Rotator Cuff Impingement Damages the Organelles of Tenocytes,Resulting in Excessive Tenocyte Apoptosis and Tendinopathy

Abstract

Background:

Rotator cuff impingement syndrome is a prevalent cause of supraspinatus tendinopathy, resulting in considerable pain and functional impairment. Excessive apoptosis of tenocytes has been recognized as a critical pathological mechanism in both supraspinatus tendinopathy and rotator cuff tears. Furthermore, mitochondrial degeneration and endoplasmic reticulum (ER) stress–induced apoptosis are significant factors in chronic multisystem diseases. However, it remains unclear whether mitochondrial damage and ER stress can also cause excessive apoptosis of tendon cells and contribute to the development of rotator cuff tendinopathy.

Purpose:

This study used a mouse model of acromion impingement to examine how mitochondrial dysfunction and ER stress in tendon cells contribute to excessive apoptosis and rotator cuff tendinopathy.

Study Design:

Controlled laboratory study.

Methods:

A total of 70 twelve-week-old male mice were randomly divided into an experimental group (n = 56), which received bilateral subacromial microclip placement, and a control group (n = 14) with normal tendon conditions. Supraspinatus tendons from the experimental group were harvested at 2, 4, 6, and 8 weeks postsurgery. Outcomes assessed included biomechanical analysis, histological analysis, gene expression, a DNA fragmentation assay (terminal deoxynucleotidyl transferase dUTP nick-end labeling [TUNEL]), immunohistochemical analysis, and transmission electron microscopy (TEM).

Results:

Biomechanical analysis indicated a significant reduction in supraspinatus tendon failure force and stiffness in the impingement group compared with the control group (P < .0001). Histological evaluation demonstrated characteristic tendinopathic changes, including cellular rounding and collagen disorganization. TUNEL assay quantification revealed elevated apoptotic indices in the experimental group relative to controls, peaking at 4 weeks (16.72%; P < .01). Gene expression analysis identified the upregulation of mitochondrial apoptotic pathway markers and ER stress mediators, with maximal expression observed at the 4-week time point. Ultrastructural analysis via TEM revealed progressive mitochondrial depletion and loss of cristae. Additionally, the ER system exhibited considerable expansion, with rough ER cisternae significantly increasing in width compared to control specimens.

Conclusion:

This study reveals that rotator cuff impingement injuries can trigger collaborative apoptotic pathways linked to mitochondria and the ER. The resulting excessive apoptosis, metabolic imbalance, and loss of tendon cells play crucial roles in the development and progression of tendinopathy.

Clinical Relevance:

The results of this study contribute meaningfully to the understanding of the early organelle-level pathological characteristics of tendinopathy.