{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T16:50:59Z","timestamp":1784307059541,"version":"3.55.0"},"reference-count":40,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2023,10,18]],"date-time":"2023-10-18T00:00:00Z","timestamp":1697587200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004366","name":"Tabriz University of Medical Sciences","doi-asserted-by":"publisher","award":["61494"],"award-info":[{"award-number":["61494"]}],"id":[{"id":"10.13039\/501100004366","id-type":"DOI","asserted-by":"publisher"}]}],"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>Many researchers focused on diverse miRNAs in the progression of osteoporosis in postmenopausal women. This study aimed to evaluate the association between plasma miRNA-21-5p and miRNA-422a with osteoporosis in postmenopausal women.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>This cross-sectional comparative study was performed on 126 randomly selected postmenopausal women aged 50\u201365, including 65 osteoporotic and 61 normal-bone mineral density (BMD) women. miRNA-21 and miRNA-422a were identified using qRT-PCR in these women. BMD was evaluated by the dual-energy X-ray absorptiometry method. A binary logistic regression model adjusted for confounders was used to evaluate the associations between plasma miRNAs\u2019 expression levels and osteoporosis. The Area Under Curve (AUC) was calculated to differentiate low BMD in the postmenopausal period using Receiver-Operator Characteristic (ROC) curves.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>miRNA-21 and miRNA-422a were significantly up-regulated in osteoporotic compared to non-osteoporotic postmenopausal women. The expression levels of miRNA-21 and miRNA-422a indicated a significant reverse correlation with both lumbar spine and femoral neck density. After adjusting the confounders, the likelihood of osteoporosis in the postmenopausal women with under the median plasma levels of miRNA-21 (OR = 0.025; 95% CI: 0.003 to 0.198, <jats:italic>p<\/jats:italic>&lt;0.001) and miRNA-422a (OR = 0.037; 95% CI: 0.007 to 0.211, <jats:italic>p<\/jats:italic>&lt;0.001) was significantly less than the women with the levels above the median. There were significant inverse correlations between miRNA-21 (<jats:italic>p<\/jats:italic>&lt;0.001, r = -0.511) and miRNA-422a (<jats:italic>p<\/jats:italic>&lt;0.001, r = -0.682) with BMD-lumbar spine as well as an inverse correlation between miRNA-21(<jats:italic>p<\/jats:italic>&lt;0.001, r = -0.374) and miRNA-422a (<jats:italic>p<\/jats:italic>&lt;0.001, r = -0.602) with BMD-femoral neck. The AUC (95%CI) for miRNA-21 and miRNA-422a was 0.84 (0.77 to 0.91) and 0.98 (0.96 to 0.99), respectively. ROC analysis illustrated that sensitivity and specificity values were 83.1% and 74%, respectively, for miRNA-21 at the cut-off point of 3.38. Also, at the cut-off point of 2.86, a sensitivity of 94% as well as a specificity of 89% was determined for miRNA-422a.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p>This study indicated that the odds of osteoporosis in postmenopausal women increased with the higher expression of plasma miRNA-21 and miRNA-422a.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0287458","type":"journal-article","created":{"date-parts":[[2023,10,18]],"date-time":"2023-10-18T17:28:29Z","timestamp":1697650109000},"page":"e0287458","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":11,"title":["Up-regulation of plasma miRNA-21 and miRNA-422a in postmenopausal osteoporosis"],"prefix":"10.1371","volume":"18","author":[{"given":"Neda","family":"Mohammadisima","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5754-4613","authenticated-orcid":true,"given":"Azizeh","family":"Farshbaf-khalili","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alireza","family":"Ostadrahimi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2023,10,18]]},"reference":[{"key":"pone.0287458.ref001","doi-asserted-by":"crossref","first-page":"3318","DOI":"10.1172\/JCI27071","article-title":"Pathogenesis of osteoporosis: concepts, conflicts, and prospects","volume":"115","author":"LG Raisz","year":"2005","journal-title":"The Journal of clinical investigation"},{"key":"pone.0287458.ref002","doi-asserted-by":"crossref","first-page":"2029","DOI":"10.2147\/TCRM.S138000","article-title":"A comprehensive overview on osteoporosis and its risk factors","volume":"14","author":"F Pouresmaeili","year":"2018","journal-title":"Ther Clin Risk Manag"},{"key":"pone.0287458.ref003","doi-asserted-by":"crossref","first-page":"16069","DOI":"10.1038\/nrdp.2016.69","article-title":"Postmenopausal osteoporosis","volume":"2","author":"R Eastell","year":"2016","journal-title":"Nat Rev Dis Primers"},{"key":"pone.0287458.ref004","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1016\/j.jocd.2013.01.004","article-title":"Selection of women aged 50\u201364 yr for bone density measurement","volume":"16","author":"WD Leslie","year":"2013","journal-title":"J Clin Densitom"},{"key":"pone.0287458.ref005","doi-asserted-by":"crossref","unstructured":"Ciuffi S, Donati S, Marini F, et al. 2020. Circulating MicroRNAs as Novel Biomarkers for Osteoporosis and Fragility Fracture Risk: Is There a Use in Assessment Risk?. 21.","DOI":"10.3390\/ijms21186927"},{"key":"pone.0287458.ref006","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1038\/sj.emboj.7601977","article-title":"Messenger RNA regulation: to translate or to degrade","volume":"27","author":"AB Shyu","year":"2008","journal-title":"Embo j"},{"key":"pone.0287458.ref007","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1038\/s41580-018-0045-7","article-title":"Regulation of microRNA function in animals","volume":"20","author":"LFR Gebert","year":"2019","journal-title":"Nature reviews Molecular cell biology"},{"key":"pone.0287458.ref008","first-page":"9191","volume":"233","author":"W Zhao","year":"2018","journal-title":"Therapeutic potential of microRNAs in osteoporosis function by regulating the biology of cells related to bone homeostasis"},{"key":"pone.0287458.ref009","doi-asserted-by":"crossref","first-page":"BSR20190667","DOI":"10.1042\/BSR20190667","article-title":"Differentially expressed circulating miRNAs in postmenopausal osteoporosis: a meta-analysis","volume":"39","author":"E Pala","year":"2019","journal-title":"Bioscience reports"},{"key":"pone.0287458.ref010","doi-asserted-by":"crossref","first-page":"e97098","DOI":"10.1371\/journal.pone.0097098","article-title":"MiR-422a as a potential cellular microRNA biomarker for postmenopausal osteoporosis","volume":"9","author":"Z Cao","year":"2014","journal-title":"PLoS One"},{"key":"pone.0287458.ref011","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1530\/EJE-16-0583","article-title":"Expression of microRNAs that regulate bone turnover in the serum of postmenopausal women with low bone mass and vertebral fractures","volume":"176","author":"MP Yavropoulou","year":"2017","journal-title":"Eur J Endocrinol"},{"key":"pone.0287458.ref012","doi-asserted-by":"crossref","first-page":"1718","DOI":"10.1002\/jbmr.2175","article-title":"Five freely circulating miRNAs and bone tissue miRNAs are associated with osteoporotic fractures","volume":"29","author":"C Seeliger","year":"2014","journal-title":"J Bone Miner Res"},{"key":"pone.0287458.ref013","first-page":"245","article-title":"The Role of Serum Expression Levels of Microrna-21 on Bone Mineral Density in Hypostrogenic Postmenopausal Women with Osteoporosis: Study on Level of RANKL, OPG, TGF\u03b2-1, Sclerostin, RANKL\/OPG Ratio, and Physical Activity","volume":"51","author":"IN Suarjana","year":"2019","journal-title":"Acta Med Indones"},{"key":"pone.0287458.ref014","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1007\/s00223-015-0036-z","article-title":"Serum Circulating MicroRNAs as Biomarkers of Osteoporotic Fracture","volume":"97","author":"L Panach","year":"2015","journal-title":"Calcif Tissue Int"},{"key":"pone.0287458.ref015","doi-asserted-by":"crossref","first-page":"553","DOI":"10.3109\/1354750X.2014.935957","article-title":"Plasma miRNA levels correlate with sensitivity to bone mineral density in postmenopausal osteoporosis patients","volume":"19","author":"H Li","year":"2014","journal-title":"Biomarkers"},{"key":"pone.0287458.ref016","doi-asserted-by":"crossref","first-page":"3","DOI":"10.15296\/ijwhr.2021.02","article-title":"Assessment of Primary Osteoporosis Status in the Postmenopausal Women of Tabriz and the Effect of Curcumin Nanomicelles, Nigella sativa Oil, and Curcumin Nanomicelles and Nigella sativa Oil Soft Capsules on Cellular-Molecular and Clinical Outcomes: A Study Protocol","volume":"9","author":"S Abdolalipour","year":"2021","journal-title":"Int. J. Women\u2019s Health Reprod. Sci"},{"key":"pone.0287458.ref017","unstructured":"Committee IR. 2005. Guidelines for data processing and analysis of the International Physical Activity Questionnaire (IPAQ)-short and long forms http:\/\/www ipaq ki se\/scoring pdf."},{"key":"pone.0287458.ref018","doi-asserted-by":"crossref","first-page":"150","DOI":"10.2188\/jea.JE20090083","article-title":"Reproducibility and relative validity of food group intake in a food frequency questionnaire developed for the Tehran Lipid and Glucose Study","volume":"20","author":"FH Esfahani","year":"2010","journal-title":"J Epidemiol"},{"key":"pone.0287458.ref019","doi-asserted-by":"crossref","first-page":"1689","DOI":"10.1017\/S1368980013002115","article-title":"Designing and developing a literature-derived, population-based dietary inflammatory index","volume":"17","author":"N Shivappa","year":"2014","journal-title":"Public Health Nutr"},{"key":"pone.0287458.ref020","doi-asserted-by":"crossref","first-page":"2359","DOI":"10.1007\/s00198-014-2794-2","article-title":"Clinician\u2019s Guide to Prevention and Treatment of Osteoporosis","volume":"25","author":"F Cosman","year":"2014","journal-title":"Osteoporosis international: a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA"},{"key":"pone.0287458.ref021","doi-asserted-by":"crossref","first-page":"e34641","DOI":"10.1371\/journal.pone.0034641","article-title":"MiR-133a in human circulating monocytes: a potential biomarker associated with postmenopausal osteoporosis","volume":"7","author":"Y Wang","year":"2012","journal-title":"PLoS One"},{"key":"pone.0287458.ref022","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1016\/j.euf.2017.02.018","article-title":"Diagnostic and prognostic microRNA biomarkers for prostate cancer in cell-free urine","volume":"4","author":"J Freds\u00f8e","year":"2018","journal-title":"European Urology Focus"},{"key":"pone.0287458.ref023","doi-asserted-by":"crossref","first-page":"bpz006","DOI":"10.1093\/biomethods\/bpz006","article-title":"Plasma or serum? A qualitative study on rodents and humans using high-throughput microRNA sequencing for circulating biomarkers","volume":"4","author":"T Dufourd","year":"2019","journal-title":"Biol Methods Protoc"},{"key":"pone.0287458.ref024","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1016\/j.omtn.2020.03.003","article-title":"The Promising Role of miR-21 as a Cancer Biomarker and Its Importance in RNA-Based Therapeutics","volume":"20","author":"D Bautista-S\u00e1nchez","year":"2020","journal-title":"Mol Ther Nucleic Acids"},{"key":"pone.0287458.ref025","doi-asserted-by":"crossref","first-page":"700","DOI":"10.3390\/ijms21030700","article-title":"Potential clinical implications of miR-1 and miR-21 in heart disease and cardioprotection","volume":"21","author":"B Kura","year":"2020","journal-title":"International journal of molecular sciences"},{"key":"pone.0287458.ref026","doi-asserted-by":"crossref","first-page":"1217","DOI":"10.1002\/jcb.24471","article-title":"Down-regulation of miR-21 biogenesis by estrogen action contributes to osteoclastic apoptosis","volume":"114","author":"T Sugatani","year":"2013","journal-title":"J Cell Biochem"},{"key":"pone.0287458.ref027","first-page":"1125","article-title":"miR\u201121 promotes osteoclastogenesis through activation of PI3K\/Akt signaling by targeting Pten in RAW264.7 cells","volume":"21","author":"S Wang","year":"2020","journal-title":"Molecular medicine reports"},{"key":"pone.0287458.ref028","doi-asserted-by":"crossref","first-page":"1561","DOI":"10.3892\/mmr.2015.3497","article-title":"MicroRNA-21 promotes osteogenic differentiation by targeting small mothers against decapentaplegic 7","volume":"12","author":"H Li","year":"2015","journal-title":"Mol Med Rep"},{"key":"pone.0287458.ref029","doi-asserted-by":"crossref","first-page":"3648","DOI":"10.1182\/blood-2010-10-311415","article-title":"A microRNA expression signature of osteoclastogenesis","volume":"117","author":"T Sugatani","year":"2011","journal-title":"Blood"},{"key":"pone.0287458.ref030","first-page":"6221","article-title":"Bone marrow stem cells-derived exosomes extracted from osteoporosis patients inhibit osteogenesis via microRNA-21\/SMAD7","volume":"22","author":"L Jiang","year":"2018","journal-title":"Eur Rev Med Pharmacol Sc"},{"key":"pone.0287458.ref031","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1016\/j.bbrc.2017.09.119","article-title":"MicroRNA-21 promotes osteogenesis of bone marrow mesenchymal stem cells via the Smad7-Smad1\/5\/8-Runx2 pathway","volume":"493","author":"X Li","year":"2017","journal-title":"Biochem Biophys Res Commun"},{"key":"pone.0287458.ref032","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1002\/jor.22884","article-title":"microRNA\u201021 promotes osteogenic differentiation of mesenchymal stem cells by the PI3K\/\u03b2\u2010catenin pathway","volume":"33","author":"YB Meng","year":"2015","journal-title":"Journal of Orthopaedic Research"},{"key":"pone.0287458.ref033","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1186\/s13287-019-1168-2","article-title":"miRNA-21 promotes osteogenesis via the PTEN\/PI3K\/Akt\/HIF-1\u03b1 pathway and enhances bone regeneration in critical size defects","volume":"10","author":"C Yang","year":"2019","journal-title":"Stem Cell Res Ther"},{"key":"pone.0287458.ref034","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1007\/s11010-015-2404-4","article-title":"MiR-21 overexpression improves osteoporosis by targeting RECK","volume":"405","author":"W Zhao","year":"2015","journal-title":"Mol Cell Biochem"},{"key":"pone.0287458.ref035","doi-asserted-by":"crossref","first-page":"479","DOI":"10.3390\/cells9020479","article-title":"The Role of miR-21 in Osteoblasts-Osteoclasts Coupling In Vitro","volume":"9","author":"A Smieszek","year":"2020","journal-title":"Cells"},{"key":"pone.0287458.ref036","first-page":"1283","volume":"47","author":"Y Wu","year":"2020","journal-title":"Knockdown of circular RNA UBAP2 inhibits the malignant behaviours of esophageal squamous cell carcinoma by microRNA-422a\/Rab10 axis"},{"key":"pone.0287458.ref037","doi-asserted-by":"crossref","first-page":"42173","DOI":"10.18632\/oncotarget.15025","article-title":"Circulating microRNA-422a is associated with lymphatic metastasis in lung cancer","volume":"8","author":"L Wu","year":"2017","journal-title":"Oncotarget"},{"key":"pone.0287458.ref038","doi-asserted-by":"crossref","first-page":"832","DOI":"10.1016\/j.biopha.2018.03.013","article-title":"MiR-422a targets MAPKK6 and regulates cell growth and apoptosis in colorectal cancer cells","volume":"104","author":"P Li","year":"2018","journal-title":"Biomedicine & Pharmacotherapy"},{"key":"pone.0287458.ref039","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1080\/15384047.2018.1433497","article-title":"MiR-422a weakened breast cancer stem cells properties by targeting 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