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 language | English |
|---|---|
| Pages (from-to) | 422-429 |
| Number of pages | 8 |
| Journal | Connective Tissue Research |
| Volume | 53 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - Oct 2012 |
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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 journal › Article
}
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 -