell proliferation. CircRNA microarray expression profiles were obtained from NP cells of degenerated and non-degenerated intervertebral disc and further validated by quantitative reverse transcription PCR (qRT-PCR). The expression data were analyzed by bioinformatics. Microarray analysis identified 7294 circRNAs differentially expressed in degenerated human IDD NP cells. Among them, 3724 circRNAs were up-regulated and 3570 circRNAs were down-regulated by more than 2 folds. After validating by qRT-PCR, we predicted the possible miRNAs of the top dysregulated circRNAs using TargetScan, and miRanda. Furthermore, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that the most modulated circRNAs regulate the viability, degradation, apoptosis and oxidative stress in NP cells, and the possible mechanism underlying IDD was discussed. These results revealed that circRNAs may play a role in IDD and might be a promising candidate molecular target for gene therapy.


2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Nan Liu ◽  
Yunyao Jiang ◽  
Min Xing ◽  
Baixiao Zhao ◽  
Jincai Hou ◽  
...  

Aging is closely connected with death, progressive physiological decline, and increased risk of diseases, such as cancer, arteriosclerosis, heart disease, hypertension, and neurodegenerative diseases. It is reported that moxibustion can treat more than 300 kinds of diseases including aging related problems and can improve immune function and physiological functions. The digital gene expression profiling of aged mice with or without moxibustion treatment was investigated and the mechanisms of moxibustion in aged mice were speculated by gene ontology and pathway analysis in the study. Almost 145 million raw reads were obtained by digital gene expression analysis and about 140 million (96.55%) were clean reads. Five differentially expressed genes with an adjusted P value < 0.05 and |log⁡2(fold  change)| > 1 were identified between the control and moxibustion groups. They were Gm6563, Gm8116, Rps26-ps1, Nat8f4, and Igkv3-12. Gene ontology analysis was carried out by the GOseq R package and functional annotations of the differentially expressed genes related to translation, mRNA export from nucleus, mRNA transport, nuclear body, acetyltransferase activity, and so on. Kyoto Encyclopedia of Genes and Genomes database was used for pathway analysis and ribosome was the most significantly enriched pathway term.


Sign in / Sign up

Export Citation Format

Share Document