Artesunate ameliorates Staphylococcus aureus-induced mandibular osteomyelitis and promotes osteogenic differentiation via NOD2/p65 signaling pathway.

Abstract

OBJECTIVE: This study aimed to investigate the effects and mechanisms of artesunate (AS) on inflammation and osteogenic differentiation under Staphylococcus aureus (S. aureus)-induced inflammatory conditions. METHODS: Alkaline phosphatase staining, Western Blotting, quantitative real-time polymerase chain reaction, and immunofluorescence staining were employed to assess the effects of AS on inflammation and osteogenic differentiation in rat bone marrow mesenchymal stem cells (rBMSCs) under S. aureus-induced inflammation. The rat models of chronic suppurative mandibular osteomyelitis were established, and mandibles were assessed by histology and micro-computed tomography after treatment with AS and/or cefuroxime axetil. RNA sequencing and the NOD2 agonist muramyl dipeptide (MDP) were used to explore mechanisms. RESULTS: In vitro, AS reduced the expression of pro-inflammatory factors and increased the expression of anti-inflammatory and osteogenic factors in rBMSCs. In vivo, AS promoted anti-inflammatory responses and new bone formation in rats, with enhanced effects when combined with cefuroxime axetil. Moreover, AS decreased NOD2 and p-p65 expression while MDP reversed the anti-inflammatory and pro-osteogenic effects of AS. CONCLUSION: AS attenuated inflammation and promoted osteogenic differentiation in rBMSCs by inhibiting the NOD2/p65 pathway. In vivo, AS facilitated the healing of chronic suppurative mandibular osteomyelitis in rats.