Department of Clinical Laboratory, National Center for Geriatrics and Gerontology, Obu, Japan.
Int J Mol Med. 2011 Jun;27(6):859-64. doi: 10.3892/ijmm.2011.644. Epub 2011 Mar 8.
It is currently recognized that the Wnt signaling pathway regulates bone mass. We have previously reported that the basic fibroblast growth factor (FGF-2) stimulates the synthesis of the vascular endothelial growth factor (VEGF) at least in part via the p44/p42 mitogen-activated protein (MAP) kinase and the stress-activated protein kinase (SAPK)/c-Jun N-terminal kinase (JNK) in osteoblast-like MC3T3-E1 cells. In the present study, we investigated the effect of Wnt3a on FGF-2-stimulated VEGF synthesis in MC3T3-E1 cells. Wnt3a significantly augmented the FGF-2-stimulated VEGF release in a dose-dependent manner in the range between 1 and 30 ng/ml. Lithium chloride and SB216763, inhibitors of glycogen synthase kinase 3β (GSK3β), enhanced the FGF-2-stimulated VEGF release. Wnt3a did not affect the phosphorylation of the p44/p42 MAP kinase, SAPK/JNK, Akt, p38 MAP kinase or the p70 S6 kinase induced by FGF-2. Wnt3a and SB216763 increased the levels of VEGF mRNA expression induced by FGF-2. These results strongly suggest that Wnt3a enhances VEGF synthesis stimulated by FGF-2 via activation of the canonical Wnt/β-catenin pathway in osteoblasts.
目前认为 Wnt 信号通路调节骨量。我们之前报道过碱性成纤维细胞生长因子（FGF-2）至少部分通过成骨样 MC3T3-E1 细胞中的 p44/p42 丝裂原活化蛋白（MAP）激酶和应激激活蛋白激酶（SAPK）/c-Jun N-末端激酶（JNK）刺激血管内皮生长因子（VEGF）的合成。在本研究中，我们研究了 Wnt3a 对 FGF-2 刺激的 MC3T3-E1 细胞中 VEGF 合成的影响。Wnt3a 以剂量依赖性方式显著增强 FGF-2 刺激的 VEGF 释放，范围在 1 至 30ng/ml 之间。糖原合酶激酶 3β（GSK3β）抑制剂氯化锂和 SB216763 增强了 FGF-2 刺激的 VEGF 释放。Wnt3a 不影响 FGF-2 诱导的 p44/p42 MAP 激酶、SAPK/JNK、Akt、p38 MAP 激酶或 p70 S6 激酶的磷酸化。Wnt3a 和 SB216763 增加了 FGF-2 诱导的 VEGF mRNA 表达水平。这些结果强烈表明 Wnt3a 通过激活成骨细胞中的经典 Wnt/β-连环蛋白途径增强 FGF-2 刺激的 VEGF 合成。
