Abstract
ObjectiveFollistatin-like protein 1 (FSTL1) is a well-known mediator of inflammation. Intervertebral disc disease is an inflammatory disorder. Here, we investigated the role of FSTL1 in the intervertebral discs inflammation.MethodsExpression of FSTL1 in nucleus pulposus tissues from rats and human was determined by immunohistochemistry staining and western blot analysis. The expression levels of tumor necrosis factor-α (TNF-α), interleukin1-β (IL-1β) and matrix metalloproteinase 13 (MMP-13) in human and rat nucleus pulposus tissues were measured by immunohistochemistry staining. The mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NFκB) signaling pathways were detected by western blotting.ResultsFSTL1 serum levels were significantly increased in lumbar disc herniation patients and had a positive correlation with Visual Analogue Scores. Additionally, FSTL1 expression was significantly increased in extrusion group compared with protrusion and control groups. Furthermore, FSTL1 expression was significantly increased in intervertebral disc degeneration models of rats. Immunohistochemistry staining demonstrated that the levels of TNF-α, IL-1β and MMP-13 were increased in the pathogenesis of intervertebral disc disease. Recombinant human FSTL1 significantly increased the production of proinflammatory cytokines in vitro. In addition, FSTL1 promoted inflammation by activating c-Jun N-terminal kinase (JNK), extracellular regulated protein kinases 1/2(ERK1/2) and NFκB signaling.ConclusionsThese data imply that FSTL1 expression was increased in the pathogenesis of intervertebral disc disease. Importantly, FSTL1 promoted inflammatory catabolism in the nucleus pulposus by activating JNK, ERK 1/2/MAPK and NFκB signaling.
Highlights
Lumbar disc herniation (LDH) is caused by intervertebral disc degeneration, trauma, spinal structural abnormalities, and genetic factors, and is prevalent in specific ethnicities
Follistatin-like protein 1 (FSTL1) serum levels were significantly increased in lumbar disc herniation patients and had a positive correlation with Visual Analogue Scores
Immunohistochemistry staining demonstrated that the levels of tumor necrosis factor-α (TNF-α), IL-1β and matrix metalloproteinase 13 (MMP-13) were increased in the pathogenesis of intervertebral disc disease
Summary
Lumbar disc herniation (LDH) is caused by intervertebral disc degeneration, trauma, spinal structural abnormalities, and genetic factors, and is prevalent in specific ethnicities. When intervertebral disc degeneration occurs, inflammatory cytokines, which regulate matrix metabolism, were significantly increased. LDH is characterized by the destruction and/or disintegration of the annulus fibrosus that leads to piercing www.impactjournals.com/oncotarget of the central nucleus pulposus increased expression of inflammatory cytokines which may directly cause severe back pain or sciatica without nerve root compression [1]. FSTL1 is an extracellular matrix protein which is widely expressed in all eukaryotic cells except for peripheral lymphocytes [3, 4]. It is widely known that mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NFκB) signaling play decisive role in lumbar disc inflammation. We determined FSTL1 expression level in the pathogenesis of LDH using human disc samples, human primary nucleus pulposus cells, and a rat needle punch model
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