Centrifugal force induces human ligamentum flavum fibroblasts inflammation through activation of JNK and p38 pathways

Yuan Hung Chao, Yang Hwei Tsuang, Jui Sheng Sun, Man Ger Sun, Ming Hong Chen

Research output: Contribution to journalArticle

7 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)422-429
Number of pages8
JournalConnective Tissue Research
Volume53
Issue number5
DOIs
Publication statusPublished - Oct 2012

Fingerprint

Ligamentum Flavum
MAP Kinase Signaling System
Fibroblasts
Chemical activation
Inflammation
p38 Mitogen-Activated Protein Kinases
Cell death
Interleukin-1
Dinoprostone
Nitric Oxide Synthase
JNK Mitogen-Activated Protein Kinases
Nitric Oxide
Cells
Cell Survival
Cell Death
Cell culture
Gene expression
Surgery
Monolayers
Interleukin-6

Keywords

  • Centrifugal force
  • Cyclooxygenase
  • Human ligamentum flavum fibroblasts
  • Inflammation
  • Mitogen-activated protein kinases
  • Nitric oxide
  • Prostaglandins

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology
  • Orthopedics and Sports Medicine
  • Rheumatology

Cite this

Centrifugal force induces human ligamentum flavum fibroblasts inflammation through activation of JNK and p38 pathways. / Chao, Yuan Hung; Tsuang, Yang Hwei; Sun, Jui Sheng; Sun, Man Ger; Chen, Ming Hong.

In: Connective Tissue Research, Vol. 53, No. 5, 10.2012, p. 422-429.

Research output: Contribution to journalArticle

Chao, Yuan Hung ; Tsuang, Yang Hwei ; Sun, Jui Sheng ; Sun, Man Ger ; Chen, Ming Hong. / Centrifugal force induces human ligamentum flavum fibroblasts inflammation through activation of JNK and p38 pathways. In: Connective Tissue Research. 2012 ; Vol. 53, No. 5. pp. 422-429.
@article{972f12be4b2144be81edaa324a816943,
title = "Centrifugal force induces human ligamentum flavum fibroblasts inflammation through activation of JNK and p38 pathways",
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.",
keywords = "Centrifugal force, Cyclooxygenase, Human ligamentum flavum fibroblasts, Inflammation, Mitogen-activated protein kinases, Nitric oxide, Prostaglandins",
author = "Chao, {Yuan Hung} and Tsuang, {Yang Hwei} and Sun, {Jui Sheng} and Sun, {Man Ger} and Chen, {Ming Hong}",
year = "2012",
month = "10",
doi = "10.3109/03008207.2012.685132",
language = "English",
volume = "53",
pages = "422--429",
journal = "Connective Tissue Research",
issn = "0300-8207",
publisher = "Informa Healthcare",
number = "5",

}

TY - JOUR

T1 - Centrifugal force induces human ligamentum flavum fibroblasts inflammation through activation of JNK and p38 pathways

AU - Chao, Yuan Hung

AU - Tsuang, Yang Hwei

AU - Sun, Jui Sheng

AU - Sun, Man Ger

AU - Chen, Ming Hong

PY - 2012/10

Y1 - 2012/10

N2 - 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.

AB - 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.

KW - Centrifugal force

KW - Cyclooxygenase

KW - Human ligamentum flavum fibroblasts

KW - Inflammation

KW - Mitogen-activated protein kinases

KW - Nitric oxide

KW - Prostaglandins

UR - http://www.scopus.com/inward/record.url?scp=84866097921&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84866097921&partnerID=8YFLogxK

U2 - 10.3109/03008207.2012.685132

DO - 10.3109/03008207.2012.685132

M3 - Article

C2 - 22506718

AN - SCOPUS:84866097921

VL - 53

SP - 422

EP - 429

JO - Connective Tissue Research

JF - Connective Tissue Research

SN - 0300-8207

IS - 5

ER -