Essential amino acid supplementation alters the p53 transcriptional response and cytokine gene expression following TKA.

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.