Osteoprotegerin
| Tumor necrosis factor receptor superfamily, member 11b (osteoprotegerin) | |||||||||||
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| Identifiers | |||||||||||
| Symbols | TNFRSF11B ; OCIF; OPG; MGC29565; TR1 | ||||||||||
| External IDs | Template:OMIM5 Template:MGI HomoloGene: 1912 | ||||||||||
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| RNA expression pattern | |||||||||||
| File:PBB GE TNFRSF11B 204932 at tn.png | |||||||||||
| File:PBB GE TNFRSF11B 204933 s at tn.png | |||||||||||
| More reference expression data | |||||||||||
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| Template:GNF Ortholog box | |||||||||||
| Species | Human | Mouse | |||||||||
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| RefSeq (mRNA) | n/a | n/a | |||||||||
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
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Osteoprotegerin, also known as osteoclastogenesis inhibitory factor (OCIF), is a cytokine and a member of the tumor necrosis factor (TNF) receptor superfamily. It is a basic glycoprotein comprising 401 amino acid residues arranged into 7 structural domains. It is found as either a 60 kDa monomer or 120 kDa dimer linked by disulfide bonds.[1] Osteoprotegerin inhibits the differentiation of macrophages into osteoclasts and also regulates the resorption of osteoclasts in vitro and in vivo. Osteoprotegerin is a RANK homolog, and works by binding to RANK ligand on osteoblast/stromal cells, thus blocking the RANK-RANK ligand interaction between osteoblast/stromal cells and osteoclast precursors. This has the effect of inhibiting the differentiation of the osteoclast precursor into a mature osteoclast. Recombinant human osteoprotegerin specifically acts on bone, increasing bone mineral density and bone volume. Osteoprotegerin has been used experimentally to decrease bone resorption in women with postmenopausal osteoporosis and in patients with lytic bone metastases.
Osteoprotegerin production is stimulated in vivo by the female sex hormone estrogen,[2] as well as the experimental osteoporosis drug, strontium ranelate.
References
- ↑ Schoppet M., et al. (2002), "RANK ligand and osteoprotegerin: paracrine regulators of bone metabolism and vascular function." Arteriosclerosis, Thrombosis, and Vascular Biology, 22: 549-553, PMID 11950689
- ↑ Khosla S. (2001), "Minireview: The OPG/RANKL/RANK System." Endocrinology, 142:5050-5055, PMID 11713196
Further reading
- Hofbauer LC, Neubauer A, Heufelder AE (2001). "Receptor activator of nuclear factor-kappaB ligand and osteoprotegerin: potential implications for the pathogenesis and treatment of malignant bone diseases". Cancer. 92 (3): 460–70. PMID 11505389.
- 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.
- Kimberley FC, Screaton GR (2005). "Following a TRAIL: update on a ligand and its five receptors". Cell Res. 14 (5): 359–72. doi:10.1038/sj.cr.7290236. PMID 15538968.
- 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.
- 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.
- Boyce BF, Xing L (2007). "Biology of RANK, RANKL, and osteoprotegerin". Arthritis Res. Ther. 9 Suppl 1: S1. doi:10.1186/ar2165. PMID 17634140.
- Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4. PMID 8125298.
- Simonet WS, Lacey DL, Dunstan CR; et al. (1997). "Osteoprotegerin: a novel secreted protein involved in the regulation of bone density". Cell. 89 (2): 309–19. doi:10.1016/S0092-8674(00)80209-3. PMID 9108485.
- Tsuda E, Goto M, Mochizuki S; et al. (1997). "Isolation of a novel cytokine from human fibroblasts that specifically inhibits osteoclastogenesis". Biochem. Biophys. Res. Commun. 234 (1): 137–42. doi:10.1006/bbrc.1997.6603. PMID 9168977.
- Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K; et al. (1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
- Tan KB, Harrop J, Reddy M; et al. (1998). "Characterization of a novel TNF-like ligand and recently described TNF ligand and TNF receptor superfamily genes and their constitutive and inducible expression in hematopoietic and non-hematopoietic cells". Gene. 204 (1–2): 35–46. PMID 9434163.
- Yamaguchi K, Kinosaki M, Goto M; et al. (1998). "Characterization of structural domains of human osteoclastogenesis inhibitory factor". J. Biol. Chem. 273 (9): 5117–23. doi:10.1074/jbc.273.9.5117. PMID 9478964.
- Yasuda H, Shima N, Nakagawa N; et al. (1998). "Identity of osteoclastogenesis inhibitory factor (OCIF) and osteoprotegerin (OPG): a mechanism by which OPG/OCIF inhibits osteoclastogenesis in vitro". Endocrinology. 139 (3): 1329–37. doi:10.1210/en.139.3.1329. PMID 9492069.
- Yasuda H, Shima N, Nakagawa N; et al. (1998). "Osteoclast differentiation factor is a ligand for osteoprotegerin/osteoclastogenesis-inhibitory factor and is identical to TRANCE/RANKL". Proc. Natl. Acad. Sci. U.S.A. 95 (7): 3597–602. doi:10.1073/pnas.95.7.3597. PMID 9520411.
- Tomoyasu A, Goto M, Fujise N; et al. (1998). "Characterization of monomeric and homodimeric forms of osteoclastogenesis inhibitory factor". Biochem. Biophys. Res. Commun. 245 (2): 382–7. doi:10.1006/bbrc.1998.8443. PMID 9571159.
- Bucay N, Sarosi I, Dunstan CR; et al. (1998). "osteoprotegerin-deficient mice develop early onset osteoporosis and arterial calcification". Genes Dev. 12 (9): 1260–8. doi:10.1101/gad.12.9.1260. PMID 9573043.
- Emery JG, McDonnell P, Burke MB; et al. (1998). "Osteoprotegerin is a receptor for the cytotoxic ligand TRAIL". J. Biol. Chem. 273 (23): 14363–7. doi:10.1074/jbc.273.23.14363. PMID 9603945.
- Morinaga T, Nakagawa N, Yasuda H; et al. (1998). "Cloning and characterization of the gene encoding human osteoprotegerin/osteoclastogenesis-inhibitory factor". Eur. J. Biochem. 254 (3): 685–91. doi:10.1046/j.1432-1327.1998.2540685.x. PMID 9688283.
External links
- Osteoprotegerin at the US National Library of Medicine Medical Subject Headings (MeSH)