Long-term exposure to weightlessness can result in bone and muscle degradation, significantly impacting musculoskeletal function. Recent studies have also indicated damage to articular cartilage due to weightlessness. This study aims to observe the effects of simulated weightlessness on the cartilage microstructure of the quadriceps muscle and the muscular knee joint in rats. A total of 30 rats were used in this study, of which 20 rats were subjected to simulated weightlessness by tail suspension, which may be suitable for clinical long-term bedridden patients. At 14 and 28 days, the microscopic morphology of knee cartilage and quadriceps femoris muscle was observed by transmission electron microscopy, and the collagen and water content of cartilage was evaluated by magnetic resonance imaging. The mitochondrial activity of knee muscle and the levels of inflammatory factors in synovial fluid were detected by enzyme-linked immunosorbent assay (ELISA). Biomechanical and histological evaluation of cartilage was performed. On day 14, T2 mapping revealed no significant loading effect. However, transmission electron microscopy revealed altered mitochondrial inner membrane structure in cartilage, with vacuolization, disrupted endoplasmic reticulum, alongside mitochondrial ultrastructural damage in muscle. ELISA results showed that a large number of mitochondria in muscle were inactivated, and the levels of inflammatory factors in synovial fluid were increased. The staining results showed slight fracture of the cartilage surface and the type II collagen-positive cells were reduced. Nanoindentation showed that the cartilage microsurface was uneven, and the elastic modulus and hardness were decreased. On day 28, T2 mapping analysis indicated increased cartilage T2 values. Transmission electron microscopy showed alterations in the structure of the mitochondrial inner membrane in cartilage, severe vacuolization, disrupted endoplasmic reticulum, and substantial mitochondrial damage in muscle tissue. Muscle mitochondrial activity was markedly decreased, inflammatory factors levels were elevated, and the cartilage surface exhibited severe damage. The type II collagen positive cells were further reduced, the micro-surface of cartilage was uneven, and the elastic modulus and hardness were significantly decreased. The weightless environment resulted in the damage of endoplasmic reticulum and mitochondria of cartilage, mitochondrial damage of quadriceps muscle, inactivation of muscle mitochondria (P=0.01), increased intra-articular inflammation (P=0.01), decreased elastic modulus and hardness (P=0.03), and damaged cartilage surface, which aggravated cartilage degeneration.
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