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Effects of nuclear factor kappa B signaling pathway in human intervertebral disc degeneration.
Spine (Phila Pa 1976). 2015 Feb 15; 40(4):224-32.S

Abstract

STUDY DESIGN

IL-1β (interleukin-1β) can activate human nucleus pulposus cells with or without nuclear factor kappa B (NF-κB) inhibition. We undertook a descriptive and mechanistic investigation of catabolic effects of NF-κB signaling pathway in intervertebral disc degenerative changes.

OBJECTIVE

To clarify the mediatory role of NF-κB signaling pathway in human intervertebral disc degeneration (IDD).

SUMMARY OF BACKGROUND DATA

IDD is a major cause of lower back pain, but the molecular mechanism behind this process is poorly understood. NF-κB is a family of transcription factors that play a central role in mediating cellular response to damage, stress, and inflammation. Growing evidence implicates chronic activation of NF-κB in many degenerative diseases, but its role in IDD has not been adequately explored.

METHODS

Human nucleus pulposus cells in monolayer culture were exposed to IL-1β, which increases matrix-degrading enzyme activity in the nucleus pulposus, with or without NF-κB inhibition by BAY11-7082; ribonucleic acid was isolated for real-time polymerase chain reaction analysis of gene expression, Western blot analysis was performed to detect the changes of protein expression.

RESULTS

NF-κB specific inhibitor BAY11-7082 significantly inhibited IL-1β-induced NF-κB activation. IL-1β-dependent gene upregulation of matrix metalloproteinase (MMP)-3, MMP-9, MMP-13, a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-4, and ADAMTS-5 was significantly reduced by NF-κB inhibition. The decreased gene expression of aggrecan and type II collagen, induced by IL-1β was also reversed by BAY11-7082. NF-κB inhibition reversed the IL-1β-induced changes of protein expression of MMP-3, MMP-9, MMP-13, ADAMTS-4, ADAMTS-5, aggrecan, and type II collagen.

CONCLUSION

These findings demonstrate that the NF-κB signaling pathway is a key mediator of IDD and represents a therapeutic target for mitigating disc degenerative diseases.

LEVEL OF EVIDENCE

N/A.

Authors+Show Affiliations

*Department of Orthopedics, Shanghai First People's Hospital Affiliated Shanghai Jiao Tong University, School of Medicine, Shanghai, China; and †Department of Paediatrics, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, China.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

25494317

Citation

Zhongyi, Sun, et al. "Effects of Nuclear Factor Kappa B Signaling Pathway in Human Intervertebral Disc Degeneration." Spine, vol. 40, no. 4, 2015, pp. 224-32.
Zhongyi S, Sai Z, Chao L, et al. Effects of nuclear factor kappa B signaling pathway in human intervertebral disc degeneration. Spine. 2015;40(4):224-32.
Zhongyi, S., Sai, Z., Chao, L., & Jiwei, T. (2015). Effects of nuclear factor kappa B signaling pathway in human intervertebral disc degeneration. Spine, 40(4), 224-32. https://doi.org/10.1097/BRS.0000000000000733
Zhongyi S, et al. Effects of Nuclear Factor Kappa B Signaling Pathway in Human Intervertebral Disc Degeneration. Spine. 2015 Feb 15;40(4):224-32. PubMed PMID: 25494317.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of nuclear factor kappa B signaling pathway in human intervertebral disc degeneration. AU - Zhongyi,Sun, AU - Sai,Zhao, AU - Chao,Liu, AU - Jiwei,Tian, PY - 2014/12/11/entrez PY - 2014/12/11/pubmed PY - 2015/12/15/medline SP - 224 EP - 32 JF - Spine JO - Spine VL - 40 IS - 4 N2 - STUDY DESIGN: IL-1β (interleukin-1β) can activate human nucleus pulposus cells with or without nuclear factor kappa B (NF-κB) inhibition. We undertook a descriptive and mechanistic investigation of catabolic effects of NF-κB signaling pathway in intervertebral disc degenerative changes. OBJECTIVE: To clarify the mediatory role of NF-κB signaling pathway in human intervertebral disc degeneration (IDD). SUMMARY OF BACKGROUND DATA: IDD is a major cause of lower back pain, but the molecular mechanism behind this process is poorly understood. NF-κB is a family of transcription factors that play a central role in mediating cellular response to damage, stress, and inflammation. Growing evidence implicates chronic activation of NF-κB in many degenerative diseases, but its role in IDD has not been adequately explored. METHODS: Human nucleus pulposus cells in monolayer culture were exposed to IL-1β, which increases matrix-degrading enzyme activity in the nucleus pulposus, with or without NF-κB inhibition by BAY11-7082; ribonucleic acid was isolated for real-time polymerase chain reaction analysis of gene expression, Western blot analysis was performed to detect the changes of protein expression. RESULTS: NF-κB specific inhibitor BAY11-7082 significantly inhibited IL-1β-induced NF-κB activation. IL-1β-dependent gene upregulation of matrix metalloproteinase (MMP)-3, MMP-9, MMP-13, a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-4, and ADAMTS-5 was significantly reduced by NF-κB inhibition. The decreased gene expression of aggrecan and type II collagen, induced by IL-1β was also reversed by BAY11-7082. NF-κB inhibition reversed the IL-1β-induced changes of protein expression of MMP-3, MMP-9, MMP-13, ADAMTS-4, ADAMTS-5, aggrecan, and type II collagen. CONCLUSION: These findings demonstrate that the NF-κB signaling pathway is a key mediator of IDD and represents a therapeutic target for mitigating disc degenerative diseases. LEVEL OF EVIDENCE: N/A. SN - 1528-1159 UR - https://www.unboundmedicine.com/medline/citation/25494317/Effects_of_nuclear_factor_kappa_B_signaling_pathway_in_human_intervertebral_disc_degeneration_ L2 - http://dx.doi.org/10.1097/BRS.0000000000000733 DB - PRIME DP - Unbound Medicine ER -