Identification of CXCL11 As Part of Chemokine Network Controlling Skeletal Muscle Development

The chemokine, CXCL12, and its receptors, CXCR4 and CXCR7, play pivotal roles during development and maintenance of limb muscles. CXCR7 additionally binds CXCL11, which uses CXCR3 as its prime receptor. Based on this cross-talk, we investigate whether CXCL11 would likewise affect development and/or function of skeletal muscles. Western blotting and immunolabelling demonstrated the developmentally restricted expression of CXCL11 in rat limb muscles, which was contrasted by the continuous expression of its receptors in proliferating and differentiating C2C12 cells as well as in late embryonic to adult rat limb muscle fibres. Consistent with a prime role in muscle formation, functional studies identified CXCL11 as a potent chemoattractant for undifferentiated C2C12 cells and further showed that CXCL11 does neither affect myoblast proliferation and differentiation nor metabolic/catabolic pathways in formed myotubes. The use of selective receptor antagonists unravelled complementary effects of CXCL11 and CXCL12 on C2C12 cell migration, which either require CXCR3/CXCR7 or CXCR4, respectively. Our findings provide new insights into the chemokine network controlling skeletal muscle development and function and, thus, might provide a base for future therapies of muscular diseases.