scholarly journals Reduced tissue osmolarity increases TRPV4 expression and pro-inflammatory cytokines in intervertebral disc cells

2016 ◽  
Vol 32 ◽  
pp. 123-136 ◽  
Author(s):  
BA Walter ◽  
◽  
D Purmessur ◽  
A Moon ◽  
J Occhiogrosso ◽  
...  
Keyword(s):  
Intervertebral Disc ◽  
Inflammatory Cytokines ◽  
Disc Cells ◽  
Pro Inflammatory Cytokines

scholarly journals For whom the disc tolls: intervertebral disc degeneration, back pain and toll-like receptors

2021 ◽  
Vol 41 ◽  
pp. 355-369
Author(s):  
DG Bisson ◽  
◽  
M Mannarino ◽  
R Racine ◽  
L Haglund
Keyword(s):  
Back Pain ◽  
Intervertebral Disc ◽  
Inflammatory Cytokines ◽  
Chronic Back Pain ◽  
Proteolytic Enzymes ◽  
Treatment Modalities ◽  
Toll Like Receptors ◽  
Disc Cells ◽  
Ivd Degeneration ◽  
Pro Inflammatory Cytokines

Intervertebral disc (IVD) degeneration is characterised by catabolic and inflammatory processes that contribute largely to tissue degradation and chronic back pain. The disc cells are responsible for the pathological production of pro-inflammatory cytokines and catabolic enzymes leading to degeneration. However, this phenotypical change is poorly understood. Growing evidence in animal and human studies implicates Toll-like receptors (TLR) and their activation through danger-associated alarmins, found increasingly in degenerating IVDs. TLR signalling results in the release of pro-inflammatory cytokines and proteolytic enzymes that can directly cause IVD degeneration and back pain. This review aims to summarise the current literature on TLR activation in IVD degeneration and discuss potential treatment modalities to alleviate the inflammatory phenotype of disc cells in order to arrest IVD degeneration and back pain.

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.

Response of Mesenchymal Stem Cells and Intervertebral Disc Cells to Inflammatory Challenge

2011 ◽  
Author(s):  
Neena Rajan ◽  
Nathaniel Stetson ◽  
Passquale Razzano ◽  
Mitchell Levine ◽  
Daniel Grande ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Intervertebral Disc ◽  
Disc Disease ◽  
Clinical Model ◽  
Injury Model ◽  
Tnf Α ◽  
Disc Cells ◽  
Ivd Degeneration ◽  
Pro Inflammatory Cytokines

Human intervertebral disc (IVD) degeneration is accompanied by elevated levels of pro-inflammatory cytokines, particularly IL-1β and TNF-α [1–3]. Cytokine secretion by disc cells increases catabolic breakdown of the tissue, resulting in a positive feedback of disc integrity loss and further inflammation [4–6]. A recent study by our group has shown that severity of degeneration in an injury model can influence the therapeutic effect of cell based repair, such as treatment with mesenchymal stem cells (MSCs) [7]. The goal of this study is to measure the response of MSCs to inflammatory challenge, and to compare this response to that of differentiated disc cells from the nucleus pulposus (NP), annulus fibrosis (AF) and end plate (EP). In this study, we investigated the effects of lipopolysaccharide (LPS) on intervertebral disc cells and MSCs viability, pro-inflammatory cytokine expression and extracellular matrix (ECM) expression. LPS is an endotoxin that induces strong immune responses in animal tissue and hence widely used as a pre-clinical model of inflammation. This approach provides an opportunity to study broad aspects of the physiological inflammatory process observed in degenerative disc disease.

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.

scholarly journals IL-1β/HMGB1 signalling promotes the inflammatory cytokines release via TLR signalling in human intervertebral disc cells

2016 ◽  
Vol 36 (5) ◽  
Author(s):  
Fang Fang ◽  
Dianming Jiang
Keyword(s):  
Intervertebral Disc ◽  
Inflammatory Cytokines ◽  
Advanced Glycation Endproducts ◽  
Clinical Signs ◽  
High Mobility ◽  
Signs And Symptoms ◽  
Regulation Mechanism ◽  
Real Time Quantitative Pcr ◽  
Disc Cells ◽  
Clinical Signs And Symptoms

Inflammation and cytokines have been recognized to correlate with intervertebral disc (IVD) degeneration (IDD), via mediating the development of clinical signs and symptoms. However, the regulation mechanism remains unclear. We aimed at investigating the regulatory role of interleukin (IL)β and high mobility group box 1 (HMGB1) in the inflammatory response in human IVD cells, and then explored the signalling pathways mediating such regulatory effect. Firstly, the promotion to inflammatory cytokines in IVD cells was examined with ELISA method. And then western blot and real time quantitative PCR were performed to analyse the expression of toll-like receptors (TLRs), receptors for advanced glycation endproducts (RAGE) and NF-κB signalling markers in the IL-1β- or (and) HMGB1-treated IVD cells. Results demonstrated that either IL-1β or HMGB1 promoted the release of the inflammatory cytokines such as prostaglandin E2 (PGE2), TNF-α, IL-6 and IL-8 in human IVD cells. And the expression of matrix metalloproteinases (MMPs) such as MMP-1, -3 and -9 was also additively up-regulated by IL-1β and HMGB1. We also found such additive promotion to the expression of TLR-2, TLR-4 and RAGE, and the NF-κB signalling in intervertebral disc cells. In summary, our study demonstrated that IL-1β and HMGB1 additively promotes the release of inflammatory cytokines and the expression of MMPs in human IVD cells. The TLRs and RAGE and the NF-κB signalling were also additively promoted by IL-1β and HMGB1. Our study implied that the additive promotion by IL-1β and HMGB1 to inflammatory cytokines and MMPs might aggravate the progression of IDD.

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.

scholarly journals Magnoflorine Alleviates “M1” Polarized Macrophage-Induced Intervertebral Disc Degeneration Through Repressing the HMGB1/Myd88/NF-κB Pathway and NLRP3 Inflammasome

2021 ◽  
Vol 12 ◽  
Author(s):  
Feng Zhao ◽  
Zhenye Guo ◽  
Fushan Hou ◽  
Wei Fan ◽  
Binqiang Wu ◽  
...  
Keyword(s):  
Intervertebral Disc ◽  
Cell Viability ◽  
Disc Degeneration ◽  
Inflammatory Cytokines ◽  
Nlrp3 Inflammasome ◽  
Cell Apoptosis ◽  
Intervertebral Disc Degeneration ◽  
Catabolic Enzymes ◽  
Related Proteins ◽  
Pro Inflammatory Cytokines

Intervertebral disc degeneration (IDD) is related to the deterioration of nucleus pulposus (NP) cells due to hypertrophic differentiation and calcification. The imbalance of pro-inflammatory (M1 type) and anti-inflammatory (M2 type) macrophages contributes to maintaining tissue integrity. Here, we aimed to probe the effect of Magnoflorine (MAG) on NP cell apoptosis mediated by “M1” polarized macrophages. THP-1 cells were treated with lipopolysaccharide (LPS) to induce “M1” polarized macrophages. Under the treatment with increasing concentrations of MAG, the expression of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α, IL-18), high mobility group box protein 1 (HMGB1), as well as myeloid differentiation factor 88 (MyD88), nuclear factor kappa B (NF-κB) and NOD-like receptor 3 (NLRP3) inflammasomes in THP-1 cells were determined. What’s more, human NP cells were treated with the conditioned medium (CM) from THP-1 cells. The NP cell viability and apoptosis were evaluated. Western blot (WB) was adopted to monitor the expression of apoptosis-related proteins (Bax, Caspase3, and Caspase9), catabolic enzymes (MMP-3, MMP-13, ADAMTS-4, and ADAMTS-5), and extracellular matrix (ECM) compositions (collagen II and aggrecan) in NP cells. As a result, LPS evidently promoted the expression of pro-inflammatory cytokines and HMGB1, the MyD88-NF-κB activation, and the NLRP3 inflammasome profile in THP-1 cells, while MAG obviously inhibited the "M1″ polarization of THP-1 cells. After treatment with “M1” polarized THP-1 cell CM, NP cell viability was decreased, while cell apoptosis, the pro-inflammatory cytokines, apoptosis-related proteins, and catabolic enzymes were distinctly up-regulated, and ECM compositions were reduced. After treatment with MAG, NP cell damages were dramatically eased. Furthermore, MAG dampened the HMGB1 expression and inactivated the MyD88/NF-κB pathway and NLRP3 inflammasome in NP cells. In conclusion, this study confirmed that MAG alleviates “M1” polarized macrophage-mediated NP cell damage by inactivating the HMGB1-MyD88-NF-κB pathway and NLRP3 inflammasome, which provides a new reference for IDD treatment.

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