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Horm Metab Res 2005; 37(3): 140-145
DOI: 10.1055/s-2005-861291
Original Basic
© Georg Thieme Verlag KG Stuttgart · New York

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

Y.  Kanno1, 2 , A.  Ishisaki1 , M.  Yoshida1 , H.  Tokuda2, 3 , O.  Numata2 , O.  Kozawa1
  • 1Department of Pharmacology, Gifu University School of Medicine, Japan
  • 2Institute of Biological Science, University of Tsukuba, Ibaraki, Japan
  • 3Department of Internal Medicine, Chubu National Hospital, National Institute for Longevity Sciences, Obu, Aichi, Japan
Weitere Informationen

Publikationsverlauf

Received 25 May 2004

Accepted after revision 20 September 2004

Publikationsdatum:
12. April 2005 (online)

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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

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Dr. Osamu Kozawa

Department of Pharmacology · Gifu University Graduate School of Medicine ·

Gifu 501-1194 · Japan

Telefon: + 81 (58) 230-6214 ·

Fax: + 81 (58) 230-6218 ·

eMail: okozawa@cc.gifu-u.ac.jp

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