Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Liu, Fanxiao, Dong, Jun, Zhou, Dongsheng, Zhang, Qingyu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove 2021
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
_version_ 1783731320171528192
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
work_keys_str_mv AT liufanxiao identificationofkeycandidategenesrelatedtoinflammatoryosteolysisassociatedwithvitamineblendeduhmwpedebrisoforthopedicimplantsbyintegratedbioinformaticsanalysisandexperimentalconfirmation
AT dongjun identificationofkeycandidategenesrelatedtoinflammatoryosteolysisassociatedwithvitamineblendeduhmwpedebrisoforthopedicimplantsbyintegratedbioinformaticsanalysisandexperimentalconfirmation
AT zhoudongsheng identificationofkeycandidategenesrelatedtoinflammatoryosteolysisassociatedwithvitamineblendeduhmwpedebrisoforthopedicimplantsbyintegratedbioinformaticsanalysisandexperimentalconfirmation
AT zhangqingyu identificationofkeycandidategenesrelatedtoinflammatoryosteolysisassociatedwithvitamineblendeduhmwpedebrisoforthopedicimplantsbyintegratedbioinformaticsanalysisandexperimentalconfirmation