Osteoprotegerin–receptor activator of nuclear factor kappa-B ligand system (OPG–RANKL system (OPG: Osteoprotegerin; RANKL: Receptor activator of nuclear factor kappa-B ligand))

The osteoprotegerin–receptor activator of nuclear factor kappa-B ligand (OPG–RANKL) system consists of RANKL, a cytokine and key osteoclastogenic factor primarily expressed on activated T cells and other cells, OPG, a soluble decoy receptor secreted mainly by CD4+ T lymphocytes, and their receptor RANK on osteoclasts, dendritic cells, and other immune cells. RANKL binds RANK to promote osteoclast differentiation, dendritic cell survival, and modulation of T cell responses; OPG acts as a physiological inhibitor by sequestering RANKL, thus preventing RANK activation. In CD4+ T cell regulation, the system modulates immune responses by influencing dendritic cell–mediated T cell activation, peripheral tolerance induction, cytokine production, and inflammation. The pathway is critical in the pathogenesis of autoimmune diseases, bone disorders, and cancer, with therapeutic targeting (e.g., denosumab) focused on disrupting RANKL–RANK interaction to control pathological bone resorption and modulate immune functions[1][3][4][5][6][2].

Other names

OPG–RANKL pathwayRANKL/OPG axisOsteoprotegerin–RANKL systemRANKL–RANK–OPG systemTumor necrosis factor ligand superfamily member 11 (RANKL, TNFSF11)Tumor necrosis factor receptor superfamily member 11B (Osteoprotegerin, OPG, TNFRSF11B)

Inhibition of RANKL–RANK interaction (by denosumab or OPG), leading to decreased osteoclast formation and modulation of immune cell activity; Neutralization of RANKL-mediated activation of monocytes and dendritic cells, altering cytokine production and T cell–dependent immune responses; Restoration or suppression of immune function via modulation of DC–T cell interactions, peripheral tolerance, or regulatory T cell induction