{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T14:19:03Z","timestamp":1760710743353,"version":"3.40.5"},"reference-count":25,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2021,9,13]],"date-time":"2021-09-13T00:00:00Z","timestamp":1631491200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Orthopaedic Surgery"],"published-print":{"date-parts":[[2021,10]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>To develop a comprehensive differential expression profile for osteoporosis based on two independent data sources.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Using a hindlimb unloading (HLU) rat model to mimic osteoporosis syndrome in humans (animal experiments), the significant differentially expressed mRNAs in osteoporosis were analyzed using RNA\u2010seq. The enriched GO terms as well as KEGG signaling pathways were also deeply investigated. Using clinical specimens to verify the functions of potential hub genes (biomarkers) for osteoporosis (clinical experiments), 128 suspected cases for osteoporosis from January 2019 to December 2020 were randomly selected and analyzed by quantitative computed tomography (QCT) as well as modified Dixon quantification (mDixon\u2010Quant) techniques in the Tianjin hospital. Among these, 80 patients out of 128 suspected cases were finally diagnosed as the osteoporosis group. Meanwhile, 48 patients were selected for osteopenia group. There was no significant age and gender difference across participant subgroups. The protein levels of potential hub genes (<jats:italic>FST<\/jats:italic>, <jats:italic>CCL3<\/jats:italic>, and <jats:italic>RAPGEF4<\/jats:italic>) were determined by ELISA double antibody sandwich method for osteopenia and osteoporosis groups from peripheral blood.<\/jats:p><\/jats:sec><jats:sec><jats:title>Result<\/jats:title><jats:p>In the RNA\u2010seq analysis, compared with control group, a total of 803 differentially expressed mRNAs were identified, including 288 up\u2010regulated and 515 down\u2010regulated mRNAs. Of these, <jats:italic>FST, CCL3, CPE, RAPGEF4, IL6, MDFI, PDZD2<\/jats:italic>, and <jats:italic>GATM<\/jats:italic> were primary hub genes (biomarkers) for osteoporosis. These differentially expressed genes were significantly enriched in GO terms related to extracellular matrix process and KEGG signaling pathways including osteoclast differentiation. In the functional experiments, the protein expression level of <jats:italic>FST<\/jats:italic>, <jats:italic>CCL3<\/jats:italic>, and <jats:italic>RAPGEF4<\/jats:italic> displayed a specific expression pattern between osteoporosis patients and control group. The protein concentration of <jats:italic>FST<\/jats:italic> was 23.63 \u00b1\u20096.39 ng\/mL in osteoporosis patients compared as 48.36 \u00b1\u20099.12 ng\/mL in osteopenia group (<jats:italic>P<\/jats:italic> &lt;\u20090.01). Meanwhile, CCL3 was 1.03 \u00b1\u20090.64 ng\/mL in osteoporosis patients <jats:italic>vs<\/jats:italic> 0.56 \u00b1\u20090.24 in osteopenia group (<jats:italic>P<\/jats:italic> &lt;\u20090.01) and <jats:italic>RAPGEF4<\/jats:italic> was 53.58 \u00b1\u200911.42 ng\/mL in osteoporosis patients <jats:italic>vs<\/jats:italic> 66.47 \u00b1\u200913.28 ng\/mL in osteopenia group (<jats:italic>P<\/jats:italic> &lt;\u20090.05), respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study has identified potential gene biomarkers (the genes with most significantly differential expression and useful for distinguishing osteoporosis from other bone disorders) and established a differential expression profile for osteoporosis, which is a valuable reference for future clinical research.<\/jats:p><\/jats:sec>","DOI":"10.1111\/os.13094","type":"journal-article","created":{"date-parts":[[2021,9,13]],"date-time":"2021-09-13T15:30:38Z","timestamp":1631547038000},"page":"2137-2144","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Investigation of Diagnostic Biomarkers for Osteoporosis Based on Differentially Expressed Gene Profile with <scp>QCT and mDixon\u2010Quant<\/scp> Techniques"],"prefix":"10.1111","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8041-0090","authenticated-orcid":false,"given":"Shan","family":"Zhu","sequence":"first","affiliation":[{"name":"Tianjin Hospital of Tianjin University  Tianjin China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aixian","family":"Tian","sequence":"additional","affiliation":[{"name":"Tianjin Hospital of Tianjin University  Tianjin China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lin","family":"Guo","sequence":"additional","affiliation":[{"name":"Tianjin Hospital of Tianjin University  Tianjin China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hua","family":"Xu","sequence":"additional","affiliation":[{"name":"Tianjin Hospital of Tianjin University  Tianjin China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaofeng","family":"Li","sequence":"additional","affiliation":[{"name":"Tianjin Hospital of Tianjin University  Tianjin China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhi","family":"Wang","sequence":"additional","affiliation":[{"name":"Tianjin Hospital of Tianjin University  Tianjin China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Feng","family":"He","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering School of Precision Instrument and Optoelectronic Engineering, Tianjin University  Tianjin China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,9,13]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/550S15a"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.7326\/AITC201708010"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0749-0690(02)00022-8"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2005.08.047"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0889-8529(02)00058-0"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-981-13-3681-2_16"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ecl.2016.11.001"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2017.21995"},{"key":"e_1_2_5_10_1","first-page":"1","article-title":"Assessment of fracture risk and its application to screening for postmenopausal osteoporosis","volume":"843","author":"WHO Study Group","year":"1994","journal-title":"World Health Organ Tech Rep Ser"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1517\/14656566.2016.1124856"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(17)30184-5"},{"key":"e_1_2_5_13_1","first-page":"31","article-title":"Validation of a new automated immunoassay for measurement of intact osteocalcin","volume":"48","author":"Fassbender WJ","year":"2002","journal-title":"Clin Lab"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2019.18343"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/os.12321"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2018.03.017"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.4253"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky1131"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.1239303"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.7861\/clinmedicine.14-2-187"},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcna.2020.06.004"},{"key":"e_1_2_5_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(19)30266-9"},{"key":"e_1_2_5_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.12281"},{"key":"e_1_2_5_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41574-020-0339-7"},{"key":"e_1_2_5_25_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201801969RR"},{"key":"e_1_2_5_26_1","doi-asserted-by":"publisher","DOI":"10.7555\/JBR.31.20150166"}],"container-title":["Orthopaedic Surgery"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/os.13094","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/os.13094","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/os.13094","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,29]],"date-time":"2023-08-29T04:40:32Z","timestamp":1693284032000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/os.13094"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,13]]},"references-count":25,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2021,10]]}},"alternative-id":["10.1111\/os.13094"],"URL":"https:\/\/doi.org\/10.1111\/os.13094","archive":["Portico"],"relation":{},"ISSN":["1757-7853","1757-7861"],"issn-type":[{"type":"print","value":"1757-7853"},{"type":"electronic","value":"1757-7861"}],"subject":[],"published":{"date-parts":[[2021,9,13]]},"assertion":[{"value":"2021-03-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-05-11","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-09-13","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}