Comprehensive Analysis of Key Genes, Signaling Pathways and miRNAs in Human Knee Osteoarthritis: Based on Bioinformatics
Background: Osteoarthritis (OA) is one of the main causes of disability in the elderly population, accompanied by a series of underlying pathologic changes, such as cartilage degradation, synovitis, subchondral bone sclerosis, and meniscus injury. The present study aimed to identify key genes, signa...
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Frontiers Media S.A.
2021-08-01
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Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2021.730587/full |
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Article |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Liang Chang Liang Chang Hao Yao Hao Yao Zhi Yao Zhi Yao Kevin Ki-Wai Ho Michael Tim-Yun Ong Bingyang Dai Wenxue Tong Jiankun Xu Jiankun Xu Ling Qin Ling Qin |
spellingShingle |
Liang Chang Liang Chang Hao Yao Hao Yao Zhi Yao Zhi Yao Kevin Ki-Wai Ho Michael Tim-Yun Ong Bingyang Dai Wenxue Tong Jiankun Xu Jiankun Xu Ling Qin Ling Qin Comprehensive Analysis of Key Genes, Signaling Pathways and miRNAs in Human Knee Osteoarthritis: Based on Bioinformatics Frontiers in Pharmacology osteoarthiritis overlapping genes signaling pathways miRNAs bioinformatics |
author_facet |
Liang Chang Liang Chang Hao Yao Hao Yao Zhi Yao Zhi Yao Kevin Ki-Wai Ho Michael Tim-Yun Ong Bingyang Dai Wenxue Tong Jiankun Xu Jiankun Xu Ling Qin Ling Qin |
author_sort |
Liang Chang |
title |
Comprehensive Analysis of Key Genes, Signaling Pathways and miRNAs in Human Knee Osteoarthritis: Based on Bioinformatics |
title_short |
Comprehensive Analysis of Key Genes, Signaling Pathways and miRNAs in Human Knee Osteoarthritis: Based on Bioinformatics |
title_full |
Comprehensive Analysis of Key Genes, Signaling Pathways and miRNAs in Human Knee Osteoarthritis: Based on Bioinformatics |
title_fullStr |
Comprehensive Analysis of Key Genes, Signaling Pathways and miRNAs in Human Knee Osteoarthritis: Based on Bioinformatics |
title_full_unstemmed |
Comprehensive Analysis of Key Genes, Signaling Pathways and miRNAs in Human Knee Osteoarthritis: Based on Bioinformatics |
title_sort |
comprehensive analysis of key genes, signaling pathways and mirnas in human knee osteoarthritis: based on bioinformatics |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Pharmacology |
issn |
1663-9812 |
publishDate |
2021-08-01 |
description |
Background: Osteoarthritis (OA) is one of the main causes of disability in the elderly population, accompanied by a series of underlying pathologic changes, such as cartilage degradation, synovitis, subchondral bone sclerosis, and meniscus injury. The present study aimed to identify key genes, signaling pathways, and miRNAs in knee OA associated with the entire joint components, and to explain the potential mechanisms using computational analysis.Methods: The differentially expressed genes (DEGs) in cartilage, synovium, subchondral bone, and meniscus were identified using the Gene Expression Omnibus 2R (GEO2R) analysis based on dataset from GSE43923, GSE12021, GSE98918, and GSE51588, respectively and visualized in Volcano Plot. Venn diagram analyses were performed to identify the overlapping DEGs (overlapping DEGs) that expressed in at least two types of tissues mentioned above. Gene Ontology (GO) enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, protein-protein interaction (PPI) analysis, and module analysis were conducted. Furthermore, qRT-PCR was performed to validate above results using our clinical specimens.Results: As a result, a total of 236 overlapping DEGs were identified, of which 160 were upregulated and 76 were downregulated. Through enrichment analysis and constructing the PPI network and miRNA-mRNA network, knee OA-related key genes, such as HEY1, AHR, VEGFA, MYC, and CXCL12 were identified. Clinical validation by qRT-PCR experiments further supported above computational results. In addition, knee OA-related key miRNAs such as miR-101, miR-181a, miR-29, miR-9, and miR-221, and pathways such as Wnt signaling, HIF-1 signaling, PI3K-Akt signaling, and axon guidance pathways were also identified. Among above identified knee OA-related key genes, pathways and miRNAs, genes such as AHR, HEY1, MYC, GAP43, and PTN, pathways like axon guidance, and miRNAs such as miR-17, miR-21, miR-155, miR-185, and miR-1 are lack of research and worthy for future investigation.Conclusion: The present informatic study for the first time provides insight to the potential therapeutic targets of knee OA by comprehensively analyzing the overlapping genes differentially expressed in multiple joint components and their relevant signaling pathways and interactive miRNAs. |
topic |
osteoarthiritis overlapping genes signaling pathways miRNAs bioinformatics |
url |
https://www.frontiersin.org/articles/10.3389/fphar.2021.730587/full |
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doaj-d932a4e9943840f3ba467b3c33ba4b3b2021-08-23T06:43:21ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122021-08-011210.3389/fphar.2021.730587730587Comprehensive Analysis of Key Genes, Signaling Pathways and miRNAs in Human Knee Osteoarthritis: Based on BioinformaticsLiang Chang0Liang Chang1Hao Yao2Hao Yao3Zhi Yao4Zhi Yao5Kevin Ki-Wai Ho6Michael Tim-Yun Ong7Bingyang Dai8Wenxue Tong9Jiankun Xu10Jiankun Xu11Ling Qin12Ling Qin13Musculoskeletal Research Laboratory, Department of Orthopedics and Traumatology, The Chinese University of Hong Kong, Hong Kong, Hong Kong, SAR ChinaInnovative Orthopaedic Biomaterial and Drug Translational Research Laboratory, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, Hong Kong, SAR ChinaMusculoskeletal Research Laboratory, Department of Orthopedics and Traumatology, The Chinese University of Hong Kong, Hong Kong, Hong Kong, SAR ChinaInnovative Orthopaedic Biomaterial and Drug Translational Research Laboratory, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, Hong Kong, SAR ChinaMusculoskeletal Research Laboratory, Department of Orthopedics and Traumatology, The Chinese University of Hong Kong, Hong Kong, Hong Kong, SAR ChinaInnovative Orthopaedic Biomaterial and Drug Translational Research Laboratory, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, Hong Kong, SAR ChinaMusculoskeletal Research Laboratory, Department of Orthopedics and Traumatology, The Chinese University of Hong Kong, Hong Kong, Hong Kong, SAR ChinaMusculoskeletal Research Laboratory, Department of Orthopedics and Traumatology, The Chinese University of Hong Kong, Hong Kong, Hong Kong, SAR ChinaMusculoskeletal Research Laboratory, Department of Orthopedics and Traumatology, The Chinese University of Hong Kong, Hong Kong, Hong Kong, SAR ChinaMusculoskeletal Research Laboratory, Department of Orthopedics and Traumatology, The Chinese University of Hong Kong, Hong Kong, Hong Kong, SAR ChinaMusculoskeletal Research Laboratory, Department of Orthopedics and Traumatology, The Chinese University of Hong Kong, Hong Kong, Hong Kong, SAR ChinaInnovative Orthopaedic Biomaterial and Drug Translational Research Laboratory, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, Hong Kong, SAR ChinaMusculoskeletal Research Laboratory, Department of Orthopedics and Traumatology, The Chinese University of Hong Kong, Hong Kong, Hong Kong, SAR ChinaInnovative Orthopaedic Biomaterial and Drug Translational Research Laboratory, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, Hong Kong, SAR ChinaBackground: Osteoarthritis (OA) is one of the main causes of disability in the elderly population, accompanied by a series of underlying pathologic changes, such as cartilage degradation, synovitis, subchondral bone sclerosis, and meniscus injury. The present study aimed to identify key genes, signaling pathways, and miRNAs in knee OA associated with the entire joint components, and to explain the potential mechanisms using computational analysis.Methods: The differentially expressed genes (DEGs) in cartilage, synovium, subchondral bone, and meniscus were identified using the Gene Expression Omnibus 2R (GEO2R) analysis based on dataset from GSE43923, GSE12021, GSE98918, and GSE51588, respectively and visualized in Volcano Plot. Venn diagram analyses were performed to identify the overlapping DEGs (overlapping DEGs) that expressed in at least two types of tissues mentioned above. Gene Ontology (GO) enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, protein-protein interaction (PPI) analysis, and module analysis were conducted. Furthermore, qRT-PCR was performed to validate above results using our clinical specimens.Results: As a result, a total of 236 overlapping DEGs were identified, of which 160 were upregulated and 76 were downregulated. Through enrichment analysis and constructing the PPI network and miRNA-mRNA network, knee OA-related key genes, such as HEY1, AHR, VEGFA, MYC, and CXCL12 were identified. Clinical validation by qRT-PCR experiments further supported above computational results. In addition, knee OA-related key miRNAs such as miR-101, miR-181a, miR-29, miR-9, and miR-221, and pathways such as Wnt signaling, HIF-1 signaling, PI3K-Akt signaling, and axon guidance pathways were also identified. Among above identified knee OA-related key genes, pathways and miRNAs, genes such as AHR, HEY1, MYC, GAP43, and PTN, pathways like axon guidance, and miRNAs such as miR-17, miR-21, miR-155, miR-185, and miR-1 are lack of research and worthy for future investigation.Conclusion: The present informatic study for the first time provides insight to the potential therapeutic targets of knee OA by comprehensively analyzing the overlapping genes differentially expressed in multiple joint components and their relevant signaling pathways and interactive miRNAs.https://www.frontiersin.org/articles/10.3389/fphar.2021.730587/fullosteoarthiritisoverlapping genessignaling pathwaysmiRNAsbioinformatics |