Reducing muscle atrophy following orthopedic surgery is critical during the post-operative period. Our previous work in total knee arthroplasty (TKA) patients showed that the vast majority of atrophy occurs within two weeks following surgery and that essential amino acid supplementation (EAAs) attenuates this atrophy. We used RNA-sequencing (RNA-seq) to identify genes associated with atrophy after TKA with and without EAAs. Analysis of over-represented gene-ontology (GO) terms revealed that p53 signaling and the Cytokine-Cytokine Receptor pathways were highly upregulated after TKA. Relative to Placebo, the EAAs group had altered expression of p53 regulators such as MDM2. This altered expression may account for differences between groups in timing of upregulation of some p53 targets such as apoptosis genes, and may account for the reduction in muscle loss in subjects receiving EAAs. Furthermore, we observed altered expression of a large number of cytokine signaling genes including TNFRSF12A, which plays a critical role in muscle atrophy, myogenesis, fibrosis and the non-canonical NF-kB pathway.

中文翻译：

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必需氨基酸补充剂改变 TKA 后 p53 转录反应和细胞因子基因表达。

减少骨科手术后的肌肉萎缩在术后期间至关重要。我们之前对全膝关节置换术 (TKA) 患者的研究表明，绝大多数萎缩发生在手术后两周内，而必需氨基酸补充剂 (EAA) 可减轻这种萎缩。我们使用 RNA 测序 (RNA-seq) 来鉴定与使用和不使用 EAA 的 TKA 后萎缩相关的基因。对过度表达的基因本体 (GO) 术语的分析显示，在 TKA 后，p53 信号传导和细胞因子-细胞因子受体通路高度上调。相对于安慰剂，EAAs 组改变了 p53 调节剂的表达，如 MDM2。这种改变的表达可能解释了组间某些 p53 靶标（如凋亡基因）上调时间的差异，并且可能解释了接受 EAA 的受试者肌肉损失减少的原因。此外，我们观察到大量细胞因子信号基因的表达发生改变，包括 TNFRSF12A，其在肌肉萎缩、肌生成、纤维化和非经典 NF-kB 通路中起关键作用。