A novel osteogenic dodecapeptide peptide (PIE), IEELEEELEAER, was purified from the protein hydrolysate of blue mussels (Mytilus edulis). PIE was identified using a capillary electrophoresis electrospray ionization-quadrupole-time of flight mass spectrometer. PIE showed a good reduction in the bone loss in ovariectomized mice, and it also increased the bone mineral density of the ovariectomized mice. PIE has a high affinity with integrins (PDB: 1L5G, 3VI4). There are 8 and 12 amino acid residues from PIE that interact with integrins 1L5G and 3VI4, respectively. PIE accelerates the transformation of G0/G1 phase cells into G2 M phase cells, which promotes the growth of osteoblasts. PIE (100 μg mL−1) can enhance alkaline phosphatase (ALP) activity by 26.48% compared with the control, and it also inhibits the growth of osteoclasts and tartrate resistant acid phosphatase (TRAP) activity. Therefore, PIE may contribute to preventing osteoporosis both in vitro and in vivo.
