5,7,3′,4′-Tetramethoxyflavone Ameliorates Cholesterol Dysregulation by Mediating SIRT1/FOXO3a/ABCA1 Signaling in Osteoarthritis Chondrocytes

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.