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Updated: Jun 8, 2025
Author Spotlight: Advancing Tendon Research by Developing Mouse Assembloids to Understand Cellular Mechanisms
Published on: March 22, 2024
Classification of distinct tendinopathy subtypes for precision therapeutics
Chenqi Tang1,2,3,4,5,6,7, Zetao Wang1,2,3,4,6,7,8, Yuanhao Xie1,2,3,4,6,7
1Department of Sports Medicine & Orthopedic Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou City, Zhejiang Province, China.
Abstract:
Rotator cuff tendinopathy is the most common tendinopathy type with the worst prognosis. Conventional treatments often elicit heterogeneous drug responses due to the diversity of tendinopathy. Hence, this study attempted a classification of 126 diseased tendons into three distinct subtypes with opposite pathogenic mechanisms based on transcriptomic and clinical features. The hypoxic atrophic subtype with white appearance (Hw) exhibits downregulated neovascularization pathways. The inflammatory proliferative subtype with white appearance (Iw) shows a moderate upregulation of inflammatory characteristics. The inflammatory proliferative subtype with red appearance (Ir) exhibits the highest levels of upregulated neovascularization and inflammatory pathways, along with severe joint dysfunction. We then established research models, including subtype-specific simulations in animal models and clinical data analysis. These revealed that glucocorticoid, a controversial commonly used drug, was only effective in treating the Ir subtype. Hence, the tendinopathy subtypes elucidated in this study have significant implications for developing precision treatment of tendinopathy.
Insights
This study classifies rotator cuff tendinopathy into three subtypes based on gene expression and clinical data. Glucocorticoid treatment is effective only for the inflammatory proliferative subtype with red appearance (Ir).
Area of Science:
- Orthopedics
- Molecular Biology
- Genomics
Background:
- Rotator cuff tendinopathy is common and has a poor prognosis.
- Current treatments yield varied results due to tendinopathy's complexity.
Purpose of the Study:
- Classify rotator cuff tendinopathy into distinct subtypes.
- Investigate subtype-specific pathogenic mechanisms and treatment responses.
Main Methods:
- Transcriptomic and clinical data analysis of 126 diseased tendons.
- Development of subtype-specific animal models and clinical data simulations.
Main Results:
- Identified three subtypes: hypoxic atrophic (Hw), inflammatory proliferative white (Iw), and inflammatory proliferative red (Ir).
- Hw showed downregulated neovascularization; Iw had moderate inflammation; Ir exhibited high inflammation and neovascularization.
- Glucocorticoid efficacy was limited to the Ir subtype.
Conclusions:
- Rotator cuff tendinopathy exhibits distinct molecular and clinical subtypes.
- Subtype classification is crucial for developing precision treatment strategies.
- Glucocorticoids are effective only for the Ir subtype, highlighting the need for targeted therapies.
