Porcine bone collagen peptides promote osteoblast proliferation and differentiation by activating the PI3K/Akt signaling pathway.

• Functional efficacies of porcine bone collagen peptides with different molecular weights (MWs) were compared. • Collagen peptides (<1 kDa) increased proliferation and cell cycle and inhibited apoptosis. • The underlying mechanism was revealed that low-MW peptides exerted their effects by activating PI3K/Akt. Collagen peptides are widely used in food and medicine industries. Given the significant role of collagen in bone structure, collagen peptides are considered promising for osteoporosis prevention and treatment. To elucidate their effect on osteoporosis, we extracted porcine collagen, digested it into peptides, and investigated their biological function using osteoblast MC3T3-E1 cells. The collagen structure was relatively stable and we prepared peptides with different molecular weights (MWs) via hydrolysis with two commercially-available enzymes (alcalase/trypsin). Low-MW (<1 kDa) peptides, mainly comprised of tripeptides, increased proliferation and promoted cell cycle progression by upregulating CDK-2, CDK-4, Cyclin B1, and Cyclin D1, and inhibited apoptosis by decreasing Bax/Bcl-2 and cleaved caspase-3 expression. Meanwhile, they upregulated p-Akt and downregulated PTEN, indicating that low-MW peptides inhibited apoptosis and promoted osteoblast proliferation and differentiation by activating PI3K/Akt pathway. Thus, we report the mechanism through which porcine bone-derived collagen peptides could be used to prevent and treat osteoporosis. [ABSTRACT FROM AUTHOR]