{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T23:16:58Z","timestamp":1791155818463,"version":"4.1.0"},"reference-count":32,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2014,12,10]],"date-time":"2014-12-10T00:00:00Z","timestamp":1418169600000},"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":[[2015,5,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>\u2003<\/jats:title>\n                    <jats:p>Cherubism is a rare genetic disorder characterized by extensive growth of a bilateral granuloma of the jaws, resulting in facial disfigurement. Cherubism is caused by gain-of-function mutations in the SH3BP2 gene, leading to overactivation of nuclear factor of activated T cells, cytoplasmic 1 (NFATc1)-dependent osteoclastogenesis. Recent findings in human and mouse cherubism have suggested that calcineurin inhibitors might be drug candidates in cherubism medical treatment. A 4-year-old boy with aggressive cherubism was treated with the calcineurin inhibitor tacrolimus for 1 year, and clinical, radiological, and molecular data were obtained. Immunohistologic analysis was performed to compare preoperative and postoperative NFATc1 staining and tartrate resistant acid phosphatase (TRAP) activity. Real-time PCR was performed to analyze the relative expression levels of OPG and RANKL. After tacrolimus therapy, the patient showed significant clinical improvement, including stabilization of jaw size and intraosseous osteogenesis. Immunohistologic analyses on granuloma showed that tacrolimus caused a significant reduction in the number of TRAP-positive osteoclasts and NFATc1 nuclear staining in multinucleated giant cells. Molecular analysis showed that tacrolimus treatment also resulted in increased OPG expression. We present the first case of effective medical therapy in cherubism. Tacrolimus enhanced bone formation by stimulating osteogenesis and inhibiting osteoclastogenesis. \u00a9 2014 American Society for Bone and Mineral Research.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jbmr.2431","type":"journal-article","created":{"date-parts":[[2014,12,10]],"date-time":"2014-12-10T06:47:54Z","timestamp":1418194074000},"page":"878-885","source":"Crossref","is-referenced-by-count":47,"title":["The Calcineurin Inhibitor Tacrolimus as a New Therapy in Severe Cherubism"],"prefix":"10.1093","volume":"30","author":[{"given":"Natacha","family":"Kadlub","sequence":"first","affiliation":[{"name":"Laboratoire de Physiopathologie Orale et Mol\u00e9culaireINSERM, UMRS 872, Equipe 5Centre de Recherche des CordeliersParisFrance"},{"name":"Centre de R\u00e9f\u00e9rences des Malformations de la Face et de la Cavit\u00e9 BuccaleParisFrance"},{"name":"Unit\u00e9s de Formation et de Recherche (UFR) de M\u00e9decine Paris DescartesUniversit\u00e9 Paris VParisFrance"},{"name":"Service de Chirurgie Maxillo-FacialeH\u00f4pital Necker Enfants MaladesAssistance Publique\u2013H\u00f4pitaux de Paris (AP-HP)ParisFrance"},{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM) UMRS1138Team Molecular Oral PathophysiologyCordeliers Research CenterUniversity Paris-DiderotUniversity Paris-Descartes, and University Pierre and Marie CurieParisFrance"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-Paule","family":"Vazquez","sequence":"additional","affiliation":[{"name":"Laboratoire de Physiopathologie Orale et Mol\u00e9culaireINSERM, UMRS 872, Equipe 5Centre de Recherche des CordeliersParisFrance"},{"name":"Centre de R\u00e9f\u00e9rences des Malformations de la Face et de la Cavit\u00e9 BuccaleParisFrance"},{"name":"Unit\u00e9s de Formation et de Recherche (UFR) de M\u00e9decine Paris DescartesUniversit\u00e9 Paris VParisFrance"},{"name":"Service de Chirurgie Maxillo-FacialeH\u00f4pital Necker 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