title: Vascular endothelial growth factor (VEGF)-induced angiogenesis in herniated disc resorption.
abstract: Intervertebral disc herniation is a major cause of low back pain and sciatica. Spontaneous resorption of herniated disc (HD) is frrequently detected by magnetic resonance imaging (MRI). Marked infiltration by macrophages and neo-vascularization are observed upon histogical examination of HD. In addition, enhanced MRI studies suggest that HD resorption occurs more frequently in those completely exposed to the epidural space and that this correlates with their degree of vascularization. We have postulated that the angiogenic factor, vascular endothelial growth factor (VEGF), may be implicated in the neo-vascularization of HD tissues. Here we demonstrate that VEGF and its receptors VEGFR-1 and VEGFR-2 are expressed in human surgical samples of HD. Using a co-culture system comprised of murine peritoneal macrophages and intervertebral disc tissue as a model of the acute phase of HD developed previously, an increase in macrophage VEGF protein and mRNA expression was observed upon exposure to disc tissue. Tumor necrosis factor alpha (TNF-alpha) was required for this induction of VEGF. Use of a novel angiogenesis assay revealed that addition of the conditioned media from the co-culture system resulted in an increase of vascular tubule formation. This effect was strongly inhibited by anti-VEGF antibody, but augmented by recombinant VEGF. We conclude that VEGF induction, under the co-culture conditions tested can result in neo-vascularization of intervertebral disc tissue and may thus play a role in the resorption of HD.
authors.affiliation: Division of Locomotorial Molecular Degeneration Research, Human Genes and Science Center, Tokyo Medical and Dental University, Graduate School of Medicine, Japan. haro.orth@tmd.ac.jp
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Haro
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Kato
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Komori
authors.forename: Motonobu
authors.initials: M
authors.lastname: Osada
authors.forename: Kenichi
authors.initials: K
authors.lastname: Shinomiya
mesh_terms: D000328:Adult; D000818:Animals; D018920:Coculture Techniques; D003470:Culture Media / Q000494:pharmacology; D046508:Culture Techniques; D016228:Endothelial Growth Factors / Q000502:physiology*; D005260:Female; D006801:Humans; D007403:Intervertebral Disc / Q000502:physiology; D007405:Intervertebral Disc Displacement / Q000503:physiopathology*; D008222:Lymphokines / Q000502:physiology*; D017737:Macrophages, Peritoneal / Q000502:physiology; D008297:Male; D051379:Mice; D008875:Middle Aged; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000502:physiology*; D012075:Remission, Spontaneous; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
chemical_list: D003470:Culture Media; D016228:Endothelial Growth Factors; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors