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Identification of Key Candidate Genes Related to Inflammatory Osteolysis Associated with Vitamin E-Blended UHMWPE Debris of Orthopedic Implants by Integrated Bioinformatics Analysis and Experimental Confirmation
PURPOSE: This study aims to identify differentially expressed genes (DEGs) in macrophages exposed to ultra-high-molecular-weight polyethylene (UHMWPE) or vitamin E-blended UHMWPE (VE-UHMWPE) particles, thereby providing potential targets for the treatment of inflammatory osteolysis. METHODS: The GSE...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Dove
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8323865/ https://www.ncbi.nlm.nih.gov/pubmed/34345178 http://dx.doi.org/10.2147/JIR.S320839 |
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author | Liu, Fanxiao Dong, Jun Zhou, Dongsheng Zhang, Qingyu |
author_facet | Liu, Fanxiao Dong, Jun Zhou, Dongsheng Zhang, Qingyu |
author_sort | Liu, Fanxiao |
collection | PubMed |
description | PURPOSE: This study aims to identify differentially expressed genes (DEGs) in macrophages exposed to ultra-high-molecular-weight polyethylene (UHMWPE) or vitamin E-blended UHMWPE (VE-UHMWPE) particles, thereby providing potential targets for the treatment of inflammatory osteolysis. METHODS: The GSE104589 dataset of genome expression in macrophages exposed to UHMWPE and VE-UHMWPE was downloaded from the Gene Expression Omnibus database to identify DEGs. Functional enrichment analysis was performed using DAVID, and the corresponding protein–protein interaction (PPI) network was constructed from the STRING database. Important modules were selected using the molecular complex detection algorithm, and hub genes were identified in cytoHubba. MicroRNAs targeting these DEGs were obtained from the TarBase, miRTarBase, and miRecords databases, while transcription factors (TFs) targeting DEGs were predicted from the ENCODE database. Finally, the top five DEGs were validated by quantitative real‐time polymerase chain reaction (qRT-PCR). RESULTS: A total of 112 DEGs (44 upregulated and 68 downregulated DEGs) were screened. Immune and inflammatory responses were significantly related in gene ontology analysis, and 18 signaling pathways were enriched according to Kyoto Encyclopedia of Genes and Genomes pathway analysis. The PPI network involving 85 nodes and 266 protein pairs indicated that IL1β, CXCL1, ICAM1, CCL5 and CCL4 showed higher degrees. qRT-PCR analysis of the top five DEGs revealed a decreasing trend in the VE-UHMWPE group compared with the UHMWPE group. Key microRNAs (hsa-miR-144, hsa-miR-21, and hsa-miR-221) and TFs (RELA and NFKB1) were predicted to be correlated with the pathogenesis of inflammatory osteolysis through microRNA-TF regulatory network analysis. CONCLUSION: The present study helps shed light on the molecular mechanisms underlying the changes in the wear-induced inflammatory process after blending vitamin E with UHMWPE. Hub genes including IL1β, CXCL1, ICAM1, CCL5, and CCL4, key microRNAs (hsa-miR-144, hsa-miR-21, and hsa-miR-221) and TFs (RELA and NFKB1) may serve as prognostic and therapeutic targets of inflammatory osteolysis. |
format | Online Article Text |
id | pubmed-8323865 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Dove |
record_format | MEDLINE/PubMed |
spelling | pubmed-83238652021-08-02 Identification of Key Candidate Genes Related to Inflammatory Osteolysis Associated with Vitamin E-Blended UHMWPE Debris of Orthopedic Implants by Integrated Bioinformatics Analysis and Experimental Confirmation Liu, Fanxiao Dong, Jun Zhou, Dongsheng Zhang, Qingyu J Inflamm Res Original Research PURPOSE: This study aims to identify differentially expressed genes (DEGs) in macrophages exposed to ultra-high-molecular-weight polyethylene (UHMWPE) or vitamin E-blended UHMWPE (VE-UHMWPE) particles, thereby providing potential targets for the treatment of inflammatory osteolysis. METHODS: The GSE104589 dataset of genome expression in macrophages exposed to UHMWPE and VE-UHMWPE was downloaded from the Gene Expression Omnibus database to identify DEGs. Functional enrichment analysis was performed using DAVID, and the corresponding protein–protein interaction (PPI) network was constructed from the STRING database. Important modules were selected using the molecular complex detection algorithm, and hub genes were identified in cytoHubba. MicroRNAs targeting these DEGs were obtained from the TarBase, miRTarBase, and miRecords databases, while transcription factors (TFs) targeting DEGs were predicted from the ENCODE database. Finally, the top five DEGs were validated by quantitative real‐time polymerase chain reaction (qRT-PCR). RESULTS: A total of 112 DEGs (44 upregulated and 68 downregulated DEGs) were screened. Immune and inflammatory responses were significantly related in gene ontology analysis, and 18 signaling pathways were enriched according to Kyoto Encyclopedia of Genes and Genomes pathway analysis. The PPI network involving 85 nodes and 266 protein pairs indicated that IL1β, CXCL1, ICAM1, CCL5 and CCL4 showed higher degrees. qRT-PCR analysis of the top five DEGs revealed a decreasing trend in the VE-UHMWPE group compared with the UHMWPE group. Key microRNAs (hsa-miR-144, hsa-miR-21, and hsa-miR-221) and TFs (RELA and NFKB1) were predicted to be correlated with the pathogenesis of inflammatory osteolysis through microRNA-TF regulatory network analysis. CONCLUSION: The present study helps shed light on the molecular mechanisms underlying the changes in the wear-induced inflammatory process after blending vitamin E with UHMWPE. Hub genes including IL1β, CXCL1, ICAM1, CCL5, and CCL4, key microRNAs (hsa-miR-144, hsa-miR-21, and hsa-miR-221) and TFs (RELA and NFKB1) may serve as prognostic and therapeutic targets of inflammatory osteolysis. Dove 2021-07-26 /pmc/articles/PMC8323865/ /pubmed/34345178 http://dx.doi.org/10.2147/JIR.S320839 Text en © 2021 Liu et al. https://creativecommons.org/licenses/by-nc/3.0/This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/ (https://creativecommons.org/licenses/by-nc/3.0/) ). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). |
spellingShingle | Original Research Liu, Fanxiao Dong, Jun Zhou, Dongsheng Zhang, Qingyu Identification of Key Candidate Genes Related to Inflammatory Osteolysis Associated with Vitamin E-Blended UHMWPE Debris of Orthopedic Implants by Integrated Bioinformatics Analysis and Experimental Confirmation |
title | Identification of Key Candidate Genes Related to Inflammatory Osteolysis Associated with Vitamin E-Blended UHMWPE Debris of Orthopedic Implants by Integrated Bioinformatics Analysis and Experimental Confirmation |
title_full | Identification of Key Candidate Genes Related to Inflammatory Osteolysis Associated with Vitamin E-Blended UHMWPE Debris of Orthopedic Implants by Integrated Bioinformatics Analysis and Experimental Confirmation |
title_fullStr | Identification of Key Candidate Genes Related to Inflammatory Osteolysis Associated with Vitamin E-Blended UHMWPE Debris of Orthopedic Implants by Integrated Bioinformatics Analysis and Experimental Confirmation |
title_full_unstemmed | Identification of Key Candidate Genes Related to Inflammatory Osteolysis Associated with Vitamin E-Blended UHMWPE Debris of Orthopedic Implants by Integrated Bioinformatics Analysis and Experimental Confirmation |
title_short | Identification of Key Candidate Genes Related to Inflammatory Osteolysis Associated with Vitamin E-Blended UHMWPE Debris of Orthopedic Implants by Integrated Bioinformatics Analysis and Experimental Confirmation |
title_sort | identification of key candidate genes related to inflammatory osteolysis associated with vitamin e-blended uhmwpe debris of orthopedic implants by integrated bioinformatics analysis and experimental confirmation |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8323865/ https://www.ncbi.nlm.nih.gov/pubmed/34345178 http://dx.doi.org/10.2147/JIR.S320839 |
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