The secretome of human dental pulp stem cells protects myoblasts from hypoxia-induced injury via the Wnt/β-catenin pathway

Human dental pulp stem cells (hDPSCs) present several advantages, including their ability to be non-invasively harvested without ethical concern. The secretome of hDPSCs can promote the functional recovery of various tissue injuries. However, the protective effects on hypoxia-induced skeletal muscle injury remain to be explored. The present study demonstrated that C2C12 myoblast coculture with hDPSCs attenuated CoCl(2)-induced hypoxic injury compared with C2C12 alone. The hDPSC secretome increased cell viability and differentiation and decreased G2/M cell cycle arrest under hypoxic conditions. These results were further verified using hDPSC-conditioned medium (hDPSC-CM). The present data revealed that the protective effects of hDPSC-CM depend on the concentration ratio of the CM. In terms of the underlying molecular mechanism, hDPSC-CM activated the Wnt/β-catenin pathway, which increased the protein levels of Wnt1, phosphorylated-glycogen synthase kinase-3β and β-catenin and the mRNA levels of Wnt target genes. By contrast, an inhibitor (XAV939) of Wnt/β-catenin diminished the protective effects of hDPSC-CM. Taken together, the findings of the present study demonstrated that the hDPSC secretome alleviated the hypoxia-induced myoblast injury potentially through regulating the Wnt/β-catenin pathway. These findings may provide new insight into a therapeutic alternative using the hDPSC secretome in skeletal muscle hypoxia-related diseases.