ArticleAnnals of the rheumatic diseases2007
Inhibition of interleukin 1-induced matrix metalloproteinase 13 expression in human chondrocytes by interferon gamma.
Article in Annals of the rheumatic diseases, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
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Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 28 citations in OpenAlex.
- 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
- In knee osteoarthritis, the production of cytokines and metalloproteinases in presence of chondrocytes and CD4Osteoarthritis and cartilage open · 2025Article
- Cell morphology as a biological fingerprint of chondrocyte phenotype in control and inflammatory conditions.Frontiers in immunology · 2023Article
- Interferon-gamma modulates articular chondrocyte and osteoblast metabolism through protein kinase R-independent and dependent mechanisms.Biochemistry and biophysics reports · 2022Article
- The essential anti-angiogenic strategies in cartilage engineering and osteoarthritic cartilage repair.Cellular and molecular life sciences : CMLS · 2022Review
- Nfib promotes chondrocyte proliferation and inhibits differentiation by mildly regulating Sox9 and its downstream genes.Molecular biology reports · 2021Article
- RIPK1 suppresses apoptosis mediated by TNF and caspase-3 in intervertebral discs.Journal of translational medicine · 2019Article
- Recent advances in understanding the regulation of metalloproteinases.F1000Research · 2019Review
- CXCL10 suppression of hem- and lymph-angiogenesis in inflamed corneas through MMP13.Angiogenesis · 2017Article
- Cytokine profiles in the joint depend on pathology, but are different between synovial fluid, cartilage tissue and cultured chondrocytes.Arthritis research & therapy · 2014Article
- Urokinase plasminogen activator system in synovial fibroblasts from osteoarthritis patients: modulation by inflammatory mediators and neuropeptides.Journal of molecular neuroscience : MN · 2014Article
- Matrilin-3 induction of IL-1 receptor antagonist is required for up-regulating collagen II and aggrecan and down-regulating ADAMTS-5 gene expression.Arthritis research & therapy · 2012Article
- Oxidative stress induced interleukin-32 mRNA expression in human bronchial epithelial cells.Respiratory research · 2012Article
- Whole blood transcriptional profiling in ankylosing spondylitis identifies novel candidate genes that might contribute to the inflammatory and tissue-destructive disease aspects.Arthritis research & therapy · 2011Article
- Defining the roles of inflammatory and anabolic cytokines in cartilage metabolism.Annals of the rheumatic diseases · 2008Review
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundDespite well-documented immunomodulation by interferon gamma (IFNgamma), its role and mechanism of regulation of matrix metalloproteinase 13 (MMP13) gene expression in human chondrocytes is unknown.
objectiveTo investigate the ability and mechanism of IFNgamma to suppress interleukin 1 (IL1)-induced MMP13 expression in articular chondrocytes.
methodsHuman chondrocytes were treated with IFNgamma or IL1beta alone or in combination. MMP13 mRNA was analysed by semiquantitative reverse transcriptase-PCR. MMP13 protein, phospho-signal transducer and activator of transcription 1 (STAT1) and p44/42 mitogen-activated protein kinase levels were measured by western blotting. MMP13 promoter luciferase, cytomegalovirus cyclic AMP response element-binding protein (CBP)/p300 plasmids and STAT1 small interfering RNA (siRNA) were transfected by the calcium phosphate method. IFNgamma receptor was also neutralised. Activator protein (AP) 1 activity was monitored by the TransAM transcription factor kit. STAT1-CBP/p300 interaction was studied by immunoprecipitation.
resultsIFNgamma potently suppressed IL1-induced expression of MMP13 and promoter activity. Blockade with neutralising IFNgamma R1 antibody revealed that MMP13 inhibition by IFNgamma is mediated by the IFN receptor. IFNgamma-stimulated activation of STAT1 was directly correlated with MMP13 suppression. Knockdown of the STAT1 gene by specific siRNA or its inhibition with fludarabine partially restored the IL1beta induction of MMP13 expression and promoter activity. IFNgamma did not alter AP1 binding ability but promoted physical interaction of STAT1 and CBP/p300 coactivator. p300 overexpression reversed IFNgamma inhibition of endogenous MMP13 mRNA expression and exogenous MMP13 promoter activity.
conclusionIFNgamma, through its receptor, activates STAT1, which binds with CBP/p300 coactivator, sequesters it from the cell system, and thus inhibits transcriptional induction of the MMP13 gene in chondrocytes. IFNgamma and its signalling pathways could be targeted therapeutically for diminishing IL1-induced cartilage degradation by MMP13 in patients with arthritis.
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