Artesunate Suppresses Osteoclastogenesis in Periodontitis by Blocking NLRP3 Inflammasome Activation

Objectives: 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. In this study, We aimed to investigate the effect of ART in ligature-induced periodontitis and explore the underlying mechanism by which ART protects against periodontitis-induced alveolar bone loss.
Methods: A conventional ligature-induced periodontitis model was generated to demonstrate the therapeutic function of ART on periodontitis. Furthermore, RNA-seq was performed to explore the potential mechanism of ART intervention for the therapy of periodontitis, accompanied by TRAP staining, Western blot, and qPCR.
Results: 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 inflammatory factors under inflammatory conditions.
Conclusions: ART contributed to the amelioration of ligature-induced periodontitis by suppressing osteoclastogenesis by blocking NLRP3 inflammasome activation and enhancing osteogenic potential via alleviating the expression of cytokines under inflammatory conditions. Our data shed light on the potential mechanism of ART treatment for the therapy of periodontitis.