Research progress in the RANK/RANKL/OPG system and its associated diseases and anti-RANKL therapy

Bone is a dynamic tissue, which is renewed continuously by modeling, resorption and remodeling in the life span. The receptor activator of NF-κB(RANK)/receptor activator of NF-κB ligand (RANKL)/osteoprotegerin(OPG)system is the key regulator of this process. The RANK/RANKL/OPG triad belongs to the tumor necrosis factor or tumor necrosis factor receptor superfamily. They control bone resorption and remodeling via regulation of the osteoclasts' differentiation and activation. As the expression of RANK and RANKL is regulated by immunocytes, while the immunocytes themselves are also affected by the RANKL/RANK signaling, the RANK/RANKL/OPG system becomes a crucial bridge between bone and immune system. The imbalance of RANK/RANKL/OPG system is associated with multiple bone metabolism diseases and secondary bone diseases of immune system disorders. The discovery of this system leads to a great advance in researches of the disease pathophysiology and the therapies. The anti-RANKL therapy has been under investigation in a series of clinical trials. This review summarizes the research progress in RANK/RANKL/OPG system and its associated diseases and the anti-RANKL therapy. Key words: Receptor activator of nuclear factor-kappa B;  RANK ligand;  Osteoprotegerin; Osteoporosis;  Arthritis,rheumatoid;  Bone neoplasms;  Anti-RANKL therapy