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HIF1\u03b1 is unstable in the presence of oxygen, but is stabilized under hypoxic conditions. However, we found that HIF1\u03b1 is destabilized by estrogen even under hypoxic conditions. Following estrogen deficiency due to menopause, HIF1\u03b1 is stabilized in osteoclasts, leading to osteoclast activation. Oral administration of a HIF1\u03b1 inhibitor protected postmenopausal osteoporosis model mice from osteoclast activation and bone loss. Thus, HIF1\u03b1 represents a promising therapeutic target in osteoporosis.<\/jats:p>","DOI":"10.1073\/pnas.1308755110","type":"journal-article","created":{"date-parts":[[2013,9,11]],"date-time":"2013-09-11T07:12:44Z","timestamp":1378883564000},"page":"16568-16573","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":171,"title":["HIF1\u03b1 is required for osteoclast activation by estrogen deficiency in postmenopausal osteoporosis"],"prefix":"10.1073","volume":"110","author":[{"given":"Yoshiteru","family":"Miyauchi","sequence":"first","affiliation":[{"name":"Departments of aOrthopedic Surgery,"},{"name":"Integrated Bone Metabolism and Immunology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuiko","family":"Sato","sequence":"additional","affiliation":[{"name":"Departments of aOrthopedic Surgery,"},{"name":"Musculoskeletal Reconstruction and Regeneration Surgery,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tami","family":"Kobayashi","sequence":"additional","affiliation":[{"name":"Departments of aOrthopedic Surgery,"},{"name":"Keio Kanrinmaru Project, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigeyuki","family":"Yoshida","sequence":"additional","affiliation":[{"name":"Department of Dentistry and Oral Surgery, School of Medicine, Keio University, Tokyo 160-8582, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoaki","family":"Mori","sequence":"additional","affiliation":[{"name":"Departments of aOrthopedic Surgery,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroya","family":"Kanagawa","sequence":"additional","affiliation":[{"name":"Departments of aOrthopedic Surgery,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eri","family":"Katsuyama","sequence":"additional","affiliation":[{"name":"Departments of aOrthopedic Surgery,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsuhiro","family":"Fujie","sequence":"additional","affiliation":[{"name":"Departments of aOrthopedic Surgery,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wu","family":"Hao","sequence":"additional","affiliation":[{"name":"Departments of aOrthopedic Surgery,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kana","family":"Miyamoto","sequence":"additional","affiliation":[{"name":"Departments of aOrthopedic Surgery,"},{"name":"Keio Kanrinmaru Project, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshimi","family":"Tando","sequence":"additional","affiliation":[{"name":"Departments of aOrthopedic Surgery,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideo","family":"Morioka","sequence":"additional","affiliation":[{"name":"Departments of aOrthopedic Surgery,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morio","family":"Matsumoto","sequence":"additional","affiliation":[{"name":"Departments of aOrthopedic Surgery,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Chambon","sequence":"additional","affiliation":[{"name":"Department of Functional Genomics, Institut de G\u00e9n\u00e9tique et de Biologie Mol\u00e9culaire et Cellulaire, Coll\u00e8ge de France, Universit\u00e9 de Strasbourg, FR-67404 Illkirch, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Randall S.","family":"Johnson","sequence":"additional","affiliation":[{"name":"Molecular Biology Section, Division of Biological Sciences, School of Medicine, University of California, San Diego, La Jolla, CA 92093; 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