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NEDD4 enhances bone‑tendon healing in rotator cuff tears by reducing fatty infiltration

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机构: [1]School of Clinical Medicine, Guizhou Medical University, Guiyang, Guizhou 550004, P.R. China [2]Department of Sports Medicine, The Beijing Jishuitan Hospital Guizhou Hospital, Guiyang, Guizhou 550014, P.R. China [3]Thyroid Disease Diagnosis and Treatment Center, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650032, P.R. China [4]Department of Urology, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou 550004, P.R. China [5]Department of Emergency Orthopedics, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou 550004, P.R. China
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Rotator cuff tears (RCT) can cause shoulder pain, weakness and stiffness, significantly affecting daily life. Analysis of the GSE103266 dataset revealed significant changes in the mTOR/PI3K/Akt signaling pathway and lipid metabolism‑related pathways, suggesting that fatty infiltration may affect RCT. The analysis indicated that the ubiquitin ligase NEDD4 plays a critical role in RCT. NEDD4 was found to be highly associated with the mTOR/PI3K/Akt signaling pathway. An RCT model in Sprague‑Dawley (SD) rats was established to study the role of NEDD4 in regulating the mTOR pathway and investigate its effects on fatty infiltration. SD rats were divided into NEDD4 overexpression and knockout groups. Tissue recovery, apoptosis and fat deposition were measured through histological staining, reverse transcription‑quantitative PCR and western blotting. Additionally, cell culture of fibro‑adipogenic progenitors and lentiviral transfection were conducted to investigate the effect of NEDD4 on adipocyte differentiation. NEDD4 overexpression significantly reduced lipid accumulation, whereas NEDD4 knockdown enhanced lipid accumulation. NEDD4 was found to regulate the mTOR pathway and the expression of adipogenesis‑related genes, promoting fat metabolism and inhibiting adipocyte differentiation. Histological analysis indicated that NEDD4 overexpression improved tissue recovery and reduced apoptosis. Targeting NEDD4 offers a potential therapeutic strategy to improve the clinical outcomes of patients with RCT by modulating the mTOR pathway and fat metabolism.

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大类 | 3 区 医学
小类 | 4 区 医学:研究与实验 4 区 肿瘤学
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第一作者机构: [1]School of Clinical Medicine, Guizhou Medical University, Guiyang, Guizhou 550004, P.R. China [2]Department of Sports Medicine, The Beijing Jishuitan Hospital Guizhou Hospital, Guiyang, Guizhou 550014, P.R. China
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通讯机构: [1]School of Clinical Medicine, Guizhou Medical University, Guiyang, Guizhou 550004, P.R. China [4]Department of Urology, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou 550004, P.R. China [5]Department of Emergency Orthopedics, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou 550004, P.R. China
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