title: Mechanism of joint destruction in rheumatoid arthritis.
abstract: The synovium in rheumatoid arthritis (RA) is characterized by an increase in lining layer thickness and infiltration of inflammatory cells into the sublining area. Fibroblasts in the lining layer develop the appearance of "transformed cells", under the influence of proto-oncogenes involved in the regulation of the cell cycle. Fibroblast and macrophage-derived cytokines such as IL-1 and TNF-alpha are present abundantly in the rheumatoid synovium and stimulate these cells to produce destructive enzymes. Other cytokines such as IL-4 and IL-10 represent a physiological attempt to reverse the inflammatory process. Adhesion molecules facilitate both the migration of cells to the joint as well as the attachment of synovium to bone and cartilage. Joint destruction is mediated by enzymes such as serine proteases, matrix metalloproteinases (MMPs) and the cathepsins. Treatments directed against various components of the inflammatory cascade have shown promise. Inhibition of MMPs or adhesion molecules, blockade of IL-1 or TNF-alpha and the use of anti-Fas antibodies to induce apoptosis offer new possibilities for the treatment of RA. More recently, the employment of genes with antiarthritic properties has shown therapeutic potential.
authors.affiliation: Department of Rheumatology, University Hospital, Zurich, Switzerland.
authors.forename: G
authors.initials: G
authors.lastname: Cunnane
authors.forename: K M
authors.initials: KM
authors.lastname: Hummel
authors.forename: U
authors.initials: U
authors.lastname: Muller-Ladner
authors.forename: R E
authors.initials: RE
authors.lastname: Gay
authors.forename: S
authors.initials: S
authors.lastname: Gay
mesh_terms: D017209:Apoptosis; D001172:Arthritis, Rheumatoid / Q000209:etiology* / Q000276:immunology / Q000473:pathology / Q000821:virology; D015815:Cell Adhesion Molecules / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis; D006801:Humans; D007596:Joints / Q000276:immunology / Q000473:pathology* / Q000821:virology; D009857:Oncogenes; D012190:Retroviridae; D013583:Synovial Membrane / Q000276:immunology / Q000473:pathology / Q000821:virology
chemical_list: D015815:Cell Adhesion Molecules; D016207:Cytokines