Achilles tendon exhibits distinct transcriptomic changes with increased mitochondrial energy production under lunar...

Within the musculoskeletal system, the effects of reduced gravity on muscle and bone are well characterized, whereas the role of tendons remains poorly understood. In this study, we investigated adaptations of the Achilles tendon to lunar gravity using RNA-seq of mice maintained on the International Space Station for 25-26 days. Compared with quadriceps femoris muscle and brown adipose tissue, more genes were upregulated in the Achilles tendon under lunar gravity. Enrichment analyses revealed significant upregulation of mitochondrial energy production, while extracellular matrix organization and collagen fiber organization were downregulated. Histological analyses revealed unchanged tendon fiber density but reduced mature collagen fibers, accompanied by increased ATP5B protein expression in the lunar gravity group. These findings indicate a tendon-specific enhancement of mitochondrial energy production under lunar gravity, potentially linked to impaired collagen maturation. Our insights may contribute to the development of therapeutic strategies for tendon degeneration associated with aging and disuse.