Evaluation of Akt/mTOR activity in muscle atrophy after rotator cuff tears in a rat model

Atrophy of the rotator cuff muscles is a factor that complicates the treatment of a massive rotator cuff tear (RCT). However, the molecular mechanisms that govern the development of muscle atrophy after RCTs have not been well defined. The Akt/mammalian target of rapamycin (mTOR) signaling pathway plays a central role in maintaining muscle mass in response to mechanical loading. The role of this pathway in the development of muscle atrophy after a massive RCT remains unknown. The purpose of this study was to investigate the regulation of the Akt/mTOR pathway in the development of muscle atrophy after a RCT and suprascapular nerve (SSN) injury. We evaluated the activity of the Akt/mTOR signaling pathway and how this pathway interacts with two atrophy‐related genes, MuRF‐1 and MAFbx, in supraspinatus muscles of rats that underwent unilateral complete rotator cuff tendon transection or SSN transection. Akt/mTOR activity was significantly reduced after tendon rupture, but increased after nerve injury. MuRF‐1 and MAFbx were only up‐regulated following denervation. These results suggest that tendon transection leads to a decrease in protein synthesis with down‐regulation of the Akt/mTOR signaling pathway, whereas denervation leads to an increase in protein degradation via up‐regulation of expression of MuRF‐1 and MAFbx. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 30:1440–1446, 2012