Exosomes from Cyclic Stretched Periodontal Ligament Cells Induced Periodontal Inflammation through miR-9-5p/SIRT1/NF-κB Signaling Pathway

Abstract Abundant evidence demonstrates that mechanical stress could induce an inflammatory response in periodontal tissue, but the precise mechanism remains unclear. In the past few years, periodontal ligament cells (PDLCs), as the most force-sensitive cells, have been investigated in depth as local immune cells, associated with activation of inflammasomes and secretion of inflammatory cytokines in response to mechanical stimuli. However, this study innovatively inspected the effect of PDLCs on the other immune cells after stretch loading to reveal the detailed mechanism by which mechanical stimuli initiate immunoreaction in periodontium. In the present study, we found that cyclic stretch could stimulate human PDLCs to secret exosomes and that these exosomes could further induce the increase of phagocytic cells in the periodontium in Sprague-Dawley rats and the M1 polarization of the cultured macrophages (including the mouse macrophage cell line RAW264.7 and the bone marrow-derived macrophages from C57BL/6 mice). Furthermore, the exosomal miR-9-5p was detected to be overexpressed after mechanical stimuli in both in vivo and in vitro experiments and could trigger M1 polarization via the SIRT1/NF-κB signaling pathway in the cultured macrophages. In summary, this study revealed that PDLCs could transmit the mechanobiological signals to immune cells by releasing exosomes and simultaneously enhance periodontal inflammation through the miR-9-5p/SIRT1/NF-κB pathway. We hope that our research can improve understanding of force-related periodontal inflammatory diseases and lead to new targets for treatment.