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© 2020 Cai et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. For attribution, the original author(s), title, publication source (PeerJ) and either DOI or URL of the article must be cited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

Background

Osteoarthritis (OA) is the most common chronic degenerative joint disease and is mainly characterized by cartilage degeneration, subcartilage bone hyperplasia, osteophyte formation and joint space stenosis. Recent studies showed that synovitis might also be an important pathological change of OA. However, the molecular mechanisms of synovitis in OA are still not well understood.

Objective

This study was designed to identify key biomarkers and immune infiltration in the synovial tissue of osteoarthritis by bioinformatics analysis.

Materials and Methods

The gene expression profiles of GSE12021, GSE55235 and GSE55457 were downloaded from the GEO database. The differentially expressed genes (DEGs) were identified by the LIMMA package in Bioconductor, and functional enrichment analyses were performed. A protein-protein interaction network (PPI) was constructed, and module analysis was performed using STRING and Cytoscape. The CIBERSORT algorithm was used to analyze the immune infiltration of synovial tissue between OA and normal controls.

Results

A total of 106 differentially expressed genes, including 68 downregulated genes and 38 upregulated genes, were detected. The PPI network was assessed, and the most significant module containing 14 hub genes was identified. Gene Ontology analysis revealed that the hub genes were significantly enriched in immune cell chemotaxis and cytokine activity. KEGG pathway analysis showed that the hub genes were significantly enriched in the rheumatoid arthritis signaling pathway, IL-17 signaling pathway and cytokine-cytokine receptor interaction signaling pathway. The immune infiltration profiles varied significantly between osteoarthritis and normal controls. Compared with normal tissue, OA synovial tissue contained a higher proportion of memory B cells, naive CD4+ T cells, regulatory T cells, resting dendritic cells and resting mast cells, while naive CD4+ T cells, activated NK cells, activated mast cells and eosinophils contributed to a relatively lower portion (P > 0.05). Finally, the expression levels of 11 hub genes were confirmed by RT-PCR.

Conclusion

The hub genes and the difference in immune infiltration in synovial tissue between osteoarthritis and normal controls might provide new insight for understanding OA development.

Details

Title
Identification of key biomarkers and immune infiltration in the synovial tissue of osteoarthritis by bioinformatics analysis
Author
Cai, Weisong; Li, Haohuan; Zhang, Yubiao; Han, Guangtao
Publication year
2020
Publication date
Jan 17, 2020
Publisher
PeerJ, Inc.
e-ISSN
21678359
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2340158627
Copyright
© 2020 Cai et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. For attribution, the original author(s), title, publication source (PeerJ) and either DOI or URL of the article must be cited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.