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Tumor necrosis factor alpha promotes the proliferation of human nucleus pulposus cells via nuclear factor-κB, c-Jun N-terminal kinase, and p38 mitogen-activated protein kinase.
Exp Biol Med (Maywood). 2015 Apr; 240(4):411-7.EB

Abstract

Although tumor necrosis factor alpha (TNF-α) is known to play a critical role in intervertebral disc (IVD) degeneration, the effect of TNF-α on nucleus pulposus (NP) cells has not yet been elucidated. The aim of this study was to explore the effect of TNF-α on proliferation of human NP cells. NP cells were treated with different concentrations of TNF-α. Cell proliferation was determined by cell counting kit-8 (CCK-8) analysis and Ki67 immunofluorescence staining, and expression of cyclin B1 was studied by quantitative real-time RT-PCR. Cell cycle was measured by flow cytometry and cell apoptosis was analyzed using an Annexin V-fluorescein isothiocyanate (FITC) & propidium iodide (PI) apoptosis detection kit. To identify the mechanism by which TNF-α induced proliferation of NP cells, selective inhibitors of major signaling pathways were used and Western blotting was carried out. Treatment with TNF-α increased cell viability (as determined by CCK-8 analysis) and expression of cyclin B1 and the number of Ki67-positive and S-phase NP cells, indicating enhancement of proliferation. Consistent with this, NP cell apoptosis was suppressed by TNF-α treatment. Moreover, inhibition of NF-κB, c-Jun N-terminal kinase (JNK), and p38 mitogen-activated protein kinase (MAPK) blocked TNF-α-stimulated proliferation of NP cells. In conclusion, the current findings suggest that the effect of TNF-α on IVD degeneration involves promotion of the proliferation of human NP cells via the NF-κB, JNK, and p38 MAPK pathways.

Authors+Show Affiliations

Medical School of Southeast University, Nanjing 210009, Jiangsu, China.Department of Orthopaedics, Zhongda Hospital, Southeast University, Nanjing 210009, Jiangsu, China.Department of Orthopaedics, Zhongda Hospital, Southeast University, Nanjing 210009, Jiangsu, China.Department of Orthopaedics, Zhongda Hospital, Southeast University, Nanjing 210009, Jiangsu, China.Department of Orthopaedics, Zhongda Hospital, Southeast University, Nanjing 210009, Jiangsu, China.Department of Surgery, Klinikum rechts der Isar, Technische Universität München, Munich D-81675, Germany.Department of Orthopaedics, Zhongda Hospital, Southeast University, Nanjing 210009, Jiangsu, China.Medical School of Southeast University, Nanjing 210009, Jiangsu, China Department of Orthopaedics, Zhongda Hospital, Southeast University, Nanjing 210009, Jiangsu, China wuxiaotao@medmail.com.cn.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

25304312

Citation

Wang, Xiao-Hu, et al. "Tumor Necrosis Factor Alpha Promotes the Proliferation of Human Nucleus Pulposus Cells Via Nuclear factor-κB, c-Jun N-terminal Kinase, and P38 Mitogen-activated Protein Kinase." Experimental Biology and Medicine (Maywood, N.J.), vol. 240, no. 4, 2015, pp. 411-7.
Wang XH, Hong X, Zhu L, et al. Tumor necrosis factor alpha promotes the proliferation of human nucleus pulposus cells via nuclear factor-κB, c-Jun N-terminal kinase, and p38 mitogen-activated protein kinase. Exp Biol Med (Maywood). 2015;240(4):411-7.
Wang, X. H., Hong, X., Zhu, L., Wang, Y. T., Bao, J. P., Liu, L., Wang, F., & Wu, X. T. (2015). Tumor necrosis factor alpha promotes the proliferation of human nucleus pulposus cells via nuclear factor-κB, c-Jun N-terminal kinase, and p38 mitogen-activated protein kinase. Experimental Biology and Medicine (Maywood, N.J.), 240(4), 411-7. https://doi.org/10.1177/1535370214554533
Wang XH, et al. Tumor Necrosis Factor Alpha Promotes the Proliferation of Human Nucleus Pulposus Cells Via Nuclear factor-κB, c-Jun N-terminal Kinase, and P38 Mitogen-activated Protein Kinase. Exp Biol Med (Maywood). 2015;240(4):411-7. PubMed PMID: 25304312.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Tumor necrosis factor alpha promotes the proliferation of human nucleus pulposus cells via nuclear factor-κB, c-Jun N-terminal kinase, and p38 mitogen-activated protein kinase. AU - Wang,Xiao-Hu, AU - Hong,Xin, AU - Zhu,Lei, AU - Wang,Yun-Tao, AU - Bao,Jun-Ping, AU - Liu,Lei, AU - Wang,Feng, AU - Wu,Xiao-Tao, Y1 - 2014/10/10/ PY - 2014/05/04/received PY - 2014/09/03/accepted PY - 2014/10/12/entrez PY - 2014/10/12/pubmed PY - 2015/7/21/medline KW - Tumor necrosis factor alpha KW - intervertebral disc degeneration KW - mitogen-activated protein kinase KW - nuclear factor-κB KW - nucleus pulposus cell KW - proliferation SP - 411 EP - 7 JF - Experimental biology and medicine (Maywood, N.J.) JO - Exp Biol Med (Maywood) VL - 240 IS - 4 N2 - Although tumor necrosis factor alpha (TNF-α) is known to play a critical role in intervertebral disc (IVD) degeneration, the effect of TNF-α on nucleus pulposus (NP) cells has not yet been elucidated. The aim of this study was to explore the effect of TNF-α on proliferation of human NP cells. NP cells were treated with different concentrations of TNF-α. Cell proliferation was determined by cell counting kit-8 (CCK-8) analysis and Ki67 immunofluorescence staining, and expression of cyclin B1 was studied by quantitative real-time RT-PCR. Cell cycle was measured by flow cytometry and cell apoptosis was analyzed using an Annexin V-fluorescein isothiocyanate (FITC) & propidium iodide (PI) apoptosis detection kit. To identify the mechanism by which TNF-α induced proliferation of NP cells, selective inhibitors of major signaling pathways were used and Western blotting was carried out. Treatment with TNF-α increased cell viability (as determined by CCK-8 analysis) and expression of cyclin B1 and the number of Ki67-positive and S-phase NP cells, indicating enhancement of proliferation. Consistent with this, NP cell apoptosis was suppressed by TNF-α treatment. Moreover, inhibition of NF-κB, c-Jun N-terminal kinase (JNK), and p38 mitogen-activated protein kinase (MAPK) blocked TNF-α-stimulated proliferation of NP cells. In conclusion, the current findings suggest that the effect of TNF-α on IVD degeneration involves promotion of the proliferation of human NP cells via the NF-κB, JNK, and p38 MAPK pathways. SN - 1535-3699 UR - https://www.unboundmedicine.com/medline/citation/25304312/Tumor_necrosis_factor_alpha_promotes_the_proliferation_of_human_nucleus_pulposus_cells_via_nuclear_factor_κB_c_Jun_N_terminal_kinase_and_p38_mitogen_activated_protein_kinase_ L2 - https://journals.sagepub.com/doi/10.1177/1535370214554533?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -