title: Induction of osteoclast-associated receptor, a key osteoclast costimulation molecule, in rheumatoid arthritis.
abstract: OBJECTIVE
  Osteoclast-associated receptor (OSCAR) is a newly identified osteoclast-specific receptor and is of key importance in the process of osteoclast costimulation. This study was undertaken to define the role of costimulation in osteoclast differentiation during inflammatory arthritis.
  
  
  METHODS
  OSCAR expression was assessed in the synovium and peripheral blood monocytes of patients with rheumatoid arthritis (RA), and associations with disease activity were assessed. Serum levels of OSCAR were determined by enzyme-linked immunosorbent assay. In vitro osteoclast assays were performed to characterize the role of OSCAR in human osteoclastogenesis. Cytokine regulation of OSCAR was investigated by reverse transcriptase-polymerase chain reaction.
  
  
  RESULTS
  OSCAR was expressed by osteoclasts at the erosion front and by mononuclear cells around synovial microvessels. Flow cytometry revealed enhanced expression of OSCAR in peripheral blood monocytes of RA patients as compared with healthy controls. OSCAR expression was correlated with disease activity and acute-phase reactant concentrations. Serum levels of soluble OSCAR were lower in RA patients than in healthy controls. Monocytes with high OSCAR expression exhibited an enhanced potential to differentiate into osteoclasts. Tumor necrosis factor alpha was identified as the main inducer of OSCAR expression in monocytes.
  
  
  CONCLUSIONS
  These data suggest that the osteoclast costimulation pathway is activated in RA. OSCAR is induced in monocytes of RA patients, facilitating their differentiation into osteoclasts and bone resorption.
authors.affiliation: Department of Internal Medicine III, Institute for Clinical Immunology, University of Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: Sonja
authors.initials: S
authors.lastname: Herman
authors.forename: Ruediger B
authors.initials: RB
authors.lastname: Müller
authors.forename: Gerhard
authors.initials: G
authors.lastname: Krönke
authors.forename: Jochen
authors.initials: J
authors.lastname: Zwerina
authors.forename: Kurt
authors.initials: K
authors.lastname: Redlich
authors.forename: Axel J
authors.initials: AJ
authors.lastname: Hueber
authors.forename: Holger
authors.initials: H
authors.lastname: Gelse
authors.forename: Elena
authors.initials: E
authors.lastname: Neumann
authors.forename: Ulf
authors.initials: U
authors.lastname: Müller-Ladner
authors.forename: Georg
authors.initials: G
authors.lastname: Schett
mesh_terms: D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000378:metabolism*; D016022:Case-Control Studies; D002454:Cell Differentiation / Q000502:physiology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism*; D010003:Osteoarthritis / Q000378:metabolism; D010010:Osteoclasts / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000097:blood / Q000378:metabolism*; D013583:Synovial Membrane / Q000098:blood supply / Q000378:metabolism*
chemical_list: C512828:OSCAR protein, human; D011956:Receptors, Cell Surface