{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T15:27:55Z","timestamp":1786116475370,"version":"build-2736575974"},"reference-count":26,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T00:00:00Z","timestamp":1785974400000},"content-version":"vor","delay-in-days":217,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["International Journal of Genomics"],"published-print":{"date-parts":[[2026,1]]},"abstract":"\n Background<\/jats:title>\n Osteoporosis and osteosarcoma impose a substantial and rising global health burden, yet their transcriptomic landscapes have not been systematically compared. We performed a multiomics characterization integrating bulk transcriptomics, coexpression network analysis, immune deconvolution, single\u2010cell RNA sequencing, and diagnostic classifier construction.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Bulk transcriptomic profiling was performed using GSE56815 (circulating blood monocytes,\n n<\/jats:italic>\n = 80; 40 low\u2010BMD\/40 high\u2010BMD) and the TARGET\u2010OS database (\n n<\/jats:italic>\n = 88 osteosarcoma tumor samples; DNA methylation\n n<\/jats:italic>\n = 86; copy number\n n<\/jats:italic>\n = 81). Differential expression was assessed by Welch\u2032s\n t<\/jats:italic>\n \u2010test with Benjamini\u2013Hochberg correction. Coexpression modules were identified by hierarchical clustering of the Top 2000 most variable probes with dynamic tree cutting. A logistic regression classifier was constructed from the Top 20 differentially expressed probes using fivefold\u2010stratified cross\u2010validation. Single\u2010cell RNA sequencing of an osteosarcoma tumor specimen (GEO accession GSM9030790) was processed with SVD\u2010based dimensionality reduction and K\u2010means clustering (\n k<\/jats:italic>\n = 8;\n n<\/jats:italic>\n = 3658 cells passing QC). In vitro validation was conducted by qRT\u2010PCR in MC3T3\u2010E1 osteoblast precursor cells and RAW264.7 osteoclast precursor cells.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Differential expression analysis identified 4347 probe sets at nominal\n p<\/jats:italic>\n < 0.05, of which 604 remained significant after Benjamini\u2013Hochberg correction. Eight coexpression modules were identified; module M0 showed a weak positive association with low\u2010BMD status (\n r<\/jats:italic>\n = 0.184), which did not reach statistical significance. Six hub genes\u2014SP7\/Osterix, RUNX2, BMP2, WNT5A, DKK1, and SOST\u2014were examined by qRT\u2010PCR: SP7, RUNX2, BMP2, and WNT5A showed significant downregulation (\n p<\/jats:italic>\n < 0.01), whereas DKK1 showed significant upregulation (\n p<\/jats:italic>\n < 0.01) and SOST showed a nonsignificant trend toward upregulation under osteoporosis\u2010simulating conditions. The diagnostic classifier achieved a moderate AUC of 0.693 (fivefold CV range: 0.48\u20130.91), with the lower bound falling below the random classifier baseline (AUC = 0.5), indicating limited discriminative capacity in some data partitions. scRNA\u2010seq resolved eight transcriptionally distinct cell clusters in the osteosarcoma specimen (3658 cells passing QC).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n This integrative multiomics study provides a comprehensive transcriptomic comparison of osteoporosis and osteosarcoma, identifies BMD\u2010associated coexpression modules with experimentally validated hub genes, and establishes a reusable analytical framework for biomarker discovery in metabolic and malignant bone disease. However, the weak module\u2010trait correlations, subthreshold classifier performance in some cross\u2010validation folds, and the use of circulating blood monocytes to study bone\u2010specific gene expression warrant cautious interpretation of the findings.<\/jats:p>\n <\/jats:sec>","DOI":"10.1155\/ijog\/9619903","type":"journal-article","created":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T10:19:57Z","timestamp":1786011597000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Multiomics Integration Reveals Coexpression Regulatory Networks in Osteoporosis and Osteosarcoma"],"prefix":"10.1155","volume":"2026","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-4975-3455","authenticated-orcid":false,"given":"Dongming","family":"Fu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0022-5827","authenticated-orcid":false,"given":"Ran","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-8266-7193","authenticated-orcid":false,"given":"Bo","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,6]]},"reference":[{"key":"e_1_2_12_1_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00198-018-4704-5"},{"key":"e_1_2_12_2_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00198-006-0172-4"},{"key":"e_1_2_12_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMcp1513724"},{"key":"e_1_2_12_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm3254"},{"key":"e_1_2_12_5_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.R109.041087"},{"key":"e_1_2_12_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2011.07.014"},{"key":"e_1_2_12_7_2","doi-asserted-by":"publisher","DOI":"10.18632\/aging.102264"},{"key":"e_1_2_12_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.prp.2023.155036"},{"key":"e_1_2_12_9_2","doi-asserted-by":"publisher","DOI":"10.1186\/s40659-024-00497-y"},{"key":"e_1_2_12_10_2","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-17-1152"},{"key":"e_1_2_12_11_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12929-024-01049-y"},{"key":"e_1_2_12_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2024.04.013"},{"key":"e_1_2_12_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-024-01782-4"},{"key":"e_1_2_12_14_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-9-559"},{"key":"e_1_2_12_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.crmeth.2023.100498"},{"key":"e_1_2_12_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.3337"},{"key":"e_1_2_12_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(01)00622-5"},{"key":"e_1_2_12_18_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.20958"},{"key":"e_1_2_12_19_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.3201241"},{"key":"e_1_2_12_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep04493"},{"key":"e_1_2_12_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2009.12.007"},{"key":"e_1_2_12_22_2","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.173"},{"key":"e_1_2_12_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cytogfr.2005.02.005"},{"key":"e_1_2_12_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature21349"},{"key":"e_1_2_12_25_2","doi-asserted-by":"publisher","DOI":"10.2307\/2531595"},{"key":"e_1_2_12_26_2","doi-asserted-by":"crossref","first-page":"e873","DOI":"10.1016\/S2665-9913(25)00105-5","article-title":"Global 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