Er Stress-Induced Macrophage Il-27 Promotes Periapical Bone Destruction

Chronic apical periodontitis (CAP) can cause oral craniomaxillofacial bone injuries, with a considerable number of patients experiencing slow healing or recurrence despite standard root canal treatment. The role of inflammatory mediators is crucial, indicating a need for more research on regulating the immune microenvironment to improve treatment outcomes. CAP samples of clinical were analyzed using cytokine PCR-ARRAY to identify highly expressed cytokines, which were validated in animal model and through cytokine neutralization experiments. The scRNA-seq dataset from GEO was used to identify cytokine sources, and bioinformatics explored regulatory mechanisms. Regulatory targets were validated using in vitro inflammatory macrophage and in vivo bone injury models. High expression of IL-27 was observed in tissues from patients with CAP accompanied by bone injury. Animal model studies also linked elevated IL-27 levels to the severity of bone damage. Integrating scRNA-seq with other methods indicates that IL-27 is mainly expressed in macrophages in the inflammatory microenvironment and may act as a biomarker for chronic inflammatory bone injuries. Reduced IL-27 secretion promotes the healing of these injuries. Transcriptomic and histological analyses revealed active endoplasmic reticulum (ER) stress in macrophages, correlating with IL-27 production. Notably, inhibiting ER stress pathways reduced IL-27 levels and promoted bone defect repair in an inflammatory environment. The induction of ER stress in inflammatory macrophages within the microenvironment of CAP leads to an excessive accumulation of IL-27, hindering bone repair. Mitigating IL-27 may facilitate the healing of CAP-related bone injuries.