AUTHOR=Zhang Mingming , Chen Ming , Li Yi , Rao Man , Wang Duanyang , Wang Zhongqi , Zhang Licheng , Yin Pengbin , Tang Peifu 

TITLE=Delayed denervation-induced muscle atrophy in Opg knockout mice

JOURNAL=Frontiers in Physiology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2023.1127474

DOI=10.3389/fphys.2023.1127474

ISSN=1664-042X

ABSTRACT=<p>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 <italic>Opg</italic> 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 <italic>Opg</italic> knockout in denervated muscle damage. Furthermore, transcriptome sequencing indicated that <italic>Opg</italic> knockout upregulated the expression of <italic>Inpp5k</italic>, <italic>Rbm3</italic>, and <italic>Tet2</italic> and downregulated that of <italic>Deptor</italic> in denervated muscle. <italic>In vitro</italic> experiments revealed that satellite cells derived from <italic>Opg</italic> knockout mice displayed a better differentiation ability than those acquired from wild-type littermates. Higher expression levels of <italic>Tet2</italic> were also observed in satellite cells derived from <italic>Opg</italic> knockout mice, which provided a possible mechanistic basis for the protective effects of <italic>Opg</italic> knockout on muscle atrophy. Taken together, our findings uncover the novel role of <italic>Opg</italic> in muscle atrophy process and extend the current understanding in the OPG/RANKL/RANK signaling axis.</p>