RANKL (Receptor Activator for Nuclear Factor κ B Ligand, osteoprotegerin ligand, TNF-related activation-induced cytokine, soluble Receptor Activator of NFkB Ligand, TNFSF11, TRANCE (TNF-related activation-induced cytokine), OPGL, ODF (Osteoclast differentiation factor))

sRANKL, receptor activator of nuclear factor (NF)-κB ligand (also: osteoprotegerin ligand, OPGL), is a part of the TNF superfamily with high similarity to other members of that protein species. (SwissProt Nr. O14788). Three isoforms are produced by alternate splicing, two type II membrane proteins (ISOFORM 1, 317 AA, and ISOFORM 3, 270 AA), and a secreted molecule (ISOFORM 2, 244 AA). ISOFORM 1 is identical to previously reported RANKL and possesses intracellular, transmembrane, and extracellular domains; ISOFORM 2 does not have the intracellular and transmembrane domains, and ISOFORM 3 does not have the intracellular domain. A soluble form arises by proteolytic processing from membrane isoforms. Although all forms are bioactive, the membrane-bound proteins seem to be the homeostatic forms, while the production of soluble RANKL signals pathological conditions. RANKL, RANK, and osteoprotegerin (OPG) have been identified as the key molecular regulation system for bone remodelling. RANKL is the main stimulatory factor for the formation of mature osteoclasts and is essential for their survival. Therefore, an increase in RANKL expression leads to bone resorption and bone loss. RANKL is produced by osteoblastic lineage cells and activated T lymphocytes. It activates its specific receptor RANK, which is located on osteoclasts and dendritic cells. The effects of RANKL are counteracted by OPG, which is secreted by various tissues and acts as an endogenous soluble receptor antagonist. Imbalances of the RANKL/OPG system have been related to the pathogenesis of Paget’s disease, benign and malignant bone tumors, postmenopausal osteoporosis, rheumatoid arthritis, bone metastases and hypercalcemia. Several studies using animal models have shown that restoring the RANKL/OPG balance (e.g. by administering OPG) reduces the severity of these disorders. Indication - Postmenopausal and senile osteoporosis - Diseases with locally increased bone resorption activity - Paget´s disease - Periodontal disease - Cardiovascular disease, arterial calcification - Inflammatory diseases - Immunological disorders - Arthritis - Oncology

• References to RANKL (Receptor Activator for Nuclear Factor κ B Ligand, osteoprotegerin ligand, TNF-related activation-induced cytokine, soluble Receptor Activator of NFkB Ligand, TNFSF11, TRANCE (TNF-related activation-induced cytokine), OPGL, ODF (Osteoclast differentiation factor))