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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\u2010related genes, in tendon\u2010derived 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\u20101. 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.<\/jats:p>","DOI":"10.1002\/iub.2771","type":"journal-article","created":{"date-parts":[[2023,7,28]],"date-time":"2023-07-28T08:49:32Z","timestamp":1690534172000},"page":"1003-1016","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Glycolipotoxicity conferred tendinopathy through ferroptosis dictation of tendon\u2010derived stem cells by YAP activation"],"prefix":"10.1002","volume":"75","author":[{"given":"Gang","family":"Wang","sequence":"first","affiliation":[{"name":"College of Fisheries and Life Science, Shanghai Ocean University  Shanghai China"},{"name":"Department of Orthopedics Shanghai Jiao Tong University School of Medicine Affiliated Sixth People's Hospital  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shikun","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Orthopedics Shanghai Jiao Tong University School of Medicine Affiliated Sixth People's Hospital  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingyu","family":"Ouyang","sequence":"additional","affiliation":[{"name":"Department of Orthopedics Shanghai Jiao Tong University School of Medicine Affiliated Sixth People's Hospital  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Orthopedics Shanghai Jiao Tong University School of Medicine Affiliated Sixth People's Hospital  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Li","sequence":"additional","affiliation":[{"name":"College of Fisheries and Life Science, Shanghai Ocean University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhixiao","family":"Yao","sequence":"additional","affiliation":[{"name":"Department of Orthopedics Shanghai Jiao Tong University School of Medicine Affiliated Sixth People's Hospital  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuai","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Orthopedics Shanghai Jiao Tong University School of Medicine Affiliated Sixth People's Hospital  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7854-5233","authenticated-orcid":false,"given":"Cunyi","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Orthopedics Shanghai Jiao Tong University School of Medicine Affiliated Sixth People's Hospital  Shanghai China"},{"name":"Shanghai Engineering Research Center for Orthopedic Material Innovation and Tissue Regeneration  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,7,28]]},"reference":[{"issue":"4","key":"e_1_2_12_2_1","first-page":"352","article-title":"Localization of collagen types I, III and V during tendon development. 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