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Inhibition of TNFR1 Attenuates LPS Induced Apoptosis and Inflammation in Human Nucleus Pulposus Cells by Regulating the NF-KB and MAPK Signalling Pathway

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Abstract

Intervertebral disc degeneration (IDD) is accompanied by nucleus pulposus (NP) cell apoptosis, inflammation, and extracellular matrix degradation. Tumour necrosis factor receptor 1 (TNFR1) is a receptor of TNF-α, and is deeply involved in the processes of IDD. However, the effect of TNFR1 inhibition on IDD is not clear. Herein, we report that TNFR1 was increased in LPS-treated HNPCs. The aim of this study was to investigate the potential therapeutic effect of TNFR1 siRNA and selective antagonists of TNFR1 (GSK1995057) on HNPC damage. The results showed that the blockade of TNFR1 by TNFR1 siRNA and GSK1995057 effectively suppressed the cell viability loss, apoptosis, and inflammation induced by LPS in HNPCs. Furthermore, we found that TNFR1 siRNA and GSK1995057 inhibited activation of the NF-KB and MAPK signalling pathways in LPS-stimulated HNPCs. In summary, the blockade of TNFR1 effectively suppressed LPS-induced apoptosis and inflammation in HNPCs through the NF-KB and MAPK signalling pathways. This revealed that the blockade of TNFR1 may provide a potential therapeutic treatment for IDD.

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Abbreviations

IDD:

Intervertebral disc degeneration

HNPCs:

Human nucleus pulposus cells

NP:

Nucleus pulposus

TNF-α:

Tumour necrosis factor α

TNFR1:

Tumour necrosis factor receptor 1

TNFR2:

Tumour necrosis factor receptor 2

MMP-13:

Matrix metalloproteinase-13

ADAMTS-4:

A disintegrin and metalloproteinase with thrombospondin motifs 4

ADAMTS-5:

A disintegrin and metalloproteinase with thrombospondin motifs 5

NF-KB:

Nuclear factor-k-gene binding k

MAPK:

Mitogen-activated protein kinase

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  1. Feng Lv and Longbiao Yang contributed equally

Authors and Affiliations

  1. Department of Pain, Zibo Central Hospital, No. 54 The communist youth league road, Zibo, 255000, Shandong Province, People’s Republic of China

    Feng Lv, Jianxiu Wang, Peiguo Zhang & Chentong Guan

  2. Department of Orthopedics, ShanDong Energy ZiBo Mining Group Co.LTD. Central Hospital, Zibo, 255120, Shandong, People’s Republic of China

    Longbiao Yang, Zhixiang Chen & Qizhao Sun

  3. Department of Orthopedic Surgery, Liaocheng People’s Hospital, Shandong First Medical University, 67 Dong Chang Xi Road, Liaocheng, 252000, Shandong, People’s Republic of China

    Yanbin Liu

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Lv, F., Yang, L., Wang, J. et al. Inhibition of TNFR1 Attenuates LPS Induced Apoptosis and Inflammation in Human Nucleus Pulposus Cells by Regulating the NF-KB and MAPK Signalling Pathway. Neurochem Res 46, 1390–1399 (2021). https://doi.org/10.1007/s11064-021-03278-1

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