Production and expression of RANTES (CCL5) by human disc cells and modulation by IL-1-β and TNF-α in 3D culture

Gruber, Helen E.; Hoelscher, Gretchen L.; Ingram, Jane A.; Bethea, Synthia; Norton, H. James; Hanley, Edward N.

doi:10.1016/j.yexmp.2014.01.002

Cited by 35 publications

(23 citation statements)

References 24 publications

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“…ACCEPTED MANUSCRIPT 16 findings are in line with recent reports on the association of CCL5/RANTES expression with discogenic pain [124] and the localisation of CCL5/RANTES and its receptors in human disc tissue [125]. The expression and release of CCL5/RANTES is further correlated with the proinflammatory mediators IL-1 and TNF-α, which are known to be up-regulated in degenerative discs [123][124][125][126].…”

Section: Accepted Manuscriptsupporting

confidence: 87%

“…The expression and release of CCL5/RANTES is further correlated with the proinflammatory mediators IL-1 and TNF-α, which are known to be up-regulated in degenerative discs [123][124][125][126]. In a similar study, specifically looking at the cytokine and chemokine expression in the nucleus pulposus, the chemokines CCL2, CCL7 and CXCL8 were found to be increased in degenerative disc specimens [127].…”

Section: Accepted Manuscriptmentioning

confidence: 83%

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Advancing the cellular and molecular therapy for intervertebral disc disease

Sakai

Grad

2015

Advanced Drug Delivery Reviews

253

220

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Section: Accepted Manuscriptsupporting

confidence: 87%

Section: Accepted Manuscriptmentioning

confidence: 83%

Advancing the cellular and molecular therapy for intervertebral disc disease

Sakai

Grad

2015

Advanced Drug Delivery Reviews

253

220

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“…They found that a total of 753 genes were differentially expressed, among which CCL20, CCL3, CCL5, CXCL2, and CXCL5 are up-regulated. Consistent with this, IVD cells treated with TNF-α markedly increase the production of CCL5, a chemoattractant for macrophages and eosinophils, and its expression is correlated with both discogenic pain and severity of disc degeneration [94]. Other macrophage chemoattractants, such as CCL3 whose expression also correlates positively with IVD tissue degeneration degree, are induced via activating the MAPK and NF-κB signaling pathways when NP cells are exposed to TNF-α [95].…”

Section: Tnf-α Amplifies the Inflammatory Responsessupporting

confidence: 63%

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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“…Similarly, the levels of matrix remodeling factors MMP-1, MMP-3, and MMP-10 are elevated in degenerative disc tissue 32, 33 . RANTES (CCL5) is produced by human disc cells in response to inflammatory stimuli in vitro and is implicated in immune signaling 34 . Both IL-1β and TNF-α play a key role in driving disc degeneration by increasing both pro-inflammatory and catabolic processes 35 .…”

Section: Discussionmentioning

confidence: 99%

Senescent intervertebral disc cells exhibit perturbed matrix homeostasis phenotype

Ngo

Patil

McGowan

et al. 2017

Mechanisms of Ageing and Development

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Aging greatly increases the risk for intervertebral disc degeneration (IDD) as a result of proteoglycan loss due to reduced synthesis and enhanced degradation of the disc matrix proteoglycan (PG). How disc matrix PG homeostasis becomes perturbed with age is not known. The goal of this study is to determine whether cellular senescence is a source of this perturbation. We demonstrated that disc cellular senescence is dramatically increased in the DNA repair-deficient Ercc1−/Δ mouse model of human progeria. In these accelerated aging mice, increased disc cellular senescence is closely associated with the rapid loss of disc PG. We also directly examine PG homeostasis in oxidative damage-induced senescent human cells using an in vitro cell culture model system. Senescence of human disc cells treated with hydrogen peroxide was confirmed by growth arrest, senescence-associated β-galactosidase activity, γH2AX foci, and acquisition of senescence-associated secretory phenotype. Senescent human disc cells also exhibited perturbed matrix PG homeostasis as evidenced by their decreased capacity to synthesize new matrix PG and enhanced degradation of aggrecan, a major matrix PG. of the disc. Our in vivo and in vitro findings altogether suggest that disc cellular senescence is an important driver of PG matrix homeostatic perturbation and PG loss.

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Production and expression of RANTES (CCL5) by human disc cells and modulation by IL-1-β and TNF-α in 3D culture

Cited by 35 publications

References 24 publications

Advancing the cellular and molecular therapy for intervertebral disc disease

Advancing the cellular and molecular therapy for intervertebral disc disease

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

Senescent intervertebral disc cells exhibit perturbed matrix homeostasis phenotype

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Production and expression of RANTES (CCL5) by human disc cells and modulation by IL-1-β and TNF-α in 3D culture

Cited by 35 publications

References 24 publications

Advancing the cellular and molecular therapy for intervertebral disc disease

Advancing the cellular and molecular therapy for intervertebral disc disease

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

Senescent intervertebral disc cells exhibit perturbed matrix homeostasis phenotype

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