SAPK/JNK Plays a Role in Transforming Growth Factor-β-induced VEGF Synthesis in Osteoblasts

Abstract

We previously reported that transforming growth factor-β (TGF-β) activates p44/p42 mitogen-activated protein (MAP) kinase and p38 MAP kinase, resulting in the stimulation of vascular endothelial growth factor (VEGF) synthesis in osteoblast-like MC3T3-E1 cells. In the present study, we investigated the involvement of stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK), another member of the MAP kinase superfamily, in TGF-β-induced VEGF synthesis in these cells. TGF-β markedly induced SAPK/JNK phosphorylation. SP600125, a specific inhibitor of SAPK/JNK, markedly reduced TGF-β-induced VEGF synthesis. SP600125 suppressed TGF-β-induced SAPK/JNK phosphorylation. PD98059, an inhibitor of upstream kinase of p44/p42 MAP kinase and SB203580, an inhibitor of p38 MAP kinase, each failed to reduce TGF-β-induced SAPK/JNK phosphorylation. A combination of SP600125 and PD98059 or SP600125 and SB203580 suppressed TGF-β-stimulated VEGF synthesis in an additive manner. These results strongly suggest that TGF-β activates SAPK/JNK in osteoblasts, and that SAPK/JNK plays a role in addition to p42/p44 MAP kinase and p38 MAP kinase in TGF-β-induced VEGF synthesis.

Key words

TGF-β - VEGF - SAPK/JNK - Osteoblast

References

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