Abstract
Objectives:
Subacromial impingement of the rotator cuff caused by variations in acromial anatomy is an extrinsic factor that leads to inflammation and degeneration of the rotator cuff, ultimately contributing to the development of tendinopathy. However, microscopic and molecular changes in the impinged tendon remain poorly understood, and a robust rat model for studying rotator cuff tendinopathy is still lacking.
Methods:
Our study was approved by the Institutional Animal Care and Use Committee. A total of 44 adult male Sprague-Dawley rats were included in the study. Animals were randomly allocated to one of four study groups: intact control group (Group 1, n=11); bilateral subacromial surgical clip placement to induce supraspinatus impingement for 2 weeks (Group 2, n=11), 4 weeks (Group 3, n=11) and 8 weeks (Group 4, n=11). At time of sacrifice, bilateral shoulder specimens were harvested for biomechanical testing, histological and quantitative real-time polymerase chain reaction (qRT-PCR) analysis. One-way analysis of variance (ANOVA) with the post-hoc Tukey test was used to analyze differences among groups.
Results:
Radiography confirmed that all microvascular clips remained in stable position in the subacromial space. Gross inspection of supraspinatus tendon specimens in the impingement groups revealed frayed and hazy tendon discoloration at the enthesis and mid-substance. Biomechanical evaluation demonstrated decreased supraspinatus tendon failure force and tissue stiffness at all time points compared to control group. Histologic specimens demonstrated significant, persistent tendinopathic changes over 8 weeks, with the mean modified Bonar scores significantly increased in the clip impingement groups compared to the control group (control: 1.56±0.86; 2 weeks group: 9.17±0.76; 4 weeks group: 9.11±0.65; and 8 weeks group: 6.56±0.50. P <0.001 for all comparisons). qRT-PCR analysis of impinged tendon specimens demonstrated upregulation of gene expression for Col3 and MMP14 in the impingement groups compared with control groups (P =0.001 and 0.015 respectively). In muscle samples, significant upregulation was seen in the expression of genes that are commonly associated with muscle atrophy (MURF1: P <0.001 and UBE2B: P <0.001) and fatty infiltration (FABP4: P =0.002, PPARγ2: P =0.006, and KLF15: P =0.001).
Conclusions:
In conclusion, we developed a novel rat model of subacromial impingement and found consistent and sustained histologic, biomechanical, and gene expression changes that are consistent with findings in human tendinopathy. This model will allow future studies to further evaluate the underlying cellular and molecular mechanisms of tendinopathy, as well as evaluation of novel therapeutic approaches for treatment of this common problem.
Gross insepction nof the specismen at all time points.
Radiography
