{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T23:17:01Z","timestamp":1791155821159,"version":"4.1.0"},"reference-count":59,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2013,10,28]],"date-time":"2013-10-28T00:00:00Z","timestamp":1382918400000},"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":[[2014,5,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>\u2003<\/jats:title>\n                    <jats:p>Cherubism is a genetic disorder of the craniofacial skeleton caused by gain-of-function mutations in the signaling adaptor protein, SH3-domain binding protein 2 (SH3BP2). In a knock-in mouse model for cherubism, we previously demonstrated that homozygous mutant mice develop T\/B cell\u2013independent systemic macrophage inflammation leading to bone erosion and joint destruction. Homozygous mice develop multiostotic bone lesions whereas cherubism lesions in humans are limited to jawbones. We identified a critical role of tumor necrosis factor \u03b1 (TNF-\u03b1) in the development of autoinflammation by creating homozygous TNF-\u03b1-deficient cherubism mutants, in which systemic inflammation and bone destruction were rescued. In this study, we examined whether postnatal administration of an anti-TNF-\u03b1 antagonist can prevent or ameliorate the disease progression in cherubism mice. Neonatal homozygous mutants, in which active inflammation has not yet developed, were treated with a high dose of etanercept (25\u2009mg\/kg, twice\/week) for 7 weeks. Etanercept-treated neonatal mice showed strong rescue of facial swelling and bone loss in jaws and calvariae. Destruction of joints was fully rescued in the high-dose group. Moreover, the high-dose treatment group showed a significant decrease in lung and liver inflammatory lesions. However, inflammation and bone loss, which were successfully treated by etanercept administration, recurred after etanercept discontinuation. No significant effect was observed in low-dose\u2013treated (0.5\u2009mg\/kg, twice\/week) and vehicle-treated groups. In contrast, when 10-week-old cherubism mice with fully active inflammation were treated with etanercept for 7 weeks, even the high-dose administration did not decrease bone loss or lung or liver inflammation. Taken together, the results suggest that anti-TNF-\u03b1 therapy may be effective in young cherubism patients, if treated before the inflammatory phase or bone resorption occurs. Therefore, early genetic diagnosis and early treatment with anti-TNF-\u03b1 antagonists may be able to prevent or ameliorate cherubism, especially in patients with a mutation in SH3BP2. \u00a9 2014 American Society for Bone and Mineral Research.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jbmr.2125","type":"journal-article","created":{"date-parts":[[2013,10,28]],"date-time":"2013-10-28T10:28:42Z","timestamp":1382956122000},"page":"1170-1182","source":"Crossref","is-referenced-by-count":35,"title":["Etanercept Administration to Neonatal SH3BP2 Knock-In Cherubism Mice Prevents TNF-\u03b1-Induced Inflammation and Bone Loss"],"prefix":"10.1093","volume":"29","author":[{"given":"Teruhito","family":"Yoshitaka","sequence":"first","affiliation":[{"name":"Department of Oral and Craniofacial SciencesSchool of Dentistry, University of Missouri\u2013Kansas CityKansas CityMOUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu","family":"Ishida","sequence":"additional","affiliation":[{"name":"Department of Periodontal Medicine, Applied Life SciencesInstitute of Biomedical and Health Sciences, Hiroshima UniversityHiroshimaJapan"},{"name":"Department of Oral and Craniofacial SciencesSchool of Dentistry, University of Missouri\u2013Kansas CityKansas CityMOUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoyuki","family":"Mukai","sequence":"additional","affiliation":[{"name":"Department of Oral and Craniofacial SciencesSchool of Dentistry, University of Missouri\u2013Kansas CityKansas CityMOUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mizuho","family":"Kittaka","sequence":"additional","affiliation":[{"name":"Department of Periodontal Medicine, Applied Life SciencesInstitute of Biomedical and Health Sciences, Hiroshima UniversityHiroshimaJapan"},{"name":"Department of Oral and Craniofacial SciencesSchool of Dentistry, University of Missouri\u2013Kansas CityKansas CityMOUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ernst J","family":"Reichenberger","sequence":"additional","affiliation":[{"name":"Department of Reconstructive Sciences, School of Dental MedicineUniversity of Connecticut Health CenterFarmingtonCTUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuyoshi","family":"Ueki","sequence":"additional","affiliation":[{"name":"Department of Oral and Craniofacial SciencesSchool of Dentistry, University of Missouri\u2013Kansas CityKansas CityMOUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2013,10,28]]},"reference":[{"issue":"6","key":"2024020318532289900_jbmr2125-bib-0001","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1067\/moe.2000.108438","article-title":"Cherubism: a 36-year long-term follow-up of 2 generations in different families and review of the 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