(PR046) Neutralization of Serum IL-23 Ameliorates Pulp Exposure-Induced MRONJ Lesions in Mice

Objective: Medication-related osteonecrosis of the jaw is a serious consequence of long-term exposure to anti-resorptive drugs such as bisphosphonates. The association of chronic inflammation and Th17 cells with MRONJ precipitation has already been confirmed in our previous studies. IL-23p19 is a potent proinflammatory cytokine that plays an important role in the differentiation of Th17 cells. Our current study aims to investigate the role of IL-23p19 in the pathogenesis of MRONJ by serum neutralization of IL-23p19 using a pulp exposure-induced MRONJ mouse model.

Methods: To examine the role of IL-23p19 in MRONJ precipitation, mice were injected with IL-23p19 neutralizing antibody along with high doses of Zoledronic acid. The maxillary first molars were exposed and the same teeth were extracted. Mice were euthanized, and maxillae were collected. Clinical, radiographic, and histologic evaluations were done to assess the protective effect of anti-IL-23p19 antibodies on MRONJ lesions.

Results: There was a significant reduction in necrotic bone areas, along with a significant reduction in the number of TRAP+ osteoclasts at the tooth extraction sites when IL-23p19 was neutralized in the Zoledronic Acid treatment group. IL-23p19 was also found to be significantly less localized in the tooth extraction site and differentiation of pathogenic Th17 cells was found to be significantly reduced in the cervical lymph nodes in this group compared to the group that received Zoledronic acid only.

Conclusion: Neutralizing IL-23p19 in serum alleviates MRONJ induced by pulp exposure. Our findings indicate that IL-23p19 is a promising therapeutic target for treating MRONJ.