Role of milk fat globule-epidermal growth factor 8 in osteoimmunology

Abstract

Milk fat globule-epidermal growth factor 8 (MFG-E8) is a glycoprotein that is abundantly expressed in various tissues and has a pivotal role in the phagocytic clearance of apoptotic cells. However, MFG-E8 has also gained significant attention because of its wide range of functions in autoimmunity, inflammation and tissue homeostasis. More recently, MFG-E8 has been identified as a critical regulator of bone homeostasis, being expressed in both, osteoblasts and osteoclasts. In addition, it was shown that MFG-E8 fulfils an active role in modulating inflammatory processes, suggesting an anti-inflammatory role of MFG-E8 and proposing it as a novel therapeutic target for inflammatory diseases. This concise review focusses on the expression and regulation of MFG-E8 in the context of inflammatory bone diseases, highlights its role in the pathophysiology of osteoimmune diseases and discusses the therapeutic potential of MFG-E8.

Figure 1

Role of MFG-E8 in health and disease. (Left) Healthy state. MFG-E8 promotes osteoblast differentiation and suppresses osteoclastogenesis. In addition, antigen-presenting cells (APCs) are not activated, thus, preventing the activation of T cells and the recruitment of neurophils (NPs). (Right) Inflammatory arthritis. Inflammatory stimuli suppress MFG-E8 expression, which leads to suppression of osteoblastogenesis and support of osteoclastogenesis. The activation of APCs by the decreased MFG-E8 expression leads to an enhanced production of pro-inflammatory cytokines, an activation of T cells and a stimulation of NP recruitment, thereby, further stimulating osteoclasts, leading to bone loss.