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

Gravity plays a fundamental role in maintaining the structure and function of biological tissues, particularly within the musculoskeletal system. In space, the absence or reduction of gravitational forces leads to musculoskeletal deterioration, posing significant challenges for astronauts and individuals experiencing prolonged immobilization. Consequently, the effects of microgravity on muscle and bone have been extensively studied. Recent research highlights the crucial role of tendons in force transmission and mechanical stability; however, their transcriptomic response to reduced gravity remains largely unexplored. Here, we examined the adaptations of the Achilles tendons to lunar gravity (1/6 of Earth gravity) using RNA sequencing of tissue samples obtained from mice reared in the International Space Station for 25-26 days. Compared to quadriceps femoris muscles and brown adipose tissue, a greater number of genes were upregulated in the Achilles tendons under reduced gravity. Enrichment analyses revealed a significant upregulation of mitochondrial energy production in the Achilles tendons exposed to reduced gravity. Meanwhile, genes associated with extracellular matrix organization and collagen integrity were downregulated. Although histological examination showed no obvious structural differences between the lunar and Earth gravity groups, the expression of Atp5b, a subunit of ATP synthase, was enhanced in the lunar gravity group. Our findings suggest that mechanical loading regulates tendons by influencing mitochondrial energy production and extracellular matrix composition. These insights may contribute to therapeutic strategies for tendon degeneration associated with aging and disuse-related conditions.