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

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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.