Receptor activator of nuclear factor

Han JH, Choi SJ, Kurihara N, Koide M, Oba Y, Roodman GD. Macrophage inflammatory protein-lalpha is an osteoclastogenic factor in myeloma that is independent of receptor activator of nuclear factor kappaB ligand. Blood 2001 97(11) 3349—3353. 

Kim MS, Day CJ, Morrison NA. MCP-1 is induced by receptor activator of nuclear factor-a B ligand, promotes human osteoclast fusion, and rescues granulocyte macrophage colony-stimulating factor suppression of osteoclast formation. J Biol Chem 2005 280(16) 16163-16169. 

Hofbauer LC, Heufelder AE (2000) Clinical review 114 hot topic. The role of receptor activator of nuclear factor-kappaB ligand and osteoprotegerin in the pathogenesis and treatment of metabolic bone diseases. J Clin Endocrinol Metab 85 2355-2363... 

Cheung J, Mak YT, Papaioannou S, Evans BA, Fogelman I, Hampson G (2003) Interleukin-6 (IL-6), IL-1, receptor activator of nuclear factor kappaB ligand (RANKL) and osteoprotegerin production by human osteoblastic cells comparison of the effects of 17-beta oestradiol and raloxifene. J Endocrinol 177 423-433... 

Takami M, Takahashi N, Udagawa N, Miyaura C, Suda K, Woo JT, Martin TJ, Nagai K, Suda T (2000) Intracellular calcium and protein kinase C mediate expression of receptor activator of nuclear factor-kappaB ligand and osteoprotegerin in osteoblasts. Endocrinology 141 4711 -4719... 

Kearns AE, Khosla S, Kostenuik PJ Receptor activator of nuclear factor kb ligand and osteoprotegerin regulation of bone remodeling in health and disease. Endocr Rev 2008 29 155. [PMID 18057140]... 

Recently, two products of the osteoblast have been identified that appear to be the final common pathway in coordinating osteoblast and osteoclast activity. The first, receptor activator of nuclear factor-KB (RANK) ligand, binds to a receptor on osteoclast progenitor cells and increases osteoclast differentiation and activity. The second, osteo-protegerin (OPG), serves as a decoy receptor for RANK ligand. When OPG binds to RANK ligand, the osteoclast-stimulation activity is prevented. The relative ratios of these two molecules determine bone turnover. 

Politou M, Meletis J, et al. Soluble receptor activator of nuclear factor kB ligand-osteoprotegerin ratio predicts survival in multiple myeloma proposal for a novel prognostic index. Blood 2003 102 1064-9. 

Inflammation is induced by the release of proinflammatory mediators from the cytosol of damaged or infected cells (Sect. 13.2.2). One of the first identified cytokines was an osteoclast activation factor later found to induce a multitude of other proinflammatory events, InterLeukin-1 (IL-1). A second was Tumor Necrosis Factor (TNF), more formally known as tumor necrosis factor-alpha, TNF-a (Sect. 13.2.2). The binding of these proteins to receptors on adjacent cells activates Nuclear Factor kappa B (NFkB), a protein in the leukocyte cytosol. The hgand-bound receptor indirectly phosphorylates an NFkB partner protein (Inhibitor of NFkB, IkB) in the cytosol. The phosphorylated IkB is targeted for destruction and its loss exposes a nuclear locahzation sequence on the NFkB protein which can now enter the nucleus where it induces the expression of important proteins, depending on the type of cell that is activated. ODAR is a Receptor Activator of Nuclear Factor kappa B (RANK), one of a large family of proinflammatory hgand receptors on leukocytes. 

These receptors mediate the effects of TNFa (TNF receptors), and of the RANK ligand, RANK-L or receptor activator of nuclear factor-kB, and its endogenous antagonist, osteoprotegerin (OPG), RANK receptors. 

RANKL receptor activator of nuclear factor kB ligand... 

Theoleyre S, Kwan Tat S, Vusio P, Blanchard F, Gallagher J, Ricard-Blum S, Fortun Y, Padrines M, Redini F, Heymann D. Characterization of osteoprotegerin binding to glycosaminoglycans by surface plasmon resonance role in the interactions with receptor activator of nuclear factor kap-paB ligand (RANKL) and RANK. Biochem Biophys Res Commun 2006 347 460-467. 

Roux S, Meignin V, Quillaid J, Meduri G, Guiochon-Mantel A, Fermand JP, Milgrom E, Mariette X. RANK (receptor activator of nuclear factor-kappa B) and RANKL expression in multiple myeloma. Br J Haematol. 2002 117 86-92. 

Mineral balance Denosumab which targets RANKL, receptor activator of nuclear factor kappa-B ligand (CD254), a member of the TNF cytokine family, is approved for bone metastases and osteoporosis. It is well known that denosumab can cause hypocalcaemia and bone loss but the incidence of hypocalcaemia caused by this mAb may be higher than previously reported and while hypocalcaemia is usually asymptomatic and transient, cardiac arrhythmias and death are possible serious outcomes [133 ]. Despite calcium and vitamin D supplementation, denosumab-treated patients with high bone turnover from metastatic bone disease or secondary hyperparathyroidism due to renal failure should be closely monitored, especially for serum calcium levels 8-14 days post denosumab [133 ]. 

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