Undaria pinnatifida-derived nanovesicles regulate bone remodeling by stimulating osteoblast differentiation and suppressing osteoclast formation

Exosomes-like nanovesicles derived from edible marine resources represent emerging food-origin bioactive carriers with potential impacts on human health. In this study, we isolated and characterized nanovesicles from Undaria pinnatifida (UPNVs) and investigated their chemical properties and regulatory functions in bone-related cell processes. Physicochemical analyses confirmed that UPNVs exhibit a spherical lipid-bilayer morphology with an average diameter of approximately 160 nm and contain characteristic membrane proteins and lipid components commonly found in plant-derived vesicles. Proteomic and biochemical profiling suggested that UPNVs harbor bioactive molecules associated with osteogenic signaling pathways. Functionally, UPNVs were associated with increased alkaline phosphatase activity and mineral deposition in MC3T3-E1 cells and primary osteoblasts, along with changes consistent with involvement of the BMP2/MAPK/SMAD1 axis and RUNX2-related differentiation. In contrast, UPNVs suppressed RANKL-induced osteoclast formation by reducing TRAP activity and downregulating c-Fos and NFATc1 expression. Oral administration of UPNVs was not associated with observable systemic toxicity and showed biodistribution primarily in the gastrointestinal tract with detectable signals in organs. These findings provide a chemical and biological characterization of edible algae–derived nanovesicles and indicate that UPNVs modulate bone-related cellular processes in vitro . Further in vivo studies incorporating bone-specific analyses are warranted to validate their potential for bone health applications. • Exosome-like nanovesicles were isolated and characterized from the edible seaweed Undaria pinnatifida . • UPNVs enhanced osteoblast differentiation and extracellular matrix mineralization in vitro . • UPNVs suppressed RANKL-induced osteoclast differentiation via downregulation of C-Fos and NFATc1. • Orally administered UPNVs showed no observable systemic toxicity under the experimental conditions used.