Scientists at the University of Louisville School of Medicine say they have found that a well-known protein, myeloid differentiation primary response gene 88 (MyD88), plays a critical role in the development and regeneration of muscles. Ashok Kumar, Ph.D., professor and distinguished university scholar in the department of anatomical sciences and neurobiology, led a team of researchers who have described the protein's importance in the growth and repair of skeletal muscles, both in postnatal development and in the regeneration of injured adult muscles.
The study (“MyD88 Promotes Myoblast Fusion in a Cell-Autonomous Manner”) is published in Nature Communications.
“Myoblast fusion is an indispensable step for skeletal muscle development, postnatal growth, and regeneration. Myeloid differentiation primary response gene 88 (MyD88) is an adaptor protein that mediates Toll-like receptors and interleukin-1 receptor signaling. Here we report a cell-autonomous role of MyD88 in the regulation of myoblast fusion. MyD88 protein levels are increased during in vitro myogenesis and in conditions that promote skeletal muscle growth in vivo. Deletion of MyD88 impairs fusion of myoblasts without affecting their survival, proliferation, or differentiation,” write the investigators.”
“MyD88 regulates non-canonical NF-κB and canonical Wnt signaling during myogenesis and promotes skeletal muscle growth and overload-induced myofiber hypertrophy in mice. Ablation of MyD88 reduces myofiber size during muscle regeneration, whereas its overexpression promotes fusion of exogenous myoblasts to injured myofibers. Our study shows that MyD88 modulates myoblast fusion and suggests that augmenting its levels may be a therapeutic approach to improve skeletal muscle formation in degenerative muscle disorders.”
Specialized progenitor or stem cells multiply to help form muscle. They differentiate into myoblasts that fuse together and subsequently form muscle fiber. Using animal models, these researchers worked with both neonatal cells and adult cells to determine that MyD88, a key signaling protein in the human body, is required in sufficient quantity for myoblasts to fuse.
Sajedah M. Hindi, Ph.D., a postdoc fellow, believes that MyD88 eventually may be used to improve the effectiveness of therapies using donor cells for the treatment of degenerative muscle disorders such as muscular dystrophies.
“Since MyD88 promotes only the fusion of myoblasts without affecting their proliferation or differentiation, enhancing the levels of MyD88 levels could be a means to enhance engraftment of exogenous myoblasts in cellular therapies,” Dr. Hindi said
Dr. Kumar adds that increasing the expression of MyD88 could be used in the treatment of rhabdomyosarcomas, cancerous tumors that develop in skeletal muscles and often affect children.
“We are investigating whether augmenting the levels of MyD88 inhibits growth of rhabdomyosarcoma in animal models,” Dr. Kumar said. “Finally, we are investigating whether the loss of MyD88 is responsible for the diminished muscle regeneration capacity in the elderly.”
