STUDY DESIGN: 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. SUMMARY OF BACKGROUND DATA: 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. CONCLUSION: 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.
STUDY DESIGN: 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. SUMMARY OF BACKGROUND DATA: 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. CONCLUSION: 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: Justin J Munns; Joe Y B Lee; Alejandro A Espinoza Orías; Ryota Takatori; Gunnar B J Andersson; Howard S An; Nozomu Inoue Journal: PLoS One Date: 2015-05-26 Impact factor: 3.240
Authors: Pekka Kuittinen; Petri Sipola; Tapani Saari; Timo Juhani Aalto; Sanna Sinikallio; Sakari Savolainen; Heikki Kröger; Veli Turunen; Ville Leinonen; Olavi Airaksinen Journal: BMC Musculoskelet Disord Date: 2014-10-16 Impact factor: 2.362