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Gene Review

Tnfsf11  -  tumor necrosis factor (ligand) superfamily...

Mus musculus

Synonyms: Ly109l, ODF, OPG, OPGL, Opgl, ...
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Disease relevance of Tnfsf11


High impact information on Tnfsf11


Chemical compound and disease context of Tnfsf11


Biological context of Tnfsf11


Anatomical context of Tnfsf11


Associations of Tnfsf11 with chemical compounds


Physical interactions of Tnfsf11

  • We identified a 21-bp sequence CTGTTTATGATGGCGAGGGGG in Oligo IV that specifically binds the RANKL-induced nuclear protein from RAW264.7 cells by performing a series of competition assays [18].
  • To investigate this possibility and to elucidate the mechanisms regulating RANKL expression, we isolated the 5'-flanking region of the murine RANKL gene and found that it contains two potential binding sites for Cbfa1 (OSE2-like sites) [19].
  • 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].

Enzymatic interactions of Tnfsf11

  • ODF rapidly converted the hyperphosphorylated form of the retinoblastoma protein (pRb) into the hypophosphorylated form [21].

Regulatory relationships of Tnfsf11


Other interactions of Tnfsf11


Analytical, diagnostic and therapeutic context of Tnfsf11

  • Transplantation and OPGL-rescue experiments in opgl-/- and rank-/- pregnant females showed that OPGL acts directly on RANK-expressing mammary epithelial cells [6].
  • Levels of RANKL and CD44 protein were measured by immunoblotting, and expression of CD44 in whole bone was determined by immunohistochemical staining [25].
  • Similarly, ELISA demonstrated decreased RANKL and increased OPG levels [26].
  • Real-time (RT)-PCR and Northern blot analysis indicated that P-LPS decreased expression of transcripts for osteocalcin (OCN) and receptor activator of nuclear factor kappaB ligand (RANKL) [26].
  • Receptor activator of NF-kappa B ligand (RANKL)/tumor necrosis factor-related activation induced cytokine (TRANCE)/osteoprotegerin ligand (OPGL)/osteoclast differentiation factor (ODF) is a membrane-bound signal transducer responsible for differentiation and maintenance of osteoclasts [27].


  1. Increased Myeloid Cell Responses to M-CSF and RANKL Cause Bone Loss and Inflammation in SH3BP2 "Cherubism" Mice. Ueki, Y., Lin, C.Y., Senoo, M., Ebihara, T., Agata, N., Onji, M., Saheki, Y., Kawai, T., Mukherjee, P.M., Reichenberger, E., Olsen, B.R. Cell (2007) [Pubmed]
  2. An increased osteoprotegerin serum release characterizes the early onset of diabetes mellitus and may contribute to endothelial cell dysfunction. Secchiero, P., Corallini, F., Pandolfi, A., Consoli, A., Candido, R., Fabris, B., Celeghini, C., Capitani, S., Zauli, G. Am. J. Pathol. (2006) [Pubmed]
  3. Gene expression of osteoclast differentiation factor is induced by lipopolysaccharide in mouse osteoblasts via Toll-like receptors. Kikuchi, T., Matsuguchi, T., Tsuboi, N., Mitani, A., Tanaka, S., Matsuoka, M., Yamamoto, G., Hishikawa, T., Noguchi, T., Yoshikai, Y. J. Immunol. (2001) [Pubmed]
  4. Expression of RANKL and OPG correlates with age-related bone loss in male C57BL/6 mice. Cao, J., Venton, L., Sakata, T., Halloran, B.P. J. Bone Miner. Res. (2003) [Pubmed]
  5. Osteoblasts provide a suitable microenvironment for the action of receptor activator of nuclear factor-kappaB ligand. Yamamoto, Y., Udagawa, N., Matsuura, S., Nakamichi, Y., Horiuchi, H., Hosoya, A., Nakamura, M., Ozawa, H., Takaoka, K., Penninger, J.M., Noguchi, T., Takahashi, N. Endocrinology (2006) [Pubmed]
  6. The osteoclast differentiation factor osteoprotegerin-ligand is essential for mammary gland development. Fata, J.E., Kong, Y.Y., Li, J., Sasaki, T., Irie-Sasaki, J., Moorehead, R.A., Elliott, R., Scully, S., Voura, E.B., Lacey, D.L., Boyle, W.J., Khokha, R., Penninger, J.M. Cell (2000) [Pubmed]
  7. Osteoclast differentiation factor mediates an essential signal for bone resorption induced by 1 alpha,25-dihydroxyvitamin D3, prostaglandin E2, or parathyroid hormone in the microenvironment of bone. Tsukii, K., Shima, N., Mochizuki, S., Yamaguchi, K., Kinosaki, M., Yano, K., Shibata, O., Udagawa, N., Yasuda, H., Suda, T., Higashio, K. Biochem. Biophys. Res. Commun. (1998) [Pubmed]
  8. Does TNF have anti-osteoclastogenic actions? Iqbal, J. Ann. N. Y. Acad. Sci. (2006) [Pubmed]
  9. 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]
  10. 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]
  11. RANKL maintains bone homeostasis through c-Fos-dependent induction of interferon-beta. Takayanagi, H., Kim, S., Matsuo, K., Suzuki, H., Suzuki, T., Sato, K., Yokochi, T., Oda, H., Nakamura, K., Ida, N., Wagner, E.F., Taniguchi, T. Nature (2002) [Pubmed]
  12. 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]
  13. Monokine induced by interferon-gamma is induced by receptor activator of nuclear factor kappa B ligand and is involved in osteoclast adhesion and migration. Kwak, H.B., Lee, S.W., Jin, H.M., Ha, H., Lee, S.H., Takeshita, S., Tanaka, S., Kim, H.M., Kim, H.H., Lee, Z.H. Blood (2005) [Pubmed]
  14. Receptor activator of NF-kappaB ligand regulates the proliferation of mammary epithelial cells via Id2. Kim, N.S., Kim, H.J., Koo, B.K., Kwon, M.C., Kim, Y.W., Cho, Y., Yokota, Y., Penninger, J.M., Kong, Y.Y. Mol. Cell. Biol. (2006) [Pubmed]
  15. Evidence that genetic deletion of the TNF receptor p60 or p80 in macrophages modulates RANKL-induced signaling. Takada, Y., Aggarwal, B.B. Blood (2004) [Pubmed]
  16. 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]
  17. Bradykinin potentiates cytokine-induced prostaglandin biosynthesis in osteoblasts by enhanced expression of cyclooxygenase 2, resulting in increased RANKL expression. Brechter, A.B., Lerner, U.H. Arthritis Rheum. (2007) [Pubmed]
  18. YY1 is involved in RANKL-induced transcription of the tartrate-resistant acid phosphatase gene in osteoclast differentiation. Shi, Z., Silveira, A., Patel, P., Feng, X. Gene (2004) [Pubmed]
  19. Cbfa1 does not regulate RANKL gene activity in stromal/osteoblastic cells. O'Brien, C.A., Kern, B., Gubrij, I., Karsenty, G., Manolagas, S.C. Bone (2002) [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. Osteoclast differentiation factor modulates cell cycle machinery and causes a delay in s phase progression in RAW264 cells. Meiyanto, E., Hoshijima, M., Ogawa, T., Ishida, N., Takeya, T. Biochem. Biophys. Res. Commun. (2001) [Pubmed]
  22. Receptor activator of NF-kappaB ligand induction via Jak2 and Stat5a in mammary epithelial cells. Srivastava, S., Matsuda, M., Hou, Z., Bailey, J.P., Kitazawa, R., Herbst, M.P., Horseman, N.D. J. Biol. Chem. (2003) [Pubmed]
  23. Fibroblastic stromal cells express receptor activator of NF-kappa B ligand and support osteoclast differentiation. Quinn, J.M., Horwood, N.J., Elliott, J., Gillespie, M.T., Martin, T.J. J. Bone Miner. Res. (2000) [Pubmed]
  24. Osteoprotegerin ligand modulates murine osteoclast survival in vitro and in vivo. Lacey, D.L., Tan, H.L., Lu, J., Kaufman, S., Van, G., Qiu, W., Rattan, A., Scully, S., Fletcher, F., Juan, T., Kelley, M., Burgess, T.L., Boyle, W.J., Polverino, A.J. Am. J. Pathol. (2000) [Pubmed]
  25. Hyaluronan increases RANKL expression in bone marrow stromal cells through CD44. Cao, J.J., Singleton, P.A., Majumdar, S., Boudignon, B., Burghardt, A., Kurimoto, P., Wronski, T.J., Bourguignon, L.Y., Halloran, B.P. J. Bone Miner. Res. (2005) [Pubmed]
  26. Cementoblast gene expression is regulated by Porphyromonas gingivalis lipopolysaccharide partially via toll-like receptor-4/MD-2. Nociti, F.H., Foster, B.L., Barros, S.P., Darveau, R.P., Somerman, M.J. J. Dent. Res. (2004) [Pubmed]
  27. Promoter structure of mouse RANKL/TRANCE/OPGL/ODF gene. Kitazawa, R., Kitazawa, S., Maeda, S. Biochim. Biophys. Acta (1999) [Pubmed]
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