The effects of microgravity on human skeletal muscle regeneration.

During long spaceflights, the microgravity condition is able to induce muscle atrophy. This process could also influence the functionality of the satellite cells (SCs), adult muscle stem cells, responsible for both growth and regeneration of skeletal muscle in adult life following injury or stress. Therefore, we studied the differentiated SCs functionality after real microgravity onboard the International Space Station (ISS) in astronaut in order to better understand atrophy mechanisms that involved skeletal muscle, and if satellite cells are affected in this process. To that end, we performed gene expression evaluation with array cards (Human Microarray 60K) and muscle-specific miRNAs analysis in SCs obtained from Vastus Lateralis skeletal muscle needle-biopsies of astronaut and controls subjects on ground. Noteworthy, we discovered a dysregulation of specific genes involved in atrophy, ubiquitin-proteasome and apoptosis pathways related to hypertrophy and atrophy in myotubes exposed to microgravity on ISS compared to myotubes on ground. Furthermore, we found an up-regulation of miR-1, miR-206, miR-133a and miR-133b in myotubes cultured on ground compared to ISS. Interestingly, by exposing both control subjects and astronaut SCs to simulated microgravity (˜0,001 g), we observed that the gene expression of oxidative and mitochondrial markers are down-regulated in myotubes subjected to simulated microgravity compared to on ground condition, confirming mostly the data obtained with the arrays. These findings suggest that the enhanced atrophy process is linked to a microRNA dysregulation together to oxidative and mitochondrial genes involvement. Therefore, thanks to this study will be possible to intervene through specific identified targets by the myomiR and gene modulation, in order to counteract the atrophy process induced by microgravity.