Tendinopathy is a condition characterized by chronic, complex, and multidimensional pathological changes in the tendons. The etiology of tendinopathy is the combination of several factors, and diabetes mellitus (DM) is a risk factor. Increasing evidence has shown that the diabetic microenvironment plays an important role in tendinopathy. However, the mechanism causing tendinopathy in patients with DM remains unclear. Our study found that ferroptosis played an important role in tendinopathy in patients with DM. In vitro, high glucose and high fat treatment was used to simulate the DM microenvironment. Results showed that such a mechanism significantly increased ferroptosis, which was characterized by mass cell death, lipid peroxide accumulation, mitochondrial morphological changes, mitochondrial membrane potential decline, iron overload, and the activation of ferroptosis-related genes, in tendon-derived stem cells cultured in vitro. In the animal studies, db/db mice were used in the DM model, and the db mice had severe tendon injury and high ACSL4 and TfR1 expressions. These phenomena could be alleviated by the ferroptosis inhibitor ferrostatin-1. In conclusion, ferroptosis is associated with tendinopathy in patients with DM, and ferroptosis targeting may be a novel approach for treating diabetic tendinopathy. Our results can provide a new strategy for managing tendinopathy clinically in patients with DM.

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糖脂毒性通过 YAP 激活对肌腱干细胞的铁死亡指令导致肌腱病

肌腱病是一种以肌腱慢性、复杂、多维病理变化为特征的疾病。肌腱病的病因是多种因素共同作用的结果，其中糖尿病（DM）是一个危险因素。越来越多的证据表明，糖尿病微环境在肌腱病中起着重要作用。然而，导致糖尿病患者肌腱病的机制仍不清楚。我们的研究发现，铁死亡在糖尿病患者的肌腱病中发挥着重要作用。在体外，采用高糖和高脂肪处理来模拟DM微环境。结果表明，这种机制显着增加了培养的肌腱来源干细胞中的铁死亡，其特征是大量细胞死亡、脂质过氧化物积累、线粒体形态改变、线粒体膜电位下降、铁超载以及铁死亡相关基因的激活。体外。在动物研究中，使用db/db小鼠建立DM模型，db小鼠肌腱损伤严重，ACSL4和TfR1高表达。铁死亡抑制剂 Ferrostatin-1 可以缓解这些现象。总之，铁死亡与糖尿病患者的肌腱病相关，铁死亡靶向治疗可能是治疗糖尿病肌腱病的新方法。我们的结果可以为临床治疗糖尿病患者肌腱病提供新策略。