Osteogenic Effects of Brown Algae <i>Sargassum fulvellum</i> -Derived Exosome-Like Nanovesicles via the BMP-2/4-MAPK-Smad1/5/8 Signaling Pathway

Osteoporosis is a prevalent metabolic bone disorder that is characterized by reduced bone mass and microarchitectural deterioration, especially in women who are postmenopausal. Brown algae such as <i>Sargassum fulvellum</i> contain bioactive compounds with potential bone health benefits. This study examined the effects of <i>S. fulvellum</i>-derived exosome-like nanovesicles (SfNVs) on osteoblast differentiation and mineralization. SfNVs were isolated via differential ultracentrifugation, characterized by nanoparticle tracking analysis, bicinchoninic acid protein assay, and NanoImaging, and subsequently applied to MC3T3-E1 osteoblasts. The SfNVs (∼208 nm) were efficiently internalized without exhibiting cytotoxicity and significantly enhanced alkaline phosphatase activity, mineralized nodule formation, and the expression of osteogenic markers, such as Runx2, ALP, OPN, and ProCOL I. In addition, the SfNVs upregulated the expression of BMP-2/4 and activated the MAPK (p38, JNK, and ERK) and Smad1/5/8 signaling pathways. Collectively, these findings indicate that SfNVs promote osteoblast differentiation and mineralization via the BMP-2/4-MAPK-Smad1/5/8 axis, thereby suggesting their potential as functional marine-derived biomaterials for the nutritional prevention of bone metabolic diseases.