Dental Pulp Stem Cell-Secreted Factors Enhance Exercise-Associated Myokine Expression in Skeletal Muscle

Exercise-induced myokines not only regulate skeletal muscle physiology but also enter circulation and exert beneficial effects on distant organs. Dental pulp stem cells (DPSCs) are considered promising tools for regenerative medicine, largely because of the diverse bioactive factors they secrete. In this study, we investigated the effects of DPSC-secreted factors (DPSC-SFs) on exercise-associated responses in skeletal muscle. C2C12 myoblasts and differentiated myotubes were treated with DPSC-SFs, and myokine expression and secretion were assessed using quantitative PCR and ELISA, respectively. In addition, DPSC-SFs were injected into the hindlimb skeletal muscles of Sprague–Dawley rats, followed by assessment of myokine expression and muscle strength. DPSC-SFs significantly increased the gene expression and protein secretion of follistatin-like 1 (FSTL1) in C2C12 myoblasts and increased the expression of FSTL1 and fibroblast growth factor 21 (FGF21) in C2C12 myotubes. Furthermore, intramuscular administration of DPSC-SFs increased the gene and protein expression of FSTL1 and FGF21 in rat skeletal muscle and was accompanied by an increase in muscle strength. These findings suggest that DPSC-SFs may induce selected molecular and functional responses associated with exercise, particularly the upregulation of the exercise-associated myokines FSTL1 and FGF21 and an increase in muscle strength.