Microbe-Dependent Exacerbated Alveolar Bone Destruction in Heterozygous Cherubism Mice
dc.contributor.author | Kittaka, Mizuho | |
dc.contributor.author | Yoshimoto, Tetsuya | |
dc.contributor.author | Schlosser, Collin | |
dc.contributor.author | Kajiya, Mikihito | |
dc.contributor.author | Kurihara, Hidemi | |
dc.contributor.author | Reichenberger, Ernst J. | |
dc.contributor.author | Ueki, Yasuyoshi | |
dc.contributor.department | Biomedical Sciences and Comprehensive Care, School of Dentistry | en_US |
dc.date.accessioned | 2020-10-08T16:39:53Z | |
dc.date.available | 2020-10-08T16:39:53Z | |
dc.date.issued | 2020-02-24 | |
dc.description.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. | en_US |
dc.identifier.citation | Kittaka, M., Yoshimoto, T., Schlosser, C., Kajiya, M., Kurihara, H., Reichenberger, E. J., & Ueki, Y. (2020). Microbe-Dependent Exacerbated Alveolar Bone Destruction in Heterozygous Cherubism Mice. JBMR Plus, 4(6), e10352. https://doi.org/10.1002/jbm4.10352 | en_US |
dc.identifier.issn | 2473-4039 | en_US |
dc.identifier.uri | https://hdl.handle.net/1805/24015 | |
dc.language.iso | en_US | en_US |
dc.publisher | American Society for Bone and Mineral Research | en_US |
dc.relation.isversionof | 10.1002/jbm4.10352 | en_US |
dc.relation.journal | JBMR Plus | en_US |
dc.rights | Attribution 4.0 International | * |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | * |
dc.source | PMC | en_US |
dc.subject | CHERUBISM | en_US |
dc.subject | ORAL MICROBES | en_US |
dc.subject | OSTEOCLASTS | en_US |
dc.subject | PERIODONTITIS | en_US |
dc.subject | SH3BP2 | en_US |
dc.title | Microbe-Dependent Exacerbated Alveolar Bone Destruction in Heterozygous Cherubism Mice | en_US |
dc.type | Article | en_US |