Exosomes Derived from BMSCs Treated with CeONPs Ameliorate Radiation-Induced Jaw Bone Injury via miR-21-5p/STAT3 Axis-Mediated Osteogenesis and ROS Scavenging.

Background/Objectives: Radiation-induced jaw bone injury is a severe and refractory complication following radiotherapy, and the key to treatment is promoting osteogenic differentiation and alleviating oxidative stress injury in irradiated BMSCs. Cerium oxide nanoparticles (CeONPs) exhibit considerable research potential in various oxidative stress injury-related diseases due to their excellent reactive oxygen species (ROS) scavenging capacity; however, its biosafety risk makes direct application in disease treatment a matter of controversy. Methods: Recent evidence suggests that treating cells with nanoparticles can regulate the content of exosomes, enhancing the regenerative potential of exosomes. Accordingly, this study was designed to explore the therapeutic effects and underlying mechanism of exosomes derived from BMSCs treated with CeONPs (BMSC-Ce-exos) in radiation-induced jaw bone injury. Results: In vitro, 25 μg/mL CeONPs were identified as the optimal treatment concentration; BMSC-Ce-exos significantly promoted the osteogenic differentiation and reduced the ROS levels of irradiated BMSCs. In vivo, BMSC-Ce-exos notably promoted bone formation and decreased the ROS levels in rats with radiation-induced jaw bone injury. miRNA sequencing revealed that BMSC-Ce-exos were highly enriched with miR-21-5p, which promoted the osteogenic differentiation and reduced the ROS levels of irradiated BMSCs through targeting STAT3. Conclusions: Collectively, these results suggest that BMSC-Ce-exos provided a potential therapeutic approach for radiation-induced jaw bone injury.