ArticleOsteoarthritis and cartilage2007
Modulation of TGF-beta signaling by proinflammatory cytokines in articular chondrocytes.
Article in Osteoarthritis and cartilage, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers, 2 of them syntheses that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
60 citing papers in PubMed, 2 syntheses or guidelines pooled it, 137 citations in OpenAlex.
- TNFα-Related Chondrocyte Inflammation Models: A Systematic Review.International journal of molecular sciences · 2024Pooled it
- An Evidence-Based Systematic Review of Human Knee Post-Traumatic Osteoarthritis (PTOA): Timeline of Clinical Presentation and Disease Markers, Comparison of Knee Joint PTOA Models and Early Disease Implications.International journal of molecular sciences · 2021Pooled it
- Efficacy and tolerability of an undenatured type II collagen supplement in modulating knee osteoarthritis symptoms: a multicenter randomized, double-blind, placebo-controlled study.Nutrition journal · 2016Trial
- PRP-activating hyaluronic acid hydrogels for immune-modulatory osteoarthritis repair.Bioactive materials · 2027Article
- Article
- Innovative tissue engineering strategies for auricular regeneration in microtia: Current advances and future perspectives.Regenerative therapy · 2025Review
- Characterizing the Long Non-Coding RNA Profile of Endometrial Mesenchymal Stem/Stromal Cell-Derived Extracellular Vesicles and Their Anti-Inflammatory Role in Osteoarthritis.International journal of molecular sciences · 2025Article
- Tracking inflammation status for improving patient prognosis: A review of current methods, unmet clinical needs and opportunities.Biotechnology advances · 2025Review
- Aging-associated Increase of GATA4 levels in Articular Cartilage is Linked to Impaired Regenerative Capacity of Chondrocytes and Osteoarthritis.bioRxiv : the preprint server for biology · 2025Article
- Functional interleukin-4 releasing microparticles impact THP-1 differentiated macrophage phenotype.Frontiers in bioengineering and biotechnology · 2024Article
- Self-assembled peptide-substance P hydrogels alleviate inflammation and ameliorate the cartilage regeneration in knee osteoarthritis.Biomaterials research · 2023Article
- TGF-β is elevated in hyperuricemic individuals and mediates urate-induced hyperinflammatory phenotype in human mononuclear cells.Arthritis research & therapy · 2023Article
- Elucidating the Focal Immunomodulatory Clues Influencing Mesenchymal Stem Cells in the Milieu of Intervertebral Disc Degeneration.Current stem cell research & therapy · 2023Article
- Nanofat lysate ameliorates pain and cartilage degradation of osteoarthritis through activation of TGF-β-Smad2/3 signaling of chondrocytes.Frontiers in pharmacology · 2023Article
- Maternal immune activation leads to defective brain-blood vessels and intracerebral hemorrhages in male offspring.The EMBO journal · 2022Article
- Regulatory network-based model to simulate the biochemical regulation of chondrocytes in healthy and osteoarthritic environments.Scientific reports · 2022Article
- DNA methylation and noncoding RNA in OA: Recent findings and methodological advances.Osteoarthritis and cartilage open · 2021Article
- Evaluation of the influence of platelet-rich plasma (PRP), platelet lysate (PL) and mechanical loading on chondrogenesis in vitro.Scientific reports · 2021Article
- Osteoarthritis-Related Inflammation Blocks TGF-β's Protective Effect on Chondrocyte Hypertrophy via (de)Phosphorylation of the SMAD2/3 Linker Region.International journal of molecular sciences · 2021Article
- Role of microRNA Shuttled in Small Extracellular Vesicles Derived From Mesenchymal Stem/Stromal Cells for Osteoarticular Disease Treatment.Frontiers in immunology · 2021Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
objectiveThe normal structure and function of articular cartilage are the result of a precisely balanced interaction between anabolic and catabolic processes. The transforming growth factor-beta (TGF-beta) family of growth factors generally exerts an anabolic or repair response; in contrast, proinflammatory cytokines such as interleukin 1 beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) exert a strong catabolic effect. Recent evidence has shown that IL-1beta, and TNF-alpha, and the TGF-beta signaling pathways share an antagonistic relationship. The aim of this study was to determine whether the modulation of the response of articular chondrocytes to TGF-beta by IL-1beta or TNF-alpha signaling pathways occurs through regulation of activity and availability of mothers against DPP (Drosophila) human homologue (Smad) proteins.
methodsHuman articular chondrocytes isolated from knee joints from patients with osteoarthritis (OA) or normal bovine chondrocytes were cultured in suspension in poly-(2-hydroxyethyl methacrylate)-coated dishes with either 10% fetal bovine serum media or serum-deprived media 6h before treatment with IL-1beta alone, TNF-alpha alone or IL-1beta followed by TGF-beta. Nuclear extracts were examined by electrophoretic mobility-shift assays (EMSA) for nuclear factor-kappa B (NF-kappaB) and Smad3/4 deoxyribonucleic acid (DNA) binding. Nuclear extracts were also subjected to the TranSignal Protein/DNA array (Panomics, Redwood City, CA) enabling the simultaneous semiquantitative assessment of DNA-binding activity of 54 different transcription factors. Nuclear phospho-Smad2/3 and total Smad7 protein expression in whole cell lysates were studied by Western blot. Cytoplasmic Smad7, type II collagen alpha 1 (COL2A1), aggrecan and SRY-related high mobility group-Box gene 9 (SOX-9) mRNA expression were measured by real-time polymerase chain reaction (PCR).
resultsThe DNA-binding activity of Smad3/4 in the TranSignal Protein/DNA array was downregulated by TNF-alpha (46%) or IL-1beta treatment (42%). EMSA analysis showed a consistent reduction in Smad3/4 DNA-binding activity in human articular chondrocytes treated with IL-1beta or TNF-alpha. TGF-beta-induced Smad3/4 DNA-binding activity and Smad2/3 phosphorylation were also reduced following pretreatment with IL-1beta in human OA and bovine chondrocytes. Real-time PCR and Western blot analysis showed that IL-1beta partially reversed the TGF-beta stimulation of Smad7 mRNA and protein levels in TGF-beta-treated human OA cells. In contrast, TGF-beta-stimulated COL2A1, aggrecan, and SOX-9 mRNA levels were abrogated by IL-1beta.
conclusionsIL-1beta or TNF-alpha exerted a suppressive effect on Smad3/4 DNA-binding activity in human articular chondrocytes, as well as on TGF-beta-induced stimulation of Smad3/4 DNA-binding activity and Smad2/3 phosphorylation in human OA and bovine articular chondrocytes. IL-1beta partially reversed the increase in TGF-beta-stimulated Smad7 mRNA or protein levels suggesting that Smad7 may not be involved in the suppression of TGF-beta signaling induced by IL-1beta or TNF-alpha in articular chondrocytes. The balance between the IL-1beta or TNF-alpha and the TGF-beta signaling pathways is crucial for maintenance of articular cartilage homeostasis and its disruption likely plays a substantial role in the pathogenesis of OA.
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