• J Shoulder Elbow Surg · Nov 2014

    Upregulation of transforming growth factor-β signaling in a rat model of rotator cuff tears.

    • Xuhui Liu, Sunil K Joshi, Bharat Ravishankar, Dominique Laron, Hubert T Kim, and Brian T Feeley.
    • Department of Veterans Affairs, San Francisco Veterans Affairs Medical Center, San Francisco, CA, USA; Department of Orthopaedic Surgery, University of California, San Francisco, CA, USA.
    • J Shoulder Elbow Surg. 2014 Nov 1; 23 (11): 1709-16.

    BackgroundMuscle atrophy, fatty infiltration, and fibrosis of the muscle have been described as important factors governing outcome after rotator cuff injury and repair. Muscle fibrosis is also thought to have a role in determining muscle compliance at the time of surgery. The transforming growth factor-β (TGF-β) pathways are highly conserved pathways that exert a potent level of control over muscle gene expression and are critical regulators of fibrosis in multiple organ systems. It has been shown that TGF-β can regulate important pathways of muscle atrophy, including the Akt/mammalian target of rapamycin pathway. The purpose of this study was to evaluate the expression of TGF-β and its downstream effectors of fibrosis after a massive rotator cuff tear (RCT) in a previously established rat model.MethodsTo simulate a massive RCT, infraspinatus and supraspinatus tenotomy and suprascapular nerve transection were performed on Sprague-Dawley rats with use of a validated model. Two and 6 weeks after surgery, supraspinatus muscles were harvested to study alterations in TGF-β signaling by Western blotting, quantitative polymerase chain reaction, and histologic analysis.ResultsThere was a significant increase in fibrosis in the rotator cuff muscle after RCT in our animal model. There was a concomitant increase in TGF-β gene and protein expression at both 2 and 6 weeks after RCT. Evaluation of the TGF-β signaling pathway revealed an increase in SMAD2 activation but not in SMAD3. There was an increase in profibrotic markers collagen I, collagen III, and α-smooth muscle actin.ConclusionsTGF-β signaling is significantly upregulated in rat supraspinatus muscles after RCTs.Copyright © 2014 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

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