Pearl mussel (Hyriopsis cumingii)-derived exosome-like nanovesicles promote osteogenesis and alleviate ovariectomy-induced bone loss in mice.

Osteoporosis is the most common metabolic bone disease that has become a serious public health concern. Food-derived exosome-like nanovesicles have recently emerged as natural functional ingredients with diverse biological activities. In this study, mantle-derived exosome-like nanovesicles from pearl mussel (PMEs) were isolated and systematically characterized. PMEs exhibited a typical cup-shaped morphology with a major size peak at approximately 116.3 nm and were enriched in bioactive lipids, osteogenesis-related proteins, and mineral elements. PMEs were efficiently internalized by osteoblasts and significantly promoted osteogenic differentiation, as evidenced by increased alkaline phosphatase activity and mineralized nodule formation in MC3T3-E1 cells. Moreover, PMEs markedly upregulated osteogenesis-related genes (Runx2, Osx, Ocn, and Opn), and enhanced β-catenin expression and nuclear accumulation. PMEs also maintained structural stability during gastrointestinal digestion and reached bone tissue following oral administration. In ovariectomized mice, PMEs administration significantly improved bone mineral density and trabecular microarchitecture, increased serum PINP levels, and reduced TRAP 5b and IL-6 levels. In addition, no detectable systemic toxicity was observed in healthy mice following PMEs administration. Collectively, these findings identify PMEs as novel food-derived nanovesicles with osteoprotective activity, supporting their potential application as functional ingredients for bone health management.