Delayed denervation-induced muscle atrophy in knockout mice.

Recent evidence has shown a crucial role for the osteoprotegerin/receptor activator of nuclear factor κ-B ligand/RANK (OPG/RANKL/RANK) signaling axis not only in bone but also in muscle tissue; however, there is still a lack of understanding of its effects on muscle atrophy. Here, we found that denervated knockout mice displayed better functional recovery and delayed muscle atrophy, especially in a specific type IIB fiber. Moreover, OPG deficiency promoted milder activation of the ubiquitin-proteasome pathway, which further verified the protective role of knockout in denervated muscle damage. Furthermore, transcriptome sequencing indicated that knockout upregulated the expression of , , and and downregulated that of in denervated muscle. experiments revealed that satellite cells derived from knockout mice displayed a better differentiation ability than those acquired from wild-type littermates. Higher expression levels of were also observed in satellite cells derived from knockout mice, which provided a possible mechanistic basis for the protective effects of knockout on muscle atrophy. Taken together, our findings uncover the novel role of in muscle atrophy process and extend the current understanding in the OPG/RANKL/RANK signaling axis.