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Anti-RANKL Inhibits Thymic Function and Causes DRONJ in Mice
Title: | Anti-RANKL Inhibits Thymic Function and Causes DRONJ in Mice |
Authors: | Nakamura, Yusuke Browse this author | Kikuiri, Takashi Browse this author →KAKEN DB | Sugiyama, Takahiro Browse this author | Maeda, Ayako Browse this author | Izumiyama, Daisuke Browse this author | Yahata, Daigo Browse this author | Yoshimura, Yoshitaka Browse this author →KAKEN DB | Shirakawa, Tetsuo Browse this author →KAKEN DB | Kitagawa, Yoshimasa Browse this author →KAKEN DB |
Issue Date: | 15-Apr-2022 |
Publisher: | Hindawi Publishing Corporation |
Journal Title: | International Journal of Dentistry |
Volume: | 2022 |
Start Page: | 9299602 |
Publisher DOI: | 10.1155/2022/9299602 |
PMID: | 35464103 |
Abstract: | Background. Denosumab, a human monoclonal antibody against receptor activator of nuclear factor-kappa B ligand (RANKL), is a novel bone antiresorptive agent used in patients with osteoporosis or metastatic bone cancer. Denosumab-related osteonecrosis of the jaw (DRONJ) has been recently reported in patients using denosumab. However, the mechanisms of DRONJ are not fully understood. Appropriate pathogenic mechanisms of DRONJ have yet to be established. Therefore, we investigated the pathogenesis of DRONJ in mice. Methods. Anti-mouse RANKL monoclonal antibody and melphalan were performed to create a mouse model of DRONJ-like lesions in female C57BL/6J mice. We examined the development of DRONJ-like lesions and immune function. Results. We showed that administration of anti-mouse RANKL monoclonal antibody and melphalan caused DRONJ-like lesions that recapitulated major clinical manifestations of the human disease, including the characteristic features of an open alveolar socket and exposed necrotic bone. In the analysis using a mouse model of DRONJ-like lesion, it was revealed that anti-mouse RANKL monoclonal antibody and melphalan suppress autoimmune regulator (AIRE) expression in the thymus and imbalanced T cell populations. Conclusion. This study suggests evidence of an immunity-based mechanism of DRONJ-like disease. This work may contribute to a better understanding of the pathogenesis of human DRONJ. |
Type: | article |
URI: | http://hdl.handle.net/2115/86511 |
Appears in Collections: | 歯学院・歯学研究院 (Graduate School of Dental Medicine / Faculty of Dental Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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