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
Further Information

Publication History

Received 25 May 2004

Accepted after revision 20 September 2004

Publication Date:
12 April 2005 (online)


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.


Dr. Osamu Kozawa

Department of Pharmacology · Gifu University Graduate School of Medicine ·

Gifu 501-1194 · Japan

Phone: + 81 (58) 230-6214 ·

Fax: + 81 (58) 230-6218 ·

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