Osteogenic peptides in collagen hydrolysates: Stimulate differentiation of MC3T3-E1 cells via β1 integrin-FAK-ERK1/2 signaling pathway and Smad1 protein

Our previous study demonstrated that orally administration of collagen hydrolysates from silver carp skin (SCH) could increase bone remodeling in chronologically aged mice. However, the active compounds and molecular mechanism were still unclear. In this study, SCH showed strong activity in promoting osteogenic differentiation of MC3T3-E1 cells and the active components in it were separated by ultrafiltration and YMC ODS-A C18 column. And then, a series of peptides containing potential osteogenic sequences were identified by LC-MS/MS and two novel peptides, GARGDKGETGEAGE (GE-14) and TGPRGPVGPA (TA-10), were synthesized for further investigation. The results indicated that peptides GE-14 and TA-10 could promote the differentiation and mineralization of MC3T3-E1 cells by positively regulating β1 integrin-FAK-ERK1/2 and Smad1 pathway, which might be due to the RGD or GPR sequences in them. These findings suggest that SCH has the potential to be developed as an effective diet supplement to prevent osteoporosis.