SPACEFLIGHT MIMICKS RAPID BONE AGING
Résumé
Objective: By providing a weightlessness environment, spaceflight induces site-specific bone loss in both human and mice but cellular mechanisms remains unclear. On the other hand, during aging, osteocyte apoptosis associated with lacunae mineral occlusions occurs and bone marrow fat increases. Here, we wanted to analyze the effects of spaceflight on osteocytes lacunae, osteocytes survival and marrow adiposity. Then, we aimed to investigate the events occurring after a short term of earth recovery.Material and Methods: Mature C57/Bl6 male mice flew on the 30-day space Russian BION-M1 high-orbit satellite mission. The Flight group was killed after landing, and the recovery group 8 days later. The ground control group was kept under spacecraft housing conditions. Osteocytes Lacunae of femur cortical sections were imaged using Synchrotron Radiation μCT (resolution 0.7 μm) and 3D shape descriptors were calculated and analysed. Medial, anterior, posterior and lateral zones were analyzed, each containing more than 1200 lacunae. Osteocytes death and bone marrow fat were investigated in femur by histology.Results: The lacunar volume fraction was significantly decreased in the Flight vs. Habitat Control group in medial zone(-33% and -38%, respectively; p<0.025). In the posterior zone, the length/width ratio was significantly decreased in the Flight vs. Habitat Control group, indicating a more spherical lacuna shape in the Flight group. Moreover, particularly in the posterior zone, the lacuna mean volume was significantly decreased and the fraction of smaller lacunae (less than 200μm3) was greater in Flight and Flight+Rec groups vs. Habitat Control. Furthermore, the ratio of empty overall lacunae was dramatically increased in Flight vs. Habitat Control group (11.44% vs. 3.64%, p<0.005) and remained elevated in the Flight+Rec group (9.71%, NS vs. Flight). Finally, femur bone marrow analyses revealed a marrow adipocytes invasion in Flight and Flight+Rec groups.Conclusion: We provide first evidences that one-month spaceflight induces osteocyte death along with decreased osteocyte lacunar volume and increases bone marrow fat, both being hallmarks of aging. No recovery was seen 8-day after landing. Given the critical role of osteocytes to orchestrate bone remodeling, their compromised survival might jeopardize bone reversibility, mainly in the most aged.