题目： | A Ubiquitin-Competitive Strategy Based on the Element Microenvironment to Treat Osteoarthritis |
作者： | Keyu Kong1, Yuqi Yang2, Yongyun Chang1, Youdong Chen2, Xiao Yang1, Jiahao Qin2, Zhuorun Song3, Shunyi Lu3, Zanjing Zhai1*, Jun Ge3*, Huiwu Li1*, and Liang Cheng2* |
单位： | 1Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People' s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200023, China. 2Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Soochow University, Suzhou 215123, China. 3Department of Orthopedic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215000, China. |
摘要： | Recent research on ferroptosis and cuproptosis has underscored the crucial role of trace element regulation in osteoarthritis (OA) treatment. However, research systematically addressing the alterations in nutrient elements in OA cartilage is lacking. This study is initiated using clinical specimens to quantify metal element concentrations in both damaged and intact cartilage to identify deficient trace elements within the inflammatory and senescent microenvironments of OA. Based on the preliminary findings of selenium (Se) and gallium (Ga) deficiencies in OA cartilage, tailored nanoparticles based on Se and Ga are designed and validated for their antioxidant ability. GaSex nanoparticles demonstrated significant efficacy in mitigating chondrocyte degeneration and extracellular matrix degradation induced by inflammatory factors and in alleviating cartilage abrasion, hyperalgesia, and abnormal gait in a destabilization of the medial meniscus (DMM) mouse model. Mechanistically, GaSex nanoparticles activated the Nrf2 pathway and competitively inhibited the ubiquitin‐mediated degradation of Gpx4, thus inhibiting ferroptosis. This study systematically designed GaSex nanoparticles based on the imbalance of trace elements within the OA knee joint microenvironment and demonstrated robust antioxidant capabilities and remarkable competitive properties for ubiquitin, thereby providing a novel therapeutic solution for OA treatment. |
影响因子： | 18.5 |
分区情况： | 一区 |
链接： | https://doi.org/10.1002/adfm.202409707 责任编辑：杜欣 |