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The role of Siglec-9/ Siglec-E in osteoclastogenesis

Siglec-9/ Siglec-E 在破骨细胞生成中的作用

基本信息

批准号：
332396515
负责人：
Dr. Ulrike Steffen
金额：
--
依托单位：
Medizinische Klinik 3 - Rheumatologie und Immunologie
依托单位国家：
德国
项目类别：
Research Grants
财政年份：
2017
资助国家：
德国
起止时间：
2016-12-31 至 2019-12-31
项目状态：
已结题

来源：
https://gepris.dfg.de/gepris/projekt/332396515?language=en
关键词：
role Siglec osteoclastogenesis

项目摘要

Sialic acid-binding immunoglobulin-like lectins (Siglecs) are transmembrane receptors that recognize sialic acid-containing structures in glycoproteins and glycolipids. Siglec-9 and its murine homologue Siglec-E belong to the CD33-related Siglec subgroup and are mainly expressed on myeloid cells. Several studies have shown Siglec-9/ Siglec-E to influence migration and cytokine release of neutrophil granulocytes and macrophages. Bone resorbing osteoclasts are giant, multinucleated cells that develop by the fusion of macrophage-like precursor cells. Whether they are also affected by Siglec-9/ Siglec-E is not known so far. Our preliminary in vitro data strongly suggest Siglec-9/ Siglec-E to increase osteoclastogenesis. In addition, the injection of antibodies directed against Siglec-E attenuated inflammation and bone destruction in a murine serum-transfer arthritis model.The goal of the proposed project is to determine the role of Siglec-9/ Siglec-E in osteoclastogenesis under homeostatic and inflammatory conditions and to investigate, whether Siglec-9/ Siglec-E might be a suitable target for the treatment of inflammatory bone loss in diseases like rheumatoid arthritis. For this purpose, we will characterize the bone phenotype of Siglec-E deficient mice under homeostatic conditions, in two non-inflammatory osteoporosis models and in two arthritis models. In addition, we will investigate the mechanisms, by which Siglec-9/ Siglec-E influences osteoclastogenesis and determine the expression pattern of Siglec-9 in the joints of patients with rheumatoid arthritis.

唾液酸结合免疫球蛋白样凝集素（Siglecs）是一种跨膜受体，可识别糖蛋白和糖脂中含有唾液酸的结构。Siglec-9及其小鼠同源物Siglec- e属于与cd33相关的Siglec亚群，主要在髓细胞上表达。一些研究表明，siglece -9/ siglece影响中性粒细胞和巨噬细胞的迁移和细胞因子释放。骨吸收破骨细胞是由巨噬细胞样前体细胞融合而成的巨大的多核细胞。目前尚不清楚它们是否也受到siglece -9/ siglece的影响。我们的初步体外数据强烈表明siglece -9/ siglece可以促进破骨细胞的发生。此外，在小鼠血清转移性关节炎模型中，注射针对siglece的抗体可减轻炎症和骨破坏。该项目的目标是确定siglece -9/ siglece在稳态和炎症条件下破骨细胞发生中的作用，并研究siglece -9/ siglece是否可能是治疗类风湿关节炎等疾病炎症性骨质流失的合适靶点。为此，我们将在稳态条件下，在两种非炎症性骨质疏松症模型和两种关节炎模型中表征siglece缺陷小鼠的骨表型。此外，我们将研究siglece -9/ siglece影响破骨细胞发生的机制，并确定siglece -9在类风湿关节炎患者关节中的表达模式。