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pmid:38304574
Identification of novel potential drugs for the treatment and prevention of osteoarthritis.
Xiaosong Han · Fan Bai · Peng Li · Xiaojin Bai · Yanli Zhang · Wenmin Wang
Biochemistry and biophysics reports · 2024 doi:10.1016/j.bbrep.2024.101647
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Experiment
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Data
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Analysis
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Execution
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Complete file
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Despite the availability of standard therapies, they are associated with potential side effects and don't provide a complete cure for patients. Consequently, there is an urgent demand for the development of novel drugs.\nMethod: The gene expression profiles (GSE64394, GSE178557 and GSE215039) of normal and OA chondrocytes samples were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified by the \"LIMMA\" R package. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment were conducted using the R package clusterProfiler. A protein-protein (PPI) interaction network was performed to identify hub genes by using the Search Tool for the Retrieval of Interacting Genes (STRING) and Cytoscape. Small molecule compounds linked to OA were predicted through the NetworkAnalyst platform. Finally, molecular docking was conducted using AutoDock and Pymol software.\nResults: We identified 98 DEGs primarily implicated in endochondral ossification, extracellular matrix degradation, and Wnt signaling pathways. 23 DEGs were closely associated with OA, and 10 hub genes were found to be potential drug targets for OA. Two new targeted compounds, tetrachlorodibenzodioxin (TCDD) and valproic acid (VPA), were screened. And they both exhibited strong binding affinity to their respective targets.\nConclusions: Reducing exposure to TCDD could be a crucial strategy in preventing OA, and VPA has gained recognition as a novel drug candidate for OA treatment.", "claims": [{"id": "claim-method", "statement": "Differential analyses of the three datasets were used by the R package limma (version 4.3.0) to determine DEGs with the criteria of |log2(FC)| > 1 and adjusted p-value <0.05 [14].", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38304574", "locator": "sections[4] \"Identification of DEGs\" paragraph 2", "quote": "Differential analyses of the three datasets were used by the R package limma (version 4.3.0) to determine DEGs with the criteria of |log2(FC)| > 1 and adjusted p-value <0.05 [14]."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The raw data of the three datasets (accession numbers GSE64394, GSE178557 and GSE215039) were downloaded from the GEO repository (https://www.ncbi.nlm.nih.gov/geo/). 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All data are publicly accessible.\nData will be made available on request."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Using limma to analyze normal and OA chondrocyte expression profiles downloaded from GEO, the study identified 98 differentially expressed genes.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:38304574", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "The gene expression profiles (GSE64394, GSE178557 and GSE215039) of normal and OA chondrocytes samples were downloaded from the Gene Expression Omnibus (GEO) database."}, {"asset": "source:pmid:38304574", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "Differentially expressed genes (DEGs) were identified by the \"LIMMA\" R package."}, {"asset": "source:pmid:38304574", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "We identified 98 DEGs primarily implicated in endochondral ossification, extracellular matrix degradation, and Wnt signaling pathways."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Using limma to analyze normal and OA chondrocyte expression profiles downloaded from GEO, the study identified 98 differentially expressed genes.", "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:38304574"], "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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