RAGE and its ligands in bone metabolism

The receptor for advanced glycation end products (RAGE), a member of the immunoglobulin super-family transmembrane proteins, has multiple ligands, thus, is implicated in the pathogenesis of various diseases, including diabetic complications, neurodegenerative disorders, and inflammatory responses. Its function in normal physiology is beginning to be defined, and recent studies have pointed to an important role for RAGE and its ligands [e.g., HMGB1 (high mobility group box 1)] in innate immune response. In addition, RAGE and its ligands are also implicated in osteoclast activation and bone remodeling. Understanding how RAGE and its ligands regulate bone remodeling may provide insight into the pathogenesis of diabetes and chronic inflammation associated bone loss. Recent progress relevant to the functions of RAGE and its ligands in bone remodeling is discussed in this review.