Microgravity-Induced Alterations in miRNA-mRNA Networks: Implications for Bone Regeneration after Femoral Injury

Rehabilitation from musculoskeletal injuries (MSKI) complicates healing dynamics typically by sustained disuse of bone and muscles. The current study examined the self-healing process post-segmental bone defect (SBD) surgery in a prolonged unloading condition after spaceflight (FLT) using epigenetic evaluation. Seven-week-old C57BL/6J male mice were acclimated for 2 weeks prior to either receiving an SBD or serving as un-operated sham controls. Surgery procedures occurred 4 days prior to launch; post-launch, the FLT mice were housed in the rodent habitats on the International Space Station (ISS) for approximately 4 weeks before euthanasia. These mice were randomized into 4 groups: 1) Sham on Ground (GRD-Sham); 2) Sham surgery housed in FLT (FLT-Sham); 3) SBD surgery on Ground (GRD-Surgery); and 4) SBD surgery housed in the FLT (FLT-Surgery). The midshaft of the ipsilateral femur (containing the fractured callus in the surgical mice) as well as the ipsilateral quadriceps tissue were used for the miRNA analysis.