{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,26]],"date-time":"2026-07-26T04:47:53Z","timestamp":1785041273766,"version":"3.55.0"},"reference-count":44,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2010,5,27]],"date-time":"2010-05-27T00:00:00Z","timestamp":1274918400000},"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":[[2010,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Monocytes differentiate into osteoclasts through stimulation of receptor activator of NF-\u03baB (RANK). Many downstream effectors of RANK play a positive role in osteoclastogenesis, but their relative importance in osteoclast differentiation is unclear. We report the discovery that activation of a single pathway downstream of RANK is sufficient for osteoclast differentiation. In this regard, introduction of constitutively activated IKK\u03b2 (IKK\u03b2SSEE) but not wild-type IKK\u03b2 into monocytes stimulates differentiation of bona fide osteoclasts in the absence of RANK ligand (RANKL). This phenomenon is independent of upstream signals because IKK\u03b2SSEE induced the development of bone-resorbing osteoclasts from RANK and IKK\u03b1 knockout monocytes and in conditions in which NEMO-IKK\u03b2 association was inhibited. NF-\u03baB p100 and p105, but not RelB, were critical mediators of this effect. Inflammatory autocrine signaling by tumor necrosis factor \u03b1 (TNF-\u03b1) and interleukin 1 (IL-1) were dispensable for the spontaneous osteoclastogenesis driven by IKK\u03b2SSEE. More important, adenoviral gene transfer of IKK\u03b2SSEE induced osteoclasts and osteolysis in calvariae and knees of mice. Our data establish the sufficiency of IKK\u03b2 activation for osteolysis and suggest that IKK\u03b2 hyperactivation may play a role in conditions of pathologic bone destruction refractory to RANK\/RANKL proximal therapeutic interventions. \u00a9 2010 American Society for Bone and Mineral Research<\/jats:p>","DOI":"10.1002\/jbmr.4","type":"journal-article","created":{"date-parts":[[2010,2,1]],"date-time":"2010-02-01T16:15:05Z","timestamp":1265040905000},"page":"1282-1294","source":"Crossref","is-referenced-by-count":51,"title":["IKK\u03b2 activation is sufficient for RANK-independent osteoclast differentiation and osteolysis"],"prefix":"10.1093","volume":"25","author":[{"given":"Jesse E","family":"Otero","sequence":"first","affiliation":[{"name":"Departments of Orthopedics and Cell Biology & Physiology, Washington University School of Medicine, St. Louis, MO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Dai","sequence":"additional","affiliation":[{"name":"Departments of Orthopedics and Cell Biology & Physiology, Washington University School of Medicine, St. Louis, MO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad A","family":"Alhawagri","sequence":"additional","affiliation":[{"name":"Departments of Orthopedics and Cell Biology & Physiology, Washington University School of Medicine, St. Louis, MO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isra","family":"Darwech","sequence":"additional","affiliation":[{"name":"Departments of Orthopedics and Cell Biology & Physiology, Washington University School of Medicine, St. Louis, MO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yousef","family":"Abu-Amer","sequence":"additional","affiliation":[{"name":"Orthopedic Research and Cell Biology & Physiology, Washington University School of Medicine, St. Louis, MO, USA"},{"name":"Departments of Orthopedics and Cell Biology & Physiology, Washington University School of Medicine, St. Louis, MO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2010,5,27]]},"reference":[{"key":"2024020320135801700_bib1","doi-asserted-by":"crossref","first-page":"427","DOI":"10.2353\/ajpath.2007.060834","article-title":"Osteoclasts: what do they do and how do they do it?","volume":"170","author":"Teitelbaum","year":"2007","journal-title":"Amer J Pathol."},{"key":"2024020320135801700_bib2","first-page":"347","article-title":"Advances in osteoclast differentiation and function. 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