Department of Orthopedic Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
Department of Pharmacology, Gifu University Graduate School of Medicine, Gifu, Japan.
Biosci Biotechnol Biochem. 2023 Nov 21;87(12):1462-1469. doi: 10.1093/bbb/zbad121.
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.
白藜芦醇是一种天然多酚,存在于葡萄中,对人体健康有益。白藜芦醇通过成骨细胞样 MC3T3-E1 细胞中的 Akt 通路调节碱性成纤维细胞生长因子(bFGF)诱导的护骨素合成。在这项研究中,我们研究了白藜芦醇对 bFGF 诱导的 MC3T3-E1 细胞中巨噬细胞集落刺激因子(M-CSF)合成的影响。bFGF 显著刺激 M-CSF 的释放和 mRNA 表达,白藜芦醇和 SRT1720(SIRT1 激活剂)可减少其表达。Inauhzin(SIRT1 抑制剂)逆转了白藜芦醇对 bFGF 诱导的 M-CSF mRNA 表达的抑制作用。Deguelin(Akt 抑制剂)和 LY294002(PI3-kinase 抑制剂)可降低 bFGF 诱导的 M-CSF 合成。Inauhzin 逆转了白藜芦醇对 bFGF 诱导的 Akt 磷酸化的抑制作用。在使用 M-CSF mRNA 表达实验的相同样本中,进一步证实了白藜芦醇对 bFGF 诱导的护骨素 mRNA 表达的抑制作用。因此,白藜芦醇通过抑制 PI3-kinase/Akt 通路减少 bFGF 诱导的 M-CSF 合成,其抑制作用通过成骨细胞中 SIRT1 的激活来介导。