Abstract
Reduced mechanical stress, such as long-term bedrest and spaceflight, negatively regulates skeletal muscle mass and function, while increased mechanical stress, such as exercise, positively regulates them. In this study, biochemical and bulk RNA-seq transcriptome analyses of skeletal muscles were performed on skeletal muscles from mice bred under altered mechanical stress conditions, including centrifugal loading (2 g) and hindlimb unloading (HLU). As a result, under increased mechanical stress conditions of 2 g, skeletal muscle hypertrophy of the slow-twitch soleus and fast-twitch quadriceps femoris was significantly induced. A Bulk RNA-seq analysis revealed that 1,016 differentially expressed genes (DEGs) in 2 g-soleus and 271 DEGs in 2 g-quadriceps femoris of HLU mice were detected. Atrogenes were downregulated in both 2 g-soleus and 2 g-quadriceps femoris, while several genes, such as extracellular matrix remodeling, were upregulated, especially in 2 g-soleus. Under reduced mechanical stress conditions of μg and HLU, skeletal muscle atrophy was significantly induced, especially in the slow-twitch soleus. Bulk RNA-seq analysis revealed that 1,828 DEGs in HLU-soleus and 1,496 DEGs in HLU-fast-twitch dominant tibialis anterior were detected. Atrogenes, which are involved in muscle atrophy, were upregulated in both HLU-soleus and HLU-tibialis anterior. On the other hand, several gene clusters associated with muscle atrophy were additively downregulated in HLU-soleus but not HLU-tibialis anterior. These results indicated that reduced mechanical stress conditions negatively regulate skeletal muscle mass in both fast-twitch and slow-twitch muscles. In contrast, increased mechanical stress conditions by centrifugal loading at 2 g positively regulate it. Furthermore, while both slow-twitch and fast-twitch dominant muscles showed similar responsiveness in atrogenes, additive genes in slow-twitch dominant muscle only showed changes in genes related to several pathways. This review summarizes the latest findings on regulating skeletal muscle mass by altering mechanical stress.
