Herman Sonja, Müller Ruediger B, Krönke Gerhard, Zwerina Jochen, Redlich Kurt, Hueber Axel J, Gelse Holger, Neumann Elena, Müller-Ladner Ulf, Schett Georg
Department of Internal Medicine III, Institute for Clinical Immunology, University of Erlangen-Nuremberg, Erlangen, Germany.
Arthritis Rheum. 2008 Oct;58(10):3041-50. doi: 10.1002/art.23943.
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.
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.
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.
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.
破骨细胞相关受体（OSCAR）是一种新发现的破骨细胞特异性受体，在破骨细胞共刺激过程中起关键作用。本研究旨在确定共刺激在炎性关节炎破骨细胞分化过程中的作用。
评估类风湿关节炎（RA）患者滑膜和外周血单核细胞中OSCAR的表达，并评估其与疾病活动度的相关性。采用酶联免疫吸附测定法测定血清OSCAR水平。进行体外破骨细胞试验以表征OSCAR在人破骨细胞生成中的作用。通过逆转录聚合酶链反应研究细胞因子对OSCAR的调节作用。
破骨细胞在侵蚀前沿表达OSCAR，滑膜微血管周围的单核细胞也表达OSCAR。流式细胞术显示，与健康对照相比，RA患者外周血单核细胞中OSCAR表达增强。OSCAR表达与疾病活动度和急性期反应物浓度相关。RA患者血清可溶性OSCAR水平低于健康对照。高表达OSCAR的单核细胞分化为破骨细胞的潜力增强。肿瘤坏死因子α被确定为单核细胞中OSCAR表达的主要诱导因子。
这些数据表明，RA中破骨细胞共刺激途径被激活。RA患者单核细胞中诱导产生OSCAR，促进其分化为破骨细胞并导致骨吸收。
