Spatholobus suberectus Stem-Derived Extracellular Vesicle-Like Particles Attenuate Glucocorticoid-Induced Osteoporosis via NRF2/HO-1 Signaling

Purpose: stem-derived extracellular vesicle-like particles (SS-EVLP) could attenuate glucocorticoid-induced osteogenic impairment and explored the potential involvement of NRF2/HO-1 signaling. Methods: SS-EVLP were isolated by ultracentrifugation and characterized by transmission electron microscopy, nanoparticle tracking analysis, and Fourier-transform infrared spectroscopy. Cellular uptake was evaluated using PKH26 labeling. In vitro, MC3T3-E1 pre-osteoblastic cells were exposed to dexamethasone (DEX) and treated with SS-EVLP. Cell viability, apoptosis, alkaline phosphatase (ALP) activity, mineralization, and protein expression were assessed by CCK-8 assay, flow cytometry, staining assays, immunofluorescence, and Western blotting. In vivo, the effects of SS-EVLP were examined in a prednisolone-induced zebrafish model by analyzing particle distribution, skeletal mineralization, osteoblast-associated signals, ALP activity, and osteogenic- and antioxidant-related gene expression. Results: . Conclusion: SS-EVLP attenuated glucocorticoid-induced osteogenic impairment in vitro and in vivo, at least partly through NRF2/HO-1 signaling. These findings support the potential of SS-EVLP as a plant-derived nanovesicle candidate for GIOP intervention.