Elevated levels of tumor necrosis factor-α and TNFR1 in recurrent herniated lumbar discs correlate with chronicity of postoperative sciatic pain

Andrade, Pablo; Hoogland, Govert; Teernstra, Onno P.M.; Aalst, Jasper van; Maren, Emiel van; Daemen, M.A.R.C.; Visser‐Vandewalle, Veerle

doi:10.1016/j.spinee.2015.10.038

Cited by 29 publications

(26 citation statements)

References 33 publications

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“…Recent research shows that the expression of proinflammatory cytokines, such as TNF‐α, IL‐1β, IL‐6, and IL8, is associated with the severity of DDD in both human and animal models (Andrade et al, ; Bachmeier et al, ; Le Maitre, Freemont, & Hoyland, ; Le Maitre, Hoyland, & Freemont, ; Sutovsky et al, ). In the current study, intradiscal injection of TNF‐α combined with degenerative culture conditions caused a marked up‐regulation of proinflammatory cytokine expression equivalent to the above‐mentioned findings in degenerated IVD.…”

Section: Discussionmentioning

confidence: 99%

An intervertebral disc whole organ culture system to investigate proinflammatory and degenerative disc disease condition

Lang

Liu

Geries

et al. 2018

J Tissue Eng Regen Med

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The aim of this study was to compare the effect of different disease initiators of degenerative disc disease (DDD) within an intervertebral disc (IVD) organ culture system and to understand the interplay between inflammation and degeneration in the early stage of DDD. Bovine caudal IVDs were cultured within a bioreactor for up to 11 days. Control group was cultured under physiological loading (0.02-0.2 MPa; 0.2 Hz; 2 hr/day) and high glucose (4.5 g/L) medium. Detrimental loading (0.32-0.5 MPa, 5 Hz; 2 hr/day) and low glucose (2 g/L) medium were applied to mimic the condition of abnormal mechanical stress and limited nutrition supply. Tumour necrosis factor alpha (TNF-α) was injected into the nucleus pulposus (100 ng per IVD) as a proinflammatory trigger. TNF-α combined with detrimental loading and low glucose medium up-regulated interleukin 1β (IL-1β), IL-6, and IL-8 gene expression in disc tissue, nitric oxide, and IL-8 release from IVD, which indicate a proinflammatory effect. The combined initiators up-regulated matrix metalloproteinase 1 gene expression, down-regulated gene expression of Type I collagen in annulus fibrosus and Type II collagen in nucleus pulposus, and reduced the cell viability. Furthermore, the combined initiators induced a degradative effect, as indicated by markedly higher glycosaminoglycan release into conditioned medium. The combination of detrimental dynamic loading, nutrient deficiency, and TNF-α intradiscal injection can synergistically simulate the proinflammatory and degenerative disease condition within DDD. This model will be of high interest to screen therapeutic agents in further preclinical studies for early intervention and treatment of DDD.

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Section: Discussionmentioning

confidence: 99%

An intervertebral disc whole organ culture system to investigate proinflammatory and degenerative disc disease condition

Lang

Liu

Geries

et al. 2018

J Tissue Eng Regen Med

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“…TNF-α levels are significantly increased in IVD samples derived from recurrent lumbar disc herniation patients and positively correlate with postoperative sciatic pain severity [135]. Moreover, there is accumulating evidence which indicates that TNF-α aggravates disc herniation by amplifying inflammatory responses and decreasing IVD cell viability [136,137].…”

Section: Tnf-α and Disc Herniationmentioning

confidence: 99%

Tumor necrosis factor-α: a key contributor to intervertebral disc degeneration

Wang¹,

Yu²,

Yan³

et al. 2017

ABBS

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Intervertebral disc (IVD) degeneration (IDD) is the most common cause leading to low back pain (LBP), which is a highly prevalent, costly, and crippling condition worldwide. Current treatments for IDD are limited to treat the symptoms and do not target the pathophysiology. Tumor necrosis factor-α (TNF-α) is one of the most potent pro-inflammatory cytokines and signals through its receptors TNFR1 and TNFR2. TNF-α is highly expressed in degenerative IVD tissues, and it is deeply involved in multiple pathological processes of disc degeneration, including matrix destruction, inflammatory responses, apoptosis, autophagy, and cell proliferation. Importantly, anti-TNF-α therapy has shown promise for mitigating disc degeneration and relieving LBP. In this review, following a brief description of TNF-α signal transduction, we mainly focus on the expression pattern and roles of TNF-α in IDD, and summarize the emerging progress regarding its inhibition as a promising biological therapeutic approach to disc degeneration and associated LBP. A better understanding will help to develop novel TNF-α-centered therapeutic interventions for degenerative disc disease.

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“…TNF-α is one type of inflammatory cytokines which is secreted by monocytes and macrophages, and plays an important role in inflammatory response, cells proliferation, and apoptosis [36,37]. TNF-α is also a critical inflammatory cytokines causing IVDD [38,39]. Andrade et al [38] found that when compared with first time lumbar disc herniation (LDH) patients, recurrent LDH patients had higher levels of TNF-α, and they discovered that TNF-α and its receptors (TNFR) were correlated with the severity of pre- and post-operative leg pain in LDH patients; conclusions which our study supports.…”

Section: Discussionmentioning

confidence: 99%

17β-Estradiol Inhibites Tumor Necrosis Factor-α Induced Apoptosis of Human Nucleus Pulposus Cells via the PI3K/Akt Pathway

et al. 2016

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BackgroundTumor necrosis factor-α (TNF-α) has been widely known to induce degeneration of nucleus pulposus cells (NPCs). 17β-estradiol (17β-E2) has been broadly proven for its function of suppressing cell apoptosis. The aim of this study is to explore whether 17β-E2 protects apoptosis of human NPCs induced by TNF-α via the PI3K/AKT pathway.Material/MethodsNPCs were divided into four groups: control, TNF-α (100 ng/mL), TNF-α (100 ng/mL) with pretreated 17β-E2 (10 um/L), TNF-α (100 ng/mL) with pretreated 17β-E2 (10 um/L) and MK2206 (10 um/L, inhibitor of the PI3K/AKT pathway). Flow cytometry was used to measure the apoptotic incidence. Inverted phase-contrast microscopy was used to accomplish the morphological observation for apoptosis of treated cells. Additionally, Cell Counting Kit 8 (CCK-8) assay was used to detected cell proliferation. Western blot and quantitative real-time PCR (qRT-PCR) were applied to explore the expression of pro-caspase-3, caspase-3/p17, cleaved PARP, PARP, Akt, and phospho-Akt (p-Akt).ResultsFirst, inverted phase-contrast microscopy, CCK-8, and flow cytometry showed that TNF-α induced marked apoptosis, which was abolished by 17β-E2. Furthermore, Western blot and qRT-PCR showed that 17β-E2 protects TNF-α which can induced apoptosis by upregulating p-Akt, whereas Akt was essentially constant. Our data revealed that p-Akt expression peaked at 24 hours in a time-dependent manner (0–48 hours) after treating with TNF-α; and the p-Akt expression generally increased in a time-dependent manner (0–48 hours) after treating with TNF-α and 17β-E2.Conclusions17β-E2 is shown to protect NPCs against TNF-α induced apoptosis by upregulating p-Akt in the PI3K/AKT pathway. 17β-E2 generally increases expression of p-Akt.

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Elevated levels of tumor necrosis factor-α and TNFR1 in recurrent herniated lumbar discs correlate with chronicity of postoperative sciatic pain

Cited by 29 publications

References 33 publications

An intervertebral disc whole organ culture system to investigate proinflammatory and degenerative disc disease condition

An intervertebral disc whole organ culture system to investigate proinflammatory and degenerative disc disease condition

Tumor necrosis factor-α: a key contributor to intervertebral disc degeneration

17β-Estradiol Inhibites Tumor Necrosis Factor-α Induced Apoptosis of Human Nucleus Pulposus Cells via the PI3K/Akt Pathway

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Elevated levels of tumor necrosis factor-α and TNFR1 in recurrent herniated lumbar discs correlate with chronicity of postoperative sciatic pain

Cited by 29 publications

References 33 publications

An intervertebral disc whole organ culture system to investigate proinflammatory and degenerative disc disease condition

An intervertebral disc whole organ culture system to investigate proinflammatory and degenerative disc disease condition

Tumor necrosis factor-&alpha;: a key contributor to intervertebral disc degeneration

17β-Estradiol Inhibites Tumor Necrosis Factor-α Induced Apoptosis of Human Nucleus Pulposus Cells via the PI3K/Akt Pathway

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Tumor necrosis factor-α: a key contributor to intervertebral disc degeneration