Unveiling the bioinformatic genes and their involved regulatory mechanisms in type 2 diabetes combined with osteoarthritis.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:39176085", "kind": "science-record", "revision": 3, "content_hash": "sha256:68aa6f0761c410d18f6d4fcf433ac8e1a29d8d12c606d7947c01890f9318b7ce", "created_at": "2026-11-01T20:29:18Z", "updated_at": "2026-11-01T22:12:32Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Unveiling the bioinformatic genes and their involved regulatory mechanisms in type 2 diabetes combined with osteoarthritis.", "doi": "10.3389/fimmu.2024.1353915", "pmid": "39176085", "authors": ["Guangming Mao", "Wenhao Xu", "Lingli Wan", "Hongpin Wang", "Shutao Xu", "Liangming Zhang", "Shiyang Li", "Jifa Zhang", "Zhongming Lai", "Yuping Lan", "Jianhui Liu"], "journal": "Frontiers in immunology", "year": 2024, "abstract": "Background: Type 2 Diabetes Mellitus (T2D) and Osteoarthritis (OA) are both prevalent diseases that significantly impact the health of patients. Increasing evidence suggests that there is a big correlation between T2D and OA, but the molecular mechanisms remain elusive. The aims of this study are to investigate the shared biomarkers and potential molecular mechanisms in T2D combined with OA.\nMethods: T2D and OA-related differentially expressed genes (DEGs) were identified via bioinformatic analysis on Gene Expression Omnibus (GEO) datasets GSE26168 and GSE114007 respectively. Subsequently, extensive target prediction and network analysis were finished with Gene Ontology (GO), protein-protein interaction (PPI), and pathway enrichment with DEGs. The transcription factors (TFs) and miRNAs coupled in co-expressed DEGs involved in T2D and OA were predicted as well. The key genes expressed both in the clinical tissues of T2D and OA were detected with western blot and qRT-PCR assay. Finally, the most promising candidate compounds were predicted with the Drug-Gene Interaction Database (DGIdb) and molecular docking.\nResults: In this study, 209 shared DEGs between T2D and OA were identified. Functional analysis disclosed that these DEGs are predominantly related to ossification, regulation of leukocyte migration, extracellular matrix (ECM) structural constituents, PI3K/AKT, and Wnt signaling pathways. Further analysis via Protein-Protein Interaction (PPI) analysis and validation with external datasets emphasized MMP9 and ANGPTL4 as crucial genes in both T2D and OA. Our findings were validated through qRT-PCR and Western blot analyses, which indicated high expression levels of these pivotal genes in T2D, OA, and T2D combined with OA cases. Additionally, the analysis of Transcription Factors (TFs)-miRNA interactions identified 7 TFs and one miRNA that jointly regulate these important genes. The Receiver Operating characteristic (ROC) analysis demonstrated the significant diagnostic potential of MMP9 and ANGPTL4.Moreover, we identified raloxifene, ezetimibe, and S-3304 as promising agents for patients with both T2D and OA.\nConclusion: This study uncovers the shared signaling pathways, biomarkers, potential therapeutics, and diagnostic models for individuals suffering from both T2D and OA. These findings not only present novel perspectives on the complex interplay between T2D and OA but also hold significant promise for improving the clinical management and prognosis of patients with this concurrent condition.", "claims": [{"id": "claim-method", "statement": "Employing RStudio software (version 4.2.1), we used the pROC package to generate Receiver Operating Characteristic (ROC) curves. Additionally, logistic regression analysis was conducted to evaluate the role of key genes in distinguishing between T2D, OA, and healthy individuals.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39176085", "locator": "sections[10] \"Diagnostic value of key genes\" paragraph 2", "quote": "Employing RStudio software (version 4.2.1), we used the pROC package to generate Receiver Operating Characteristic (ROC) curves. Additionally, logistic regression analysis was conducted to evaluate the role of key genes in distinguishing between T2D, OA, and healthy individuals."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The original contributions presented in the study are included in the article/ Supplementary Material . Further inquiries can be directed to the corresponding authors.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39176085", "locator": "sections[27] \"Data availability statement\" paragraph 2", "quote": "The original contributions presented in the study are included in the article/ Supplementary Material . Further inquiries can be directed to the corresponding authors."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The ANGPTL4-and-MMP9 multi-marker diagnostic model achieved an AUC of 0.980 for T2D and 0.855 for OA.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:39176085", "locator": "sections[22] \"Evaluation of key genes in T2D and OA\" paragraph 2", "quote": "The ROC results demonstrated that this multi-marker model effectively predicted the diagnosis of T2D (AUC = 0.980) and OA (AUC = 0.855) ( Figures 6C, F ), highlighting its potential clinical utility."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The ANGPTL4-and-MMP9 multi-marker diagnostic model achieved an AUC of 0.980 for T2D and 0.855 for OA.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:39176085"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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Finally, the most promisi", "findings were validated through qRT-PCR and Western blot analyses, which indicated high expression le", "sue samples of NC, T2D, OA and T2D+OA. (C–E) Western blot was used to determine the protein expression", ". 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