Thermal-Enzymatic Production of Egg Yolk-Derived Osteogenic Peptides for Promoting Adolescent Bone Growth

Protein-rich byproducts from food processing serve as promising sources for the generation of bioactive peptides with health-promoting properties, including the regulation of osteoblast proliferation and bone formation. Defatted egg yolk powder, a nutrient-dense natural matrix, is rich in bioactive precursors. However, the high phosphorylation and compact tertiary structure of its constituent proteins hinder the efficient release of osteogenic peptides. Here, we developed a thermal-enzymatic approach to efficiently produce hydrolyzed egg yolk peptide (YPEP) with enhanced bone-anabolic activity. YPEP enhanced bone development in adolescent models by activating osteoblasts, driving longitudinal growth, and improving trabecular microstructure. Proteomic profiling identified an osteogenic peptide, namely FRTPPFGGF (FR9), which targets the epidermal growth factor receptor (EGFR). FR9 markedly enhanced the proliferation and differentiation of murine MC3T3-E1 preosteoblasts. These findings underscore the osteogenic potential of YPEP and suggest the use of FR9 as a promising functional ingredient for promoting bone development during adolescence.