Department of Pharmacology, Gifu University Graduate School of Medicine, Gifu, Japan.
Cell Biochem Funct. 2011 Jul;29(5):371-7. doi: 10.1002/cbf.1759. Epub 2011 Apr 13.
It is recognized that Wnt3a affects bone metabolism via the canonical Wnt/β-catenin signalling pathway. We have previously shown that transforming growth factor-β (TGF-β) stimulates the synthesis of vascular endothelial growth factor (VEGF) via p44/p42 mitogen-activated protein (MAP) kinase, stress-activated protein kinase (SAPK)/c-Jun N-terminal kinase (JNK) and p38 MAP kinase in osteoblast-like MC3T3-E1 cells. In the present study, we investigated the effect of Wnt3a on TGF-β-stimulated VEGF synthesis in these cells. Wnt3a, which alone had little effect on the VEGF levels, significantly enhanced the TGF-β-stimulated VEGF release. Lithium chloride and SB216763, inhibitors of glycogen synthase kinase 3β, markedly amplified the TGF-β-stimulated VEGF release. Wnt3a failed to affect the TGF-β-induced phosphorylation of Smad2, p44/p42 MAP kinase, p38 MAP kinase or SAPK/JNK. Wnt3a and lithium chloride strengthened the VEGF mRNA expression induced by TGF-β. These results strongly suggest that Wnt3a upregulates VEGF synthesis stimulated by TGF-β via activation of the canonical pathway in osteoblasts.
人们认识到，Wnt3a 通过经典的 Wnt/β-连环蛋白信号通路影响骨代谢。我们之前已经表明，转化生长因子-β（TGF-β）通过 p44/p42 有丝分裂原激活蛋白（MAP）激酶、应激激活蛋白激酶（SAPK）/c-Jun N 末端激酶（JNK）和 p38 MAP 激酶刺激成骨细胞样 MC3T3-E1 细胞中血管内皮生长因子（VEGF）的合成。在本研究中，我们研究了 Wnt3a 对这些细胞中 TGF-β 刺激的 VEGF 合成的影响。Wnt3a 单独对 VEGF 水平影响不大，但显著增强了 TGF-β 刺激的 VEGF 释放。糖原合成酶激酶 3β 的抑制剂氯化锂和 SB216763 显著放大了 TGF-β 刺激的 VEGF 释放。Wnt3a 未能影响 TGF-β 诱导的 Smad2、p44/p42 MAP 激酶、p38 MAP 激酶或 SAPK/JNK 的磷酸化。Wnt3a 和氯化锂增强了 TGF-β 诱导的 VEGF mRNA 表达。这些结果强烈表明，Wnt3a 通过激活成骨细胞中的经典途径，上调 TGF-β 刺激的 VEGF 合成。
