AJSM - 2026-04-01 - Journal Article
Rotator Cuff Impingement Damages the Organelles of Tenocytes, Resulting in Excessive Tenocyte Apoptosis and Tendinopathy.
Yu S, Wei K, Deng XH, Mou Y, Wang T, Shu H, Sun X, Nie M
Topics
Key Takeaway
Subacromial microclip impingement in mice peaks tenocyte apoptosis at 4 weeks (TUNEL index 16.72%), driven by concurrent mitochondrial cristae loss and rough ER cisternae expansion.
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Summary
This controlled laboratory study used bilateral subacromial microclip placement in 12-week-old male mice to determine whether mitochondrial dysfunction and ER stress drive tenocyte apoptosis in rotator cuff tendinopathy. Impingement produced significant reductions in supraspinatus failure force and stiffness (P<0.0001), with TUNEL-confirmed apoptosis peaking at 4 weeks (16.72%) and TEM demonstrating progressive mitochondrial cristae loss and rough ER cisternae dilation. Gene expression confirmed concurrent upregulation of both mitochondrial apoptotic pathway markers and ER stress mediators, identifying a dual organelle-mediated apoptotic mechanism.
Key Limitation
The microclip impingement model produces acute mechanical compression rather than the chronic repetitive microtrauma of clinical impingement syndrome, limiting direct translational validity of the apoptotic timeline to human disease.
Original 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.