The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

TNFRSF11B  -  tumor necrosis factor receptor superfamily...

Homo sapiens

Synonyms: OCIF, OPG, Osteoclastogenesis inhibitory factor, Osteoprotegerin, TR1, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of TNFRSF11B


Psychiatry related information on TNFRSF11B


High impact information on TNFRSF11B

  • Here we show that osteoprotegerin, a secreted 'decoy' receptor that inhibits osteoclast activity, also blocks behaviors indicative of pain in mice with bone cancer [14].
  • These results demonstrate that excessive tumor-induced bone destruction is involved in the generation of bone cancer pain and that osteoprotegerin may provide an effective treatment for this common human condition [14].
  • Osteoprotegerin blocks bone cancer-induced skeletal destruction, skeletal pain and pain-related neurochemical reorganization of the spinal cord [14].
  • RANKL, RANK, and OPG are three key molecules that regulate osteoclast recruitment and function [15].
  • At the same time, bone resorption is inhibited by decreased IL-6 and increased OPG secretion into the bone microenvironment [16].

Chemical compound and disease context of TNFRSF11B


Biological context of TNFRSF11B

  • A mutation in the gene TNFRSF11B encoding osteoprotegerin causes an idiopathic hyperphosphatasia phenotype [22].
  • Idiopathic hyperphosphatasia and TNFRSF11B mutations: relationships between phenotype and genotype [23].
  • MATERIALS AND METHODS: We screened for polymorphisms of the TNFRSF11B gene by DNA sequencing of the proximal promoter, coding exons, and intron-exon boundaries in 20 PDB patients and 10 controls [24].
  • The distribution of TNFRSF11B haplotypes significantly differed in sporadic PDB cases and controls (chi(2) = 30.2, df = 9, p < 0.001) because of over-representation of haplotypes containing the G1181 allele in cases [24].
  • RESULTS: Both patients had a homozygous deletion of TNFRSF11B, with identical break points, on chromosome 8q24 [25].

Anatomical context of TNFRSF11B


Associations of TNFRSF11B with chemical compounds


Physical interactions of TNFRSF11B

  • Reciprocal immunoprecipitation experiments revealed that while not associated with P-Selectin, OPG is physically complexed with vWF both within the WPB and following secretion from endothelial cells [29].
  • BACKGROUND: Osteoprotegerin (OPG) is involved in the regulation of bone turnover through binding to the receptor activator of nuclear factor kappaB ligand (RANKL), and has also been reported to be a potential survival factor for several different cell types [30].
  • OCIF is a heparin-binding basic glycoprotein and has been isolated as a monomer with an apparent molecular weight (Mr) of 60,000 and a homodimer with a Mr of 120,000 [31].
  • The potential survival effects of OPG are mediated through binding to a member of the TNF super family, TNF-related Apoptosis Inducing Ligand (TRAIL), preventing association between TRAIL and its death-inducing receptors present on a number of tumour cell types [32].
  • The discovery that OPG can bind to and inhibit the activity of TRAIL (TNF-related apoptosis-inducing ligand) triggered extensive research into the potential role of OPG in the regulation of tumour cell survival [33].
  • These data suggest that OPG can bind both RANKL and TRAIL and that the affinity of OPG for these two ligands is of a similar order of magnitude [34].

Co-localisations of TNFRSF11B


Regulatory relationships of TNFRSF11B


Other interactions of TNFRSF11B

  • Medium conditioned by cocultures of MG63 cells with myeloma cells had a reduced effect on TRAIL/Apo2L-induced apoptosis, reflecting the decreased concentrations of OPG in cocultures of myeloma cells with bone cells [2].
  • However, IL-6 and transforming growth factor-beta had little effect on OPG/OCIF mRNA levels in HPDL [26].
  • In summary, the intracellular localization of OPG in HUVEC, in association with vWF, together with its rapid and sustained secretory response to inflammatory stimuli, strongly support a modulatory role in vascular injury, inflammation and hemostasis [29].
  • This mechanism has been highlighted by the discovery of osteoprotegerin (OPG), a soluble tumor necrosis factor (TNF) family member that inhibits osteoclast formation [37].
  • The OPG/GAPDH mRNA levels in iliac bone before surgery correlated with serum osteocalcin (r = 0.52, P < 0.01), but not with bone resorption markers [38].

Analytical, diagnostic and therapeutic context of TNFRSF11B

  • Genetic markers near TNFRSF11B were evaluated by both a PCR method that involved sequence-tagged site-content mapping of a deletion of TNFRSF11B and PCR spanning the DNA break points [25].
  • Despite high OPG levels, the persistence of osteoclastogenesis can be related to the formation of the OPG/TRAIL complex demonstrated by immunoprecipitation experiments and the addition of anti-TRAIL antibody which decreases OC formation [1].
  • Immunohistochemistry of OPG protein expression in the rat distal femur metaphysis revealed that it was localized predominantly in preosteoblasts, osteoblasts, lining cells, and the osteoid layer, with occasional immunoreactivity in osteocytes and cells of the bone marrow [4].
  • Northern blot analyses also showed that HGFs, HPDLs, and HPCs, but not HGKs, expressed OPG/OCIF transcripts of approximately 2.5 kb [26].
  • Immunohistochemistry and in situ hybridization revealed OPG immunoreactivity and mRNA expression surrounding calcified areas in the medial layer (Mönckeberg's sclerosis), whereas OPG was mainly expressed adjacent to calcified neointimal lesions (atherosclerosis) [39].


  1. T cells support osteoclastogenesis in an in vitro model derived from human multiple myeloma bone disease: the role of the OPG/TRAIL interaction. Colucci, S., Brunetti, G., Rizzi, R., Zonno, A., Mori, G., Colaianni, G., Del Prete, D., Faccio, R., Liso, A., Capalbo, S., Liso, V., Zallone, A., Grano, M. Blood (2004) [Pubmed]
  2. Osteoprotegerin is a soluble decoy receptor for tumor necrosis factor-related apoptosis-inducing ligand/Apo2 ligand and can function as a paracrine survival factor for human myeloma cells. Shipman, C.M., Croucher, P.I. Cancer Res. (2003) [Pubmed]
  3. Relation of TNF-related apoptosis-inducing ligand (TRAIL) receptor and FLICE-inhibitory protein expression to TRAIL-induced apoptosis of melanoma. Zhang, X.D., Franco, A., Myers, K., Gray, C., Nguyen, T., Hersey, P. Cancer Res. (1999) [Pubmed]
  4. In vivo demonstration that human parathyroid hormone 1-38 inhibits the expression of osteoprotegerin in bone with the kinetics of an immediate early gene. Onyia, J.E., Miles, R.R., Yang, X., Halladay, D.L., Hale, J., Glasebrook, A., McClure, D., Seno, G., Churgay, L., Chandrasekhar, S., Martin, T.J. J. Bone Miner. Res. (2000) [Pubmed]
  5. Hypocalcemic effect of osteoclastogenesis inhibitory factor/osteoprotegerin in the thyroparathyroidectomized rat. Yamamoto, M., Murakami, T., Nishikawa, M., Tsuda, E., Mochizuki, S., Higashio, K., Akatsu, T., Motoyoshi, K., Nagata, N. Endocrinology (1998) [Pubmed]
  6. CLINICAL Review #: the role of receptor activator of nuclear factor-kappaB (RANK)/RANK ligand/osteoprotegerin: clinical implications. Vega, D., Maalouf, N.M., Sakhaee, K. J. Clin. Endocrinol. Metab. (2007) [Pubmed]
  7. OPG is regulated by beta-catenin and mediates resistance to TRAIL-induced apoptosis in colon cancer. De Toni, E.N., Thieme, S.E., Herbst, A., Behrens, A., Stieber, P., Jung, A., Blum, H., Göke, B., Kolligs, F.T. Clin. Cancer Res. (2008) [Pubmed]
  8. Osteoprotegerin Lys3Asn polymorphism and the risk of fracture in older women. Moffett, S.P., Oakley, J.I., Cauley, J.A., Lui, L.Y., Ensrud, K.E., Taylor, B.C., Hillier, T.A., Hochberg, M.C., Li, J., Cayabyab, S., Lee, J.M., Peltz, G., Cummings, S.R., Zmuda, J.M. J. Clin. Endocrinol. Metab. (2008) [Pubmed]
  9. Plasma osteoprotegerin levels predict cardiovascular and all-cause mortality and deterioration of kidney function in type 1 diabetic patients with nephropathy. Jorsal, A., Tarnow, L., Flyvbjerg, A., Parving, H.H., Rossing, P., Rasmussen, L.M. Diabetologia (2008) [Pubmed]
  10. Osteoprotegerin serum levels in children with type 1 diabetes: a potential modulating role in bone status. Galluzzi, F., Stagi, S., Salti, R., Toni, S., Piscitelli, E., Simonini, G., Falcini, F., Chiarelli, F. Eur. J. Endocrinol. (2005) [Pubmed]
  11. Serum osteoprotegerin in adolescent girls with anorexia nervosa. Misra, M., Soyka, L.A., Miller, K.K., Herzog, D.B., Grinspoon, S., De Chen, D., Neubauer, G., Klibanski, A. J. Clin. Endocrinol. Metab. (2003) [Pubmed]
  12. Plasma osteoprotegerin as a biochemical marker for vascular dementia and Alzheimer's disease. Emanuele, E., Peros, E., Scioli, G.A., D'Angelo, A., Olivieri, C., Montagna, L., Geroldi, D. Int. J. Mol. Med. (2004) [Pubmed]
  13. Bone mineral density, bone turnover, and osteoprotegerin in depressed women with and without borderline personality disorder. Kahl, K.G., Greggersen, W., Rudolf, S., Stoeckelhuber, B.M., Bergmann-Koester, C.U., Dibbelt, L., Schweiger, U. Psychosomatic medicine. (2006) [Pubmed]
  14. Osteoprotegerin blocks bone cancer-induced skeletal destruction, skeletal pain and pain-related neurochemical reorganization of the spinal cord. Honore, P., Luger, N.M., Sabino, M.A., Schwei, M.J., Rogers, S.D., Mach, D.B., O'keefe, P.F., Ramnaraine, M.L., Clohisy, D.R., Mantyh, P.W. Nat. Med. (2000) [Pubmed]
  15. Modulation of osteoclast differentiation and function by the new members of the tumor necrosis factor receptor and ligand families. Suda, T., Takahashi, N., Udagawa, N., Jimi, E., Gillespie, M.T., Martin, T.J. Endocr. Rev. (1999) [Pubmed]
  16. Concerted action of androgens and mechanical strain shifts bone metabolism from high turnover into an osteoanabolic mode. Liegibel, U.M., Sommer, U., Tomakidi, P., Hilscher, U., Van Den Heuvel, L., Pirzer, R., Hillmeier, J., Nawroth, P., Kasperk, C. J. Exp. Med. (2002) [Pubmed]
  17. Increased levels of serum osteoprotegerin in hypothyroid patients and its normalization with restoration of normal thyroid function. Nagasaki, T., Inaba, M., Jono, S., Hiura, Y., Tahara, H., Shirakawa, K., Onoda, N., Ishikawa, T., Ishimura, E., Nishizawa, Y. Eur. J. Endocrinol. (2005) [Pubmed]
  18. Osteoprotegerin is bound, internalized, and degraded by multiple myeloma cells. Standal, T., Seidel, C., Hjertner, Ø., Plesner, T., Sanderson, R.D., Waage, A., Borset, M., Sundan, A. Blood (2002) [Pubmed]
  19. Circulating estradiol and osteoprotegerin as determinants of bone turnover and bone density in postmenopausal women. Rogers, A., Saleh, G., Hannon, R.A., Greenfield, D., Eastell, R. J. Clin. Endocrinol. Metab. (2002) [Pubmed]
  20. Interleukin-6 and osteoprotegerin systems in Paget's disease of bone: relationship to risedronate treatment. Mossetti, G., Rendina, D., De Filippo, G., Viceconti, R., Di Domenico, G., Cioffi, M., Postiglione, L., Nunziata, V. Bone (2005) [Pubmed]
  21. The effect of zoledronic acid and osteoprotegerin on growth of human lung cancer in the tibias of nude mice. Tannehill-Gregg, S.H., Levine, A.L., Nadella, M.V., Iguchi, H., Rosol, T.J. Clin. Exp. Metastasis (2006) [Pubmed]
  22. A mutation in the gene TNFRSF11B encoding osteoprotegerin causes an idiopathic hyperphosphatasia phenotype. Cundy, T., Hegde, M., Naot, D., Chong, B., King, A., Wallace, R., Mulley, J., Love, D.R., Seidel, J., Fawkner, M., Banovic, T., Callon, K.E., Grey, A.B., Reid, I.R., Middleton-Hardie, C.A., Cornish, J. Hum. Mol. Genet. (2002) [Pubmed]
  23. Idiopathic hyperphosphatasia and TNFRSF11B mutations: relationships between phenotype and genotype. Chong, B., Hegde, M., Fawkner, M., Simonet, S., Cassinelli, H., Coker, M., Kanis, J., Seidel, J., Tau, C., Tüysüz, B., Yüksel, B., Love, D. J. Bone Miner. Res. (2003) [Pubmed]
  24. Susceptibility to Paget's disease of bone is influenced by a common polymorphic variant of osteoprotegerin. Daroszewska, A., Hocking, L.J., McGuigan, F.E., Langdahl, B., Stone, M.D., Cundy, T., Nicholson, G.C., Fraser, W.D., Ralston, S.H. J. Bone Miner. Res. (2004) [Pubmed]
  25. Osteoprotegerin deficiency and juvenile Paget's disease. Whyte, M.P., Obrecht, S.E., Finnegan, P.M., Jones, J.L., Podgornik, M.N., McAlister, W.H., Mumm, S. N. Engl. J. Med. (2002) [Pubmed]
  26. Expression of osteoprotegerin (osteoclastogenesis inhibitory factor) in cultures of human dental mesenchymal cells and epithelial cells. Sakata, M., Shiba, H., Komatsuzawa, H., Fujita, T., Ohta, K., Sugai, M., Suginaka, H., Kurihara, H. J. Bone Miner. Res. (1999) [Pubmed]
  27. Characterization of structural domains of human osteoclastogenesis inhibitory factor. Yamaguchi, K., Kinosaki, M., Goto, M., Kobayashi, F., Tsuda, E., Morinaga, T., Higashio, K. J. Biol. Chem. (1998) [Pubmed]
  28. Evidence of a role for osteoprotegerin in the pathogenesis of pulmonary arterial hypertension. Lawrie, A., Waterman, E., Southwood, M., Evans, D., Suntharalingam, J., Francis, S., Crossman, D., Croucher, P., Morrell, N., Newman, C. Am. J. Pathol. (2008) [Pubmed]
  29. Osteoprotegerin (OPG) is localized to the Weibel-Palade bodies of human vascular endothelial cells and is physically associated with von Willebrand factor. Zannettino, A.C., Holding, C.A., Diamond, P., Atkins, G.J., Kostakis, P., Farrugia, A., Gamble, J., To, L.B., Findlay, D.M., Haynes, D.R. J. Cell. Physiol. (2005) [Pubmed]
  30. Expression of osteoprotegerin (OPG), TNF related apoptosis inducing ligand (TRAIL), and receptor activator of nuclear factor kappaB ligand (RANKL) in human breast tumours. Van Poznak, C., Cross, S.S., Saggese, M., Hudis, C., Panageas, K.S., Norton, L., Coleman, R.E., Holen, I. J. Clin. Pathol. (2006) [Pubmed]
  31. Isolation of a novel cytokine from human fibroblasts that specifically inhibits osteoclastogenesis. Tsuda, E., Goto, M., Mochizuki, S., Yano, K., Kobayashi, F., Morinaga, T., Higashio, K. Biochem. Biophys. Res. Commun. (1997) [Pubmed]
  32. Osteoprotegerin (OPG) produced by bone marrow stromal cells protects breast cancer cells from TRAIL-induced apoptosis. Neville-Webbe, H.L., Cross, N.A., Eaton, C.L., Nyambo, R., Evans, C.A., Coleman, R.E., Holen, I. Breast Cancer Res. Treat. (2004) [Pubmed]
  33. Role of osteoprotegerin (OPG) in cancer. Holen, I., Shipman, C.M. Clin. Sci. (2006) [Pubmed]
  34. Investigating the interaction between osteoprotegerin and receptor activator of NF-kappaB or tumor necrosis factor-related apoptosis-inducing ligand: evidence for a pivotal role for osteoprotegerin in regulating two distinct pathways. Vitovski, S., Phillips, J.S., Sayers, J., Croucher, P.I. J. Biol. Chem. (2007) [Pubmed]
  35. Activation of peroxisome proliferator-activated receptor gamma inhibits osteoprotegerin gene expression in human aortic smooth muscle cells. Fu, M., Zhang, J., Lin Yg, Y., Zhu, X., Willson, T.M., Chen, Y.E. Biochem. Biophys. Res. Commun. (2002) [Pubmed]
  36. Interleukin-11 as an osteoprotegerin-inducing factor in culture medium of blastic cells from a patient with acute megakaryocytic leukemia complicated with osteosclerosis. Sato, T., Matsunaga, T., Kida, M., Morii, K., Machida, T., Kawano, Y., Nakamura, K., Kuribayashi, K., Takada, K., Iyama, S., Sato, Y., Takayama, T., Takahashi, M., Kato, J., Chokki, M., Niitsu, Y. Am. J. Hematol. (2004) [Pubmed]
  37. Interleukins in the control of osteoclast differentiation. Martin, T.J., Romas, E., Gillespie, M.T. Crit. Rev. Eukaryot. Gene Expr. (1998) [Pubmed]
  38. Skeletal changes in osteoprotegerin and receptor activator of nuclear factor-kappab ligand mRNA levels in primary hyperparathyroidism: effect of parathyroidectomy and association with bone metabolism. Stilgren, L.S., Rettmer, E., Eriksen, E.F., Hegedüs, L., Beck-Nielsen, H., Abrahamsen, B. Bone (2004) [Pubmed]
  39. Localization of osteoprotegerin, tumor necrosis factor-related apoptosis-inducing ligand, and receptor activator of nuclear factor-kappaB ligand in Mönckeberg's sclerosis and atherosclerosis. Schoppet, M., Al-Fakhri, N., Franke, F.E., Katz, N., Barth, P.J., Maisch, B., Preissner, K.T., Hofbauer, L.C. J. Clin. Endocrinol. Metab. (2004) [Pubmed]
WikiGenes - Universities