Sika deer bone peptide attenuates ovariectomy-induced osteoporosis in mice via PPAR-γ/Axin2/Wnt signaling pathway

Sika deer bone peptides (DBP-1-3) were extracted and purified from fresh deer bones. In ovariectomized (OVX) osteoporotic mice, DBP-1-3 increased serum calcitonin (CT), estradiol (E2), and 1,25(OH) 2 D 3 while reducing Ca 2+ and bone gla protein (BGP). Micro-CT analysis revealed improved trabecular bone structure, with increased bone volume/total volume (BV/TV), trabecular number (Tb.N), and thickness (Tb.Th), and decreased trabecular separation (Tb.Sp). Mechanistically, DBP-1-3 downregulated PPAR-γ and Axin2 while upregulating β-catenin, suggesting inhibition of the PPAR-γ/Axin2 pathway and activation of Wnt signaling. These findings indicate that DBP-1-3 alleviates osteoporosis by modulating bone metabolism and enhancing bone microstructure, potentially via PPAR-γ/Axin2/Wnt regulation. • DBP-1-3 elevates serum calcitonin (CT) while reducing bone Gla protein (BGP). • DBP-1-3 raises E2 and 1,25(OH)₂D₃, but lowers serum Ca 2+ . • DBP-1-3 stimulates osteoblast activity, bone mineralization, and formation. • DBP-1-3 increases the thickness and number of bone trabeculae. • Its mechanism may involve inhibiting PPAR-γ/Axin2 and activating Wnt signaling.