ArticleThe American journal of pathology2009
Local interleukin-1-driven joint pathology is dependent on toll-like receptor 4 activation.
Article in The American journal of pathology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 55 citations in OpenAlex.
- Exosomal miRNAs involvement in pathogenesis, diagnosis, and treatment of rheumatoid arthritis.Heliyon · 2025Review
- Fibrotic pathways and fibroblast-like synoviocyte phenotypes in osteoarthritis.Frontiers in immunology · 2024Review
- Direct tissue-sensing reprograms TLR4Communications biology · 2021Article
- Lipopolysaccharide Binding Protein and CD14, Cofactors of Toll-like Receptors, Are Essential for Low-Grade Inflammation-Induced Exacerbation of Cartilage Damage in Mouse Models of Posttraumatic Osteoarthritis.Arthritis & rheumatology (Hoboken, N.J.) · 2021Article
- Bone erosions in rheumatoid arthritis: recent developments in pathogenesis and therapeutic implications.Journal of musculoskeletal & neuronal interactions · 2018Review
- TLRs, future potential therapeutic targets for RA.Autoimmunity reviews · 2017Review
- Extracellular vesicles in the pathogenesis of rheumatoid arthritis and osteoarthritis.Arthritis research & therapy · 2016Review
- Article
- Bartonella quintana lipopolysaccharide (LPS): structure and characteristics of a potent TLR4 antagonist for in-vitro and in-vivo applications.Scientific reports · 2016Article
- Toll-like receptors and chronic inflammation in rheumatic diseases: new developments.Nature reviews. Rheumatology · 2016Review
- Identification of a Novel Toll-like Receptor 7 Endogenous Ligand in Rheumatoid Arthritis Synovial Fluid That Can Provoke Arthritic Joint Inflammation.Arthritis & rheumatology (Hoboken, N.J.) · 2016Article
- Negative regulation of TLR signaling in myeloid cells--implications for autoimmune diseases.Immunological reviews · 2016Review
- Regulatory Role of IL-1R8 in Immunity and Disease.Frontiers in immunology · 2016Review
- TLR4 signalling in osteoarthritis--finding targets for candidate DMOADs.Nature reviews. Rheumatology · 2015Review
- Ligation of TLR5 promotes myeloid cell infiltration and differentiation into mature osteoclasts in rheumatoid arthritis and experimental arthritis.Journal of immunology (Baltimore, Md. : 1950) · 2014Article
- TLR2 deletion promotes arthritis through reduction of IL-10.Journal of leukocyte biology · 2013Article
- TLR4-mediated IL-12 production enhances IFN-γ and IL-1β production, which inhibits TGF-β production and promotes antibody-induced joint inflammation.Arthritis research & therapy · 2012Article
- Impact of IL-1 signalling on experimental uveitis and arthritis.Annals of the rheumatic diseases · 2012Article
- TIR8/SIGIRR is an Interleukin-1 Receptor/Toll Like Receptor Family Member with Regulatory Functions in Inflammation and Immunity.Frontiers in immunology · 2012Article
- Tenascin-C induces inflammatory mediators and matrix degradation in osteoarthritic cartilage.BMC musculoskeletal disorders · 2011Article
Corrections and comments
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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
Toll-like receptors (TLRs) may contribute to the pathogenesis of chronic inflammatory destructive diseases through the recognition of endogenous ligands produced on either inflammation or degeneration of the extracellular matrix. The presence of endogenous TLR agonists has been reported in rheumatoid joints. In the present study, we investigated the significance of TLR2 and TLR4 activation by locally- produced endogenous ligands in the severity of joint inflammation and destruction. Local joint pathology independent of systemic immune activation was induced by overexpression of interleukin (IL)-1 and TNF in naive joints using adenoviral gene transfer. Here, we report that at certain doses, IL-1-induced local joint inflammation, cartilage proteoglycan depletion, and bone erosion are dependent on TLR4 activation, whereas TLR2 activation is not significantly involved. In comparison, tumor necrosis factor alpha-driven joint pathology seemed to be less dependent on TLR2 and TLR4. The severity of IL-1-induced bone erosion and irreversible cartilage destruction was markedly reduced in TLR4(-/-) mice, even though the degree of inflammation was similar, suggesting uncoupled processes. Furthermore, the expression of cathepsin K, a marker for osteoclast activity, induced by IL-1beta was dependent on TLR4. Overexpression of IL-1beta in the joint as well as ex vivo IL-1 stimulation of patellae provoked the release of endogenous TLR4 agonists capable of inducing TLR4-mediated cytokine production. These data emphasize the potential relevance of TLR4 activation in rheumatoid arthritis, particularly with respect to IL-1-mediated joint pathology.
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