Impact of immunoglobulin G and Fc-gamma-receptors on osteoblast and osteoclast development and function in vitro and in vivo

自身免疫性疾病是发达国家预期寿命和生活质量下降的主要原因。免疫球蛋白G （IgG）抗体在类风湿关节炎等自身免疫性疾病的组织炎症和破坏中发挥重要作用。IgG抗体有效识别健康组织（自身抗体），招募包括中性粒细胞和巨噬细胞在内的先天免疫效应细胞，导致目标组织（如关节）的炎症。此外，可以识别软骨破坏和大面积骨侵蚀，导致关节功能损伤。骨稳态是由破骨细胞介导的平衡骨吸收和成骨细胞生成骨来调节的。在类风湿关节炎期间，这种平衡被破坏，依赖破骨细胞的骨破坏占主导地位。本项目将研究引起组织炎症的自身抗体和破坏骨骼的破骨细胞之间的串扰。我们将分析在破骨细胞成熟过程中识别IgG抗体所需的细胞表面受体（所谓的fcy受体）的表达模式，以及这些受体的激活对破骨细胞发育的影响，激活以及由此导致的体外和体内骨稳态的变化。

Autoimmune diseases are a major cause for reduced life expectancy and quality of life in the developed countries. Immunoglobulin G (IgG) antibodies play a major role in tissue inflammation and destruction during autoimmune diseases such as rheumatoid arthritis. IgG antibodies recognising healthy tissues (autoantibodies) efficiently, recruit innate immune effector cells including neutrophils and macrophages resulting in inflammation of the target tissue such as the joints. In addition, cartilage destruction and large areas of bone erosion can be identified, resulting in functional impairment of the joints. Bone homeostasis is regulated by balanced bone resorption mediated by osteoclasts and bone generation by osteoblasts. During rheumatoid arthritis this balance is impaired and osteoclasts dependent bone destruction predominates. This project will study the crosstalk between autoantibodies causing tissue inflammation and osteoclasts responsible for bone destruction. We will analyse the expression pattern of cell surface receptors necessary for recognition of IgG antibodies (so called Fcy-receptors) during osteoclast maturation and the impact of activation of these receptors on osteoclast development, activation and the resulting changes in bone homeostasis in vitro and in vivo.