title: Amplifying elements of arthritis and joint destruction.
abstract: Rheumatoid arthritis (RA) is a systemic autoimmune disease characterised by chronic joint inflammation and variable degrees of bone and cartilage erosion. Studies in animal models of arthritis provide insight into elements which can amplify destructive features. The presence of immune complexes in the joint makes arthritis more erosive. Although considerable bone erosion still occurs in the absence of FcgammaR triggering by immune complexes, through cytokine-induced RANKL and direct osteoclast activation, cartilage erosion is heavily dependent on the FcgammaR pathway. T cell factors such as IFNgamma and IL17 further amplify erosion through upregulation of the damaging FcgammaRI and stimulation of the influx of granulocytes, respectively. Apart from immune elements, environmental pressure and components of tissue damage contribute through innate pathways. Spontaneous T cell-dependent arthritis in IL1Ra-/- mice is absent under germ-free conditions, and markedly suppressed in TLR4-deficient mice. Moreover, TLR4 blocking with a receptor antagonist suppresses erosive arthritis.
authors.affiliation: Rheumatology Research and Advanced Therapeutics, Radboud University Nijmegen Medical Center, Geert Grooteplein 26, 6525 GA Nijmegen, The Netherlands. w.vandenberg@reuma.umcn.nl
authors.forename: Wim B
authors.initials: WB
authors.lastname: van den Berg
authors.forename: Peter L
authors.initials: PL
authors.lastname: van Lent
authors.forename: Leo A B
authors.initials: LA
authors.lastname: Joosten
authors.forename: Shahla
authors.initials: S
authors.lastname: Abdollahi-Roodsaz
authors.forename: Marije I
authors.initials: MI
authors.lastname: Koenders
mesh_terms: D000818:Animals; D000936:Antigen-Antibody Complex / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000473:pathology; D001862:Bone Resorption / Q000276:immunology; D002358:Cartilage, Articular / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D020381:Interleukin-17 / Q000276:immunology; D007596:Joints / Q000276:immunology* / Q000473:pathology; D051379:Mice; D013601:T-Lymphocytes / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000276:immunology
chemical_list: D000936:Antigen-Antibody Complex; D020381:Interleukin-17; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D007371:Interferon-gamma