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）抗体在自身免疫性疾病（如类风湿性关节炎）期间的组织炎症和破坏中起主要作用。IgG抗体有效识别健康组织（自身抗体），募集先天性免疫效应细胞，包括中性粒细胞和巨噬细胞，导致靶组织（如关节）炎症。此外，可以识别软骨破坏和大面积骨质侵蚀，导致关节功能受损。骨稳态通过破骨细胞介导的平衡骨吸收和成骨细胞介导的骨生成来调节。在类风湿性关节炎期间，这种平衡受损，破骨细胞依赖性骨破坏占主导地位。本计画将研究造成组织发炎的自体抗体与造成骨质破坏的破骨细胞之间的相互影响。我们将分析在破骨细胞成熟过程中识别IgG抗体（所谓的Fc γ受体）所必需的细胞表面受体的表达模式，以及这些受体的激活对破骨细胞发育、激活和由此产生的骨稳态变化的影响。

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.