| Description |
Bone remodeling is a continuous process that maintains bone strength and function through osteoclast-mediated bone resorption, followed by osteoblast-driven matrix deposition and mineralization. This sequence of cellular events is highly influenced by mechanical stimuli. Consequently, reduced mechanical load—such as during injury, prolonged bed rest, ageing, or spaceflight—can disrupt this balance, leading to decreased bone quality.While the role of mechanical stimuli and its relation to bone remodeling are extensively studied, the time-dependent dynamics of bone remodeling in relation to physical training and reduced mechanical loading remain completely unexplored. In this work, we investigate how reduced mechanical load and physical activity affect bone properties, morphology, and remodeling dynamics. To achieve this, we have designed a complex experimental setup followed by a combination of state-of-the-art techniques. Adult female Wistar rats underwent endurance(weight-bearing) and resistance (treadmill) training, followed by Hindlimb Unloading and enhanced Partial Weight Bearing to mimic reduced mechanical load and in parallel, spaceflight conditions. In vivo, assessments included performance monitoring during physical training and body composition analysis (EchoMRI). Subsequently, we took advantage of newly developed approachBEE-ST (Bones and tEEth Spatio-Temporal growth monitoring) which enabled to evaluate remodeling dynamics of femur, humerus, and calvaria. Moreover, to refine the bone mechanical properties and morphology of different experimental conditions, micro-computed tomography was performed. Our results demonstrate that physical training before mechanical unloading preserves bone density, morphology, and function and as a first once precisely quantify these events. Furthermore, we show that mechanical unloading alone leads to a pronounced increase in bone resorption. Rats subjected to training exhibited enhanced load-carrying capacity, bearing up to three times their body weight. These findings underscore the critical role of physical training in mitigating the effects of reduced mechanical load and reveal, for the first time, the spatiotemporal dynamics of bone remodeling during this process. Our complex approach provides valuable insights for various clinical applications and future space missions, ensuring crew health.
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