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 ␣ was identified as the main inducer of OSCAR expression in monocytes.Conclusion. 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.

Collagen Induces Maturation of Human Monocyte-Derived Dendritic Cells by Signaling through Osteoclast-Associated Receptor

“…OSCAR-expressing mononuclear cells were detected in perivascular areas of the synovium (13). The RA synovium is considered an ectopic lymphoid organ (35).…”

“…Although OSCAR is expressed in resting myeloid cells (9,13), it may not be functional because the ligand accessibility is limited. We hypothesize that the OSCAR-collagen signaling plays a pivotal role in pathology, such as in RA, where ligands become available due to ongoing tissue remodeling.…”

“…OSCAR is expressed on mononuclear cells surrounding synovial microvessels and on multinucleated giant cells at the bone resorption areas. OSCAR was also found to be upregulated in peripheral blood monocytes from RA patients compared with healthy subjects, and its expression correlated to disease activity (13).…”

Effects of inflammatory and anti‐inflammatory cytokines on the bone

“…It is likely that TNF plays a critical role in synergistically enhancing osteoclast-mediated bone resorption by interacting with RANKL. It has been suggested that TNF also contributes to osteoclast formation in the arthritic joint by upregulating the expression of osteoclast-associated receptor (OSCAR) on osteoclasts and their precursors [26,27]. Of interest, there is evidence from clinical trials that the effects of targeting TNF in patients with RA (by neutralizing antibodies or soluble receptors such as adalimumab, certolizumab, etanercept, golimumab and infliximab) may be accompanied by an apparent dissociation of the beneficial effects of TNF-a blockade on signs and symptoms of inflammation without a commensurate inhibition of focal articular bone erosions.…”

The roles of immune cells in bone healing; what we know, do not know and future perspectives

“…Likewise, excessive stimulation of macrophages with lipopolysaccharide can decrease their production of BMP-2 causing a delayed bone healing [108]. Additionally, within a chronic inflammatory milieu, monocytes have a higher potential to differentiate into osteoclasts through TNF-a dependent mechanism [109]. Excessively activated NK cells could mediate cytotoxicity against allogeneic or autologous MSCs [62,[110][111][112][113].…”