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5,7,3',4'-tetramethoxyflavone ameliorates cholesterol dysregulation by mediating SIRT1/FOXO3a/ABCA1 signaling in osteoarthritis chondrocytes.

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机构: [1]Department of Pathology, Ganzhou People's Hospital, Ganzhou, 341000, China. [2]College of Pharmacy, Gannan Medical University, Ganzhou, 341000, China. [3]Department of Orthopedics, the First Affiliated Hospital of Gannan Medical University, Ganzhou, 341000, China. [4]Key Laboratory of Traditional Chinese Medicine & New Pharmacy Development, Guangdong Medical University, Dongguan, 523808, China.
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Dyslipidemia has been associated with the development of osteoarthritis. Our previous study found that 5,7,3',4'-tetramethoxyflavone (TMF) exhibited protective activities against the pathological changes of osteoarthritis. Aim: To investigate the roles of TMF in regulating ABCA1-mediated cholesterol metabolism. Methods: Knockdown and overexpression were employed to study gene functions. Protein-protein interaction was investigated by co-immunoprecipitation, and the subcellular locations of proteins were studied by immunofluorescence. Results: IL-1β decreased ABCA1 expression and induced apoptosis. Therapeutically, TMF ameliorated the effects of IL-1β. FOXO3a knockdown expression abrogated the effects of TMF, and FOXO3a overexpression increased ABCA1 expression by interacting with LXRα. TMF promoted FOXO3a nuclear translocation by activating SIRT1 expression. Conclusions: TMF ameliorates cholesterol dysregulation by increasing the expression of FOXO3a/LXRα/ABCA1 signaling through SIRT1 in C28/I2 cells.

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出版当年[2020]版:
大类 | 2 区 医学
小类 | 3 区 药物化学
最新[2025]版:
大类 | 4 区 医学
小类 | 4 区 药物化学
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第一作者机构: [1]Department of Pathology, Ganzhou People's Hospital, Ganzhou, 341000, China.
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