{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T14:37:24Z","timestamp":1782311844582,"version":"3.54.5"},"reference-count":46,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,1,21]],"date-time":"2021-01-21T00:00:00Z","timestamp":1611187200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Osteoporosis is a metabolic bone disease characterized by decreased bone mineral density and abnormal bone quality. Monocytes can secret cytokines for bone resorption, resulting in bone mass loss. However, the mechanism by which monocytes subpopulations lead to osteoporosis remains unclear. The aim of this study was to identify genes associated with osteoporosis in monocytes subsets.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Three microarray datasets including GSE7158 (transcription of low\/high-peak bone mass), GSE101489 (transcription of CD16+\/CD16\u2212 monocyte) and GSE93883 (miRNA expression profile of primary osteoporosis) were derived from the Gene Expression Omnibus (GEO) database and analyzed with GEO2R tool to identify differentially expressed genes (DEGs). Functional enrichment was analyzed using Metascape database and GSEA software. STRING was utilized for the Protein\u2013Protein Interaction Network construct. The hub genes were screened out using the Cytoscape software. Related miRNAs were predicted in miRWalk, miRDB, and TargetScan databases.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Total 368 DEGs from GSE7158 were screened out, which were mostly enriched in signaling, positive regulation of biological process and immune system process. The hub genes were clustered into two modules by PPI network analysis. We identified 15 overlapping DGEs between GSE101489 and GSE7158 microarray datasets. Moreover, all of them were up-regulated genes in both datasets. Then, nine key genes were screened out from above 15 overlapping DEGs using Cytoscape software. It is a remarkable fact that the nine genes were all in one hub gene module of GSE7158. Additionally, 183 target miRNAs were predicted according to the above nine DEGs. After cross-verification with miRNA express profile dataset for osteoporosis (GSE93883), 12 DEmiRNAs were selected. Finally, a miRNA-mRNA network was constructed with the nine key genes and 12 miRNAs, which were involved in osteoporosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our analysis results constructed a gene expression framework in monocyte subsets for osteoporosis. This approach could provide a novel insight into osteoporosis.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2020.581878","type":"journal-article","created":{"date-parts":[[2021,1,21]],"date-time":"2021-01-21T09:21:30Z","timestamp":1611220890000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Integrative Analyses of Genes Associated With Osteoporosis in CD16+ Monocyte"],"prefix":"10.3389","volume":"11","author":[{"given":"Bin","family":"Hu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangan","family":"Kong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Dai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiu","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruifeng","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,1,21]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1007\/s00198-014-2794-2","article-title":"Clinician\u2019s Guide to Prevention and Treatment of Osteoporosis","volume":"25","author":"Cosman","year":"2014","journal-title":"Osteoporosis Int J Established As Result Cooperation Between Eur Foundation Osteoporosis Natl Osteoporosis Foundation USA"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.2269","article-title":"The recent prevalence of osteoporosis and low bone mass in the United States based on bone mineral density at the femoral neck or lumbar spine","volume":"29","author":"Wright","year":"2014","journal-title":"J Bone Mineral Res Off J Am Soc Bone Mineral Res"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(17)30184-5","article-title":"Use of bone turnover markers in postmenopausal osteoporosis","volume":"5","author":"Eastell","year":"2017","journal-title":"Lancet Diabetes Endocrinol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1038\/nature01658","article-title":"Osteoclast differentiation and activation","volume":"423","author":"Boyle","year":"2003","journal-title":"Nature"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0116792","article-title":"Attenuated monocyte apoptosis, a new mechanism for osteoporosis suggested by a transcriptome-wide expression study of monocytes","volume":"10","author":"Liu","year":"2015","journal-title":"PloS One"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1177\/1557988317721642","article-title":"The Role of Monocyte Percentage in Osteoporosis in Male Rheumatic Diseases","volume":"11","author":"Su","year":"2017","journal-title":"Am J Men\u2019s Health"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000016793","article-title":"The predictive role of monocyte-to-lymphocyte ratio in osteoporosis patient","volume":"98","author":"Gao","year":"2019","journal-title":"Medicine"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1007\/s00223-019-00555-8","article-title":"Long Noncoding RNA Analyses for Osteoporosis Risk in Caucasian Women","volume":"105","author":"Zhou","year":"2019","journal-title":"Calcified Tissue Int"},{"key":"B9","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1186\/s12920-015-0149-2","article-title":"MiRNA profiling of whole trabecular bone: identification of osteoporosis-related changes in MiRNAs in human hip bones","volume":"8","author":"De-Ugarte","year":"2015","journal-title":"BMC Med Genomics"},{"key":"B10","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1016\/j.bone.2015.05.027","article-title":"Differentially circulating miRNAs after recent osteoporotic fractures can influence osteogenic differentiation","volume":"79","author":"Weilner","year":"2015","journal-title":"Bone"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.138","article-title":"Identification of a gene module associated with BMD through the integration of network analysis and genome-wide association data","volume":"25","author":"Farber","year":"2010","journal-title":"J Bone Mineral Res Off J Am Soc Bone Mineral Res"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V74.7.2527.2527","article-title":"Identification and characterization of a novel monocyte subpopulation in human peripheral blood","volume":"74","author":"Passlick","year":"1989","journal-title":"Blood"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-042617-053119","article-title":"Nonclassical Monocytes in Health and Disease","volume":"37","author":"Narasimhan","year":"2019","journal-title":"Annu Rev Immunol"},{"key":"B14","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1111\/ijlh.12216","article-title":"CD14+ CD16+ monocytes rather than CD14+ CD51\/61+ monocytes are a potential cytological marker of circulating osteoclast precursors in multiple myeloma. A preliminary study","volume":"37","author":"?>Petitprez","year":"2015","journal-title":"Int J Lab Hematol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2020.00104","article-title":"Bioinformatic Analysis Identifies Potential Key Genes in the Pathogenesis of Turner Syndrome","volume":"11","author":"Wang","year":"2020","journal-title":"Front Endocrinol"},{"key":"B16","doi-asserted-by":"publisher","first-page":"2236","DOI":"10.1038\/s41467-019-10951-1","article-title":"A systems biology approach uncovers cell-specific gene regulatory effects of genetic associations in multiple sclerosis","volume":"10","author":"Madireddy","year":"2019","journal-title":"Nat Commun"},{"key":"B17","doi-asserted-by":"publisher","first-page":"1523","DOI":"10.1038\/s41467-019-09234-6","article-title":"Metascape provides a biologist-oriented resource for the analysis of systems-level datasets","volume":"10","author":"Zhou","year":"2019","journal-title":"Nat Commun"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1038\/75556","article-title":"Gene ontology: tool for the unification of biology. The Gene Ontology Consortium","volume":"25","author":"Ashburner","year":"2000","journal-title":"Nat Genet"},{"key":"B19","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1093\/nar\/28.1.27","article-title":"KEGG: kyoto encyclopedia of genes and genomes","volume":"28","author":"Kanehisa","year":"2000","journal-title":"Nucleic Acids Res"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1038\/ng1180","article-title":"PGC-1alpha-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes","volume":"34","author":"Mootha","year":"2003","journal-title":"Nat Genet"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0506580102","article-title":"Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles","volume":"102","author":"Subramanian","year":"2005","journal-title":"Proc Natl Acad Sci U States A"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky1131","article-title":"STRING v11: protein-protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets","volume":"47","author":"Szklarczyk","year":"2019","journal-title":"Nucleic Acids Res"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkz757","article-title":"miRDB: an online database for prediction of functional microRNA targets","volume":"48","author":"Chen","year":"2020","journal-title":"Nucleic Acids Res"},{"key":"B24","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/j.cell.2004.12.035","article-title":"Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets","volume":"120","author":"Lewis","year":"2005","journal-title":"Cell"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.05005","article-title":"Predicting effective microRNA target sites in mammalian mRNAs","volume":"4","author":"Agarwal","year":"2015","journal-title":"eLife"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1038\/306378a0","article-title":"An interleukin 1 like factor stimulates bone resorption in vitro","volume":"306","author":"Gowen","year":"1983","journal-title":"Nature"},{"key":"B27","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1007\/BF02407164","article-title":"Monocytes mediate osteoclastic bone resorption by prostaglandin production","volume":"31","author":"Dominguez","year":"1980","journal-title":"Calcified Tissue Int"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.87.18.7260","article-title":"Origin of osteoclasts: mature monocytes and macrophages are capable of differentiating into osteoclasts under a suitable microenvironment prepared by bone marrow-derived stromal cells","volume":"87","author":"Udagawa","year":"1990","journal-title":"Proc Natl Acad Sci U States A"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2000.02379.x","article-title":"Characterization of osteoclast precursors in human blood","volume":"111","author":"Shalhoub","year":"2000","journal-title":"Br J Haematol"},{"key":"B30","doi-asserted-by":"publisher","first-page":"17290","DOI":"10.1038\/s41598-019-53843-6","article-title":"Monocytes affect bone mineral density in pre- and postmenopausal women through ribonucleoprotein complex biogenesis by integrative bioinformatics analysis","volume":"9","author":"Xiao","year":"2019","journal-title":"Sci Rep"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1007\/s00198-015-3250-7","article-title":"Circulating monocytes: an appropriate model for bone-related study","volume":"26","author":"Zhou","year":"2015","journal-title":"Osteoporosis Int J Established As Result Cooperation Between Eur Foundation Osteoporosis Natl Osteoporosis Foundation USA"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellimm.2014.03.019","article-title":"Monocyte subsets in man and other species","volume":"289","author":"Ziegler-Heitbrock","year":"2014","journal-title":"Cell Immunol"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1007\/s002230001210","article-title":"Differential changes in regional bone mineral density in healthy Chinese: age-related and sex-dependent","volume":"68","author":"Yao","year":"2001","journal-title":"Calcified Tissue Int"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1002\/pmic.200700480","article-title":"Proteomic analysis of circulating monocytes in Chinese premenopausal females with extremely discordant bone mineral density","volume":"8","author":"Deng","year":"2008","journal-title":"Proteomics"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2019.10353","article-title":"Pathway and network analysis of genes related to osteoporosis","volume":"20","author":"Guo","year":"2019","journal-title":"Mol Med Rep"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1096\/fasebj.14.3.523","article-title":"Best5: a novel interferon-inducible gene expressed during bone formation","volume":"14","author":"Grewal","year":"2000","journal-title":"FASEB J Off Publ Fed Am Soc Exp Biol"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2017-12-820571","article-title":"Blood-induced bone loss in murine hemophilic arthropathy is prevented by blocking the iRhom2\/ADAM17\/TNF-\u03b1 pathway","volume":"132","author":"Haxaire","year":"2018","journal-title":"Blood"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2014.06.001","article-title":"Osteoclasts: more than \u2018bone eaters\u2019","volume":"20","author":"Charles","year":"2014","journal-title":"Trends Mol Med"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1172\/JCI28550","article-title":"Estrogen deficiency and bone loss: an inflammatory tale","volume":"116","author":"Weitzmann","year":"2006","journal-title":"J Clin Investigation"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2015.00184","article-title":"Regulatory T cell-mediated anti-inflammatory effects promote successful tissue repair in both indirect and direct manners","volume":"6","author":"Lei","year":"2015","journal-title":"Front Pharmacol"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1210\/endo.137.6.8641199","article-title":"A role for CD8+ T lymphocytes in osteoclast differentiation in vitro","volume":"137","author":"John","year":"1996","journal-title":"Endocrinology"},{"key":"B42","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1016\/j.abb.2010.05.027","article-title":"The immune system and bone","volume":"503","author":"Pacifici","year":"2010","journal-title":"Arch Biochem Biophysics"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.021908.132557","article-title":"Blood monocytes: development, heterogeneity, and relationship with dendritic cells","volume":"27","author":"Auffray","year":"2009","journal-title":"Annu Rev Immunol"},{"key":"B44","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1556\/EuJMI.2.2012.2.1","article-title":"Monocytes in health and disease - Minireview","volume":"2","author":"Karlmark","year":"2012","journal-title":"Eur J Microbiol Immunol"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfv017","article-title":"Altered monocyte expression and expansion of non-classical monocyte subset in IgA nephropathy patients","volume":"30","author":"Cox","year":"2015","journal-title":"Nephrol Dialysis Transplant Off Publ Eur Dialysis Transplant Assoc Eur Renal Assoc"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.00505","article-title":"What Are the Peripheral Blood Determinants for Increased Osteoclast Formation in the Various Inflammatory Diseases Associated With Bone Loss","volume":"10","author":"de Vries","year":"2019","journal-title":"Front Immunol"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2020.581878\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,1,21]],"date-time":"2021-01-21T09:21:32Z","timestamp":1611220892000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2020.581878\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,21]]},"references-count":46,"alternative-id":["10.3389\/fendo.2020.581878"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2020.581878","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,21]]},"article-number":"581878"}}