Improvement Effect and Regulation Mechanism of Oyster Peptide on Dexamethasone-Induced Osteoporotic Rats.

The increasing global population of the elderly and rising life expectancy have made osteoporosis a more severe public health issue, necessitating the development of safer and more effective therapeutic strategies. This study investigated the osteoprotective effects of low, medium, and high doses of oyster peptide (OP) in dexamethasone (DEX)-induced osteoporotic rats. Pathological analysis showed that OP treatment effectively mitigated bone loss and repaired bone microarchitecture deterioration caused by DEX administration. In the OP groups, levels of the osteogenic markers osteocalcin (OCN) and osteoprotegerin (OPG) were significantly higher than in the DEX group. Moreover, levels of the osteoclastic markers RANKL, Cathepsin K (Cath-K), MMP-9, C-terminal telopeptide of type I collagen (CTX-1), and Deoxypyridine (DPD) were significantly lower. Bone proteomic analysis of the DEX and OP groups revealed that differentially expressed proteins were significantly enriched in pathways related to extracellular matrix and structural reorganization, ECM-receptor interaction, and PI3K-Akt signaling. Furthermore, virtual screening simulations indicated that peptides with lengths ranging from 11 to 20 amino acid residues were involved in modulating the activity of key receptors in these pathways, including Integrins α5β1, Integrins αvβ3, and EGFR. Collectively, these results demonstrate the significant potential of OP as a novel therapeutic agent for osteoporosis.