{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T22:56:49Z","timestamp":1791845809192,"version":"4.3.4"},"reference-count":36,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2010,7,20]],"date-time":"2010-07-20T00:00:00Z","timestamp":1279584000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100013541","name":"European Calcified Tissue Society","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100013541","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2010,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The NF\u03baB pathway plays a critical role in the regulation of osteoclast activity, and activation of the pathway is dependent on I\u03baB kinase (IKK), which phosphorylates I\u03baB, targeting it for proteasomal degradation. Pharmacological inhibitors of IKK exhibit anti\u2010inflammatory properties and prevent bone erosions in models of inflammatory arthritis. However, the effects of these agents on osteoblast function and ovariectomy\u2010induced bone loss remain unknown. Here we examined the effects of the IKK inhibitors celastrol, BMS\u2010345541, and parthenolide on bone cell function\n                    <jats:italic>in vitro<\/jats:italic>\n                    and ovariectomy\u2010induced bone loss\n                    <jats:italic>in vivo<\/jats:italic>\n                    . All three compounds inhibited RANKL\u2010induced signaling in osteoclasts, caused osteoclast apoptosis, and inhibited osteoclast formation. Although parthenolide and BMS\u2010345541 had no inhibitory effects on osteoblast function, celastrol prevented IL1\u03b2\u2010induced TAK1 activation and inhibited osteoblast growth, differentiation, and bone nodule formation. The selective IKK inhibitors parthenolide and BMS\u2010345541 prevented ovariectomy\u2010induced bone loss by inhibiting osteoclastic bone resorption. We conclude that pharmacological inhibitors of IKK inhibit several critical signaling pathways in osteoclasts necessary for cell survival, formation, and activity\n                    <jats:italic>in vitro<\/jats:italic>\n                    and bone loss\n                    <jats:italic>in vivo<\/jats:italic>\n                    . Accordingly, IKK inhibitors may be of value in the prevention and treatment of bone diseases characterized by increased bone loss such as postmenopausal osteoporosis.\u2014Idris, A. I., Krishnan, M., Simic, P., Landao\u2010Bassonga, E., Mollat, P., Vukicevic, S., Ralston, S. H. Small molecule inhibitors of I\u03baB kinase signaling inhibit osteoclast formation\n                    <jats:italic>in vitro<\/jats:italic>\n                    and prevent ovariectomy\u2010induced bone loss\n                    <jats:italic>in vivo. FASEB J<\/jats:italic>\n                    . 24, 4545\u20134555 (2010).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.10-164095","type":"journal-article","created":{"date-parts":[[2010,7,21]],"date-time":"2010-07-21T00:07:45Z","timestamp":1279670865000},"page":"4545-4555","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["Small molecule inhibitors of I\u03baB kinase signaling inhibit osteoclast formation\n                    <i>in vitro<\/i>\n                    and prevent ovariectomy\u2010induced bone loss\n                    <i>in vivo<\/i>"],"prefix":"10.1096","volume":"24","author":[{"given":"Aymen I.","family":"Idris","sequence":"first","affiliation":[{"name":"Rheumatic Diseases Unit Institute of Genetic and Molecular Medicine University of Edinburgh General Western Hospital  Edinburgh UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maala","family":"Krishnan","sequence":"additional","affiliation":[{"name":"Rheumatic Diseases Unit Institute of Genetic and Molecular Medicine University of Edinburgh General Western Hospital  Edinburgh UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petra","family":"Simic","sequence":"additional","affiliation":[{"name":"Department of Anatomy Medical School University of Zagreb  Zagreb Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Euphemie","family":"Landao\u2010Bassonga","sequence":"additional","affiliation":[{"name":"Rheumatic Diseases Unit Institute of Genetic and Molecular Medicine University of Edinburgh General Western Hospital  Edinburgh UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Mollat","sequence":"additional","affiliation":[{"name":"Galapagos Soci\u00e9t\u00e9 par Actions Simplifi\u00e9e Unipersonnelle  Romainville France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Slobodan","family":"Vukicevic","sequence":"additional","affiliation":[{"name":"Department of Anatomy Medical School University of Zagreb  Zagreb Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stuart H.","family":"Ralston","sequence":"additional","affiliation":[{"name":"Rheumatic Diseases Unit Institute of Genetic and Molecular Medicine University of Edinburgh General Western Hospital  Edinburgh UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2010,7,20]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.289.5484.1504"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1197-1285"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1080\/15216540500137669"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.13.8.1015"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)63016-7"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.97.4.1566"},{"key":"e_1_2_6_8_1","first-page":"54841","article-title":"Osteoclast differentiation is impaired in the absence of inhibitor of kappa B kinase alpha","volume":"279","author":"Chaisson M. 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