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PMID: 8200985 Published · ppublish English Journal Article

Induction of vascular endothelial growth factor expression by prostaglandin E2 and E1 in osteoblasts.

The Journal of clinical investigation ·Vol. 93 ·No. 6 ·1994-06-00 ·Pages 2490-6

Harada S, Nagy JA, Sullivan KA, Thomas KA, Endo N, Rodan GA, Rodan SB

Abstract

PGE1 and PGE2 are potent stimulators of bone formation. Osteogenesis is strongly dependent on angiogenesis. Vascular endothelial growth factor (VEFG), a secreted endothelial cell-specific mitogen, has been implicated in physiological and pathological angiogenesis. The aim of this study was to examine the possible role of VEGF in PG stimulation of bone formation. We found that in rat calvaria-derived osteoblast-enriched cells and in the osteoblastic RCT-3 cell line PGE2 and E1 increased VEGF mRNA and protein levels. The increased expression of VEGF mRNA produced by PGE2 was rapid (maximal at 1 h), transient (declined by 3 h), potentiated by cycloheximide, and abolished by actinomycin D. PGE2 had no effect on VEGF mRNA stability, suggesting transcriptional regulation of VEGF expression by PGF2. Rp-cAMP, a cAMP antagonist, suppressed VEGF mRNA induced by PGE2, indicating cAMP mediation. The upregulation of VEGF expression by PGE2 in the preosteoblastic RCT-1 cells was potentiated by treatment with retinoic acid, which induces the differentiation of these cells. The upregulation of VEGF mRNA by PGE2 was inhibited by dexamethasone treatment. In addition, Northern blot analysis showed that VEGF mRNA is expressed in adult rat tibia. In summary, we documented, for the first time, the expression of VEGF in osteoblasts and in bone tissue. Stimulation of VEGF expression by PGs and its suppression by glucocorticoids, which, respectively, stimulate and suppress bone formation, strongly implicate the involvement of VEGF in bone metabolism.

MeSH Terms
Alprostadil/pharmacology Animals Base Sequence Cells, Cultured Cyclic AMP/physiology Cycloheximide/pharmacology Dactinomycin/pharmacology Dexamethasone/pharmacology Dinoprostone/pharmacology Endothelial Growth Factors/biosynthesis,genetics Female Lymphokines/biosynthesis,genetics Molecular Sequence Data Osteoblasts/drug effects,metabolism Pregnancy RNA, Messenger/analysis Rats Rats, Sprague-Dawley Tibia/metabolism Vascular Endothelial Growth Factor A Vascular Endothelial Growth Factors
Chemicals
Endothelial Growth Factors Lymphokines RNA, Messenger Vascular Endothelial Growth Factor A Vascular Endothelial Growth Factors Dactinomycin Dexamethasone Cycloheximide Cyclic AMP Alprostadil Dinoprostone
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Harada S
Department of Bone Biology and Osteoporosis Research, Merck Research Laboratories, West Point, Pennsylvania 19486.
Nagy J A
Sullivan K A
Thomas K A
Endo N
Rodan G A
Rodan S B
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Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI117258
Published
1994-06-00
Pages
2490-6
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC294462
Subset
IM
External Links
PubMed source DOI: 10.1172/JCI117258 PMC Full Text View journal details
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