RANKL (Receptor Activator for Nuclear Factor κ B Ligand), also known as TNF-related activation-induced cytokine (TRANCE), osteoprotegerin ligand (OPGL), and ODF (osteoclast differentiation factor) is a molecule important in bone metabolism. This natural and necessary surface-bound molecule activates osteoclasts, cells involved in bone resorption. Overproduction of RANKL is implicated in a variety of degenerative bone diseases, such as rheumatoid arthritis and osteomyelitis.

RANKL also has a function in the immune system, where it is expressed by T helper cells and is thought to be involved in dendritic cell maturation. This protein was shown to be a dentritic cell survival factor and is involved in the regulation of T cell-dependent immune response. T cell activation was reported to induce expression of the RANKL gene and lead to an increase of osteoclastogenesis and bone loss. This protein was shown to activate antiapoptotic kinase AKT/PKB through a signaling complex involving SRC kinase and tumor necrosis factor receptor-associated factor (TRAF) 6, which indicated this protein may have a role in the regulation of cell apoptosis. Targeted disruption of the related gene in mice led to severe osteopetrosis and a lack of osteoclasts. The deficient mice exhibited defects in early differentiation of T and B lymphocytes, and failed to form lobulo-alveolar mammary structures during pregnancy. Two alternatively spliced transcript variants have been found.^[1]

See also

• RANK
• Osteoprotegerin
• Osteoimmunology

References

Further reading