title: Mechanisms of disease: the molecular and cellular basis of joint destruction in rheumatoid arthritis.
abstract: Rheumatoid arthritis is a complex systemic disease that ultimately leads to the progressive destruction of articular and periarticular structures. Novel data indicate that the innate immune system (through activation of Toll-like receptors) is involved in articular pathophysiology, including the recruitment of inflammatory cells, and that periarticular factors such as adipocytokines contribute to the perpetuation of joint inflammation. The deleterious process of joint destruction is mediated by intracellular signaling pathways involving transcription factors, such as nuclear factor kappaB, cytokines, chemokines, growth factors, cellular ligands, and adhesion molecules. Advances in molecular biology techniques have identified T-cell-independent and B-cell-independent pathways that operate at different stages of the disease. Cytokine-independent pathways appear to be responsible for maintaining basic disease activity that is not affected by currently available therapies. Using this knowledge in combination with gene-transfer and gene-silencing approaches, bench-to-bedside strategies will be developed, thus enabling the creation of novel treatments for rheumatoid arthritis.
authors.affiliation: Department of Internal Medicine and Rheumatology, Justus-Liebig University Giessen, Kerckhoff-Clinic, Bad Nauheim, Germany.
authors.forename: Ulf
authors.initials: U
authors.lastname: Müller-Ladner
authors.forename: Thomas
authors.initials: T
authors.lastname: Pap
authors.forename: Renate E
authors.initials: RE
authors.lastname: Gay
authors.forename: Michel
authors.initials: M
authors.lastname: Neidhart
authors.forename: Steffen
authors.initials: S
authors.lastname: Gay
mesh_terms: D000818:Animals; D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D001402:B-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000378:metabolism*; D018450:Disease Progression; D006801:Humans; D007113:Immunity, Innate / Q000502:physiology*; D007596:Joints / Q000473:pathology*; D011379:Prognosis; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D016207:Cytokines