• Spine · Feb 2012

    The angiogenic capacity from ligamentum flavum subsequent to inflammation: a critical component of the pathomechanism of hypertrophy.

    • Hong Joo Moon, Youn-Kwan Park, Youngjoon Ryu, Jong-Hyun Kim, Taek-Hyun Kwon, Hung-Seob Chung, and Joo Han Kim.
    • Department of Neurosurgery, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Korea.
    • Spine. 2012 Feb 1;37(3):E147-55.

    Study DesignIn vitro study about angiogenic potentiality of ligamentum flavum (LF) cells using coculture of human lumbar LF cells and activated macropage-like THP-1 cells.ObjectiveTo test our hypothesis that activated LF, which was exposed to inflammation, induces angiogenesis, thus resulting in hypertrophy.Summary Of Background DataInflammatory 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.MethodsTo 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.ResultsLarger 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.ConclusionLF 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.

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