{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T23:36:58Z","timestamp":1784763418416,"version":"3.55.0"},"reference-count":67,"publisher":"The Endocrine Society","issue":"8","license":[{"start":{"date-parts":[[2020,6,1]],"date-time":"2020-06-01T00:00:00Z","timestamp":1590969600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AR059781"],"award-info":[{"award-number":["R01AR059781"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P20GM109036"],"award-info":[{"award-number":["P20GM109036"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01MH107354"],"award-info":[{"award-number":["R01MH107354"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01MH104680"],"award-info":[{"award-number":["R01MH104680"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01GM109068"],"award-info":[{"award-number":["R01GM109068"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AR069055"],"award-info":[{"award-number":["R01AR069055"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U19AG055373"],"award-info":[{"award-number":["U19AG055373"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Purpose<\/jats:title>\n                  <jats:p>Menopause is a crucial physiological transition during a woman\u2019s life, and it occurs with growing risks of health issues like osteoporosis. To identify postmenopausal osteoporosis-related genes, we performed transcriptome-wide expression analyses for human peripheral blood monocytes (PBMs) using Affymetrix 1.0 ST arrays in 40 Caucasian postmenopausal women with discordant bone mineral density (BMD) levels.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We performed multiscale embedded gene coexpression network analysis (MEGENA) to study functionally orchestrating clusters of differentially expressed genes in the form of functional networks. Gene sets net correlations analysis (GSNCA) was applied to assess how the coexpression structure of a predefined gene set differs in high and low BMD groups. Bayesian network (BN) analysis was used to identify important regulation patterns between potential risk genes for osteoporosis. A small interfering ribonucleic acid (siRNA)-based gene silencing in vitro experiment was performed to validate the findings from BN analysis.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Result<\/jats:title>\n                  <jats:p>MEGENA showed that the \u201cT cell receptor signaling pathway\u201d and the \u201costeoclast differentiation pathway\u201d were significantly enriched in the identified compact network, which is significantly correlated with BMD variation. GSNCA revealed that the coexpression structure of the \u201cSignaling by TGF-beta receptor complex pathway\u201d is significantly different between the 2 BMD discordant groups; the hub genes in the postmenopausal low and high BMD group are FURIN and SMAD3 respectively. With siRNA in vitro experiments, we confirmed the regulation relationship of TGFBR2\u2013SMAD7 and TGFBR1\u2013SMURF2.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Main Conclusion<\/jats:title>\n                  <jats:p>The present study suggests that biological signals involved in monocyte recruitment, monocyte\/macrophage lineage development, osteoclast formation, and osteoclast differentiation might function together in PBMs that contribute to the pathogenesis of postmenopausal osteoporosis.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1210\/clinem\/dgaa319","type":"journal-article","created":{"date-parts":[[2020,6,2]],"date-time":"2020-06-02T03:40:39Z","timestamp":1591069239000},"page":"2678-2691","source":"Crossref","is-referenced-by-count":12,"title":["Network-based Transcriptome-wide Expression Study for Postmenopausal Osteoporosis"],"prefix":"10.1210","volume":"105","author":[{"given":"Lan","family":"Zhang","sequence":"first","affiliation":[{"name":"Center for Biomedical informatics and Genomics, Department of Medicine, Tulane University, New Orleans, Louisiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tian-Liu","family":"Peng","sequence":"additional","affiliation":[{"name":"Institute of Reproduction and Stem Cell Engineering, School of Basic Medical Science, Central South University, Changsha, Hunan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Le","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Reproduction and Stem Cell Engineering, School of Basic Medical Science, Central South University, Changsha, Hunan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang-He","family":"Meng","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular and Statistical Genetics, College of Life 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