Imaging mass cytometry unveils functional and spatial remodeling of peri-lesional cells in jaw osteonecrosis.

Medication-related osteonecrosis of the jaw (MRONJ) is a severe complication associated with antiresorptive therapy, characterized by compromised bone and soft tissue integrity. However, the underlying tissue-level mechanisms remain poorly understood. To uncover cell functions and spatial organization surrounding ONJ lesions, imaging mass cytometry is used to profile lesions at single-cell resolution across epithelial, stromal, and vascular regions. Widespread immune infiltration is observed, with regulatory T cells, M2-like macrophages, exhausted T cells, and natural killer cells shifting from dispersed to clustered spatial patterns, indicating altered immune organization. Epithelial regions show reduced epithelial marker expression and disrupted architecture despite elevated proliferation-related markers, while fibroblasts and endothelial cells display signs of activation. Functional profiling reveals concurrent proliferative, apoptotic, and stress-associated signatures across multiple cell populations. This comprehensive spatial and functional atlas provides insights into the pathophysiology of MRONJ and may inform future therapeutic strategies aimed at restoring tissue homeostasis and promoting effective healing.