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

Fanxiao Liu, Jun Dong, Dongsheng Zhou, Qingyu Zhang Department of Orthopaedics, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, People’s Republic of ChinaCorrespondence: Qingyu ZhangDepartment of Orthopaedics, Shandong Provincial Hospital Affi...

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Autores principales:	Liu F, Dong J, Zhou D, Zhang Q
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2021
Materias:	inflammatory osteolysis aseptic loosening bioinformatics analysis ve-uhmwpe macrophages Pathology RB1-214 Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/665e2f418fc0450fabe929cef17e25f9
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spelling	oai:doaj.org-article:665e2f418fc0450fabe929cef17e25f92021-12-02T18:05:21ZIdentification of Key Candidate Genes Related to Inflammatory Osteolysis Associated with Vitamin E-Blended UHMWPE Debris of Orthopedic Implants by Integrated Bioinformatics Analysis and Experimental Confirmation1178-7031https://doaj.org/article/665e2f418fc0450fabe929cef17e25f92021-07-01T00:00:00Zhttps://www.dovepress.com/identification-of-key-candidate-genes-related-to-inflammatory-osteolys-peer-reviewed-fulltext-article-JIRhttps://doaj.org/toc/1178-7031Fanxiao Liu, Jun Dong, Dongsheng Zhou, Qingyu Zhang Department of Orthopaedics, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, People’s Republic of ChinaCorrespondence: Qingyu ZhangDepartment of Orthopaedics, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, People’s Republic of ChinaTel/Fax +86-0531-68773201Email zqy2008512@126.comPurpose: 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.Keywords: inflammatory osteolysis, aseptic loosening, bioinformatics analysis, VE-UHMWPE, macrophagesLiu FDong JZhou DZhang QDove Medical Pressarticleinflammatory osteolysisaseptic looseningbioinformatics analysisve-uhmwpemacrophagesPathologyRB1-214Therapeutics. PharmacologyRM1-950ENJournal of Inflammation Research, Vol Volume 14, Pp 3537-3554 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	inflammatory osteolysis aseptic loosening bioinformatics analysis ve-uhmwpe macrophages Pathology RB1-214 Therapeutics. Pharmacology RM1-950
spellingShingle	inflammatory osteolysis aseptic loosening bioinformatics analysis ve-uhmwpe macrophages Pathology RB1-214 Therapeutics. Pharmacology RM1-950 Liu F Dong J Zhou D Zhang Q 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
description	Fanxiao Liu, Jun Dong, Dongsheng Zhou, Qingyu Zhang Department of Orthopaedics, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, People’s Republic of ChinaCorrespondence: Qingyu ZhangDepartment of Orthopaedics, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, People’s Republic of ChinaTel/Fax +86-0531-68773201Email zqy2008512@126.comPurpose: 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.Keywords: inflammatory osteolysis, aseptic loosening, bioinformatics analysis, VE-UHMWPE, macrophages
format	article
author	Liu F Dong J Zhou D Zhang Q
author_facet	Liu F Dong J Zhou D Zhang Q
author_sort	Liu F
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_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_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_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
publisher	Dove Medical Press
publishDate	2021
url	https://doaj.org/article/665e2f418fc0450fabe929cef17e25f9
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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

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