Tumor Necrosis Factor&agr; Modulates Matrix Production and Catabolism in Nucleus Pulposus Tissue

  title={Tumor Necrosis Factor\&agr; Modulates Matrix Production and Catabolism in Nucleus Pulposus Tissue},
  author={Cheryle A. S{\'e}guin and Robert M. Pilliar and Peter J. Roughley and Rita A Kandel},
Study Design. This study examines changes in the production of extracellular matrix molecules as well as the induction of tissue degradation in in vitro formed nucleus pulposus (NP) tissues following incubation with tumor necrosis factor (TNF)&agr;. Objective. To characterize the response of NP cells to TNF-&agr;, a proinflammatory cytokine present in herniated NP tissues. Summary of Background Data. TNF-&agr; is a proinflammatory cytokine expressed by NP cells of degenerate intervertebral… 

TNF-&agr; Induces MMP2 Gelatinase Activity and MT1-MMP Expression in an In Vitro Model of Nucleus Pulposus Tissue Degeneration

The findings elucidate the regulation of gelatinase activity and identify a mechanism whereby TNF-&agr; may contribute to matrix degradation in NP tissue, which is thought to contribute to the pathophysiology of intervertebral disc degeneration by up-regulating MMPs.

p38 MAPK Inhibition in Nucleus Pulposus Cells: A Potential Target for Treating Intervertebral Disc Degeneration

The data support further analysis of these effects on the anabolic/catabolic balance of nucleus pulposus cells and suggest that molecular techniques blocking this signal could provide a therapeutic approach to slow the course of intervertebral disc degeneration.

Apoptosis and gene expression of collagenases but not gelatinases in rabbit disc fragment cultures.

Cultured disc fragments swell and undergo necrotic and apoptotic cell death combined with a catabolic gene response and gene expression of proinflammatory and chemoattractant proteins.

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The effects of inflammatory cytokines on the FAK expression were found to be concentration dependent, with greater correlation shown by IL-8 than TNF-&agr;.

Increased expression of matrix metalloproteinase-10, nerve growth factor and substance P in the painful degenerate intervertebral disc

MMP-10 expression is increased in the symptomatic degenerate IVD, where it may contribute to matrix degradation and initiation of nociception and suggest differences in the pathways involved in matrix degradation between painful and pain-free IVD degeneration.

Biologic Response of Degenerative Living Human Nucleus Pulposus Cells to Treatment with Cytokines

The biologic responsiveness to treatment of rhBMP-2, TGF-β, TNF-α, and IL-1β in the degenerative living human IVD can be different according to the degree of degeneration of the IVD.

Inflammatory Kinetics and Efficacy of Anti-inflammatory Treatments on Human Nucleus Pulposus Cells

Anti-inflammatory treatments were most effective when applied early in the inflammatory process, when targeting the source of the inflammation, and no anti-inflammatories significantly reduced cytokine levels compared with TNF control.

Sp1 downregulates proinflammatory cytokine‑induced catabolic gene expression in nucleus pulposus cells.

The results provide pharmacological and genetic evidence of the importance of Sp1 in catabolic enzyme gene regulation during TNF‑α stimulation and suggest that Sp1 may represent an effective target in reducing intervertebral disc‑associated ECM loss.

Photobiomodulation of extracellular matrix enzymes in human nucleus pulposus cells as a potential treatment for intervertebral disk degeneration

Results showed that PBM selectively inhibited the production of ECM-modifying enzymes in a dose- and wavelength-dependent manner, suggesting that it could be a novel tool for treating symptomatic IVD degeneration.



Induction of matrix metalloproteinase-2 and -3 activity in ovine nucleus pulposus cells grown in three-dimensional agarose gel culture by interleukin-1β: a potential pathway of disc degeneration

Evaluated MMP-2 (gelatinase-A) and M MP-3 (stromelysin) produced by cultured ovine nucleus pulposus cells stimulated with interleukin-1β indicated that elevated levels of proM MP-2 and proMMP-3 were present in media samples in response to the IL-1 β treatment.

Human Nucleus Pulposis Can Respond to a Pro-inflammatory Stimulus

It is concluded that both scoliotic and degenerate human nucleus pulposus can respond to an exogenous pro-inflammatory stimulus by secreting increased amounts of IL-6, IL-8, and PGE2 but not TNF-&agr; and that degenerate disc tissue is more sensitive to a pro- inflammatory stimulus than its scoliosis counterpart.

Effect of Chondroitinase ABC on Matrix Metalloproteinases and Inflammatory Mediators Produced by Intervertebral Disc of Rabbit In Vitro

The collagenase activity in the anulus fibrosus was increased by chondroitinase ABC with interleukin-1, which may support the hypothesis that some proteolytic activities are involved in the chemonucleolytic process by chONDroitinases ABC treatment.

Exogenous Tumor Necrosis Factor-Alpha Mimics Nucleus Pulposus-Induced Neuropathology: Molecular, Histologic, and Behavioral Comparisons in Rats

Evidence is reinforced that exogenous tumor necrosis factor-alpha applied in vivo to rat nerve roots produced neuropathologic changes and behavior deficits that mimicked experimental studies with herniated nucleus pulposus applied to nerve roots.

Selective Inhibition of Tumor Necrosis Factor-&agr; Prevents Nucleus Pulposus-Induced Thrombus Formation, Intraneural Edema, and Reduction of Nerve Conduction Velocity: Possible Implications for Future Pharmacologic Treatment Strategies of Sciatica

The data indicate that tumor necrosis factor-&agr; is involved in the basic pathophysiologic events leading to nerve root structural and functional changes after local application of nucleus pulposus.

Expression of monocyte chemoattractant protein‐1 in primary cultures of rabbit intervertebral disc cells

2002 SSE Award Competition in Basic Science: Expression of major matrix metalloproteinases is associated with intervertebral disc degradation and resorption

The data suggest that major MMPs play an important role in the degradation of the IVD, evidenced by the high correlation of MMP expression with the formation of clefts and tears, and implicate a leading function for M MPs in IVD degeneration resulting in the loss of normal disc function, eventually leading to low-back pain.

Influence of Macrophage Infiltration of Herniated Disc Tissue on the Production of Matrix Metalloproteinases Leading to Disc Resorption

Results suggest that peripheral blood mononuclear cells infiltrating extruded discs may secrete a variety of biologic materials capable of further recruiting monocytes into herniated discs in an autocrine fashion.

Murine Nucleus Pulposus‐Derived Cells Secrete Interleukins‐1‐β, ‐6, and ‐10 and Granulocyte‐Macrophage Colony‐Stimulating Factor in Cell Culture

Cultured murine disc‐derived cells have the capacity to secrete proinflammatory cytokines and interleukin‐10 in the absence of inflammatory cells, and this finding supports the hypothesis that disc‐ derived cells are capable of initiating or amplifying an inflammatory process.

Changes in mRNA and Protein Levels of Proteoglycans of the Anulus Fibrosus and Nucleus Pulposus During Intervertebral Disc Degeneration

Changes in mRNA and protein levels of aggrecan, versican, biglycan, decorin and fibromodulin in the anulus fibrosus and the nucleus pulposus at different stages of tissue degeneration are investigated to investigate changes in biochemical and biomechanical properties of the disc.