CXCL14 Enhances Myocyte Fusion and Activates the FAK-ERK5 Signaling Pathway in Skeletal Muscle Stem Cells and Myoblasts

Skeletal muscle regeneration is essential for maintaining muscle function throughout life and is regulated by numerous growth factors, cytokines and their associated signaling pathways. In this study, we investigated the role of C-X-C motif chemokine ligand 14 (CXCL14) in myogenic differentiation using skeletal muscle stem cells (MuSC) and the mouse myoblast C2C12 cell line. Notably, CXCL14 significantly enhanced myocyte fusion. To elucidate the underlying regulatory mechanisms, we examined fusion-associated signaling pathways and found that CXCL14 activates the focal adhesion kinase-extracellular regulated protein kinase 5 (FAK-ERK5) signaling pathway. Our findings identify the CXCL14-FAK-ERK5 signaling axis as a positive regulator of myocyte fusion. Furthermore, by establishing fibro-adipogenic progenitors (FAPs) as the primary source of CXCL14 and demonstrating its pro-fusion activity, this study provides new insight into the paracrine regulation from FAPs to MuSCs during muscle regeneration.