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

Abstract

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 upregulation of expression of MuRF-1 and MAFbx. ß

Muscle atrophy and fatty infiltration after an acute rotator cuff repair in a sheep model

“…Akt and mTOR are also linked to other important pathways including the SREBP-1/adipogenesis pathway 32 and TGF-B and pro-fibrotic pathways 33,34 . Previous studies in small animal model show that Akt and mTOR have altered gene expression patterns after mechanical unloading and denervation, and respond differently to these signals 11 .…”

“…The following rabbit-anti-sheep primary antibodies were used at dilutions of 1:200: SREBP-1 20,21 (Novus Biologicals, Littleton, CO), PPARg 20,22,23 (Santa Cruz Biotechnology, Santa Cruz, CA), p-AKT 11,24 (Cell Signaling Technology), and p-mTOR 11,24 (Cell Signaling Technology). IRDye 800 CW Goat anti-Rabbit IgG (H+L) secondary antibody (LI-COR Biosciences, Lincoln, NE) was used at a dilution of 1:10,000.…”

“…qRT-PCR was performed to quantify the expression of aSMA 25,26 , Col-1 26 , Col-3 26 , MuRF-1 11,27 , MAFbx 11, 27 , MMP-13 28,29 , PPARg, and SREBP-1 using a Light Cycler 480 SYBR Green I Master kit (Roche Applied Bioscience Inc.). Primer sequences are listed in Table 1.…”

“…Animal models are useful tools to study the molecular mechanisms of muscle atrophy, fatty infiltration, and fibrosis that are observed in the setting of rotator cuff tears in patients. While there are multiple RCTs studies conducted in rat or mouse models [9][10][11][12] , the sheep model, as a larger animal model, may more closely mirror the pathophysiologic changes observed in human RCTs 13 since the infraspinatus tendons of sheep…”

A Novel Modified Simulated Annealing Algorithm and Big Data Sampling Analysis based Sports Effect Evaluation Mode

“…As for the training, the intrinsic relationship between functional action system in action mode, function assessment before training, training according to the results of functional assessment action or the actions to correct practice, functional training system and function system is the key link in the functional training, functional action system known as action assessment system, on the basis of the test results to decide whether to do the training or action to correct exercise. Decision function structure and function to improve the structure as function training from the human body movement function, through the integration of sports quality and proprioception promote human body movement function exercise that is the practice logic function training [1,2,3].…”