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J. Biochem, 2003, Vol. 133, No. 5 633-639
© 2003 Japanese Biochemical Society

MOLECULAR BIOLOGY

Vascular Endothelial Growth Factor Principally Acts as the Main Angiogenic Factor in the Early Stage of Human Osteoblastogenesis

Takayuki Furumatsu+,1,2,3, Zheng Nan Shen1,2, Akira Kawai2, Keiichiro Nishida2, Hironori Manabe1,2, Toshitaka Oohashi1, Hajime Inoue2 and Yoshifumi Ninomiya1

1 Department of Molecular Biology and Biochemistry, 2 Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine and Dentistry, 2-5-1 Shikata-cho, Okayama, 700-8558; and 3 Department of Orthopaedic Surgery, Kochi Municipal Central Hospital, 2-7-33 Sakurai-cho, Kochi, 780-0821

Vascular endothelial growth factor (VEGF)–mediated angiogenesis is essential for bone formation. However, the effect of VEGF on osteoblastic cells during osteoblastogenesis is still controversial. The aim of this study was to clarify the relationship between osteoblastic cells derived from human mesenchymal stem cells (MSCs) and VEGF in the early stage of osteoblastic differentiation. Continuous dexamethasone treatment with a low concentration stimulated osteoblastogenesis of MSCs and the expression of VEGF121 mRNA. The VEGF secretion from osteoblastic cells also increased along with osteoblastogenesis. Neuropilin-1, which mainly binds VEGF165, was detected at all stages during early osteoblastogenesis, but VEGF receptor-1 and -2 were not detected on RT-PCR analyses. In this study, VEGF had no direct effect on the proliferation of osteoblastic cells. However, the secreted VEGF in the conditioned medium of osteoblastic cells exhibited high angiogenic power as to endothelial cell proliferation. Our findings indicated that VEGF121 principally acts as the main angiogenic factor in the early stage of human osteoblastogenesis. The present study also demonstrated the differential expression of VEGF121 during osteoblastogenesis. The increase of VEGF in the early stage might be a useful marker of induction of bone formation due to human MSCs.

+ To whom correspondence should be addressed. Tel: +81-86-235-7273, Fax: +81-86-223-9727, E-mail: takamatino{at}yahoo.co.jp


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