UCLA

Introduction: Medication-related osteonecrosis of the jaw is a complication that occurs in patients who are taking anti-resorptive drugs such as bisphosphonates. We previously showed that chronic inflammation and Th17 cells are associated with MRONJ development. Differentiation of Th17 cells is highly dependent on IL-23p19, a potent proinflammatory cytokine. In this current study, we investigated the role of IL-23p19 in the pathogenesis of MRONJ using a pulp exposure-induced MRONJ mouse model. Methodology: To examine the functional role of IL-23p19, anti-IL-23p19 antibody was administered into mice receiving high doses of Zoledronic acid. The maxillary first molars were exposed and then extracted. Mice were euthanized and maxillae, cervical lymph nodes, spleen, and blood serum were collected. MicroCT, serum ELISA, histologic evaluations, and qRT-PCR were done to assess the protective effect of IL-23p19 neutralizing antibody on MRONJ lesions. Results: There was a significant reduction in the number of empty lacunae and necrotic bone areas in the neutralizing IL-23p19 injection groups, without any significant reduction in the number of TRAP+ osteoclasts at the site of tooth extraction. There was also a significant reduction in the tissue localization of IL-23p19 and less differentiation of Th17 cell occurring in the cervical lymph nodes upon serum neutralization of IL-23p19. Conclusion: Serum neutralization of IL-23p19 ameliorates pulp exposure-induced MRONJ. Our study suggests that IL-23p19 is a putative therapeutic target for treating MRONJ lesions.