Effect and Mechanism of Apoptotic Bodies from Inflammatory Periodontal Ligament Stem Cells on Macrophage M1 Polarisation.

Abstract

BACKGROUND: Periodontitis is a widespread infective disease that causes inflammation and periodontal tissue defects. The host's immune regulatory mechanisms play a critical role in the pathogenesis and progression of periodontitis. Among these, macrophages are central to the immune response in periodontitis and participate in the clearance of apoptotic cells. Apoptotic bodies (ABs) are inflammatory factors released during cell apoptosis that are associated with various inflammatory diseases. METHODS: In this study, we isolated ABs from inflammatory periodontal ligament stem cells (PDLSCs) and investigated the effect on THP-1 macrophages. We explored the molecular mechanism that PDLSC-derived ABs (PD-ABs) regulate macrophages in vitro through mRNA-seq and inhibitors of signalling pathways. Finally, we verified that PD-ABs promoted periodontitis-induced alveolar bone defects in vivo. RESULT: Our results demonstrated that PD-ABs induced M1 polarisation, increasing CD86, INOS and IL-6 expression through activating the OSM/JAK2/STAT3 axis. Inhibiting JAK2 prevented M1 polarisation. Additionally, these findings were validated in a mouse periodontitis model. PD-ABs promoted alveolar bone loss in periodontitis mice and induced M1 polarisation, which could be inhibited by JAK2 inhibitors. CONCLUSION: PD-ABs are a potential pathogenesis of periodontitis that induces M1 polarisation via the OSM/JAK2/STAT3 axis. These findings provide new insights into the potential pathogenesis and therapeutic strategies for periodontitis, offering a novel approach to modulate macrophage polarisation and inflammation.