Skeletal muscle atrophy as a consequence of acute and chronic illness, immobilisation, muscular dystrophies and aging, leads to severe muscle weakness, inactivity and increased mortality. Mechanical loading is thought to be the primary driver for skeletal muscle hypertrophy, however the extent to which mechanical loading can offset muscle catabolism has not been thoroughly explored. In vitro 3D-models of skeletal muscle provide a controllable, high throughput environment and mitigating many of the ethical and methodological constraints present during in vivo experimentation. This work aimed to determine if mechanical loading would offset dexamethasone (DEX) induced skeletal muscle atrophy, in muscle engineered using the C2C12 murine cell line. Mechanical loading successfully offset myotube atrophy and functional degeneration associated with DEX regardless of whether the loading occurred before or after 24 h of DEX treatment. Furthermore, mechanical load prevented increases in MuRF-1 and MAFbx mRNA expression, critical regulators of muscle atrophy. Overall, we demonstrate the application of tissue engineered muscle to study skeletal muscle health and disease, offering great potential for future use to better understand treatment modalities for skeletal muscle atrophy.

急性和慢性疾病、制动、肌肉营养不良和衰老导致的骨骼肌萎缩会导致严重的肌肉无力、不活动和死亡率增加。机械负荷被认为是骨骼肌肥大的主要驱动因素，但是机械负荷可以抵消肌肉分解代谢的程度尚未得到彻底探索。骨骼肌的体外 3D 模型提供了一个可控的高通量环境，并减轻了体内实验过程中存在的许多伦理和方法限制。这项工作旨在确定在使用 C2C12 小鼠细胞系工程改造的肌肉中，机械负荷是否会抵消地塞米松 (DEX) 诱导的骨骼肌萎缩。机械负荷成功地抵消了与 DEX 相关的肌管萎缩和功能退化，无论负荷发生在 DEX 治疗 24 小时之前还是之后。此外，机械负荷阻止了肌肉萎缩的关键调节因子 MuRF-1 和 MAFbx mRNA 表达的增加。总体而言，我们展示了组织工程肌肉在研究骨骼肌健康和疾病中的应用，为未来更好地了解骨骼肌萎缩的治疗方式提供了巨大的潜力。