{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T21:27:03Z","timestamp":1791149223228,"version":"4.1.0"},"reference-count":39,"publisher":"National Academy of Sciences","issue":"10","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2008,3,11]]},"abstract":"<jats:p>\n                    NF-\u03baB inducing kinase (NIK) is required for osteoclastogenesis in response to pathologic stimuli, and its loss leads to functional blockade of both alternative and classical NF-\u03baB caused by cytoplasmic retention by p100. We now show that deletion of p100 restores the capacity of NIK-deficient osteoclast (OC) precursors to differentiate and normalizes RelB and p65 signaling. Differentiation of\n                    <jats:italic>NIK<\/jats:italic>\n                    \u2212\/\u2212 precursors is also restored by overexpression of RelB, but not p65. Additionally,\n                    <jats:italic>RelB<\/jats:italic>\n                    \u2212\/\u2212 precursors fail to form OCs in culture, and this defect is rescued by re-expression of RelB, but not by overexpression of p65. To further support the role of RelB in OCs, we challenged\n                    <jats:italic>RelB<\/jats:italic>\n                    \u2212\/\u2212 mice with TNF-\u03b1\n                    <jats:italic>in vivo<\/jats:italic>\n                    and found a diminished osteoclastogenic response. We then examined tumor-induced osteolysis in both\n                    <jats:italic>RelB<\/jats:italic>\n                    \u2212\/\u2212 and\n                    <jats:italic>NIK<\/jats:italic>\n                    \u2212\/\u2212 mice by using the B16 melanoma model. Growth of tumor cells in the bone marrow was similar to WT controls, but the absence of either RelB or NIK completely blocked the tumor-induced loss of trabecular bone. Thus, the alternative NF-\u03baB pathway, culminating in activation of RelB, has a key and specific role in the differentiation of OCs that cannot be compensated for by p65.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0708576105","type":"journal-article","created":{"date-parts":[[2008,3,5]],"date-time":"2008-03-05T20:58:53Z","timestamp":1204750733000},"page":"3897-3902","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":133,"title":["RelB is the NF-\u03baB subunit downstream of NIK responsible for osteoclast differentiation"],"prefix":"10.1073","volume":"105","author":[{"given":"Sergio","family":"Vaira","sequence":"first","affiliation":[{"name":"*Division of Bone and Mineral Diseases, Department of Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trevor","family":"Johnson","sequence":"additional","affiliation":[{"name":"*Division of Bone and Mineral Diseases, Department of Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela C.","family":"Hirbe","sequence":"additional","affiliation":[{"name":"Division of Biology and Biomedical Sciences,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad","family":"Alhawagri","sequence":"additional","affiliation":[{"name":"*Division of Bone and Mineral Diseases, Department of Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Imani","family":"Anwisye","sequence":"additional","affiliation":[{"name":"*Division of Bone and Mineral Diseases, Department of Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benedicte","family":"Sammut","sequence":"additional","affiliation":[{"name":"*Division of Bone and Mineral Diseases, Department of Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"O'Neal","sequence":"additional","affiliation":[{"name":"Division of Biology and Biomedical Sciences,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Zou","sequence":"additional","affiliation":[{"name":"Department of Pathology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine N.","family":"Weilbaecher","sequence":"additional","affiliation":[{"name":"Division of Molecular Oncology, Department of Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Faccio","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Washington University School of Medicine, St. Louis, MO 63110"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah Veis","family":"Novack","sequence":"additional","affiliation":[{"name":"*Division of Bone and Mineral Diseases, Department of Medicine,"},{"name":"Department of Pathology,"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2008,3,11]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1228704"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/mcb.13.3.1572-1582.1993"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/mcb.12.2.674-684.1992"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/376167a0"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.167.3.1592"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(95)90416-6"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/1521-4141(200201)32:1<1::AID-IMMU1>3.0.CO;2-S"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.171.8.3963"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20011885"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.167.4.1909"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/cdg534"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(03)00227-2"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1207221"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1329805"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7600391"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2004-02-0412"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.165.2.804"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.191.9.1477"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20030116"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M406392200"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(95)90506-5"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2007.08.039"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.11.24.3482"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1197-1285"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M208619200"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1054"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.C400258200"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20042081"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.172.2.752"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI23763"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.173.8.4838"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1203236"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1210\/endo.142.3.8031"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI10530"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1058453"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.187.2.185"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-09-048686"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2234372100"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth779"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.0708576105","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T17:00:55Z","timestamp":1649782855000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.0708576105"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,3,11]]},"references-count":39,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2008,3,11]]}},"alternative-id":["10.1073\/pnas.0708576105"],"URL":"https:\/\/doi.org\/10.1073\/pnas.0708576105","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,3,11]]},"assertion":[{"value":"2007-09-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2008-03-11","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}