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Lysyl oxidase inhibits TNF-α induced rat nucleus pulposus cell apoptosis via regulating Fas/FasL pathway and the p53 pathways.
Life Sci. 2020 Nov 01; 260:118483.LS

Abstract

AIMS

Intervertebral disc degeneration (IVDD) has been regarded as the main cause of low back pain, which affects 80% of adults and still lack effective treatment. In IVDD, nucleus pulposus (NP) cell apoptosis has widely existed. Lysyl oxidase (LOX) has been demonstrated to protect chondrocyte against apoptosis in the TNF-α-treated human chondrocytes. Therefore, in this study, we investigated the anti-apoptosis effect of LOX on TNF-α-treated rat NP cells.

MAIN METHODS

Real-time quantitative reverse transcription-polymerase chain reaction (RT-qPCR) and western blot analyses were used to detect the expression of LOX in TNF-α-treated rat NP cells. Then, the toxicity of exogenous LOX and its protective effect was evaluated by Cell Counting kit-8 (CCK-8). NP cell apoptosis was evaluated by flow cytometry analysis and TUNEL assay. The regulatory effects of LOX on the expression of extracellular matrix (ECM) molecules in TNF-α-treated rat NP cells were measured by RT-qPCR, western blot, and ELISA analyses. The molecular mechanism of LOX in regulating NP cell apoptosis was investigated by RT-qPCR and western blot analyses.

KEY FINDINGS

The expression of LOX in TNF-α-treated rat NP cells was significantly decreased. Exogenous LOX preserved the cell viability, reduced the rate of apoptosis and improved the ECM secretion in TNF-α-treated rat NP cells. Further molecular mechanism investigation showed that LOX inhibited the Fas/FasL and p53 pathways.

SIGNIFICANCES

LOX played an anti-apoptotic role in TNF-α-treated rat NP cells which could be a promising reagent in IVDD treatment.

Authors+Show Affiliations

Key Laboratory of Biorheological Science and Technology, Ministry of Education, Bioengineering College, Chongqing University, Chongqing 400044, China.Key Laboratory of Biorheological Science and Technology, Ministry of Education, Bioengineering College, Chongqing University, Chongqing 400044, China.Key Laboratory of Biorheological Science and Technology, Ministry of Education, Bioengineering College, Chongqing University, Chongqing 400044, China.Key Laboratory of Biorheological Science and Technology, Ministry of Education, Bioengineering College, Chongqing University, Chongqing 400044, China.Key Laboratory of Biorheological Science and Technology, Ministry of Education, Bioengineering College, Chongqing University, Chongqing 400044, China.Key Laboratory of Biorheological Science and Technology, Ministry of Education, Bioengineering College, Chongqing University, Chongqing 400044, China.Key Laboratory of Biorheological Science and Technology, Ministry of Education, Bioengineering College, Chongqing University, Chongqing 400044, China. Electronic address: xtt_92@126.com.Key Laboratory of Biorheological Science and Technology, Ministry of Education, Bioengineering College, Chongqing University, Chongqing 400044, China. Electronic address: yanglibme@126.com.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32979358

Citation

Zhao, Runze, et al. "Lysyl Oxidase Inhibits TNF-α Induced Rat Nucleus Pulposus Cell Apoptosis Via Regulating Fas/FasL Pathway and the P53 Pathways." Life Sciences, vol. 260, 2020, p. 118483.
Zhao R, Liu W, Wang M, et al. Lysyl oxidase inhibits TNF-α induced rat nucleus pulposus cell apoptosis via regulating Fas/FasL pathway and the p53 pathways. Life Sci. 2020;260:118483.
Zhao, R., Liu, W., Wang, M., Zhang, Y., Pan, L., Feng, F., Xia, T., & Yang, L. (2020). Lysyl oxidase inhibits TNF-α induced rat nucleus pulposus cell apoptosis via regulating Fas/FasL pathway and the p53 pathways. Life Sciences, 260, 118483. https://doi.org/10.1016/j.lfs.2020.118483
Zhao R, et al. Lysyl Oxidase Inhibits TNF-α Induced Rat Nucleus Pulposus Cell Apoptosis Via Regulating Fas/FasL Pathway and the P53 Pathways. Life Sci. 2020 Nov 1;260:118483. PubMed PMID: 32979358.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Lysyl oxidase inhibits TNF-α induced rat nucleus pulposus cell apoptosis via regulating Fas/FasL pathway and the p53 pathways. AU - Zhao,Runze, AU - Liu,Wanqian, AU - Wang,Mengyue, AU - Zhang,Yu, AU - Pan,Lianhong, AU - Feng,Fan, AU - Xia,Tingting, AU - Yang,Li, Y1 - 2020/10/13/ PY - 2020/05/23/received PY - 2020/09/13/revised PY - 2020/09/18/accepted PY - 2020/9/27/pubmed PY - 2020/11/28/medline PY - 2020/9/26/entrez KW - ECM synthesis KW - Fas/FasL KW - Intervertebral disc degeneration KW - Lysyl oxidase KW - Nucleus pulposus cellular apoptosis KW - Phosphorylated p53 SP - 118483 EP - 118483 JF - Life sciences JO - Life Sci VL - 260 N2 - AIMS: Intervertebral disc degeneration (IVDD) has been regarded as the main cause of low back pain, which affects 80% of adults and still lack effective treatment. In IVDD, nucleus pulposus (NP) cell apoptosis has widely existed. Lysyl oxidase (LOX) has been demonstrated to protect chondrocyte against apoptosis in the TNF-α-treated human chondrocytes. Therefore, in this study, we investigated the anti-apoptosis effect of LOX on TNF-α-treated rat NP cells. MAIN METHODS: Real-time quantitative reverse transcription-polymerase chain reaction (RT-qPCR) and western blot analyses were used to detect the expression of LOX in TNF-α-treated rat NP cells. Then, the toxicity of exogenous LOX and its protective effect was evaluated by Cell Counting kit-8 (CCK-8). NP cell apoptosis was evaluated by flow cytometry analysis and TUNEL assay. The regulatory effects of LOX on the expression of extracellular matrix (ECM) molecules in TNF-α-treated rat NP cells were measured by RT-qPCR, western blot, and ELISA analyses. The molecular mechanism of LOX in regulating NP cell apoptosis was investigated by RT-qPCR and western blot analyses. KEY FINDINGS: The expression of LOX in TNF-α-treated rat NP cells was significantly decreased. Exogenous LOX preserved the cell viability, reduced the rate of apoptosis and improved the ECM secretion in TNF-α-treated rat NP cells. Further molecular mechanism investigation showed that LOX inhibited the Fas/FasL and p53 pathways. SIGNIFICANCES: LOX played an anti-apoptotic role in TNF-α-treated rat NP cells which could be a promising reagent in IVDD treatment. SN - 1879-0631 UR - https://www.unboundmedicine.com/medline/citation/32979358/Lysyl_oxidase_inhibits_TNF_α_induced_rat_nucleus_pulposus_cell_apoptosis_via_regulating_Fas/FasL_pathway_and_the_p53_pathways_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0024-3205(20)31236-4 DB - PRIME DP - Unbound Medicine ER -