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

8 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

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

Fingerprint Dive into the research topics of 'Centrifugal force induces human ligamentum flavum fibroblasts inflammation through activation of JNK and p38 pathways'. Together they form a unique fingerprint.

  • Cite this