{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T05:29:51Z","timestamp":1790746191716,"version":"4.1.0"},"reference-count":25,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2018,4,18]],"date-time":"2018-04-18T00:00:00Z","timestamp":1524009600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"},{"start":{"date-parts":[[2018,5,22]],"date-time":"2018-05-22T00:00:00Z","timestamp":1526947200000},"content-version":"vor","delay-in-days":34,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000072","name":"National Institute of Dental and Craniofacial Research","doi-asserted-by":"publisher","award":["R01DE025870"],"award-info":[{"award-number":["R01DE025870"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["R21AR070953"],"award-info":[{"award-number":["R21AR070953"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["asbmr.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2018,8,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:sec>\n                  <jats:title>\u2003<\/jats:title>\n                  <jats:p>Cherubism is a craniofacial disorder characterized by maxillary and mandibular bone destruction. Gain-of-function mutations in the SH3-domain binding protein 2 (SH3BP2) are responsible for the excessive bone resorption caused by fibrous inflammatory lesions. A homozygous knock-in (KI) mouse model for cherubism (Sh3bp2KI\/KI) develops autoinflammation resulting in systemic bone destruction. Although administration of the TNF-\u03b1 blocker etanercept to neonatal Sh3bp2KI\/KI mice prevented the disease onset, this therapy was not effective for adult Sh3bp2KI\/KI mice or human cherubism patients who already had lesions. Because genetic ablation of spleen tyrosine kinase (SYK) in myeloid cells rescues Sh3bp2KI\/KI mice from inflammation, we examined whether SYK inhibitor administration can improve fully developed cherubism symptoms in adult Sh3bp2KI\/KI mice. Entospletinib (GS-9973) was intraperitoneally injected into 10-week-old Sh3bp2KI\/KI mice every day for 6 weeks. Treatment with GS-9973 improved facial swelling and histomorphometric analysis of lung and liver tissue showed that GS-9973 administration significantly reduced inflammatory infiltrates associated with decreased levels of serum TNF-\u03b1. Micro\u2013computed tomography (\u03bcCT) analysis showed that GS-9973 treatment reduced bone erosion in mandibles, calvariae, and ankle and elbow joints of Sh3bp2KI\/KI mice compared to Sh3bp2KI\/KI mice treated with dimethyl sulfoxide (DMSO). Taken together, the results demonstrate that administration of the SYK inhibitor ameliorates an already established cherubism phenotype in mice, suggesting that pharmacological inhibition of SYK may be a treatment option for cherubism patients with active disease progression. \u00a9 2018 American Society for Bone and Mineral Research.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1002\/jbmr.3449","type":"journal-article","created":{"date-parts":[[2018,4,18]],"date-time":"2018-04-18T19:37:56Z","timestamp":1524080276000},"page":"1513-1519","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Second-Generation SYK Inhibitor Entospletinib Ameliorates Fully Established Inflammation and Bone Destruction in the Cherubism Mouse Model"],"prefix":"10.1093","volume":"33","author":[{"given":"Tetsuya","family":"Yoshimoto","sequence":"first","affiliation":[{"name":"Department of Oral and Craniofacial SciencesSchool of DentistryUniversity of Missouri\u2013Kansas City (UMKC)MOUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuhide","family":"Hayashi","sequence":"additional","affiliation":[{"name":"Department of Dental Materials ScienceAichi Gakuin University School of DentistryNagoyaJapan"},{"name":"Department of Oral and Craniofacial SciencesSchool of DentistryUniversity of Missouri\u2013Kansas City (UMKC)MOUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshio","family":"Kondo","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and BiochemistryOkayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesOkayamaJapan"},{"name":"Department of Oral and Craniofacial SciencesSchool of DentistryUniversity of Missouri\u2013Kansas City (UMKC)MOUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mizuho","family":"Kittaka","sequence":"additional","affiliation":[{"name":"Department of Oral and Craniofacial SciencesSchool of DentistryUniversity of Missouri\u2013Kansas City (UMKC)MOUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ernst J","family":"Reichenberger","sequence":"additional","affiliation":[{"name":"Department of Reconstructive SciencesSchool of Dental MedicineUniversity of Connecticut HealthFarmingtonCTUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuyoshi","family":"Ueki","sequence":"additional","affiliation":[{"name":"Center of Excellence in the Study of Dental and Musculoskeletal Tissues (CEMT)University of Missouri\u2013Kansas City (UMKC)Kansas CityMOUSA"},{"name":"Department of Oral and Craniofacial SciencesSchool of DentistryUniversity of Missouri\u2013Kansas City (UMKC)MOUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2018,4,18]]},"reference":[{"issue":"Suppl 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