Dominance of chemokine ligand 2 and matrix metalloproteinase-2 and -9 and suppression of pro-inflammatory cytokines in the epidural compartment after intervertebral disc extrusion in a canine model

2014 ◽  
Vol 14 (12) ◽  
pp. 2976-2984 ◽  
Author(s):  
Philemon Karli ◽  
Valentine Martlé ◽  
Kenny Bossens ◽  
Artur Summerfield ◽  
Marcus G. Doherr ◽  
...  
Keyword(s):  
Matrix Metalloproteinase ◽  
Intervertebral Disc ◽  
Inflammatory Cytokines ◽  
Canine Model ◽  
Matrix Metalloproteinase 2 ◽  
Chemokine Ligand ◽  
Chemokine Ligand 2 ◽  
Disc Extrusion ◽  
Pro Inflammatory Cytokines

scholarly journals Synergistic Effects of Acidic pH and Pro-Inflammatory Cytokines IL-1β and TNF-α for Cell-Based Intervertebral Disc Regeneration

2020 ◽  
Vol 10 (24) ◽  
pp. 9009
Author(s):  
Chiara Borrelli ◽  
Conor T. Buckley
Keyword(s):  
Intervertebral Disc ◽  
Cell Viability ◽  
Inflammatory Cytokines ◽  
Cell Function ◽  
Synergistic Effects ◽  
Dominant Factor ◽  
Disc Regeneration ◽  
Tnf Α ◽  
Intervertebral Disc Regeneration ◽  
Pro Inflammatory Cytokines

The intervertebral disc (IVD) relies mainly on diffusion through the cartilaginous endplates (CEP) to regulate the nutrient and metabolites exchange, thus creating a challenging microenvironment. Degeneration of the IVD is associated with intradiscal acidification and elevated levels of pro-inflammatory cytokines. However, the synergistic impact of these microenvironmental factors for cell-based therapies remains to be elucidated. The aim of this study was to investigate the effects of low pH and physiological levels of interleukin-1ß (IL-1β) and tumour necrosis factor-α (TNF-α) on nasal chondrocytes (NCs) and subsequently compare their matrix forming capacity to nucleus pulposus (NP) cells in acidic and inflamed culture conditions. NCs and NP cells were cultured in low glucose and low oxygen at different pH conditions (pH 7.1, 6.8 and 6.5) and supplemented with physiological levels of IL-1β and TNF-α. Results showed that acidosis played a pivotal role in influencing cell viability and matrix accumulation, while inflammatory cytokine supplementation had a minor impact. This study demonstrates that intradiscal pH is a dominant factor in determining cell viability and subsequent cell function when compared to physiologically relevant inflammatory conditions. Moreover, we found that NCs allowed for improved cell viability and more effective NP-like matrix synthesis compared to NP cells, and therefore may represent an alternative and appropriate cell choice for disc regeneration.

scholarly journals Effects of IL-1β, IL-20, and BMP-2 on Intervertebral Disc Inflammation under Hypoxia

2020 ◽  
Vol 9 (1) ◽  
pp. 140 ◽  
Author(s):  
Yu-Hsiang Hsu ◽  
Ruey-Mo Lin ◽  
Yi-Shu Chiu ◽  
Wen-Lung Liu ◽  
Kuo-Yuan Huang
Keyword(s):  
Intervertebral Disc ◽  
Inflammatory Cytokines ◽  
Disc Herniation ◽  
Healing Process ◽  
Hypoxia Inducible Factor ◽  
Hypoxic Condition ◽  
Bone Morphogenetic Protein 2 ◽  
Intervertebral Disc Herniation ◽  
Monocyte Chemoattractant Protein 1 ◽  
Pro Inflammatory Cytokines

Intervertebral disc (IVD) is an avascular tissue under hypoxic condition after adulthood. Our previous data showed that inflammatory cytokines (interleukin (IL)-1β), IL-20, and bone morphogenetic protein-2 (BMP-2) play important roles in the healing process after disc injury. In the current study, we investigated whether IL-1β, IL-20, or BMP-2 modulate the expression of pro-inflammatory cytokines, chemotaxis factor, and angiogenesis factor on IVD cells under hypoxia. IVD cells were isolated from patients with intervertebral disc herniation (HIVD) at the levels of L4–5 and L5–S1. We found that the expression of IL-1β, IL-20, BMP-2, hypoxia-inducible factor (HIF)-1α, IL-6, IL-8, angiogenetic factor (vascular endothelial growth factor (VEGF)), chemotactic factor (monocyte chemoattractant protein 1 (MCP-1)), and matrix metalloproteinase-3 (MMP-3) was upregulated in IVD cells under hypoxia conditions. In addition, IL-1β upregulated the expression of pro-inflammatory cytokines (IL-6 and IL-8), VEGF, MCP-1, and disc degradation factor (MMP-3) in IVD cells under hypoxia conditions. IL-20 upregulated MCP-1 and VEGF expression. BMP-2 also upregulated the expression of MCP-1, VEGF, and IL-8 in IVD cells under hypoxia conditions. Treatment with antibody against IL-1β decreased VEGF and MMP-3 expression, while treatment with IL-20 or BMP-2 antibodies decreased MCP-1, VEGF, and MMP-3 expression. Moreover, IL-1β modulated both the expression of IL-20 and BMP-2, but IL-20 only modulated BMP-2 either under a hypoxic or normoxic condition. Therefore, we concluded that the inflammation, chemotaxis, matrix degradation, and angiogenesis after disc herniation are influenced by the hypoxic condition and controlled by IL-1β, IL-20, and BMP-2.

Inhibition of the Extracellular Signal-regulated Kinase Pathway Restores the Discogenic Phenotype of Inflammatory Intervertebral Disc Cells

2021 ◽  
Author(s):  
Adel Tekari ◽  
Alessandro Marazza ◽  
Benjamin Gantenbein
Keyword(s):  
Intervertebral Disc ◽  
Nucleus Pulposus ◽  
Inflammatory Cytokines ◽  
Gelatin Zymography ◽  
Erk Pathway ◽  
Nucleus Pulposus Cells ◽  
Necrosis Factor Alpha ◽  
Extracellular Signal Regulated Kinase ◽  
Extracellular Signal ◽  
Pro Inflammatory Cytokines

Abstract Background: Intervertebral disc (IVD) degeneration is a spinal disease caused by trauma and/or repetitive mechanical overloading of the spine which triggers inflammatory response pathways. Long-term disc inflammation may lead to development of spinal pseudoarthrosis. The aim of the present study was to elucidate the role of the extracellular signal-regulated kinase (ERK) pathway in inflammation-induced IVD cells. Methods: Inflammatory human nucleus pulposus cells (NPC) were stimulated using tumor necrosis factor alpha (TNFα) and the ERK pathway was blocked using a selective molecule-based inhibitor U0126. Gene expression of catabolic and anabolic events, pro-inflammatory, and NPC markers were investigated. The enzymatic activity of matrix metalloproteinases (MMP)2/9 were determined by gelatin zymography. The cytoxicity of U0126 concentrations on NPC was quantified using resazurin assay, and the specificity of U0126 on ERK1/2 signaling was determined.Results: The pro-inflammatory cytokines like MMP3/13 and interleukin 6 in nucleus pulposus (NP) inflammatory conditions were down-regulated by U0126 and a trend towards an increase of the NP-specific collagen type 2, aggrecan and keratin 19 was observed suggesting a recovery of the NP phenotype. U0126 does not seem to have effect on prostaglandin production, aggrecanases and some anabolic genes. We confirmed that U0126 selectively blocks the ERK phosphorylation and U0126 affects the cells metabolic activity only for high concentrations. Conclusions: Inhibition of ERK signaling down-regulates important metalloproteinase, pro-inflammatory cytokines, and up-regulates NP markers in order to restore the discogenic phenotype of inflammatory NPC.

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