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Cited by 69Spine and Intervertebral Disc PathologyOsteoarthritis Treatment and MechanismsPain Mechanisms and Treatments

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Differential expression of p38 MAPK α, β, γ, δ isoforms in nucleus pulposus modulates macrophage polarization in intervertebral disc degeneration

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Yang, Chen, Cao, Peng, Gao, Yang, Wu, Ming, Lin, Yun, Tian, Ye, Yuan, Wen·2016·Scientific Reports
DOI 10.1038/srep22182PMC PMC4766431
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Abstract

P38MAPK mediates cytokine induced inflammation in nucleus pulposus (NP) cells and involves in multiple cellular processes which are related to intervertebral disc degeneration (IDD). The aim of this study was to investigate the expression, activation and function of p38 MAPK isoforms (α,β, γ and δ) in degenerative NP and the effect of p38 activation in NP cells on macrophage polarization. P38 α, β and δ isoforms are preferential expressed, whereas the p38γ isoform is absent in human NP tissue. LV-sh-p38α, sh-p38β transfection in NP cells significantly decreased the ADAMTS-4,-5, MMP-13,CCL3 expression and restored collagen-II and aggrecan expression upon IL-1β stimulation. As compared with p38α and p38β, p38δ exhibited an opposite effect on ADAMTS-4,-5, MMP-13 and aggrecan expression in NP cells. Furthermore, the production of GM-CSF and IFNγ which were trigged by p38α or p38β in NP cells induced macrophage polarization into M1 phenotype. Our finding indicates that p38 MAPK α, β and δ isoform are predominantly expressed and activated in IDD. P38 positive NP cells modulate macrophage polarization through the production of GM-CSF and IFNγ. Hence, Our study suggests that selectively targeting p38 isoforms could ameliorate the inflammation in IDD and regard IDD progression.

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  • The MAPK signaling pathway and its upstream and downstream pathways are involved in the regulation of inflammation and macrophage polarization, especially M1 polarization of macrophages.

    “The MAPK signaling pathway and its upstream and downstream pathways are involved in the regulation of inflammation and macrophage polarization, especially M1 polarization of macrophages.38”

    From Sphingosine Kinase 1 Aggravates Liver Fibrosis by Mediating Macrophage Recruitment and Polarization (2024) · cites this paper as [38]

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Metadata

Authors
Yang, C., Cao, P., Gao, Y., Wu, M., Lin, Y., Tian, Y., & Yuan, W.
Affiliations
  • Shanghai Changzheng Hospital (CN)
  • Second Military Medical University (CN)
Corresponding author
  • Tian, Ye
  • Yuan, Wen
ORCID
Venue
Scientific Reports
Publisher
Springer Science and Business Media LLC
Published
2016-02-25
Volume
6
Issue
1
Pages
22182-22182
ISSN
2045-2322 (ISSN-L)
DOI
10.1038/srep22182
PMC
PMC4766431
OpenAlex
W2417056655
Cited by
69
References
0
Citations by year
2026: 2 · 2025: 4 · 2024: 13 · 2023: 14 · 2022: 13 · 2021: 5 · 2020: 6 · 2019: 3 · 2018: 5 · 2017: 4
FWCI
3.64
Type
journal article
Language
en
Open access
Licence
Locations
  • Scientific Reports (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
Science and Technology Commission of Shanghai Municipality
Topics
  • Health Sciences › Medicine › Orthopedics and Sports Medicine › Spine and Intervertebral Disc Pathology
  • Health Sciences › Medicine › Rheumatology › Osteoarthritis Treatment and Mechanisms
  • Health Sciences › Medicine › Physiology (medical) › Pain Mechanisms and Treatments
Keywords
intervertebral disc degeneration, nucleus pulposus cells, macrophage polarization, M1 macrophage phenotype, GM-CSF, interferon-gamma, ADAMTS-4, ADAMTS5, MMP-13, CCL3, aggrecan, type II collagen, IL-1β, inflammation, p38δ, p38α, p38β
MeSH terms
Nucleus Pulposus, ADAMTS Proteins, Adolescent, Adult, Aged, Cell Differentiation, Humans, Isoenzymes, Macrophages, Middle Aged, Granulocyte-Macrophage Colony-Stimulating Factor, Collagen Type II, p38 Mitogen-Activated Protein Kinases, Matrix Metalloproteinase 13, Interleukin-1beta, Chemokine CCL3, Intervertebral Disc Degeneration

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