Evaluating the role of subacromial impingement in rotator cuff tendinopathy: development and analysis of a novel rat model.

Abstract

Subacromial impingement of the rotator cuff caused by variations in acromial anatomy or altered glenohumeral kinematics leads to inflammation and degeneration of the rotator cuff, ultimately contributing to the development of tendinopathy. However, the underlying cellular and molecular changes in the impinged tendon remain poorly understood. Because the rat is an accepted model for rotator cuff studies, we have developed a rat model to study rotator cuff tendinopathy. Forty-four adult male Sprague-Dawley rats were allocated to one of 4 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). Bilateral shoulder specimens were harvested for biomechanical testing, histology, and quantitative real-time polymerase chain reaction (qRT-PCR) analysis. 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 changes in tendon morphology at the enthesis and midsubstance. Biomechanical evaluation demonstrated decreased supraspinatus tendon failure force and tissue stiffness at all time points compared with control tendons. Semiquantitative scoring of histologic specimens demonstrated significant, persistent tendinopathic changes over 8 weeks. qRT-PCR analysis of impinged tendon specimens demonstrated upregulation of gene expression for Col3 and Mmp14 in the impingement groups compared with control groups. In muscle samples, significant upregulation was seen in the expression of genes that are commonly associated with muscle atrophy (MuRF1 and Ube2b) and fatty infiltration (Fabp4, Pparg2, and Klf15). This newrat subacromial impingement model creates cellular and molecular changes consistent with the development of rotator cuff tendinopathy. The results of this study may serve as a baseline for future investigation.