Centrifugal force induces human ligamentum flavum fibroblasts inflammation through activation of JNK and p38 pathways
Journal
Connective Tissue Research
Journal Volume
53
Journal Issue
5
Pages
422-429
Date Issued
2012
Author(s)
Abstract
Inflammation has been proposed to be an important causative factor in ligamentum flavum hypertrophy. However, the mechanisms of mechanical load on inflammation of ligamentum flavum remain unclear. In this study, we used an in vitro model of human ligamentum flavum fibroblasts subjected to centrifugal force to elucidate the effects of mechanical load on cultured human ligamentum flavum fibroblasts; we further studied its molecular and biochemical mechanisms. Human ligamentum flavum fibroblasts were obtained from six patients undergoing lumbar spine surgery. Monolayer cultures of human ligamentum flavum fibroblasts were subjected to different magnitudes of centrifugal forces. Cell viability, cell death, biochemical response, and molecular response to centrifugal forces were analyzed. It was found that centrifugal stress significantly suppressed cell viability without inducing cell death. Centrifugal force at 67.1 g/cm 2 for 60 min significantly increases the production of prostaglandin E2 and nitric oxide as well as gene expression of proinflammatory cytokines, including interleukin (IL)-1α, IL-1β and IL-6, showed that centrifugal force-dependent induction of cyclooxygense-2 and inducible NO synthase required JNK and p38 mitogen-activated protein kinase, but not ERK 1/2 activities. This study suggested that centrifugal force does induce inflammatory responses in human ligamentum flavum fibroblasts. The activation of both JNK and p38 mitogen-activated protein kinase mechanotransduction cascades is a crucial intracellular mechanism that mediates cyclooxygense-2/prostaglandin E2 and inducible NO synthase/nitric oxide production. ? 2012 Informa Healthcare USA, Inc.
SDGs
Other Subjects
cyclooxygenase 2; inducible nitric oxide synthase; interleukin 1alpha; interleukin 1beta; interleukin 6; mitogen activated protein kinase p38; nitric oxide; prostaglandin E2; stress activated protein kinase; adult; aged; article; centrifugal force; enzyme activation; enzyme activity; enzyme induction; female; fibroblast; force; human; human cell; inflammation; ligamentum flavum; male; mechanical stress; nucleotide sequence; prostaglandin synthesis; protein expression; Adult; Aged; Biomechanics; Cell Death; Cell Survival; Collagen Type I; Cyclooxygenase 2; Cytokines; Dinoprostone; Enzyme Activation; Female; Fibroblasts; Gene Expression Regulation; Humans; Inflammation; Inflammation Mediators; JNK Mitogen-Activated Protein Kinases; Ligamentum Flavum; Male; MAP Kinase Signaling System; Middle Aged; Models, Biological; Nitric Oxide; Nitric Oxide Synthase Type II; p38 Mitogen-Activated Protein Kinases; Stress, Mechanical
Type
journal article