Blue mussel (Mytilus edulis) protein hydrolysate promotes mouse mesenchymal stem cell differentiation into osteoblasts through up-regulation of bone morphogenetic protein

•Blue mussel protein hydrolysates (BMPH) were produced by enzymatic hydrolysis.•BMPH < 1 kDa promoted MSCs differentiation into osteoblast.•Activations of BMP-2 signal pathways by BMPH < 1 kDa were involved in osteoblast differentiation.•MAPK pathway was also involved in osteoblast differentiation.

Seafood provides a range of health benefits due to its high-protein level. In this study, the osteogenic effect of blue mussel (Mytilus edulis) protein hydrolysates (BMPH) on osteoblast differentiation were examined using mouse mesenchymal stem cells (MSCs). A preparation we called BMPH < 1 kDa which showed the highest osteogenic effect in MSCs, was prepared by peptic hydrolysis. BMPH < 1 kDa treatment stimulated osteoblast differentiation with alkaline phosphatase (ALP) induction, osteocalcin and type I collagen activity as well as calcium deposition. Osteoblast differentiation stimulated by BMPH < 1 kDa treatment was achieved by expression of osteogenic lineage markers, such as bone morphogenetic protein-2 (BMP-2), and downstream signal and transcription factors, including p-Smad1/5/8, Dlx5, runt-related transcription factor 2 (Runx2), and osterix. BMPH < 1 kDa activated phosphorylation of mitogen-activated protein kinases. Adding noggin, a BMP antagonist, inhibited BMPH < 1 kDa-induced ALP activity in MSCs. Taken together, our results show that BMPH < 1 kDa promoted osteoblast differentiation by activating BMP-2.