ArticleThe Journal of biological chemistry2014
CCN2 suppresses catabolic effects of interleukin-1β through α5β1 and αVβ3 integrins in nucleus pulposus cells: implications in intervertebral disc degeneration.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 54 citations in OpenAlex.
- The impact of garlic and its active metabolites on degenerative musculoskeletal diseases.Frontiers in pharmacology · 2026Review
- ITGBL1 and RPN1 Mark a Fibrotic NP Subpopulation with Coupled Integrin Signaling and N-Glycosylation Programs in IVDD.Journal of inflammation research · 2026Article
- Nucleus pulposus cell network modelling in the intervertebral disc.NPJ systems biology and applications · 2025Article
- Current Therapeutic Strategies of Intervertebral Disc Regenerative Medicine.Molecular diagnosis & therapy · 2024Review
- Collagen II enrichment through scAAV6-RNAi-mediated inhibition of matrix-metalloproteinases 3 and 13 in degenerative nucleus-pulposus cells degenerative disc disease and biological treatment strategies.Experimental biology and medicine (Maywood, N.J.) · 2024Article
- Roles of focal adhesion proteins in skeleton and diseases.Acta pharmaceutica Sinica. B · 2023Review
- Extracellular matrix in intervertebral disc: basic and translational implications.Cell and tissue research · 2022Review
- Irisin Ameliorates Intervertebral Disc Degeneration by Activating LATS/YAP/CTGF Signaling.Oxidative medicine and cellular longevity · 2022Article
- Uncovering the secretome of mesenchymal stromal cells exposed to healthy, traumatic, and degenerative intervertebral discs: a proteomic analysis.Stem cell research & therapy · 2021Article
- Biomaterials-Induced Stem Cells Specific Differentiation Into Intervertebral Disc Lineage Cells.Frontiers in bioengineering and biotechnology · 2020Review
- TNF-α Regulates ITGβ1 and SYND4 Expression in Nucleus Pulposus Cells: Activation of FAK/PI3K Signaling.Inflammation · 2019Article
- Reactive Oxygen Species Are Involved in the Development of Gastric Cancer and Gastric Cancer-Related Depression through ABL1-Mediated Inflammation Signaling Pathway.Oxidative medicine and cellular longevity · 2019Article
- Ligustrazine Prevents Intervertebral Disc Degeneration via Suppression of Aberrant TGFBioMed research international · 2019Article
- CCN family member 2/connective tissue growth factor (CCN2/CTGF) is regulated by Wnt-β-catenin signaling in nucleus pulposus cells.Arthritis research & therapy · 2018Article
- A novel mouse model of intervertebral disc degeneration shows altered cell fate and matrix homeostasis.Matrix biology : journal of the International Society for Matrix Biology · 2018Article
- Ghrelin protects against nucleus pulposus degeneration through inhibition of NF-κB signaling pathway and activation of Akt signaling pathway.Oncotarget · 2017Article
- Pullulan microbeads/Si-HPMC hydrogel injectable system for the sustained delivery of GDF-5 and TGF-β1: new insight into intervertebral disc regenerative medicine.Drug delivery · 2017Article
- Collagen type II is downregulated in the degenerative nucleus pulposus and contributes to the degeneration and apoptosis of human nucleus pulposus cells.Molecular medicine reports · 2017Article
- Regulation of human nucleus pulposus cells by peptide-coupled substrates.Acta biomaterialia · 2017Article
- Molecular Therapy for Degenerative Disc Disease: Clues from Secretome Analysis of the Notochordal Cell-Rich Nucleus Pulposus.Scientific reports · 2017Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
The objective of the study was to examine the regulation of CCN2 by inflammatory cytokines, IL-1β, and TNF-α and to determine whether CCN2 modulates IL-1β-dependent catabolic gene expression in nucleus pulposus (NP) cells. IL-1β and TNF-α suppress CCN2 mRNA and protein expression in an NF-κB-dependent but MAPK-independent manner. The conserved κB sites located at -93/-86 and -546/-537 bp in the CCN2 promoter mediated this suppression. On the other hand, treatment of NP cells with IL-1β in combination with CCN2 suppressed the inductive effect of IL-1β on catabolic genes, including MMP-3, ADAMTS-5, syndecan 4, and prolyl hydroxylase 3. Likewise, silencing of CCN2 in human NP cells resulted in elevated basal expression of several catabolic genes and inflammatory cytokines like IL-6, IL-4, and IL-12 as measured by gene expression and cytokine protein array, respectively. Interestingly, the suppressive effect of CCN2 on IL-1β was independent of modulation of NF-κB signaling. Using disintegrins, echistatin, and VLO4, peptide inhibitors to αvβ3 and α5β1 integrins, we showed that CCN2 binding to both integrins was required for the inhibition of IL-1β-induced catabolic gene expression. It is noteworthy that analysis of human tissues showed a trend of altered expression of these integrins during degeneration. Taken together, these results suggest that CCN2 and inflammatory cytokines form a functional negative feedback loop in NP cells that may be important in the pathogenesis of disc disease.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.