Induction of osteoclast-associated receptor, a key osteoclast costimulation molecule, in rheumatoid arthritis.
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.
Herman
Sonja
S
Department of Internal Medicine III, Institute for Clinical Immunology, University of Erlangen-Nuremberg, Erlangen, Germany.
Müller
Ruediger B
RB
Krönke
Gerhard
G
Zwerina
Jochen
J
Redlich
Kurt
K
Hueber
Axel J
AJ
Gelse
Holger
H
Neumann
Elena
E
Müller-Ladner
Ulf
U
Schett
Georg
G
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*
C512828:OSCAR protein, human; D011956:Receptors, Cell Surface