Tendinopathy is one of the most prevalent musculoskeletal disorders, significantly affecting the quality of life of patients. Treatment outcomes can be improved with an early diagnosis and timely targeted interventions. Increasing evidence indicates that ROS and endoplasmic reticulum (ER) stress play key roles in modulating the differentiation processes of tendon-derived stem cells (TDSCs), thereby contributing to the initiation and progression of tendinopathy. However, the relationship between ONOO^– and the differentiation process, as well as the various stages of tendinopathy, remains unexplored. Herein, we developed two highly specific and sensitive fluorescent probes (Rod-Cl and Rod-Br) for detecting ONOO^– in the ER. Rod-Br can detect basal levels of ONOO^– in the ER of TDSCs and measure ONOO^– levels in primary TDSCs stimulated by interleukin-1β over various durations, allowing for comparisons between chondrogenic and osteogenic differentiation and ER stress levels. Additionally, we examined ONOO^– variations in different stages of tendinopathy and treatment rat models in vivo and discussed the potential mechanisms. This research provides a robust tool for analyzing ONOO^– dynamics in the tenogenic and osteogenic differentiation of TDSCs, offering new insights into the pathophysiology and treatment of tendinopathy.

中文翻译：

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监测原代肌腱来源干细胞中内质网过氧亚硝酸盐的波动并深入了解肌腱病


肌腱病是最普遍的肌肉骨骼疾病之一，严重影响患者的生活质量。通过早期诊断和及时的针对性干预，可以改善治疗结果。越来越多的证据表明，ROS 和内质网 （ER） 应激在调节肌腱来源干细胞 （TDSC） 的分化过程中起关键作用，从而促进肌腱病的发生和发展。然而，^ONOO– 与分化过程以及肌腱病的各个阶段之间的关系仍未得到探索。在此，我们开发了两种高度特异性和灵敏的荧光探针（Rod-Cl 和 Rod-Br）用于检测 ER 中的 ^ONOO– 。Rod-Br 可以检测 TDSC 内质网中 ONOO^– 的基础水平，并测量在不同持续时间内受白细胞介素-1β 刺激的原发性 TDSCs 中的 ONOO^– 水平，允许比较软骨形成和成骨分化以及 ER 应激水平。此外，我们检查了肌腱病不同阶段和体内治疗大鼠模型的 ONOO^– 变化，并讨论了潜在的机制。这项研究为分析 TDSC 肌腱发生和成骨分化中的 ONOO^– 动力学提供了强大的工具，为肌腱病的病理生理学和治疗提供了新的见解。