Resveratrol inhibits basic fibroblast growth factor-induced macrophage colony-stimulating factor synthesis via the PI3-kinase/Akt pathway in osteoblasts

• Published in: Bioscience, biotechnology, and biochemistry Vol. 87; no. 12; pp. 1462 - 1469
• Main Authors: Kuroyanagi, Gen, Hioki, Tomoyuki, Tachi, Junko, Matsushima-Nishiwaki, Rie, Iida, Hiroki, Tokuda, Haruhiko, Kozawa, Osamu
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 21.11.2023
• Subjects: Animals; Fibroblast Growth Factor 2 - drug effects; Fibroblast Growth Factor 2 - metabolism; Macrophage Colony-Stimulating Factor - drug effects; Macrophage Colony-Stimulating Factor - metabolism; Mice; Osteoblasts - metabolism; Osteoprotegerin - drug effects; Osteoprotegerin - metabolism; Phosphatidylinositol 3-Kinase - drug effects; Phosphatidylinositol 3-Kinase - metabolism; Phosphatidylinositol 3-Kinase - pharmacology; Proto-Oncogene Proteins c-akt - metabolism; Resveratrol - pharmacology; RNA, Messenger - genetics; RNA, Messenger - metabolism; Sirtuin 1 - genetics; Sirtuin 1 - metabolism; sirtuin 1; osteoblast; resveratrol; macrophage colony-stimulating factor; basic fibroblast growth factor
• ISSN: 1347-6947; 1347-6947
• DOI: 10.1093/bbb/zbad121

ABSTRACT Resveratrol is a natural polyphenol found in grapes and beneficial for human health. Resveratrol regulates basic fibroblast growth factor (bFGF)-induced osteoprotegerin synthesis through Akt pathway in osteoblast-like MC3T3-E1 cells. In this study, we investigated resveratrol effects on bFGF-induced macrophage colony-stimulating factor (M-CSF) synthesis in MC3T3-E1 cells. bFGF significantly stimulated release and mRNA expression of M-CSF, which was reduced by resveratrol and SRT1720, sirtuin 1 (SIRT1) activator. Inauhzin, SIRT1 inhibitor, reversed inhibitory effects of resveratrol on bFGF-induced mRNA expression of M-CSF. Deguelin, Akt inhibitor, and LY294002, phosphatidylinositol 3-kinase (PI3-kinase) inhibitor, reduced bFGF-induced M-CSF synthesis. Inauhzin reversed inhibitory effects of resveratrol on bFGF-induced Akt phosphorylation. Suppressive effect of resveratrol on bFGF-induced osteoprotegerin mRNA expression was confirmed in the identical samples using in experiment of M-CSF mRNA expression. Therefore, resveratrol reduces bFGF-induced M-CSF synthesis in addition to osteoprotegerin synthesis by inhibiting PI3-kinase/Akt pathway and suppressive effects are mediated through SIRT1 activation in osteoblasts. Graphical Abstract Graphical Abstract Schematic illustration of the regulatory mechanism of resveratrol on bFGF-induced M-CSF and OPG syntheses in osteoblasts.