Inhibitory Effect of.-Derived Extracellular Vesicles Loaded with Celecoxib on Osteoclast Differentiation in Periodontitis.

Abstract

PURPOSE: Alveolar bone resorption in periodontitis is the primary clinical cause of tooth loss. This study aimed to investigate the inhibitory effect of.-derived extracellular vesicles (AC-EVs) loaded with celecoxib (ACEV@CEL) on alveolar bone resorption. METHODS: AC-EVs were isolated using gradient centrifugation in combination with ultracentrifugation, after which celecoxib was incorporated via ultrasonication to generate ACEV@CEL. Subsequently, a rat periodontitis model was established, and local administration was performed to systematically evaluate the biocompatibility and therapeutic effects on alveolar bone resorption. In vitro, after determining the optimal administration dose for each treatment group, we confirmed that RAW264.7 cells were able to internalize AC-EVs and ACEV@CEL. In the established in vitro periodontitis model, ACEV@CEL significantly inhibited osteoclast differentiation, and this inhibitory effect was stronger than that of either AC-EVs or celecoxib alone. RESULTS: In vivo, ACEV@CEL exhibited good biocompatibility and effectively suppressed alveolar bone resorption in rats with periodontitis. In vitro, ACEV@CEL was internalized by RAW264.7 cells and inhibited their differentiation into osteoclasts. CONCLUSION: ACEV@CEL is able to suppress osteoclast differentiation under periodontitis conditions, while demonstrating favorable biocompatibility and safety, suggesting its potential as a therapeutic agent for periodontitis and warranting further long-term investigation.