{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:46:35Z","timestamp":1786977995725,"version":"build-2736575974"},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2014,6,16]],"date-time":"2014-06-16T00:00:00Z","timestamp":1402876800000},"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":[[2014,12,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>\u2003<\/jats:title>\n                    <jats:p>Osteoporosis is a disease characterized by low bone mass, leading to an increased risk of fragility fractures. GATA4 is a zinc-finger transcription factor that is important in several tissues, such as the heart and intestines, and has recently been shown to be a pioneer factor for estrogen receptor alpha (ER\u03b1) in osteoblast-like cells. Herein, we demonstrate that GATA4 is necessary for estrogen-mediated transcription and estrogen-independent mineralization in vitro. In vivo deletion of GATA4, driven by Cre-recombinase in osteoblasts, results in perinatal lethality, decreased trabecular bone properties, and abnormal bone development. Microarray analysis revealed GATA4 suppression of TGF\u03b2 signaling, necessary for osteoblast progenitor maintenance, and concomitant activation of BMP signaling, necessary for mineralization. Indeed, pSMAD1\/5\/8 signaling, downstream of BMP signaling, is decreased in the trabecular region of conditional knockout femurs, and pSMAD2\/3, downstream of TGF\u03b2 signaling, is increased in the same region. Together, these experiments demonstrate the necessity of GATA4 in osteoblasts. Understanding the role of GATA4 to regulate the tissue specificity of estrogen-mediated osteoblast gene regulation and estrogen-independent bone differentiation may help to develop therapies for postmenopausal osteoporosis. \u00a9 2014 American Society for Bone and Mineral Research.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jbmr.2296","type":"journal-article","created":{"date-parts":[[2014,6,16]],"date-time":"2014-06-16T20:14:06Z","timestamp":1402949646000},"page":"2676-2687","source":"Crossref","is-referenced-by-count":40,"title":["GATA4 Is Essential for Bone Mineralization via ER\u03b1 and TGF\u03b2\/BMP Pathways"],"prefix":"10.1093","volume":"29","author":[{"given":"Miriam","family":"G\u00fcemes","sequence":"first","affiliation":[{"name":"University of California, Los Angeles (UCLA)\/Orthopaedic Hospital Department of Orthopaedic Surgery and the Orthopaedic Hospital Research CenterDavid Geffen School of Medicine at UCLALos AngelesCAUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandro J","family":"Garcia","sequence":"additional","affiliation":[{"name":"University of California, Los Angeles (UCLA)\/Orthopaedic Hospital Department of Orthopaedic Surgery and the Orthopaedic Hospital Research CenterDavid Geffen School of Medicine at UCLALos AngelesCAUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana","family":"Rigueur","sequence":"additional","affiliation":[{"name":"Department of MolecularCell and Developmental Biology, UCLALos AngelesCAUSA"},{"name":"University of California, Los Angeles (UCLA)\/Orthopaedic Hospital Department of Orthopaedic Surgery and the Orthopaedic Hospital Research CenterDavid Geffen School of Medicine at UCLALos AngelesCAUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Runke","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and GynecologyJonsson Comprehensive Cancer 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UCLALos AngelesCAUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Atti","sequence":"additional","affiliation":[{"name":"Division of Diagnostic and Surgical SciencesUCLA School of DentistryLos AngelesCAUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sotirios","family":"Tetradis","sequence":"additional","affiliation":[{"name":"Division of Diagnostic and Surgical SciencesUCLA School of DentistryLos AngelesCAUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno","family":"P\u00e9ault","sequence":"additional","affiliation":[{"name":"Centre for Cardiovascular Science and Centre for Regenerative MedicineUniversity of EdinburghEdinburghUK"},{"name":"University of California, Los Angeles (UCLA)\/Orthopaedic Hospital Department of Orthopaedic Surgery and the Orthopaedic Hospital Research CenterDavid Geffen School of Medicine at UCLALos AngelesCAUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Lyons","sequence":"additional","affiliation":[{"name":"Department of MolecularCell and Developmental Biology, UCLALos AngelesCAUSA"},{"name":"University of California, Los Angeles (UCLA)\/Orthopaedic Hospital Department of Orthopaedic Surgery and the Orthopaedic Hospital Research CenterDavid Geffen School of Medicine at UCLALos AngelesCAUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gustavo A","family":"Miranda-Carboni","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and GynecologyJonsson Comprehensive Cancer Center, David Geffen School of Medicine at UCLALos AngelesCAUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan A","family":"Krum","sequence":"additional","affiliation":[{"name":"University of Tennessee Health Science CenterDepartment of Orthopaedic Surgery and Biomedical EngineeringMemphisTNUSA"},{"name":"University 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