Department of Sports Medicine & Orthopedic Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou City, Zhejiang Province, China.
Institute of Sports Medicine, Zhejiang University, Hangzhou City, Zhejiang Province, China.
Nat Commun. 2024 Nov 1;15(1):9460. doi: 10.1038/s41467-024-53826-w.
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.
肩袖肌腱病是最常见的肌腱病类型，预后最差。由于肌腱病的多样性，传统的治疗方法往往会引起异质的药物反应。因此，本研究试图根据转录组和临床特征将 126 条患病肌腱分为三种不同的亚型，它们具有相反的发病机制。表现为白色外观的缺氧萎缩型（Hw）表现出新生血管途径的下调。表现为白色外观的炎症增殖型（Iw）显示出炎症特征的适度上调。表现为红色外观的炎症增殖型（Ir）表现出最高水平的上调新生血管和炎症途径，以及严重的关节功能障碍。然后，我们建立了研究模型，包括动物模型中的亚型特异性模拟和临床数据分析。结果表明，糖皮质激素是一种有争议的常用药物，仅对 Ir 亚型有效。因此，本研究中阐明的肌腱病亚型对开发肌腱病的精准治疗具有重要意义。
