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

被引:33
作者
Liu, Xuhui [1 ,2 ]
Joshi, Sunil K. [1 ,2 ]
Ravishankar, Bharat [1 ,2 ]
Laron, Dominique [2 ]
Kim, Hubert T. [1 ,2 ]
Feeley, Brian T. [2 ]
机构
[1] San Francisco VA Med Ctr, Dept Vet Affairs, San Francisco, CA USA
[2] Univ Calif San Francisco, Dept Orthopaed Surg, San Francisco, CA 94158 USA
基金
美国国家卫生研究院;
关键词
Massive rotator cuff tear; transforming growth factor-beta; fibrosis; SUPRASCAPULAR NERVE INJURY; SKELETAL-MUSCLE; FATTY INFILTRATION; MESENCHYMAL TRANSITION; ARTHROSCOPIC REPAIR; INTERVAL SLIDES; SCAR FORMATION; ATROPHY; FIBROSIS; SMAD2;
D O I
10.1016/j.jse.2014.02.029
中图分类号
R826.8 [整形外科学]; R782.2 [口腔颌面部整形外科学]; R726.2 [小儿整形外科学]; R62 [整形外科学(修复外科学)];
学科分类号
摘要
Background: Muscle 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-beta (TGF-beta) 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-beta 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-beta and its downstream effectors of fibrosis after a massive rotator cuff tear (RCT) in a previously established rat model. Methods: To 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-beta signaling by Western blotting, quantitative polymerase chain reaction, and histologic analysis. Results: There was a significant increase in fibrosis in the rotator cuff muscle after RCT in our animal model. There was a concomitant increase in TGF-beta gene and protein expression at both 2 and 6 weeks after RCT. Evaluation of the TGF-beta signaling pathway revealed an increase in SMAD2 activation but not in SMAD3. There was an increase in profibrotic markers collagen I, collagen III, and alpha-smooth muscle actin. Conclusions: TGF-beta signaling is significantly upregulated in rat supraspinatus muscles after RCTs. (C) 2014 Journal of Shoulder and Elbow Surgery Board of Trustees.
引用
收藏
页码:1709 / 1716
页数:8
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