{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T17:59:49Z","timestamp":1790359189099,"version":"4.1.0"},"reference-count":33,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T00:00:00Z","timestamp":1786492800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Inflammatory bowel disease (IBD) and osteoporosis (OP) often co-occur, with IBD accelerating OP onset, though the underlying mechanisms remain unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Based on gene expression data from the GEO database, differential expression analysis was performed using the limma package to identify genes dysregulated in both IBD and OP. Weighted Gene Co-expression Network Analysis (WGCNA) was employed to explore the associations between genes and phenotypes. Candidate genes were obtained by intersecting differentially expressed genes with key WGCNA modules, followed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses. To further focus on apoptosis-related mechanisms, the candidate genes were intersected with an apoptosis-related gene set and refined using lasso regression. Core genes were identified through differential expression validation and receiver operating characteristic curve analysis. Subsequently, their potential functions and regulatory networks were explored via multidimensional analysis, gene set enrichment analysis, and Pearson correlation analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>WNT1 and S100A8 are closely associated with the progression of both inflammatory bowel disease and osteoporosis. Gene Set Enrichment Analysis revealed that WNT1 is primarily enriched in cell cycle checkpoint signaling, chromosome organization, neuroactive ligand signaling, and neuroactive ligand\u2013receptor interaction. In contrast, S100A8 is mainly enriched in adaptive immune response, adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily, inflammatory bowel disease, and leishmaniasis. Pearson correlation analysis showed that WNT1 is correlated with TSPAN32, POU3F3, NXPH3, EGFL7, LHX3, TNNI2, HMX1, FAM3A, IBTK, and ZNF747, while S100A8 is correlated with MMP3, SLC6A14, MMP10, S100A9, AQP9, S100A12, CXCL6, CXCR1, SLC38A4, and NCF2.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>WNT1 and S100A8, which are associated with apoptosis, play critical roles in both inflammatory bowel disease and osteoporosis, providing new potential therapeutic targets and a theoretical basis for clinical diagnosis and treatment.<\/jats:p>\n                  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Peery","year":"2019","journal-title":"Gastroenterology"},{"issue":"36","key":"pone.0356002.ref017","doi-asserted-by":"crossref","first-page":"6628","DOI":"10.3748\/wjg.v23.i36.6628","article-title":"Glucocorticosteroid therapy in inflammatory bowel diseases: from clinical practice to molecular biology","volume":"23","author":"K Dubois-Camacho","year":"2017","journal-title":"World J Gastroenterol"},{"issue":"7","key":"pone.0356002.ref018","doi-asserted-by":"crossref","first-page":"3613","DOI":"10.1210\/en.2005-0717","article-title":"Glucocorticoid regulation of osteoclast differentiation and expression of receptor activator of nuclear factor-kappaB (NF-kappaB) ligand, osteoprotegerin, and receptor activator of NF-kappaB in mouse calvarial bones","volume":"147","author":"C Swanson","year":"2006","journal-title":"Endocrinology"},{"issue":"10","key":"pone.0356002.ref019","doi-asserted-by":"crossref","first-page":"4382","DOI":"10.1210\/endo.140.10.7034","article-title":"Stimulation of 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Shen","year":"2022","journal-title":"Imeta"},{"key":"pone.0356002.ref025","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.steroids.2015.07.006","article-title":"Variance of spinal osteoporosis induced by dexamethasone and methylprednisolone and its associated mechanism","volume":"102","author":"H Ren","year":"2015","journal-title":"Steroids"},{"key":"pone.0356002.ref026","doi-asserted-by":"crossref","first-page":"102469","DOI":"10.1016\/j.redox.2022.102469","article-title":"MPST deficiency promotes intestinal epithelial cell apoptosis and aggravates inflammatory bowel disease via AKT","volume":"56","author":"J Zhang","year":"2022","journal-title":"Redox Biol"},{"issue":"8","key":"pone.0356002.ref027","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1016\/S2468-1253(19)30173-6","article-title":"Comorbidities in inflammatory bowel disease: a call for action","volume":"4","author":"M Argollo","year":"2019","journal-title":"Lancet Gastroenterol 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