Hanyu Gao,1 Shoucheng Yin,1 Yuanzheng Yan,2 Yining Jin,1 Muzhou Jiang,1 Yanqing Liu,1 Lijie Lu,1 Ziming Ge,1 Yunzhu Cai,3 Hongyan Wang,1 Chen Li,1 Yaping Pan,1 Li Lin1 1Department of Periodontology, School and Hospital of Stomatology, China Medical University, Shenyang, Liaoning, Peopleâs Republic of China; 2Department of Periodontology, Suzhou Stomatological Hospital, Suzhou, Jiangsu, Peopleâs Republic of China; 3Department of Pediatric Dentistry, School and Hospital of Stomatology, China Medical University, Shenyang, Liaoning, Peopleâs Republic of ChinaCorrespondence: Li Lin, Email linli@cmu.edu.cnPurpose: Alveolar bone resorption in periodontitis is the primary clinical cause of tooth loss. This study aimed to investigate the inhibitory effect of Allium cepa L.-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. The process begins with onions, leading to AC-EVs, followed by density gradient centrifugation, ultracentrifugation and ultrasound, resulting in ACEV@CEL. Celecoxib is added during ultracentrifugation. In vivo testing involves a periodontitis model in rats, assessing biocompatibility and alveolar bone resorption inhibitory ability. In vitro testing uses RAW264.7 cells to evaluate AC-EVs and ACEV@CELâs ability to inhibit osteoclast differentiation. Result analysis compares Celecoxib or AC-EVs with ACEV@CEL.Graphical abstract showing the preparation of ACEV@CEL and their therapeutic effects in periodontitis. ACEV@CEL is generated via ultrasonication and applied in a rat periodontitis model and RAW264.7 cells, demonstrating good biocompatibility, reduced alveolar bone resorption, and inhibition of osteoclast differentiation.Keywords: periodontitis, plant-derived extracellular vesicles, osteoclast
Gao et al. (Wed,) studied this question.