title: Vascular endothelial growth factor-A is a survival factor for nucleus pulposus cells in the intervertebral disc.
abstract: 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.
authors.affiliation: Department of Orthopedic Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Fujita
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Imai
authors.forename: Toru
authors.initials: T
authors.lastname: Suzuki
authors.forename: Masayuki
authors.initials: M
authors.lastname: Yamada
authors.forename: Ken
authors.initials: K
authors.lastname: Ninomiya
authors.forename: Kana
authors.initials: K
authors.lastname: Miyamoto
authors.forename: Ryotaro
authors.initials: R
authors.lastname: Iwasaki
authors.forename: Hideo
authors.initials: H
authors.lastname: Morioka
authors.forename: Morio
authors.initials: M
authors.lastname: Matsumoto
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Chiba
authors.forename: Shinya
authors.initials: S
authors.lastname: Watanabe
authors.forename: Toshio
authors.initials: T
authors.lastname: Suda
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Toyama
authors.forename: Takeshi
authors.initials: T
authors.lastname: Miyamoto
mesh_terms: 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
chemical_list: D042461:Vascular Endothelial Growth Factor A; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2