Effects of vascular endothelial growth factor (VEGF) on MC3T3-E1.
Osteogenesis and angiogenesis are closely correlated. Vascular endothelial growth factor (VEGF) is believed to play a critical role in skeletal development.


OBJECTIVE
To investigate whether VEGF has direct effects on bone cells activities and to better understand how VEGF promotes bone remodeling.


METHODS
MC3T3-E1 cell line was cultured with and without VEGF in vitro. The cells in both control and test groups were collected at different culture time points of 24, 48 and 72 h. Real-time polymerase chain reaction (qPCR) was carried out to quantify the mRNA expression of VEGF receptor (VEGFR2), alkaline phosphatase (ALP) and osteocalcin (OCN), osteoprotegerin (OPG) and receptor activator of nuclear factor kappa β ligand (RANKL).


RESULTS
The expression of VEGFR2 significantly increased by 53% at 24 h and remained increased by 8% at 72 h compared to control (p < 0.05). ALP showed an early increase by 73% at 24 h (p < 0.001), but dropped by 14 and 41% at 48 and 72 h, respectively (p < 0.05). OCN was down-regulated by 41% at 24 h but then up-regulated by 149% at 72 h (p < 0.001). The expression of OPG significantly decreased by 7% at 24 h (p < 0.001) while dramatically increased by 133% at 72 h (p < 0.001). RANKL remained unchanged at all three time points (p > 0.05).


CONCLUSIONS
VEGF promotes bone remodeling by direct effects on osteoblastic cells via regulating gene expression of ALP, OCN, and OPG through VEGFR2 signaling pathway.
Orthodontics, Faculty of Dentistry, The University of Hong Kong, 34 Hospital Road, Hong Kong SAR, China.
Y Y
YY
Tan
Y-Q
YQ
Yang
L
L
Chai
R W K
RW
Wong
A B M
AB
Rabie
D016475:3T3 Cells; D000469:Alkaline Phosphatase / Q000032:analysis / Q000187:drug effects; D000818:Animals; D016723:Bone Remodeling / Q000187:drug effects; D051379:Mice; D010006:Osteoblasts / Q000187:drug effects*; D015675:Osteocalcin / Q000032:analysis / Q000187:drug effects; D010012:Osteogenesis / Q000187:drug effects*; D053244:Osteoprotegerin / Q000032:analysis / Q000187:drug effects; D016133:Polymerase Chain Reaction / Q000379:methods; D053245:RANK Ligand / Q000032:analysis / Q000187:drug effects; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000032:analysis / Q000187:drug effects
D053244:Osteoprotegerin; D053245:RANK Ligand; C506031:Tnfrsf11b protein, mouse; C505689:Tnfsf11 protein, mouse; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D015675:Osteocalcin; D040301:Vascular Endothelial Growth Factor Receptor-2; D000469:Alkaline Phosphatase