Wnt3a upregulates prostaglandin F2α-stimulated vascular endothelial growth factor synthesis in osteoblasts

Kondo,Akira; Tokuda,Haruhiko; Mizutani,Jun; Matsushima-Nishiwaki,Rie; Kozawa,Osamu; Otsuka,Takanobu

doi:10.3892/mmr.2012.916

Wnt3a upregulates prostaglandin F2α-stimulated vascular endothelial growth factor synthesis in osteoblasts

Authors:
- Akira Kondo
- Haruhiko Tokuda
- Jun Mizutani
- Rie Matsushima-Nishiwaki
- Osamu Kozawa
- Takanobu Otsuka
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Affiliations: Department of Pharmacology, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan, Department of Orthopedic Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan
Published online on: May 15, 2012 https://doi.org/10.3892/mmr.2012.916
Pages: 421-425

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Abstract

It is known that Wnt3a affects bone metabolism via the canonical Wnt/β-catenin signaling pathway. We have previously shown that prostaglandin F2α (PGF2α) stimulates the synthesis of vascular endothelial growth factor (VEGF) and interleukin-6 (IL-6) via mitogen-activated protein (MAP) kinases, including p44/p42 MAP kinase, p38 MAP kinase and stress-activated protein kinase (SAPK)/c-Jun N-terminal kinase (JNK) in osteoblast-like MC3T3-E1 cells. In the present study, we investigated the effects of Wnt3a on the synthesis of VEGF or IL-6 stimulated by PGF2α in MC3T3-E1 cells using an ELISA kit and various antibodies. Cells were cultured and pretreated with various doses of Wnt3a or SB216763, an inhibitor of glycogen synthase kinase 3β, prior to western blotting. Wnt3a significantly enhanced the PGF2α-stimulated VEGF release but had little effect on the PGF2α-stimulated IL-6 release. SB216763 markedly amplified the PGF2α-stimulated VEGF release without affecting the IL-6 release, similar to Wnt3a. Wnt3a failed to affect the PGF2α-induced phosphorylation of p44/p42 MAP kinase, p38 MAP kinase or SAPK/JNK. These results strongly suggest that Wnt3a upregulates VEGF synthesis stimulated by PGF2α via activation of the canonical pathway in osteoblasts without affecting IL-6 synthesis.

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