Wnt3a upregulates transforming growth factor-β-stimulated VEGF synthesis in osteoblasts

✍ Scribed by Hideo Natsume; Haruhiko Tokuda; Rie Matsushima-Nishiwaki; Kenji Kato; Kengo Yamakawa; Takanobu Otsuka; Osamu Kozawa

• Book ID: 101818860
• Publisher: John Wiley and Sons
• Year: 2011
• Tongue: English
• Weight: 210 KB
• Volume: 29
• Category: Article
• ISSN: 0263-6484
• DOI: 10.1002/cbf.1759

✦ Synopsis

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. Copyright © 2011 John Wiley & Sons, Ltd.