The miR-223-3p from Salivary Exosome Regulates Pyroptosis through NLRP3-Caspase 1-GSDMD signal axis in Periodontitis.

Salivary exosomes contain various components and play an important role in oral diseases. We found that the expression of miR-223-3p in salivary exosomes was down regulated in inflammatory gingival tissue, and NLRP3 was the target of miR-223-3p. It has been reported that NLRP3 was involved in the formation of inflammasome and induced a type of cell death by cleaving gsdermin D (GSDMD), which is called pyroptosis. The purpose of this study was to investigate the role of miR-223-3p in NLRP3 inflammasome activation and pyroptosis. We found that miR-223-3p down regulated the activation of NLRP3, IL-1 β and caspase-1, and then released the pyroptosis of THP-1-derived macrophages inducing by Porphyromonas gingivalis -LPS ( P. gingivalis -LPS). In addition, NLRP3, and GSDMD was highly active in inflammatory gingival tissue compared with healthy controls. In summary, we hypothesized that miR-223-3p in salivary exosomes regulates GSDMD-mediated pyroptosis by targeting NLRP3. Detection of miR-223-3p expression in salivary exosomes could be used as an important non-invasive method to diagnose and evaluate the severity of periodontitis.

Author Correction: Heterogeneous Porphyromonas gingivalis LPS modulates immuno-inflammatory response, antioxidant defense and cytoskeletal dynamics in human gingival fibroblasts

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Ginsenoside Rb3 Inhibits Pro-Inflammatory Cytokines via MAPK/AKT/NF-κB Pathways and Attenuates Rat Alveolar Bone Resorption in Response to Porphyromonas gingivalis LPS

Conventional treatments for chronic periodontitis are less effective in controlling inflammation and often relapse. Therefore, it is necessary to explore an immunomodulatory medication as an adjuvant. Ginsenoside Rb3 (Rb3), one of the most abundant active components of ginseng, has been found to possess anti-inflammatory and immunomodulatory properties. Here, we detected the anti-inflammatory effect of Rb3 on Porphyromonas gingivalis LPS-stimulated human periodontal ligament cells and experimental periodontitis rats for the first time. We found that the expression of pro-inflammatory mediators, including IL-1β, IL-6 and IL-8, upregulated by lipopolysaccharide (LPS) stimulation was remarkably downregulated by Rb3 treatment in a dose-dependent manner at both transcriptional and translational levels. Network pharmacological analysis of Rb3 showed that the mitogen-activated protein kinase (MAPK) signaling pathway had the highest richness and that p38, JNK, and ERK molecules were potential targets of Rb3 in humans. Western blot analysis revealed that Rb3 significantly suppressed the phosphorylation of p38 MAPK and p65 NF-κB, as well as decreased the expression of total AKT. In experimental periodontitis rat models, reductions in alveolar bone resorption and osteoclast generation were observed in the Rb3 treatment group. Thus, we can conclude that Rb3 ameliorated Porphyromonas gingivalis LPS-induced inflammation by inhibiting the MAPK/AKT/NF-κB signaling pathways and attenuated alveolar bone resorption in experimental periodontitis rats.