title: The angiogenic capacity from ligamentum flavum subsequent to inflammation: a critical component of the pathomechanism of hypertrophy.
abstract: METHODS
  In vitro study about angiogenic potentiality of ligamentum flavum (LF) cells using coculture of human lumbar LF cells and activated macropage-like THP-1 cells.
  
  
  OBJECTIVE
  To test our hypothesis that activated LF, which was exposed to inflammation, induces angiogenesis, thus resulting in hypertrophy.
  
  
  BACKGROUND
  Inflammatory reactions after mechanical stress produce fibrosis and scarring of the LF that result in hypertrophy, a major pathological feature of spinal stenosis. This study evaluated the roles of LF cells in the pathomechanism of hypertrophy, focusing on angiogenesis.
  
  
  METHODS
  To determine their response to the inflammatory reaction, human LF cells were cocultured with phorbol myristate acetate-stimulated macrophage-like THP-1 cells. The conditioned media were assayed for tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, IL-8, vascular endothelial growth factor (VEGF), and transforming growth factor (TGF)-β1. Naïve and macrophage-exposed LF cells that responded to TNF-α/IL-1β were compared using the same outcome measures. Hypertrophied LF tissue was stained by TGF-β1 primary antibody using immunohistochemical method.
  
  
  RESULTS
  Larger quantities of IL-6, IL-8, and VEGF were secreted by cocultured cells than by macrophages alone and LF cells alone combined. Prior macrophage exposure increased the secretion of IL-8 and VEGF in response to TNF-α/IL-1β stimulation whereas IL-6 production was increased in response to IL-1β. The coculture appeared to increase TGF-β1 secretion but the level was lower than that for macrophage-like cells alone and LF cells alone combined.
  
  
  CONCLUSIONS
  LF cells interact with macrophage-like cells to produce angiogenesis-related factors except TGF-β1. Activated LF cells that have been exposed to macrophage, can impact the inducement of angiogenesis-related factors, suggesting that fibrosis and scarring during inflammatory reaction is the major pathomechanism of LF hypertrophy.
authors.affiliation: Department of Neurosurgery, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Korea.
authors.forename: Hong Joo
authors.initials: HJ
authors.lastname: Moon
authors.forename: Youn-Kwan
authors.initials: YK
authors.lastname: Park
authors.forename: Youngjoon
authors.initials: Y
authors.lastname: Ryu
authors.forename: Jong-Hyun
authors.initials: JH
authors.lastname: Kim
authors.forename: Taek-Hyun
authors.initials: TH
authors.lastname: Kwon
authors.forename: Hung-Seob
authors.initials: HS
authors.lastname: Chung
authors.forename: Joo Han
authors.initials: JH
authors.lastname: Kim
mesh_terms: D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D018920:Coculture Techniques; D005355:Fibrosis; D006801:Humans; D006984:Hypertrophy / Q000473:pathology / Q000503:physiopathology; D007249:Inflammation / Q000473:pathology / Q000503:physiopathology; D017843:Ligamentum Flavum / Q000166:cytology / Q000473:pathology*; D008264:Macrophages / Q000473:pathology; D009000:Monocytes / Q000473:pathology; D018919:Neovascularization, Physiologic / Q000502:physiology; D013130:Spinal Stenosis / Q000473:pathology*