Peptides from sea cucumber intestine: Preparation and promoting cartilage callus formation in mice with tibial fractures by promoting the polarization of M1 to M2 macrophages

The high-value-added compounds of sea cucumber (Stichopus japonicus) intestine have not been exploited in sea cucumber processing. Here, low molecular weight peptides from the sea cucumber intestine (SCIP) were pre-pared using papain, and the effect of SCIP on promoting cartilage callus formation and their underlying mechanisms were studied. The results exhibited that the SCIP supplement markedly increased the area of the cartilage callus and ameliorated the early inflammatory environment at the fracture site by modulating the levels of inflammatory factors. Furthermore, SCIP promoted the polarization of M1 to M2 macrophages and finally promoted the differentiation of mesenchymal stem cells into chondrocytes at the fracture site through M2-like macrophage-mediated TGF-family factors and secretion of exosomes. This is the first report that SCIP can pro-mote cartilage callus formation in mice with tibial fractures by promoting the polarization of M1 to M2 mac-rophages. SCIP might be considered raw material for developing nutraceutical additives.