Fe3O4 Magnetic Nanoparticles and Static Magnetic Field Stimulated BMSC-Derived Exosomes Promoted Osteogenesis and Alleviated Oxidative Stress in Irradiated BMSCs Through miR-429/NOG Pathway

Radiation-induced bone injury, characterized by oxidative stress damage and impaired osteogenesis, lacks effective treatments. Exosome-based therapies have recently emerged as a safe and effective modality for radiation damage, and their functional capacity can be further potentiated through tailored preconditioning strategies—such as nanoparticle induction or physical stimulation. This study developed a novel exosome-based therapy by preconditioning bone marrow mesenchymal stem cells (BMSCs) with Iron oxide (Fe3O4) magnetic nanoparticles (MNPs, 50 µg/mL) and a static magnetic field (SMF, 100 mT). Exosomes derived from these preconditioned cells (BMSC-Fe3O4-SMF-Exos) exhibited enhanced yield and dual functionality. In irradiated BMSCs, BMSC-Fe3O4-SMF-Exos significantly promoted osteogenic differentiation, restoring alkaline phosphatase activity, mineralization, and expression of RUNX2, OCN, and COL1A1. They concurrently alleviated oxidative stress by scavenging reactive oxygen species, reducing malondialdehyde, and boosting superoxide dismutase activity. Mechanistically, miR-429 was found to be highly enriched in BMSC-Fe3O4-SMF-Exos, which directly targeted Noggin (NOG). Our functional validation experiments also confirmed that overexpression of miR-429 could inhibit NOG, alleviate oxidative stress and rescue the osteogenic differentiation of irradiated BMSCs. In conclusion, exosomes derived from preconditioning BMSCs with Fe3O4 MNPs and SMF mitigate radiation-induced damage via the miR-429/NOG pathway, presenting a promising cell-free strategy for bone regeneration.