From Wikipedia, the free encyclopedia
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]
[edit] See also
[edit] References
[edit] 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. 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.
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Proteins: clusters of differentiation (see also list of human clusters of differentiation) |
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| 1-50 |
CD1 ( a-c, 1A, 1D, 1E) - CD2 - CD3 ( γ, δ, ε) - CD4 - CD5 - CD6 - CD7 - CD8 ( a) - CD9 - CD10 - CD11 ( a, b, c) - CD13 - CD14 - CD15 - CD16 ( A, B) - CD18 - CD19 - CD20 - CD21 - CD22 - CD23 - CD24 - CD25 - CD26 - CD27 - CD28 - CD29 - CD30 - CD31 - CD32 ( A, B) - CD33 - CD34 - CD35 - CD36 - CD37 - CD38 - CD39 - CD40 - CD41- CD42 ( a, b, c, d) - CD43 - CD44 - CD45 - CD46 - CD47 - CD48 - CD49 ( a, b, c, d, e, f) - CD50
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| 51-100 |
CD51 - CD52 - CD53 - CD54 - CD55 - CD56 - CD57- CD58 - CD59 - CD61 - CD62 ( E, L, P) - CD63 - CD64 - CD66 ( a, b, c, d, e, f) - CD68 - CD69 - CD70 - CD71 - CD72 - CD73 - CD74 - CD79 ( a, b) - CD80 - CD81 - CD82 - CD83 - CD84 - CD85 ( a, d, e, h, j, k) - CD86 - CD87 - CD88 - CD89 - CD90 - CD91- CD92 - CD93 - CD94 - CD95 - CD97 - CD98 - CD99 - CD100
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| 101-150 |
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| 151-200 |
CD151 - CD152 - CD153 - CD154 - CD155 - CD156 ( a, b, c) - CD157 - CD158 ( a, d, e, i, k) - CD159 ( a, c) - CD160 - CD161 - CD162 - CD163 - CD164 - CD166 - CD167 ( a, b) - CD168 - CD169 - CD170 - CD171 - CD172 ( a, b, g) - CD174 - CD177 - CD178 - CD179 ( a, b) - CD181 - CD182 - CD183 - CD184 - CD185 - CD186 - CD191 - CD192 - CD193 - CD194 - CD195 - CD196 - CD197 - CDw198 - CDw199 - CD200
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| 201-250 |
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| 251-300 |
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| 301-350 |
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