Induction of osteoclast‐associated receptor, a key osteoclast costimulation molecule, in rheumatoid arthritis

破骨细胞 类风湿性关节炎 肿瘤坏死因子α 医学 免疫学 单核细胞 骨吸收 外周血单个核细胞 关节炎 流式细胞术 细胞因子 受体 内科学 癌症研究 内分泌学 化学 体外 生物化学
作者
Sonja Herman,Ruediger B. Müller,Gerhard Krönke,Jochen Zwerina,Kurt Redlich,Axel J. Hueber,Holger Gelse,Elena Neumann,Ulf Müller‐Ladner,Georg Schett
出处
期刊:Arthritis & Rheumatism [Wiley]
卷期号:58 (10): 3041-3050 被引量:87
标识
DOI:10.1002/art.23943
摘要

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 α 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.
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