Supplementary Information Files for Mechanical loading of tissue engineered skeletal muscle prevents dexamethasone induced myotube atrophy

Supplementary Information Files for Mechanical loading of tissue engineered skeletal muscle prevents dexamethasone induced myotube atrophySkeletal 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.

本数据集包含针对组织工程化骨骼肌机械负荷的研究补充信息文件，旨在研究地塞米松诱导的肌管萎缩。骨骼肌萎缩作为急性与慢性疾病、固定、肌肉萎缩症及衰老的后果，导致肌肉严重虚弱、不活动性增加及死亡率上升。机械负荷被认为是骨骼肌肥大的主要驱动力，然而，机械负荷能够抵消肌肉分解的程度尚未得到充分研究。体外三维骨骼肌模型提供了一个可控、高通量环境，并缓解了体内实验中存在的许多伦理和方法学限制。本研究旨在确定机械负荷是否能够抵消使用C2C12小鼠细胞系构建的肌管中地塞米松（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，无论这种负荷是在DEX治疗前的24小时内发生还是在之后。此外，机械负荷防止了MuRF-1和MAFbx mRNA表达的增加，这些是肌肉萎缩的关键调节因子。总体而言，本研究展示了组织工程化肌肉在研究骨骼肌健康与疾病中的应用，为未来更好地理解骨骼肌萎缩的治疗方法提供了巨大潜力。