Artesunate ameliorates ligature-induced periodontitis by attenuating NLRP3 inflammasome-mediated osteoclastogenesis and enhancing osteogenic differentiation

Periodontitis, arguably the greatest common infective chronic inflammatory disease, is characterized by an imbalance of the host immune system and excessive osteoclastogenesis activity with severe alveolar bone loss. Nevertheless, in consideration of the harmful effects of repeated treatment, more sensible intervention drugs for periodontitis need to be developed. Artesunate (ART), derived from Artemisia annua L., has shown remarkable pharmacokinetic and clinical value, as well as anti-inflammatory and immunomodulatory effects in various immune and chronic diseases due to its endoperoxide group. However, the role of ART in mediating periodontitis-induced alveolar bone resorption has not been examined. In this study, ART treatment effectively ameliorated ligature-induced periodontitis via attenuating osteoclast formation in a dose-dependent manner. Mechanistically, RNA-seq revealed that ART dramatically reduced the enrichment of NLRP3 inflammasome-related genes. Concordant with our study, MCC950, a specific inhibitor of NLRP3 inflammasome, also greatly restrained osteoclastogenesis, suggesting that ART suppressed osteoclast formation by blocking NLRP3 inflammasome activation. In addition to regulating osteoclastogenesis, ART significantly enhanced osteogenic differentiation by alleviating the expression of cytokines in inflammatory conditions. Our data shed light on the probably potential mechanism of ART treatment for the intervention of periodontitis.