ArticleArthritis research & therapy2007
Interleukin-1 receptor antagonist delivered directly and by gene therapy inhibits matrix degradation in the intact degenerate human intervertebral disc: an in situ zymographic and gene therapy study.
Article in Arthritis research & therapy, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.
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Who cites it
74 citing papers in PubMed, 159 citations in OpenAlex.
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- Genes for bad backs.Gene therapy · 2025Article
- Identification of signature genes and relationship with immune cell infiltration in intervertebral disc degeneration.Frontiers in genetics · 2025Article
- Molecular Mechanisms of Intervertebral Disc Degeneration Induced byBioMed research international · 2025Review
- Tailorable bimetallic nanozyme mitigates intervertebral disc degeneration by inhibiting oxidative stress and inflammageing.Theranostics · 2025Article
- Velutin Inhibits IL-1β-Induced Nucleus Pulposus Inflammatory and Extracellular Matrix Degradation Attenuating Mouse Intervertebral Disc Degeneration via the NF-κB and MAPK Pathways.Mediators of inflammation · 2025Article
- S100A6 Regulates nucleus pulposus cell apoptosis via Wnt/β-catenin signaling pathway: an in vitro and in vivo study.Molecular medicine (Cambridge, Mass.) · 2024Article
- Progress in regulating inflammatory biomaterials for intervertebral disc regeneration.Bioactive materials · 2024Review
- Cytokine Inhibitors Upregulate Extracellular Matrix Anabolism of Human Intervertebral Discs under Alginate Beads and Alginate-Embedded Explant Cultures.International journal of molecular sciences · 2023Article
- Role of ferroptosis and immune infiltration in intervertebral disc degeneration: novel insights from bioinformatics analyses.Frontiers in cell and developmental biology · 2023Article
- Human 3D nucleus pulposus microtissue model to evaluate the potential of pre-conditioned nasal chondrocytes for the repair of degenerated intervertebral disc.Frontiers in bioengineering and biotechnology · 2023Article
- Elucidating the Focal Immunomodulatory Clues Influencing Mesenchymal Stem Cells in the Milieu of Intervertebral Disc Degeneration.Current stem cell research & therapy · 2023Article
- L-type Voltage-Gated calcium channels partly mediate Mechanotransduction in the intervertebral disc.JOR spine · 2022Article
- Self-Assembling Peptide Hydrogels as Functional Tools to Tackle Intervertebral Disc Degeneration.Gels (Basel, Switzerland) · 2022Review
- Gene Therapy in Orthopaedics: Progress and Challenges in Pre-Clinical Development and Translation.Frontiers in bioengineering and biotechnology · 2022Review
- Silencing ATF3 Might Delay TBHP-Induced Intervertebral Disc Degeneration by Repressing NPC Ferroptosis, Apoptosis, and ECM Degradation.Oxidative medicine and cellular longevity · 2022Article
- Regulating the fate of stem cells for regenerating the intervertebral disc degeneration.World journal of stem cells · 2021Review
- ISSLS prize in basic science 2021: a novel inducible system to regulate transgene expression of TIMP1.European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society · 2021Article
- Painful intervertebral disc degeneration and inflammation: from laboratory evidence to clinical interventions.Bone research · 2021Review
- Mesenchymal Stem Cell-Derived Exosomes as a Novel Strategy for the Treatment of Intervertebral Disc Degeneration.Frontiers in cell and developmental biology · 2021Review
14 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Data implicate IL-1 in the altered matrix biology that characterizes human intervertebral disc (IVD) degeneration. In the current study we investigated the enzymic mechanism by which IL-1 induces matrix degradation in degeneration of the human IVD, and whether the IL-1 inhibitor IL-1 receptor antagonist (IL-1Ra) will inhibit degradation. A combination of in situ zymography (ISZ) and immunohistochemistry was used to examine the effects of IL-1 and IL-1Ra on matrix degradation and metal-dependent protease (MDP) expression in explants of non-degenerate and degenerate human IVDs. ISZ employed three substrates (gelatin, collagen, casein) and different challenges (IL-1beta, IL-1Ra and enzyme inhibitors). Immunohistochemistry was undertaken for MDPs. In addition, IL-1Ra was introduced into degenerate IVD explants using genetically engineered constructs. The novel findings from this study are: IL-1Ra delivered directly onto explants of degenerate IVDs eliminates matrix degradation as assessed by multi-substrate ISZ; there is a direct relationship between matrix degradation assessed by ISZ and MDP expression defined by immunohistochemistry; single injections of IVD cells engineered to over-express IL-1Ra significantly inhibit MDP expression for two weeks. Our findings show that IL-1 is a key cytokine driving matrix degradation in the degenerate IVD. Furthermore, IL-1Ra delivered directly or by gene therapy inhibits IVD matrix degradation. IL-1Ra could be used therapeutically to inhibit degeneration of the IVD.
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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 OpenQuestion graph.