Tumor necrosis factor α deficiency promotes myogenesis and muscle regeneration.

Tumor necrosis factor α (TNFα) exhibits diverse biological functions; however, its regulatory roles in myogenesis are not fully understood. In the present study, we explored the function of in myoblast proliferation, differentiation, migration, and myotube fusion in primary myoblasts and C2C12 cells. To this end, we constructed muscle-conditional knockout ( -CKO) mice and compared them with mice to assess the effects of knockout on skeletal muscles. Results indicated that -CKO mice displayed phenotypes such as accelerated muscle development, enhanced regenerative capacity, and improved exercise endurance compared to mice, with no significant differences observed in major visceral organs or skeletal structure. Using label-free proteomic analysis, we found that -CKO altered the distribution of several muscle development-related proteins, such as Hira, Casz1, Casp7, Arhgap10, Gas1, Diaph1, Map3k20, Cfl2, and Igf2, in the nucleus and cytoplasm. Gene set enrichment analysis (GSEA) further revealed that deficiency resulted in positive enrichment in oxidative phosphorylation and MyoD targets and negative enrichment in JAK-STAT signaling. These findings suggest that -CKO positively regulates muscle growth and development, possibly via these newly identified targets and pathways.