Expression and regulation of vascular endothelial growth factor in osteoblasts.
Bone formation is linked closely to angiogenesis. Because prostaglandin E2 (PGE2) is a potent stimulator of bone formation, its effects were evaluated on vascular endothelial growth factor, a secreted endothelial cell-specific mitogen, and a potent angiogenic protein. Prostaglandin E2 increased vascular endothelial growth factor protein in conditioned media of osteoblastic RCT-3 cells within 3 hours. Prostaglandin E2 also increased the steady-state levels of vascular endothelial growth factor mRNA in a dose-dependent manner. The increased expression of vascular endothelial growth factor mRNA produced by PGE2 was rapid (maximal at 1 hour) and was enhanced by the protein synthesis inhibitor cycloheximide (5 micrograms/ml). The increase in vascular endothelial growth factor mRNA by PGE2 was inhibited strongly by pretreatment for 3 hours with dexamethasone (10(-7) M). Stimulation of vascular endothelial growth factor by PGE2 and its suppression by dexamethasone implicate the involvement of vascular endothelial growth factor in bone metabolism.
Harada
S
S
Department of Bone Biology and Osteoporosis Research, Merck Research Laboratories, West Point, PA 19486, USA.
Rodan
S B
SB
Rodan
G A
GA
D000818:Animals; D002460:Cell Line; D003513:Cycloheximide / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology; D016228:Endothelial Growth Factors / Q000096:biosynthesis* / Q000378:metabolism / Q000502:physiology; D015870:Gene Expression; D066298:In Vitro Techniques; D008222:Lymphokines / Q000096:biosynthesis* / Q000378:metabolism / Q000502:physiology; D010006:Osteoblasts / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D008222:Lymphokines; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D003907:Dexamethasone; D003513:Cycloheximide; D015232:Dinoprostone