{"doi":"10.1002/jbm4.10352","title":"Microbe‐Dependent Exacerbated Alveolar Bone Destruction in Heterozygous Cherubism Mice","abstract":"ABSTRACT Cherubism (OMIM#118400) is a craniofacial disorder characterized by destructive jaw expansion. Gain‐of‐function mutations in SH3‐domain binding protein 2 (SH3BP2) are responsible for this rare disorder. We have previously shown that homozygous knock‐in (KI) mice ( Sh3bp2 KI/KI ) recapitulate human cherubism by developing inflammatory lesions in the jaw. However, it remains unknown why heterozygous KI mice ( Sh3bp2 KI/+ ) do not recapitulate the excessive jawbone destruction in human cherubism, even though all mutations are heterozygous in humans. We hypothesized that Sh3bp2 KI/+ mice need to be challenged for developing exacerbated jawbone destruction and that bacterial stimulation in the oral cavity may be involved in the mechanism. In this study, we applied a ligature‐induced periodontitis model to Sh3bp2 KI/+ mice to induce inflammatory alveolar bone destruction. Ligature placement induced alveolar bone resorption with gingival inflammation. Quantification of alveolar bone volume revealed that Sh3bp2 KI/+ mice developed more severe bone loss (male: 43.0% ± 10.6%, female: 42.6% ± 10.4%) compared with Sh3bp2 +/+ mice (male: 25.8% ± 4.0%, female: 30.9% ± 6.5%). Measurement of bone loss by the cement‐enamel junction–alveolar bone crest distance showed no difference between Sh3bp2 KI/+ and Sh3bp2 +/+ mice. The number of osteoclasts on the alveolar bone surface was higher in male Sh3bp2 KI/+ mice, but not in females, compared with Sh3bp2 +/+ mice. In contrast, inflammatory cytokine levels in gingiva were comparable between Sh3bp2 KI/+ and Sh3bp2 +/+ mice with ligatures. Genetic deletion of the spleen tyrosine kinase in myeloid cells and antibiotic treatment suppressed alveolar bone loss in Sh3bp2 KI/+ mice, suggesting that increased osteoclast differentiation and function mediated by SYK and accumulation of oral bacteria are responsible for the increased alveolar bone loss in Sh3bp2 KI/+ mice with ligature‐induced periodontitis. High amounts of oral bacterial load caused by insufficient oral hygiene could be a trigger for the initiation of jawbone destruction in human cherubism. © 2020 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.","journal":"JBMR Plus","year":2020,"id":109543,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":9,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9578,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":447098,"name":"Tetsuya Yoshimoto","orcid":"0000-0003-1221-7402","position":1,"is_corresponding":false},{"id":523296,"name":"Collin Schlosser","orcid":null,"position":2,"is_corresponding":false},{"id":303714,"name":"Mikihito Kajiya","orcid":"0000-0001-6652-0007","position":3,"is_corresponding":false},{"id":303724,"name":"Hidemi Kurihara","orcid":"0009-0006-3629-6706","position":4,"is_corresponding":false},{"id":522340,"name":"Ernst Reichenberger","orcid":"0000-0003-2229-2481","position":5,"is_corresponding":false},{"id":447099,"name":"Yasuyoshi Ueki","orcid":"0000-0002-8660-626X","position":6,"is_corresponding":false},{"id":447097,"name":"Mizuho Kittaka","orcid":"0000-0002-3626-1638","position":0,"is_corresponding":true}],"reference_count":10,"raw_metadata":null,"created_at":"2026-07-18T23:12:50.712357Z","pmid":"32537546","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}