Abstract
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. 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.
Highlights
Myoblast fusion is an indispensable step for skeletal muscle development, postnatal growth, and regeneration
Quantitative analysis of dystrophinstained sections showed that the average myofiber cross-sectional area (CSA) was significantly reduced in tibialis anterior (TA) muscle of 2-week-old Myeloid differentiation primary response gene 88 (MyD88)-KO mice compared with age-matched WT mice (Fig. 1d–f)
A few studies have previously investigated the role of MyD88 in skeletal muscle, they were focused toward understanding the role of Toll-like receptors (TLRs) and associated inflammatory response in models of chronic muscle injuries such as muscular dystrophy[52,53,54] or ischemic injury[53, 55], which involves divergent inflammatory response and myopathy[56]
Summary
Myoblast fusion is an indispensable step for skeletal muscle development, postnatal growth, and regeneration. MyD88 regulates non-canonical NF-κB and canonical Wnt signaling during myogenesis and promotes skeletal muscle growth and overloadinduced myofiber hypertrophy in mice. Myoblast fusion is a critical step for development of skeletal muscle during embryogenesis, and for satellite cell-mediated regeneration of injured myofibers in adults[3, 4]. Myoblast fusion involves an array of signaling pathways that are activated as a result of the recruitment of specific cell-surface proteins between fusion partners or as a part of the myogenic differentiation program[14, 18]. Activation of the canonical Wnt pathway promotes myoblast fusion in vitro[20] and during regeneration of skeletal muscle in adult mice[21]. Apical signaling mechanisms that regulate the activation of various profusion pathways during myogenesis remain unknown
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
