{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T21:02:08Z","timestamp":1792270928515,"version":"4.4.0"},"reference-count":24,"publisher":"Rockefeller University Press","issue":"5","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2005,9,5]]},"abstract":"<jats:p>Osteoclasts are derived from myeloid lineage cells, and their differentiation is supported by various osteotropic factors, including the tumor necrosis factor (TNF) family member TNF-related activation-induced cytokine (TRANCE). Genetic deletion of TRANCE or its receptor, receptor activator of nuclear factor \u03baB (RANK), results in severely osteopetrotic mice with no osteoclasts in their bones. TNF receptor-associated factor (TRAF) 6 is a key signaling adaptor for RANK, and its deficiency leads to similar osteopetrosis. Hence, the current paradigm holds that TRANCE\u2013RANK interaction and subsequent signaling via TRAF6 are essential for the generation of functional osteoclasts. Surprisingly, we show that hematopoietic precursors from TRANCE-, RANK-, or TRAF6-null mice can become osteoclasts in vitro when they are stimulated with TNF-\u03b1 in the presence of cofactors such as TGF-\u03b2. We provide direct evidence against the current paradigm that the TRANCE\u2013RANK\u2013TRAF6 pathway is essential for osteoclast differentiation and suggest the potential existence of alternative routes for osteoclast differentiation.<\/jats:p>","DOI":"10.1084\/jem.20050978","type":"journal-article","created":{"date-parts":[[2005,9,7]],"date-time":"2005-09-07T00:45:35Z","timestamp":1126053935000},"page":"589-595","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":330,"title":["Osteoclast differentiation independent of the TRANCE\u2013RANK\u2013TRAF6 axis"],"prefix":"10.1084","volume":"202","author":[{"given":"Nacksung","family":"Kim","sequence":"first","affiliation":[{"name":"1Medical Research Center for Gene Regulation, Chonnam National University Medical School, Gwangju 501-746, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuho","family":"Kadono","sequence":"additional","affiliation":[{"name":"2Abramson Family Cancer Research Institute, Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masamichi","family":"Takami","sequence":"additional","affiliation":[{"name":"3Department of Biochemistry, School of Dentistry, Showa University, Shinagawa-ku, Tokyo 142-8555, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junwon","family":"Lee","sequence":"additional","affiliation":[{"name":"1Medical Research Center for Gene Regulation, Chonnam National University Medical School, Gwangju 501-746, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seoung-Hoon","family":"Lee","sequence":"additional","affiliation":[{"name":"2Abramson Family Cancer Research Institute, Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fumihiko","family":"Okada","sequence":"additional","affiliation":[{"name":"2Abramson Family Cancer Research Institute, Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jung Ha","family":"Kim","sequence":"additional","affiliation":[{"name":"1Medical Research Center for Gene Regulation, Chonnam National University Medical School, Gwangju 501-746, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Kobayashi","sequence":"additional","affiliation":[{"name":"2Abramson Family Cancer Research Institute, Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul R.","family":"Odgren","sequence":"additional","affiliation":[{"name":"4Department of Cell Biology, University of Massachusetts Medical School, Worcester, MA 01655"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyasu","family":"Nakano","sequence":"additional","affiliation":[{"name":"5Department of Immunology, Juntendo University School of Medicine, Bunkyo-ku, Tokyo 113-8421, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-Chen","family":"Yeh","sequence":"additional","affiliation":[{"name":"6Department of Medical Biophysics, University of Toronto, Toronto, Ontario, M5G 2C1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sun-Kyeong","family":"Lee","sequence":"additional","affiliation":[{"name":"7Division of Endocrinology, Department of Medicine, University of Connecticut Health Center, Farmington, CT 06030"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph A.","family":"Lorenzo","sequence":"additional","affiliation":[{"name":"7Division of Endocrinology, Department of Medicine, University of Connecticut Health Center, Farmington, CT 06030"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongwon","family":"Choi","sequence":"additional","affiliation":[{"name":"2Abramson Family Cancer Research Institute, Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2005,9,6]]},"reference":[{"key":"2023072513161940400_BIB1","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1038\/nature01658","volume":"423","year":"2003","journal-title":"Nature."},{"key":"2023072513161940400_BIB2","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1210\/edrv.20.3.0367","volume":"20","year":"1999","journal-title":"Endocr. 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