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pmid:37303521
Unearths IFNB1 immune infiltrates in SOP-related ossification of ligamentum flavum pathogenesis.
You Zhang · Hongwei Huang · Honglin Chen · Peng Zhang · Yu Liu · Yanchi Gan · Xianwei Yan · Bin Xie · Hao Liu · Bowen He · Jingjing Tang · Gengyang Shen · Xiaobing Jiang · Hui Ren
Heliyon · 2023 doi:10.1016/j.heliyon.2023.e16722
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Complete file
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Growing evidences show a correlation between senile osteoporosis (SOP) and OLF, but the fundamental relationship between SOP and OLF remains unclear. Therefore, the purpose of this work is to investigate unique SOP-related genes and their potential functions in OLF.\nMethods: Gene Expression Omnibus (GEO) database was utilized to gather the mRNA expression data (GSE106253) and then analyzed by R software. A variety of methods, including ssGSEA, machine learning (LASSO and SVM-RFE), GO and KEGG enrichment, PPI network, transcription factor enrichment analysis (TFEA), GSEA and xCells were employed to verified the critical genes and signaling pathways. Furthermore, ligamentum flavum cells were cultured and used in vitro to identify the expression of the core genes.\nResults: The preliminary identification of 236 SODEGs revealed their involvement in BP pathways associated with ossification, inflammation, and immune response, including the TNF signaling pathway, PI3K/AKT signaling pathway and osteoclast differentiation. Four down-regulated genes (SERPINE1, SOCS3, AKT1, CCL2) and one up-regulated gene (IFNB1) were among the five hub SODEGs that were validated. Additionally, they were performed by ssGSEA and xCell to show the relationship of immune cells infiltrating in OLF. The most fundamental gene, IFNB1, which was only found in the classical ossification- and inflammation-related pathways, suggested that it may affect OLF via regulating the inflammatory response. In vitro experiment, we found that IFNB1 expression was dramatically higher in cells cocultured with osteogenic induction than in controls.\nConclusion: As far as we are concerned, this is the first observation using transcriptome data mining to reveal distinct SOP-related gene profiles between OLF and normal controls. Five hub SODEGs were ultimately found using bioinformatics algorithms and experimental verification. These genes may mediate intricate inflammatory/immune responses or signaling pathways in the pathogenesis of OLF, according to the thorough functional annotations. Since IFNB1 was discovered to be a key gene and was connected to numerous immune infiltrates in OLF, it is possible that IFNB1 expression has a substantial impact on the pathogenesis of OLF. Our research will give rise to new possibilities for potential therapeutics that target SOP reverent genes and immune-associated pathways in OLF.", "claims": [{"id": "claim-method", "statement": "The raw data was utilized to perform data normalization by R software.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37303521", "locator": "sections[4] \"Identification of SOP-related DEGs in OLF\" paragraph 2", "quote": "The raw data was utilized to perform data normalization by R software."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Data associated with this study has been deposited at NCBI; GSE106253.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37303521", "locator": "sections[24] \"Data availability statement\" paragraph 2", "quote": "Data associated with this study has been deposited at NCBI; GSE106253."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The preliminary identification of 236 SODEGs revealed their involvement in BP pathways associated with ossification, inflammation, and immune response, including the TNF signaling pathway, PI3K/AKT signaling pathway and osteoclast differentiation.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:37303521", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "The preliminary identification of 236 SODEGs revealed their involvement in BP pathways associated with ossification, inflammation, and immune response, including the TNF signaling pathway, PI3K/AKT signaling pathway and osteoclast differentiation."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The preliminary identification of 236 SODEGs revealed their involvement in BP pathways associated with ossification, inflammation, and immune response, including the TNF signaling pathway, PI3K/AKT signaling pathway and osteoclast differentiation.", "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:37303521"], "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. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE106253"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE106253"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:37303521", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1016/j.heliyon.2023.e16722", "sha256": "sha256:d84bdb6f849db5f1e4946e5deee55ac3799e5943ae74af00b0dfc44aa097ab8b", "bytes": 56115, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1016/j.heliyon.2023.e16722", "version": null, "note": "Full article fetched from PMC; 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