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Tumor necrosis factor (ligand) superfamily, member 11

PDB rendering based on 1s55.
Available structures
External IDs OMIM602642 MGI1100089 HomoloGene2744 GeneCards: TNFSF11 Gene
RNA expression pattern
PBB GE TNFSF11 210643 at tn.png
PBB GE TNFSF11 211153 s at tn.png
More reference expression data
Species Human Mouse
Entrez 8600 21943
Ensembl ENSG00000120659 ENSMUSG00000022015
UniProt O14788 Q059M3
RefSeq (mRNA) NM_003701 NM_011613
RefSeq (protein) NP_003692 NP_035743
Location (UCSC) Chr 13:
42.03 - 42.08 Mb
Chr 14:
77.01 - 77.04 Mb
PubMed search [1] [2]

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 found on osteoblasts serves to activate osteoclasts, which are the cells involved in bone resorption. Overproduction of RANKL is implicated in a variety of degenerative bone diseases, such as rheumatoid arthritis and psoriatic arthritis.

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


Further reading

  • Whyte M (2006). "The long and the short of bone therapy". N Engl J Med 354 (8): 860–3. doi:10.1056/NEJMe068003. PMID 16495400.  link
  • Buckley KA, Fraser WD (2003). "Receptor activator for nuclear factor kappaB ligand and osteoprotegerin: regulators of bone physiology and immune responses/potential therapeutic agents and biochemical markers.". Ann. Clin. Biochem. 39 (Pt 6): 551–6. doi:10.1258/000456302760413324. PMID 12564836. 
  • Jeffcoate W (2005). "Vascular calcification and osteolysis in diabetic neuropathy-is RANK-L the missing link?". Diabetologia 47 (9): 1488–92. doi:10.1007/s00125-004-1477-5. PMID 15322748. 
  • Collin-Osdoby P (2005). "Regulation of vascular calcification by osteoclast regulatory factors RANKL and osteoprotegerin.". Circ. Res. 95 (11): 1046–57. doi:10.1161/01.RES.0000149165.99974.12. PMID 15564564. 
  • Whyte MP, Mumm S (2005). "Heritable disorders of the RANKL/OPG/RANK signaling pathway.". Journal of musculoskeletal & neuronal interactions 4 (3): 254–67. PMID 15615493. 
  • Clohisy DR, Mantyh PW (2005). "Bone cancer pain and the role of RANKL/OPG.". Journal of musculoskeletal & neuronal interactions 4 (3): 293–300. PMID 15615497. 
  • Anandarajah AP, Schwarz EM (2006). "Anti-RANKL therapy for inflammatory bone disorders: Mechanisms and potential clinical applications.". J. Cell. Biochem. 97 (2): 226–32. doi:10.1002/jcb.20674. PMID 16240334. 
  • Baud'huin M, Duplomb L, Ruiz Velasco C, et al. (2007). "Key roles of the OPG-RANK-RANKL system in bone oncology.". Expert Rev Anticancer Ther 7 (2): 221–32. doi:10.1586/14737140.7.2.221. PMID 17288531. 
  • Yogo K, Ishida-Kitagawa N, Takeya T (2007). "Negative autoregulation of RANKL and c-Src signaling in osteoclasts.". J. Bone Miner. Metab. 25 (4): 205–10. doi:10.1007/s00774-007-0751-2. PMID 17593489. 
  • Boyce BF, Xing L (2007). "Biology of RANK, RANKL, and osteoprotegerin.". Arthritis Res. Ther. 9 Suppl 1: S1. doi:10.1186/ar2165. PMID 17634140. 
  • McClung M (2007). "Role of RANKL inhibition in osteoporosis.". Arthritis Res. Ther. 9 Suppl 1: S3. doi:10.1186/ar2167. PMID 17634142. 

External links



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