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Anti-RANKL Inhibits Thymic Function and Causes DRONJ in Mice

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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
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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