{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T09:45:15Z","timestamp":1791884715917,"version":"4.3.4"},"reference-count":65,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2008,5,1]],"date-time":"2008-05-01T00:00:00Z","timestamp":1209600000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2008,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Introduction: Osteoporosis is characterized by low BMD. Studies have shown that B cells may participate in osteoclastogenesis through expression of osteoclast-related factors, such as RANKL, transforming growth factor \u03b2 (TGFB), and osteoprotegerin (OPG). However, the in vivo significance of B cells in human bone metabolism and osteoporosis is still largely unknown, particularly at the systematic gene expression level.<\/jats:p><jats:p>Materials and Methods: In this study, Affymetrix HG-U133A GeneChip arrays were used to identify genes differentially expressed in B cells between 10 low and 10 high BMD postmenopausal women. Significance of differential expression was tested by t-test and adjusted for multiple testing with the Benjamini and Hochberg (BH) procedure (adjusted p \u2264 0.05).<\/jats:p><jats:p>Results: Twenty-nine genes were downregulated in the low versus high BMD group. These genes were further analyzed using Ingenuity Pathways Analysis (Ingenuity Systems). A network involving estrogen receptor 1 (ESR1) and mitogen activated protein kinase 3 (MAPK3) was identified. Real-time RT-PCR confirmed differential expression of eight genes, including ESR1, MAPK3, methyl CpG binding protein 2 (MECP2), proline-serine-threonine phosphatase interacting protein 1 (PSTPIP1), Scr-like-adaptor (SLA), serine\/threonine kinase 11 (STK11), WNK lysine-deficient protein kinase 1 (WNK1), and zinc finger protein 446 (ZNF446).<\/jats:p><jats:p>Conclusions: This is the first in vivo genome-wide expression study on human B cells in relation to osteoporosis. Our results highlight the significance of B cells in the etiology of osteoporosis and suggest a novel mechanism for postmenopausal osteoporosis (i.e., that downregulation of ESR1 and MAPK3 in B cells regulates secretion of factors, leading to increased osteoclastogenesis or decreased osteoblastogenesis).<\/jats:p>","DOI":"10.1359\/jbmr.080105","type":"journal-article","created":{"date-parts":[[2008,2,5]],"date-time":"2008-02-05T18:40:45Z","timestamp":1202236845000},"page":"644-654","source":"Crossref","is-referenced-by-count":82,"title":["In Vivo Genome-Wide Expression Study on Human Circulating B Cells Suggests a Novel<i>ESR1<\/i>and<i>MAPK3<\/i>Network for Postmenopausal Osteoporosis"],"prefix":"10.1093","volume":"23","author":[{"given":"Peng","family":"Xiao","sequence":"first","affiliation":[{"name":"Osteoporosis Research Center and Department of Biomedical Sciences, Creighton University, Omaha, Nebraska, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Chen","sequence":"additional","affiliation":[{"name":"Key Laboratory of Protein Chemistry and Developmental Biology of Education Committee, College of Life Sciences, Hunan Normal University, Changsha, Hunan, China"},{"name":"Osteoporosis Research Center and Department of Biomedical Sciences, Creighton University, Omaha, Nebraska, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Jiang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Protein Chemistry and Developmental Biology of Education Committee, College of Life Sciences, Hunan Normal University, Changsha, Hunan, China"},{"name":"Osteoporosis Research Center and Department of Biomedical Sciences, Creighton University, Omaha, Nebraska, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao-Zhong","family":"Liu","sequence":"additional","affiliation":[{"name":"Departments of Orthopedic Surgery and Basic Medical Sciences, University of Missouri\u2013Kansas City, Kansas City, Missouri, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Pan","sequence":"additional","affiliation":[{"name":"Key Laboratory of Biomedical Information Engineering of Ministry of Education and Institute of Molecular Genetics, College of Life Science and Technology, Xi'an Jiaotong University, Xi'an, Shanxi, China"},{"name":"Osteoporosis Research Center and Department of Biomedical Sciences, Creighton University, Omaha, Nebraska, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tie-Lin","family":"Yang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Biomedical Information Engineering of Ministry of Education and Institute of Molecular Genetics, College of Life Science and Technology, Xi'an Jiaotong University, Xi'an, Shanxi, China"},{"name":"Osteoporosis Research Center and Department of Biomedical Sciences, Creighton University, Omaha, Nebraska, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zi-Hui","family":"Tang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Protein Chemistry and Developmental Biology of Education Committee, College of Life Sciences, Hunan Normal University, Changsha, Hunan, China"},{"name":"Osteoporosis Research Center and Department of Biomedical Sciences, Creighton University, Omaha, Nebraska, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer A","family":"Larsen","sequence":"additional","affiliation":[{"name":"Osteoporosis Research Center and Department of Biomedical Sciences, Creighton University, Omaha, Nebraska, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joan M","family":"Lappe","sequence":"additional","affiliation":[{"name":"Osteoporosis Research Center and Department of Biomedical Sciences, Creighton University, Omaha, Nebraska, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert R","family":"Recker","sequence":"additional","affiliation":[{"name":"Osteoporosis Research Center and Department of Biomedical Sciences, Creighton University, Omaha, Nebraska, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong-Wen","family":"Deng","sequence":"additional","affiliation":[{"name":"Key Laboratory of Biomedical Information Engineering of Ministry of Education and Institute of Molecular Genetics, College of Life Science and Technology, Xi'an Jiaotong University, Xi'an, Shanxi, China"},{"name":"Departments of Orthopedic Surgery and Basic Medical Sciences, University of Missouri\u2013Kansas City, Kansas City, Missouri, USA"},{"name":"Key Laboratory of Protein Chemistry and Developmental Biology of Education Committee, College of Life Sciences, Hunan Normal University, Changsha, Hunan, China"},{"name":"Osteoporosis Research Center and Department of Biomedical Sciences, Creighton 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