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

Wang, Cheng; Yu, Xiaohua; Yan, Yongping; Yang, Wei; Zhang, Shujun; Xiang, Yong‐Xiao; Zhang, Jian; Wang, Wenjun

doi:10.1093/abbs/gmw112

Cited by 92 publications

(75 citation statements)

References 168 publications

(160 reference statements)

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“…Notably, the number of NP cells continues to decrease during disc degeneration because certain pathological factors, such as mechanical overloading, limited nutrient supply and increased inflammation processes, induce NP cell apoptosis [5, 36-38]. When the number of NP cells decreases to an adequately low level, NP matrix homeostasis is obviously destroyed, and the disc degeneration process is initiated and further exacerbated [24].…”

Section: Discussionmentioning

confidence: 99%

N-Cadherin Maintains the Healthy Biology of Nucleus Pulposus Cells under High-Magnitude Compression

Wang

Leng²,

Zhao³

et al. 2017

Cell Physiol Biochem

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Background/Aims: Mechanical load can regulate disc nucleus pulposus (NP) biology in terms of cell viability, matrix homeostasis and cell phenotype. N-cadherin (N-CDH) is a molecular marker of NP cells. This study investigated the role of N-CDH in maintaining NP cell phenotype, NP matrix synthesis and NP cell viability under high-magnitude compression. Methods: Rat NP cells seeded on scaffolds were perfusion-cultured using a self-developed perfusion bioreactor for 5 days. NP cell biology in terms of cell apoptosis, matrix biosynthesis and cell phenotype was studied after the cells were subjected to different compressive magnitudes (low- and high-magnitudes: 2% and 20% compressive deformation, respectively). Non-loaded NP cells were used as controls. Lentivirus-mediated N-CDH overexpression was used to further investigate the role of N-CDH under high-magnitude compression. Results: The 20% deformation compression condition significantly decreased N-CDH expression compared with the 2% deformation compression and control conditions. Meanwhile, 20% deformation compression increased the number of apoptotic NP cells, up-regulated the expression of Bax and cleaved-caspase-3 and down-regulated the expression of Bcl-2, matrix macromolecules (aggrecan and collagen II) and NP cell markers (glypican-3, CAXII and keratin-19) compared with 2% deformation compression. Additionally, N-CDH overexpression attenuated the effects of 20% deformation compression on NP cell biology in relation to the designated parameters. Conclusion: N-CDH helps to restore the cell viability, matrix biosynthesis and cellular phenotype of NP cells under high-magnitude compression.

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Section: Discussionmentioning

confidence: 99%

N-Cadherin Maintains the Healthy Biology of Nucleus Pulposus Cells under High-Magnitude Compression

Wang

Leng²,

Zhao³

et al. 2017

Cell Physiol Biochem

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“…IVDD is a multifactorial process characterized by intracellular and biochemical changes in intervertebral discs (IVD) cells which lead to structural deterioration of IVDs. Although the pathogenesis of IVDD is not fully understood, tumour necrosis factor (TNF)‐α is reported to play a crucial role in the development of IVDD …”

Section: Introductionmentioning

confidence: 99%

Polydatin suppresses nucleus pulposus cell senescence, promotes matrix homeostasis and attenuates intervertebral disc degeneration in rats

Wang

Huang

Lin

et al. 2018

J Cellular Molecular Medi

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Intervertebral disc degeneration (IVDD) is one of the major causes of low back pain. Polydatin (PD) has been shown to exert multiple pharmacological effects on different diseases; here, we test the therapeutic potential of PD for IVDD. In in‐vitro experiments, we confirmed PD is nontoxic to nucleus pulposus cells (NPCs) under the concentration of 400 μmol/L. Furthermore, PD was able to decrease the level of senescence in TNF‐α‐treated NPCs, as indicated by β‐gal staining as well as senescence markers p53 and p16 expression. In the aspect of extracellular matrix (ECM), PD not only reduced metalloproteinase 3 (MMP‐3), metalloproteinase 13 (MMP‐13) and a disintegrin‐like and metalloproteinase thrombospondin type 1 motif 4 (ADAMTS‐4) expression, but also increased aggrecan and collagen II levels. Mitochondrion is closely related to cellular senescence and ECM homeostasis; mechanistically, we found PD may rescue TNF‐α‐induced mitochondrial dysfunction, and it may also promote Nrf2 expression and activity. Silencing Nrf2 partly abolished the protective effects of PD on mitochondrial homeostasis, senescence and ECM homeostasis in TNF‐α‐treated NPCs. Correspondingly, PD ameliorated IVDD in rat model by promoting Nrf2 activity, preserving ECM and inhibiting senescence in nucleus pulposus cells. To sum up, our study suggests that PD exerts protective effects in NPCs against IVDD and reveals the underlying mechanism of PD on Nrf2 activation in NPCs.

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“…Resident cell apoptosis and ECM degeneration is the main pathological phenomenon in IDD progression, and inflammatory mediators play an important role in the process . In line with other studies, we previously mimicked the inflammatory environment using TNF‐α to promote cell apoptosis and ECM catabolism . Moreover, to clarify the protective effect of RADA‐KPSS peptide scaffolds on TNF‐α‐treated NPCs, we compared cells with or without TNF‐α treatment on RADA16‐I peptide scaffolds.…”

Section: Discussionmentioning

confidence: 99%

“…In particular, TNF‐α, a typical inflammatory cytokine, can increase cell apoptosis and inhibit cell physiological properties in many degenerative processes . TNF‐α can enhance matrix‐degrading enzyme activity and increase excessive apoptosis in nucleus pulposus cells (NPCs) . In addition, the nuclear factor‐κB (NF‐κB) signaling pathway, which plays a crucial role in the activity of catabolic proteins and inflammatory mediators, is upregulated in human degenerated disks and has an important role in matrix catabolism .…”

Section: Introductionmentioning

confidence: 99%

Functional self‐assembled peptide scaffold inhibits tumor necrosis factor‐alpha‐induced inflammation and apoptosis in nucleus pulposus cells by suppressing nuclear factor‐κB signaling

Cheng

et al. 2017

J Biomedical Materials Res

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Although nucleus pulposus (NP) tissue engineering has achieved tremendous success, researches still face the huge obstacles in maintaining cell survival and function. A novel functional self-assembled peptide RADA-KPSS was constructed by conjugating BMP-7 short active fragment (KPSS) to the C-terminus of RADA16-I that displays anti-inflammatory and anti-apoptosis effects. However, whether this functional self-assembled RADA-KPSS peptide can alleviate inflammation and NPC apoptosis induced by tumor necrosis factor-alpha (TNF-α) has not been studied. Therefore, we cultured NPCs treated with TNF-α for 48 h with the RADA-KPSS peptide, and compared the results to those with RADA16-I peptide. The cell apoptosis rate, inflammatory mediator secretion, expression of matrix-degrading enzymes, and extracellular matrix (ECM) protein levels were evaluated. The expression of nuclear factor-κB-p65 (NF-κB-p65) protein was also tested. TNF-α-treated NPCs cultured with the RADA16-I peptide showed up-regulated gene expression for matrix-degrading enzymes, such as matrix metalloproteinases-3 (MMP-3), MMP-9, and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS-4), and down-regulated gene expression for ECM proteins such as aggrecan, collagen II, and Sox-9. The RADA-KPSS peptide could attenuate the expression of MMP-3, MMP-9, and ADAMTS-4, promote accumulation of ECM proteins, and increase secretion of glycosaminoglycan as compared with the RADA16-I peptide. Moreover, the TNF-α-damaged NPCs was further demonstrated to inhibit NF-κB-p65, IL-1, IL-6, and prostaglandin E-2 proteins and decrease cell apoptosis in RADA-KPSS peptide. In conclusion, the functional self-assembled RADA-KPSS peptides have anti-inflammatory and anti-apoptotic effects by promoting anabolic processes and inhibiting catabolic processes in intervertebral disk degeneration. These peptides may be feasible for clinical applications in NP tissue engineering. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1082-1091, 2018.

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

Cited by 92 publications

References 168 publications

N-Cadherin Maintains the Healthy Biology of Nucleus Pulposus Cells under High-Magnitude Compression

N-Cadherin Maintains the Healthy Biology of Nucleus Pulposus Cells under High-Magnitude Compression

Polydatin suppresses nucleus pulposus cell senescence, promotes matrix homeostasis and attenuates intervertebral disc degeneration in rats

Functional self‐assembled peptide scaffold inhibits tumor necrosis factor‐alpha‐induced inflammation and apoptosis in nucleus pulposus cells by suppressing nuclear factor‐κB signaling

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