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Gene Review

Tnfrsf11b  -  tumor necrosis factor receptor superfamily...

Mus musculus

Synonyms: OCIF, OPG, Ocif, Opg, Osteoclastogenesis inhibitory factor, ...
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Disease relevance of Tnfrsf11b

  • High systemic levels of osteoprotegerin (OPG) in OPG transgenic mice cause osteopetrosis with normal tooth eruption and bone elongation and inhibit the development and activity of endosteal, but not periosteal, osteoclasts [1].
  • Osteoprotegerin (OPG)/osteoclastogenesis inhibitory factor (OCIF) is a recently identified cytokine that belongs to the tumor necrosis factor receptor superfamily and regulates bone mass by inhibiting osteoclastic bone resorption [2].
  • We determined that the breast cancer cell lines MDA-MB-231, MCF-7, and T47D as well as primary breast cancers do not express RANKL but express OPG and RANK [3].
  • The OPG effectively inhibits wear debris-induced osteoclastogenesis and osteolysis [4].
  • METHODS: A recombinant adeno-associated virus (rAAV) vector co-expressing OPG (rAAV-OPG-IRES-EGFP) was generated [4].

Psychiatry related information on Tnfrsf11b

  • Passive administration of osteoprotegerin, the soluble decoy receptor of TRANCE/RANKL, is efficient in blocking disease progression, but may not find widespread clinical use due to patient compliance problems and the expected high costs [5].

High impact information on Tnfrsf11b

  • In vitro, osteoclast differentiation from precursor cells is blocked in a dose-dependent manner by recombinant OPG [6].
  • Osteoprotegerin: a novel secreted protein involved in the regulation of bone density [6].
  • In vivo, hepatic expression of OPG in transgenic mice results in a profound yet nonlethal osteopetrosis, coincident with a decrease in later stages of osteoclast differentiation [6].
  • Unexpectedly, OPG-deficient mice also exhibit medial calcification of the aorta and renal arteries, suggesting that regulation of OPG, its signaling pathway, or its ligand(s) may play a role in the long observed association between osteoporosis and vascular calcification [7].
  • Adolescent and adult OPG-/- mice exhibit a decrease in total bone density characterized by severe trabecular and cortical bone porosity, marked thinning of the parietal bones of the skull, and a high incidence of fractures [7].

Chemical compound and disease context of Tnfrsf11b


Biological context of Tnfrsf11b

  • These findings indicate that the OPG/OPGL/RANK signaling pathway may play an important role in both pathological and physiological calcification processes [1].
  • OPG/OCIF is a secreted member of the tumor necrosis factor receptor family and inhibits osteoclastogenesis by interrupting the cell-to-cell interaction [13].
  • Here we report the expression cloning of a ligand for OPG/OCIF from a complementary DNA library of mouse stromal cells [13].
  • The up-regulation of OPG/OCIF mRNA by TGF-beta1 in ST2 cells did not require de novo protein synthesis and involved both a transcriptional and a post-transcriptional mechanism [2].
  • However, the roles of RANKL and OPG in innate immunity remain obscure [14].

Anatomical context of Tnfrsf11b


Associations of Tnfrsf11b with chemical compounds

  • In murine bone marrow cultures, TGF-beta1 markedly inhibited the formation of tartrate-resistant acid phosphatase-positive multinucleated osteoclast-like cells in the presence of 1,25-dihydroxyvitamin D3, whose effect was significantly reversed by a neutralizing antibody against OPG/OCIF [2].
  • Receptor Activator of NF-{kappa}B Ligand and Osteoprotegerin Regulate Proinflammatory Cytokine Production in Mice [14].
  • Stimulation of (45)Ca release by dexamethasone and hydrocortisone in calvariae was blocked by OPG [18].
  • OPG/OCIF, a secreted member of the tumor necrosis factor (TNF) receptor family, inhibited differentiation and activation of osteoclasts [19].
  • Recombinant human OPG, like indomethacin, was found to cause osteoclasts to detach from the bone surface and attach to the adjacent endocranial membrane (periosteum) [17].

Physical interactions of Tnfrsf11b

  • Receptor activator of NF-kB Ligand (RANKL) is an essential requirement for osteoclastogenesis and its activity is neutralized by binding to the soluble decoy receptor osteoprotegerin (OPG) [20].

Regulatory relationships of Tnfrsf11b


Other interactions of Tnfrsf11b


Analytical, diagnostic and therapeutic context of Tnfrsf11b


  1. Osteoprotegerin reverses osteoporosis by inhibiting endosteal osteoclasts and prevents vascular calcification by blocking a process resembling osteoclastogenesis. Min, H., Morony, S., Sarosi, I., Dunstan, C.R., Capparelli, C., Scully, S., Van, G., Kaufman, S., Kostenuik, P.J., Lacey, D.L., Boyle, W.J., Simonet, W.S. J. Exp. Med. (2000) [Pubmed]
  2. Transforming growth factor-beta stimulates the production of osteoprotegerin/osteoclastogenesis inhibitory factor by bone marrow stromal cells. Takai, H., Kanematsu, M., Yano, K., Tsuda, E., Higashio, K., Ikeda, K., Watanabe, K., Yamada, Y. J. Biol. Chem. (1998) [Pubmed]
  3. Breast cancer cells interact with osteoblasts to support osteoclast formation. Thomas, R.J., Guise, T.A., Yin, J.J., Elliott, J., Horwood, N.J., Martin, T.J., Gillespie, M.T. Endocrinology (1999) [Pubmed]
  4. Recombinant adeno-associated virus-mediated osteoprotegerin gene therapy inhibits wear debris-induced osteolysis. Ulrich-Vinther, M., Carmody, E.E., Goater, J.J., S balle, K., O'Keefe, R.J., Schwarz, E.M. The Journal of bone and joint surgery. American volume. (2002) [Pubmed]
  5. Protection against osteoporosis by active immunization with TRANCE/RANKL displayed on virus-like particles. Spohn, G., Schwarz, K., Maurer, P., Illges, H., Rajasekaran, N., Choi, Y., Jennings, G.T., Bachmann, M.F. J. Immunol. (2005) [Pubmed]
  6. Osteoprotegerin: a novel secreted protein involved in the regulation of bone density. Simonet, W.S., Lacey, D.L., Dunstan, C.R., Kelley, M., Chang, M.S., Lüthy, R., Nguyen, H.Q., Wooden, S., Bennett, L., Boone, T., Shimamoto, G., DeRose, M., Elliott, R., Colombero, A., Tan, H.L., Trail, G., Sullivan, J., Davy, E., Bucay, N., Renshaw-Gegg, L., Hughes, T.M., Hill, D., Pattison, W., Campbell, P., Sander, S., Van, G., Tarpley, J., Derby, P., Lee, R., Boyle, W.J. Cell (1997) [Pubmed]
  7. osteoprotegerin-deficient mice develop early onset osteoporosis and arterial calcification. Bucay, N., Sarosi, I., Dunstan, C.R., Morony, S., Tarpley, J., Capparelli, C., Scully, S., Tan, H.L., Xu, W., Lacey, D.L., Boyle, W.J., Simonet, W.S. Genes Dev. (1998) [Pubmed]
  8. The inhibition of RANKL causes greater suppression of bone resorption and hypercalcemia compared with bisphosphonates in two models of humoral hypercalcemia of malignancy. Morony, S., Warmington, K., Adamu, S., Asuncion, F., Geng, Z., Grisanti, M., Tan, H.L., Capparelli, C., Starnes, C., Weimann, B., Dunstan, C.R., Kostenuik, P.J. Endocrinology (2005) [Pubmed]
  9. Osteoprotegerin: a physiological and pharmacological inhibitor of bone resorption. Kostenuik, P.J., Shalhoub, V. Curr. Pharm. Des. (2001) [Pubmed]
  10. Molecular control of bone remodeling and osteoporosis. Kong, Y.Y., Penninger, J.M. Exp. Gerontol. (2000) [Pubmed]
  11. 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]
  12. Inhibition of bone resorption, rather than direct cytotoxicity, mediates the anti-tumour actions of ibandronate and osteoprotegerin in a murine model of breast cancer bone metastasis. Zheng, Y., Zhou, H., Brennan, K., Blair, J.M., Modzelewski, J.R., Seibel, M.J., Dunstan, C.R. Bone (2007) [Pubmed]
  13. Osteoclast differentiation factor is a ligand for osteoprotegerin/osteoclastogenesis-inhibitory factor and is identical to TRANCE/RANKL. Yasuda, H., Shima, N., Nakagawa, N., Yamaguchi, K., Kinosaki, M., Mochizuki, S., Tomoyasu, A., Yano, K., Goto, M., Murakami, A., Tsuda, E., Morinaga, T., Higashio, K., Udagawa, N., Takahashi, N., Suda, T. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  14. Receptor Activator of NF-{kappa}B Ligand and Osteoprotegerin Regulate Proinflammatory Cytokine Production in Mice. Maruyama, K., Takada, Y., Ray, N., Kishimoto, Y., Penninger, J.M., Yasuda, H., Matsuo, K. J. Immunol. (2006) [Pubmed]
  15. Induction of osteoclast differentiation by Runx2 through receptor activator of nuclear factor-kappa B ligand (RANKL) and osteoprotegerin regulation and partial rescue of osteoclastogenesis in Runx2-/- mice by RANKL transgene. Enomoto, H., Shiojiri, S., Hoshi, K., Furuichi, T., Fukuyama, R., Yoshida, C.A., Kanatani, N., Nakamura, R., Mizuno, A., Zanma, A., Yano, K., Yasuda, H., Higashio, K., Takada, K., Komori, T. J. Biol. Chem. (2003) [Pubmed]
  16. Cellular, molecular, and genetic determinants of tooth eruption. Wise, G.E., Frazier-Bowers, S., D'Souza, R.N. Crit. Rev. Oral Biol. Med. (2002) [Pubmed]
  17. Osteoprotegerin is produced when prostaglandin synthesis is inhibited causing osteoclasts to detach from the surface of mouse parietal bone and attach to the endocranial membrane. O'Brien, E.A., Williams, J.H., Marshall, M.J. Bone (2001) [Pubmed]
  18. Glucocorticoid regulation of osteoclast differentiation and expression of receptor activator of nuclear factor-kappaB (NF-kappaB) ligand, osteoprotegerin, and receptor activator of NF-kappaB in mouse calvarial bones. Swanson, C., Lorentzon, M., Conaway, H.H., Lerner, U.H. Endocrinology (2006) [Pubmed]
  19. A novel molecular mechanism modulating osteoclast differentiation and function. Yasuda, H., Shima, N., Nakagawa, N., Yamaguchi, K., Kinosaki, M., Goto, M., Mochizuki, S.I., Tsuda, E., Morinaga, T., Udagawa, N., Takahashi, N., Suda, T., Higashio, K. Bone (1999) [Pubmed]
  20. Relevance of an in vitro osteoclastogenesis system to study receptor activator of NF-kB ligand and osteoprotegerin biological activities. Wittrant, Y., Theoleyre, S., Couillaud, S., Dunstan, C., Heymann, D., Rédini, F. Exp. Cell Res. (2004) [Pubmed]
  21. Interleukin-18 up-regulates osteoprotegerin expression in stromal/osteoblastic cells. Makiishi-Shimobayashi, C., Tsujimura, T., Iwasaki, T., Yamada, N., Sugihara, A., Okamura, H., Hayashi , S., Terada, N. Biochem. Biophys. Res. Commun. (2001) [Pubmed]
  22. Identification and characterization of mouse bone marrow stromal cell lines immortalized by temperature-sensitive SV40 T antigen: supportive activity for osteoclast differentiation. Takeshita, S., Arai, S., Kudo, A. Bone (2001) [Pubmed]
  23. Lipopolysaccharide-induced osteoclastogenesis in Src homology 2-domain phosphatase-1-deficient viable motheaten mice. Hayashi, S., Tsuneto, M., Yamada, T., Nose, M., Yoshino, M., Shultz, L.D., Yamazaki, H. Endocrinology (2004) [Pubmed]
  24. Parathyroid hormone stimulates TRANCE and inhibits osteoprotegerin messenger ribonucleic acid expression in murine bone marrow cultures: correlation with osteoclast-like cell formation. Lee, S.K., Lorenzo, J.A. Endocrinology (1999) [Pubmed]
  25. Canonical Wnt signaling in differentiated osteoblasts controls osteoclast differentiation. Glass, D.A., Bialek, P., Ahn, J.D., Starbuck, M., Patel, M.S., Clevers, H., Taketo, M.M., Long, F., McMahon, A.P., Lang, R.A., Karsenty, G. Dev. Cell (2005) [Pubmed]
  26. Expression of osteoprotegerin, receptor activator of NF-kappaB ligand (osteoprotegerin ligand) and related proinflammatory cytokines during fracture healing. Kon, T., Cho, T.J., Aizawa, T., Yamazaki, M., Nooh, N., Graves, D., Gerstenfeld, L.C., Einhorn, T.A. J. Bone Miner. Res. (2001) [Pubmed]
  27. Double mutations in klotho and osteoprotegerin gene loci rescued osteopetrotic phenotype. Yamashita, T., Okada, S., Higashio, K., Nabeshima, Y., Noda, M. Endocrinology (2002) [Pubmed]
  28. Opg, Rank, and Rankl in tooth development: co-ordination of odontogenesis and osteogenesis. Ohazama, A., Courtney, J.M., Sharpe, P.T. J. Dent. Res. (2004) [Pubmed]
  29. Attenuation of bone mass and increase of osteoclast formation in decoy receptor 3 transgenic mice. Tang, C.H., Hsu, T.L., Lin, W.W., Lai, M.Z., Yang, R.S., Hsieh, S.L., Fu, W.M. J. Biol. Chem. (2007) [Pubmed]
  30. Adrenergic stimulation of osteoclastogenesis mediated by expression of osteoclast differentiation factor in MC3T3-E1 osteoblast-like cells. Takeuchi, T., Tsuboi, T., Arai, M., Togari, A. Biochem. Pharmacol. (2001) [Pubmed]
  31. Severe osteoporosis in mice lacking osteoclastogenesis inhibitory factor/osteoprotegerin. Mizuno, A., Amizuka, N., Irie, K., Murakami, A., Fujise, N., Kanno, T., Sato, Y., Nakagawa, N., Yasuda, H., Mochizuki, S., Gomibuchi, T., Yano, K., Shima, N., Washida, N., Tsuda, E., Morinaga, T., Higashio, K., Ozawa, H. Biochem. Biophys. Res. Commun. (1998) [Pubmed]
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