Mesenchymal Stem Cells Promote IL-6 Secretion and Suppress the Gene Expression of Proinflammatory Cytokines in Contractile C2C12 Myotubes.

Sarcopenia is not only a major cause of disability but also a risk factor for obesity and diabetes in elderly persons. Exercise is an effective method for improving the sarcopenic condition by inducing the secretion of interleukin (IL)-6, which has the capacities to both promote muscle hypertrophy and regulate lipid metabolism and glucose homeostasis, by skeletal muscle. We previously showed that mesenchymal stem cells (MSCs) promote IL-6 secretion by lipopolysaccharide-stimulated C2C12 mouse skeletal muscle myotubes via paracrine mechanisms. Therefore, in this study, we investigated the effect of paracrine actions of MSCs on IL-6 and proinflammatory cytokine expression in contractile C2C12 myotubes by applying electrical stimulation. IL-6 secretion by C2C12 myotubes was increased by electrical stimulation, and a more significant increase in IL-6 secretion was observed in electrically stimulated C2C12 myotubes cultured in conditioned medium from MSCs. The activation of nuclear factor-κB in C2C12 myotubes was also promoted by the combination of conditioned medium from MSCs and electrical stimulation. Moreover, the increases in tumor necrosis factor-α and IL-1β mRNA expression in C2C12 myotubes induced by electrical stimulation were suppressed by culture in conditioned medium from MSCs. The present findings suggest that MSCs transplantation or injection of their extracellular vesicles improve the therapeutic effect of exercise against sarcopenia without exacerbating inflammation.