Figure 1: Representation of the TRAIL/OPG/RANKL system. Osteoprotegerin (OPG) is a secreted glycoprotein, whose predominant and more bioactive extracellular form is a disulphide-linked dimer. By acting as a decoy receptor for TRAIL and RANKL, OPG regulates many processes, such as cell apoptosis/survival and necroptosis, immune surveillance and host defence, and bone resorption. Moreover, OPG binds glycosaminoglycans such as heparin sulfate proteoglycans (HSPG), whereby it regulates monocyte chemotaxis, OPG release, and fibrosis. As for TRAIL, it is expressed as a transmembrane protein, which can be cleaved and released as a soluble molecule, which combines with two other molecules of TRAIL to form a trimeric ligand. TRAIL homotrimers bind to their specific receptors, which include two death receptors, TRAIL-R1 and TRAIL-R2, and three decoy receptors, TRAIL-R3, TRAIL-R4, and osteoprotegerin (OPG). Likewise, RANKL can be found in both membrane-bound and soluble forms. When it is released as a soluble molecule, RANKL combines with two other molecules of RANKL to form a trimeric ligand, which binds to its receptor RANK. HSPG is heparin sulfate proteoglycans; OPG is osteoprotegerin; R is receptor; RANK is receptor activator of nuclear factor kappa-B, RANKL is receptor activator of nuclear factor kappa-B ligand; TRAIL is TNF-related apoptosis-inducing ligand.