OSCAR-collagen signaling in monocytes plays a proinflammatory role and may contribute to the pathogenesis of rheumatoid arthritis
OSCAR-collagen signaling in monocytes plays a proinflammatory role and may contribute to the pathogenesis of rheumatoid arthritis
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DOI：
10.1002/eji.201545986
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发表时间：
2016-04-01
影响因子：
5.4
通讯作者：
Panina, Svetlana
中科院分区：
文献类型：
--
作者：
Schultz, Heidi S.;Guo, Li;Panina, Svetlana
破骨细胞相关受体（OSCAR）是由人骨髓细胞表达的活化受体。I型胶原（ColI）和II型胶原（ColII）充当OSCAR的配体。OSCAR-胶原相互作用刺激RANK依赖性破骨细胞生成。我们最近报道，OSCAR促进单核细胞来源的树突状细胞的功能成熟。OSCAR在患有活动性疾病的类风湿性关节炎（RA）患者的单核细胞上上调，并且这些单核细胞显示出增加的破骨细胞生成潜能。在目前的研究中，我们已经解决了单核细胞上的OSCAR-胶原相互作用的功能作用。我们发现，OSCAR-ColII信号促进单核细胞的存活。此外，ColII刺激健康供体单核细胞释放促炎细胞因子，这可以被抗OSCAR单克隆抗体完全阻断。来自RA患者滑液的单核细胞以OSCAR依赖性方式分泌TNF-α和IL-8。全球RNA分析表明，与RA发病机制相关的多个信号通路的组成部分在转录水平上由单核细胞中的OSCAR调节。因此，OSCAR可以在单核细胞衍生的细胞中发挥促炎作用，并可能在多个水平上对RA发病机制起关键作用。
Osteoclast-associated receptor (OSCAR) is an activating receptor expressed by human myeloid cells. Collagen type I (ColI) and collagen type II (ColII) serve as ligands for OSCAR. OSCAR-collagen interaction stimulates RANK-dependent osteoclastogenesis. We have recently reported that OSCAR promotes functional maturation of monocyte-derived dendritic cells. OSCAR is upregulated on monocytes from rheumatoid arthritis (RA) patients with active disease, and these monocytes show an increased proosteoclastogenic potential. In the current study, we have addressed a functional role for an OSCAR-collagen interaction on monocytes. We show that OSCAR-ColII signaling promoted the survival of monocytes. Moreover, ColII stimulated the release of proinflammatory cytokines by monocytes from healthy donors, which could be completely blocked by an anti-OSCAR monoclonal antibody. Mononuclear cells from the synovial fluid of RA patients plated on ColII secreted TNF-alpha and IL-8 in an OSCAR-dependent manner. Global RNA profiling showed that components of multiple signaling pathways relevant to RA pathogenesis are regulated at the transcriptional level by OSCAR in monocytes. Thus, OSCAR can play a proinflammatory role in monocyte-derived cells and may contribute crucially on multiple levels to RA pathogenesis.