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pmid:39906135

Identification and Validation of Pivotal Genes in Osteoarthritis Combined with WGCNA Analysis.

Chengzhuo Yang · Xinhua Chen · Jin Liu · Wenhao Wang · Lihua Sun · Youhong Xie · Qing Chang

Journal of inflammation research · 2025 doi:10.2147/JIR.S504717

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complete

Experiment

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Data

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Execution

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title
Identification and Validation of Pivotal Genes in Osteoarthritis Combined with WGCNA Analysis.
doi
10.2147/JIR.S504717
pmid
39906135
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Chengzhuo Yang
[1]
Xinhua Chen
[2]
Jin Liu
[3]
Wenhao Wang
[4]
Lihua Sun
[5]
Youhong Xie
[6]
Qing Chang
journal
Journal of inflammation research
year
2025
abstract
Introduction: The prevalence of osteoarthritis (OA), the most common chronic joint condition, is increasing due to the aging population and escalating obesity rates, leading to a significant impact on human health and well-being. Thus, analyzing the key targets of OA through bioinformatics can help discover new biomarkers to improve its diagnosis. Methods: The microarray and RNA-seq results were screened from the Gene Expression Omnibus (GEO) database. Functional enrichment analyses, protein-protein interaction (PPI) analysis, and weighted gene co-expression network analysis (WGCNA) of the DEGs were performed. RT-qPCR and WB were further performed to verify the hub gene expression in OA rat. Results: In this study, 35 key genes were identified through differential expression analysis and weighted gene co-expression network analysis (WGCNA) using the GSE169077 and GSE114007 datasets. Enrichment analysis revealed that these key genes were predominantly enriched in the HIF-1 signaling pathway, ECM-receptor interaction, and FoxO signaling pathway. Through the integration of protein-protein interaction (PPI) analysis, validation in animal models and ROC curve analysis, four pivotal genes (GADD45B, CLDN5, HILPDA and CDKN1B) were finally identified. Conclusion: In conclusion, these identified key genes could serve as novel targets for predicting and treating OA, offering fresh insights into its etiology and pathogenesis.
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Through the integration of protein-protein interaction (PPI) analysis, validation in animal models and ROC curve analysis, four pivotal genes (GADD45B, CLDN5, HILPDA and CDKN1B) were finally identified.
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ing), Scale bar = 50 µm (SO/FG staining).(C) RT-qPCR for the levels of the hub genes in rat OA mo
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Thus, analyzing the key targets of OA through bioinformatics can help discover new biomarkers to improve its diagnosis.\nMethods: The microarray and RNA-seq results were screened from the Gene Expression Omnibus (GEO) database. Functional enrichment analyses, protein-protein interaction (PPI) analysis, and weighted gene co-expression network analysis (WGCNA) of the DEGs were performed. RT-qPCR and WB were further performed to verify the hub gene expression in OA rat.\nResults: In this study, 35 key genes were identified through differential expression analysis and weighted gene co-expression network analysis (WGCNA) using the GSE169077 and GSE114007 datasets. Enrichment analysis revealed that these key genes were predominantly enriched in the HIF-1 signaling pathway, ECM-receptor interaction, and FoxO signaling pathway. Through the integration of protein-protein interaction (PPI) analysis, validation in animal models and ROC curve analysis, four pivotal genes (GADD45B, CLDN5, HILPDA and CDKN1B) were finally identified.\nConclusion: In conclusion, these identified key genes could serve as novel targets for predicting and treating OA, offering fresh insights into its etiology and pathogenesis.", "claims": [{"id": "claim-method", "statement": "Differentially expressed genes (DEGs) was performed using limma software package of R software.15", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39906135", "locator": "sections[4] \"Differentially Expressed Genes (DEGs) Analysis\" paragraph 2", "quote": "Differentially expressed genes (DEGs) was performed using limma software package of R software.15"}], "state": "complete"}, {"id": "claim-data-access", "statement": "Raw data from the GSE169077 and GSE114007 datasets were downloaded. 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The GSE169077 dataset comprised 5 normal and 6 OA pool samples, with each pool containing 5 individual samples.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "Raw data from the GSE169077 and GSE114007 datasets were downloaded. The GSE169077 dataset comprised 5 normal and 6 OA pool samples, with each pool containing 5 individual samples.", "access_statement_kind": "repository_route_statement", "sample_accessions": ["GSM3130531", "GSM3130532", "GSM3130533", "GSM3130534", "GSM3130535", "GSM3130536", "GSM3130537", "GSM3130538", "GSM3130539", "GSM3130540", "GSM3130541", "GSM3130542", "GSM3130543", "GSM3130544", "GSM3130545", "GSM3130546", "GSM3130547", "GSM3130548", "GSM3130549", "GSM3130550", "GSM3130551", "GSM3130552", "GSM3130553", "GSM3130554", "GSM3130555", "GSM3130556", "GSM3130557", "GSM3130558", "GSM3130559", "GSM3130560", "GSM3130561", "GSM3130562", "GSM3130563", "GSM3130564", "GSM3130565", "GSM3130566", "GSM3130567", "GSM3130568"], "sample_count": 38, "group_sizes": null, "group_sizes_basis": null, "platform": "11154;18573", "taxon": "Homo sapiens", "title": "Identification of transcription factors responsible for dysregulated networks in human osteoarthritis cartilage by global gene expression analysis", "resolution_checked_at": "2026-11-01T15:39:54Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE169077", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE169077", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE169077", "version": null, "note": "Raw data from the GSE169077 and GSE114007 datasets were downloaded. The GSE169077 dataset comprised 5 normal and 6 OA pool samples, with each pool containing 5 individual samples.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "Raw data from the GSE169077 and GSE114007 datasets were downloaded. 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Methods: The microarray and RNA-seq results were screened from the G"], "order_basis": "paper_text_order:413", "id": "assay:1"}, {"role": "data_generation", "definition_id": "rna_seq", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["e its diagnosis. Methods: The microarray and RNA-seq results were screened from the Gene Expressi"], "order_basis": "paper_text_order:428", "id": "assay:2"}, {"role": "data_generation", "definition_id": "qpcr", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["analysis (WGCNA) of the DEGs were performed. RT-qPCR and WB were further performed to verify the", "lysis (WGCNA) of the DEGs were performed. RT-qPCR and WB were further performed to verify the", "ing), Scale bar = 50 µm (SO/FG staining).(C) RT-qPCR for the levels of the hub genes in rat OA mo", "), Scale bar = 50 µm (SO/FG staining).(C) RT-qPCR for the levels of the hub genes in rat OA mo"], "order_basis": "paper_text_order:668", "id": "assay:3"}, {"role": "data_generation", "definition_id": "animal_model", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["rmed to verify the hub gene expression in OA rat. Results: In this study, 35 key genes were i", "7, three days after the end of modeling, the rats were sacrificed, the synovium and cartilage of th", "of OA, we successfully established OA models in rats (Figure 6A and B). The histopathological res", "ents Pathogen-free adult male Sprague–Dawley rats (8 weeks old, weighing 280–300 g) were obtai"], "order_basis": "paper_text_order:746", "id": "assay:4"}, {"role": "data_generation", "definition_id": "western_blot", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["CLDN5, HILPDA, and CDKN1B in OA rat model by Western blotting (Figure 6E). Figure 6Validation of the expre", "rve analysis. AUC, area under the curve. (E) Western blotting and semi-quantitative analysis of protein, n"], "order_basis": "paper_text_order:6633", "id": "assay:5"}, {"role": "analysis", "definition_id": "differential_expression", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["Differentially expressed genes (DEGs) was performed using limma software package of R software.15"], "order_basis": "consumes_earlier_output", "id": "assay:6"}]}