Vascular endothelial growth factor-A is a survival factor for nucleus pulposus cells in the intervertebral disc.
The intervertebral disc (IVD) is composed of two avascular tissue types, the nucleus pulposus (NP) and the annulus fibrosus (AF). IVDs is the largest avascular tissue in the human body, however, how these tissues are maintained without a blood supply is poorly understood. Here we show that vascular endothelial growth factor-A (VEGF-A) is highly expressed in NP and that VEGF-A plays a role in NP survival. High VEGF-A expression in NP was detected by microarray analysis, and NP was positive for the hypoxic probe pimonidazole and hypoxia-responsive genes. VEGF-A expression in NP was promoted by hypoxic conditions in vitro. NP cells also expressed the membrane-bound VEGF receptor-1 (VEGFR-1), and the number of apoptotic cells in cultured cell model of NP increased following treatment with VEGFR-1-Fc, which traps VEGF-A in NP. These results indicate that NP is a hypoxic tissue, and that VEGF-A functions in NP survival in an autocrine/paracrine manner.
Fujita
Nobuyuki
N
Department of Orthopedic Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
Imai
Jun-ichi
J
Suzuki
Toru
T
Yamada
Masayuki
M
Ninomiya
Ken
K
Miyamoto
Kana
K
Iwasaki
Ryotaro
R
Morioka
Hideo
H
Matsumoto
Morio
M
Chiba
Kazuhiro
K
Watanabe
Shinya
S
Suda
Toshio
T
Toyama
Yoshiaki
Y
Miyamoto
Takeshi
T
D000818:Animals; D015687:Cell Hypoxia; D002462:Cell Membrane / Q000201:enzymology; D002470:Cell Survival; D016922:Cellular Senescence; D007403:Intervertebral Disc / Q000166:cytology* / Q000378:metabolism*; D051379:Mice; D019899:Paracrine Communication; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000235:genetics / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics / Q000378:metabolism
D042461:Vascular Endothelial Growth Factor A; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2