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18 - Wnt/Frizzled receptor signaling in osteoporosis

from PART V - PHYSIOLOGICAL FUNCTIONS AND DRUG TARGETING OF GPCRS

Published online by Cambridge University Press:  05 June 2012

Georges Rawadi
Affiliation:
Galapagos, Romainville
Sandra Siehler
Affiliation:
Novartis Institute for Biomedical Research
Graeme Milligan
Affiliation:
University of Glasgow
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Summary

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Chapter
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G Protein-Coupled Receptors
Structure, Signaling, and Physiology
, pp. 398 - 414
Publisher: Cambridge University Press
Print publication year: 2010

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References

Wodarz, A., Nusse, R., Mechanisms of Wnt signaling in development, Annu Rev Cell Dev Biol (1998) 59–88.CrossRefGoogle ScholarPubMed
Polakis, P., Wnt signaling and cancer, Genes Dev 15 (2000) 1837–1851.Google Scholar
Nusse, R., The Wnt gene family in tumorigenesis and in normal development, J Steroid Biochem Mol Biol 1–3 (1992) 9–12.CrossRefGoogle ScholarPubMed
Baron, R., Rawadi, G., Targeting the Wnt/beta-catenin pathway to regulate bone formation in the adult skeleton, Endocrinology. 6 (2007) 2635–2643.CrossRefGoogle Scholar
Rawadi, G., Roman-Roman, S., Wnt signalling pathway: a new target for the treatment of osteoporosis, Expert Opin Ther Targets. 5 (2005) 1063–1077.CrossRefGoogle Scholar
Bhanot, P., et al., A new member of the frizzled family from Drosophila functions as a Wingless receptor, Nature 6588 (1996) 225–230.CrossRefGoogle Scholar
Yang-Snyder, J., Miller, J.R., Brown, J.D., Lai, C.J., Moon, R.T., A frizzled homolog functions in a vertebrate Wnt signaling pathway, Curr Biol 10 (1996) 1302–1306.CrossRefGoogle Scholar
Umbhauer, M., Djiane, A., Goisset, C., Penzo-Mendez, A., Riou, J.F., Boucaut, J.C., Shi, D.L., The C-terminal cytoplasmic Lys-thr-X-X-X-Trp motif in frizzled receptors mediates Wnt/beta-catenin signalling, Embo J 18 (2000) 4944–4954.CrossRefGoogle Scholar
Malbon, C.C., Wang, H., Moon, R.T., Wnt signaling and heterotrimeric G-proteins: strange bedfellows or a classic romance?, Biochem Biophys Res Commun 3 (2001) 589–593.CrossRefGoogle Scholar
Malbon, C.C., Frizzleds: new members of the superfamily of G-protein-coupled receptors, Front Biosci (2004) 1048–1058.CrossRefGoogle ScholarPubMed
Alcedo, J., Noll, M., Hedgehog and its patched-smoothened receptor complex: a novel signalling mechanism at the cell surface, Biol Chem 7 (1997) 583–590.Google Scholar
Heuvel, M., Hedgehog signalling: off the shelf modulation, Curr Biol 17 (2003) R686–688.CrossRefGoogle Scholar
Semenov, M.V., Habas, R., Macdonald, B.T., He, X., SnapShot: Noncanonical Wnt Signaling Pathways, Cell. 7 (2007) 1378.Google Scholar
Semenov, M., Tamai, K., He, X., SOST is a ligand for LRP5/LRP6 and a WNT signaling inhibitor, J Biol Chem (2005) 20.Google Scholar
Veeman, M.T., Axelrod, J.D., Moon, R.T., A second canon. Functions and mechanisms of beta-catenin-independent Wnt signaling, Dev Cell. 3 (2003) 367–377.CrossRefGoogle Scholar
Wehrli, M., et al., arrow encodes an LDL-receptor-related protein essential for Wingless signalling, Nature 6803 (2000) 527–530.Google Scholar
Tamai, K., et al., LDL-receptor-related proteins in Wnt signal transduction, Nature 6803 (2000) 530–535.Google Scholar
Labalette, C., Renard, C.A., Neuveut, C., Buendia, M.A., Wei, Y., Interaction and functional cooperation between the LIM protein FHL2, CBP/p300, and beta-catenin, Mol Cell Biol 24 (2004) 10689–10702.CrossRefGoogle ScholarPubMed
Levy, L., Wei, Y., Labalette, C., Wu, Y., Renard, C.A., Buendia, M.A., Neuveut, C., Acetylation of beta-catenin by p300 regulates beta-catenin-Tcf4 interaction, Mol Cell Biol 8 (2004) 3404–3414.CrossRefGoogle Scholar
Wang, S., Krinks, M., Moos, M., Jr., Frzb-1, , an antagonist of Wnt-1 and Wnt-8, does not block signaling by Wnts -3A, -5A, or -11, Biochem Biophys Res Commun 2 (1997) 502–504.CrossRefGoogle Scholar
Wang, S., Krinks, M., Lin, K., Luyten, F.P., Moos, M., Jr., Frzb, a secreted protein expressed in the Spemann organizer, binds and inhibits Wnt-8, Cell 6 (1997) 757–766.CrossRefGoogle Scholar
Lin, K., Wang, S., Julius, M.A., Kitajewski, J., Moos, M., Jr., Luyten, F.P., The cysteine-rich frizzled domain of Frzb-1 is required and sufficient for modulation of Wnt signaling, Proc Natl Acad Sci U S A 21 (1997) 11196–11200.CrossRefGoogle Scholar
Leyns, L., Bouwmeester, T., Kim, S.H., Piccolo, S., Robertis, E.M., Frzb-1 is a secreted antagonist of Wnt signaling expressed in the Spemann organizer, Cell 6 (1997) 747–756.CrossRefGoogle Scholar
Finch, P.W., et al., Purification and molecular cloning of a secreted, Frizzled-related antagonist of Wnt action, Proc Natl Acad Sci U S A 13 (1997) 6770–6775.CrossRefGoogle Scholar
Kawano, Y., Kypta, R., Secreted antagonists of the Wnt signalling pathway, J Cell Sci Pt 13 (2003) 2627–2634.CrossRefGoogle Scholar
Hsieh, J.C., et al., A new secreted protein that binds to Wnt proteins and inhibits their activities, Nature 6726 (1999) 431–436.CrossRefGoogle Scholar
Mao, B., Wu, W., Li, Y., Hoppe, D., Stannek, P., Glinka, A., Niehrs, C., LDL-receptor-related protein 6 is a receptor for Dickkopf proteins, Nature 6835 (2001) 321–325.CrossRefGoogle Scholar
Bafico, A., Liu, G., Yaniv, A., Gazit, A., Aaronson, S.A., Novel mechanism of Wnt signalling inhibition mediated by Dickkopf-1 interaction with LRP6/Arrow, Nat Cell Biol 7 (2001) 683–686.CrossRefGoogle Scholar
Krupnik, V.E., et al., Functional and structural diversity of the human Dickkopf gene family, Gene 2 (1999) 301–313.CrossRefGoogle Scholar
Mao, B., et al., Kremen proteins are Dickkopf receptors that regulate Wnt/beta-catenin signalling, Nature 6889 (2002) 664–667.CrossRefGoogle Scholar
Mao, B., Niehrs, C., Kremen2 modulates Dickkopf2 activity during Wnt/LRP6 signaling, Gene 1–2 (2003) 179–183.CrossRefGoogle ScholarPubMed
Balemans, W., et al., Increased bone density in sclerosteosis is due to the deficiency of a novel secreted protein (SOST), Hum Mol Genet 5 (2001) 537–543.CrossRefGoogle Scholar
Brunkow, M.E., et al., Bone dysplasia sclerosteosis results from loss of the SOST gene product, a novel cystine knot-containing protein, Am J Hum Genet 3 (2001) 577–589.CrossRefGoogle Scholar
Steitz, M.C., Wickenheisser, J.K., Siegfried, E., Overexpression of zeste white 3 blocks wingless signaling in the Drosophila embryonic midgut, Dev Biol 2 (1998) 218–233.CrossRefGoogle Scholar
Winkler, D.G., et al., Sclerostin inhibition of Wnt-3a-induced C3H10T1/2 cell differentiation is indirect and mediated by bone morphogenetic proteins, J Biol Chem 4 (2005) 2498–2502.CrossRefGoogle Scholar
Li, X., et al., Sclerostin Binds to LRP5/6 and Antagonizes Canonical Wnt Signaling, J Biol Chem 20 (2005) 19883–19887.CrossRefGoogle Scholar
Hall, A., Rho GTPases and the control of cell behaviour, Biochem Soc Trans. Pt 5 (2005) 891–895.CrossRefGoogle ScholarPubMed
Habas, R., He, X., Activation of Rho and Rac by Wnt/frizzled signaling, Methods Enzymol. (2006) 500–511.CrossRefGoogle ScholarPubMed
DasGupta, R., Fuchs, E., Multiple roles for activated LEF/TCF transcription complexes during hair follicle development and differentiation, Development 20 (1999) 4557–4568.Google Scholar
Slusarski, D.C., Corces, V.G., Moon, R.T., Interaction of Wnt and a Frizzled homologue triggers G-protein-linked phosphatidylinositol signalling, Nature 6658 (1997) 410–413.CrossRefGoogle Scholar
Slusarski, D.C., Yang-Snyder, J., Busa, W.B., Moon, R.T., Modulation of embryonic intracellular Ca2+ signaling by Wnt-5A, Dev Biol 1 (1997) 114–120.CrossRefGoogle Scholar
Sheldahl, L.C., Park, M., Malbon, C.C., Moon, R.T., Protein kinase C is differentially stimulated by Wnt and Frizzled homologs in a G-protein-dependent manner, Curr Biol 13 (1999) 695–698.CrossRefGoogle Scholar
Kuhl, M., Sheldahl, L.C., Malbon, C.C., Moon, R.T., Ca(2+)/calmodulin-dependent protein kinase II is stimulated by Wnt and Frizzled homologs and promotes ventral cell fates in Xenopus, J Biol Chem 17 (2000) 12701–12711.CrossRefGoogle Scholar
Weeraratna, A.T., Jiang, Y., Hostetter, G., Rosenblatt, K., Duray, P., Bittner, M., Trent, J.M., Wnt5a signaling directly affects cell motility and invasion of metastatic melanoma, Cancer Cell. 3 (2002) 279–288.CrossRefGoogle Scholar
Saneyoshi, T., Kume, S., Amasaki, Y., Mikoshiba, K., The Wnt/calcium pathway activates NF-AT and promotes ventral cell fate in Xenopus embryos, Nature 6886 (2002) 295–299.CrossRefGoogle Scholar
Pandur, P., Maurus, D., Kuhl, M., Increasingly complex: new players enter the Wnt signaling network, Bioessays 10 (2002) 881–884.CrossRefGoogle Scholar
Xu, Q., et al., Vascular development in the retina and inner ear: control by Norrin and Frizzled-4, a high-affinity ligand-receptor pair, Cell 6 (2004) 883–895.CrossRefGoogle Scholar
Clevers, H., Wnt signaling: Ig-norrin the dogma, Curr Biol 11 (2004) R436–437.CrossRefGoogle Scholar
Penzo-Mendez, A., Umbhauer, M., Djiane, A., Boucaut, J.C., Riou, J.F., Activation of Gbetagamma signaling downstream of Wnt-11/Xfz7 regulates Cdc42 activity during Xenopus gastrulation, Dev Biol 2 (2003) 302–314.CrossRefGoogle Scholar
Wang, H.Y., Malbon, C.C., Wnt signaling, Ca2+, and cyclic GMP: visualizing Frizzled functions, Science 5625 (2003) 1529–1530.CrossRefGoogle Scholar
Dejmek, J., Dib, K., Jonsson, M., Andersson, T., Wnt-5a and G-protein signaling are required for collagen-induced DDR1 receptor activation and normal mammary cell adhesion, Int J Cancer 3 (2003) 344–351.CrossRefGoogle Scholar
Klingensmith, J., Nusse, R., Signaling by wingless in Drosophila, Dev Biol 2 (1994) 396–414.CrossRefGoogle Scholar
Nusse, R., Varmus, H.E., Many tumors induced by the mouse mammary tumor virus contain a provirus integrated in the same region of the host genome, Cell 1 (1982) 99–109.CrossRefGoogle Scholar
Roelink, H., Wagenaar, E., Silva, S. Lopes, Nusse, R., Wnt-3, a gene activated by proviral insertion in mouse mammary tumors, is homologous to int-1/Wnt-1 and is normally expressed in mouse embryos and adult brain, Proc Natl Acad Sci U S A 12 (1990) 4519–4523.CrossRefGoogle Scholar
Lyuksyutova, A.I., et al., Anterior-posterior guidance of commissural axons by Wnt-frizzled signaling, Science 5652 (2003) 1984–1988.CrossRefGoogle Scholar
Wang, Y., Thekdi, N., Smallwood, P.M., Macke, J.P., Nathans, J., Frizzled-3 is required for the development of major fiber tracts in the rostral CNS, J Neurosci 19 (2002) 8563–8573.CrossRefGoogle Scholar
Wang, Y., Huso, D., Cahill, H., Ryugo, D., Nathans, J., Progressive cerebellar, auditory, and esophageal dysfunction caused by targeted disruption of the frizzled-4 gene, J Neurosci 13 (2001) 4761–4771.CrossRefGoogle Scholar
Ishikawa, T., Tamai, Y., Zorn, A.M., Yoshida, H., Seldin, M.F., Nishikawa, S., Taketo, M.M., Mouse Wnt receptor gene Fzd5 is essential for yolk sac and placental angiogenesis, Development 1 (2001) 25–33.Google Scholar
Guo, N., Hawkins, C., Nathans, J., Frizzled6 controls hair patterning in mice, Proc Natl Acad Sci U S A 25 (2004) 9277–9281.CrossRefGoogle Scholar
Wu, Q.L., Zierold, C., Ranheim, E.A., Dysregulation of Frizzled 6 is a critical component of B-cell leukemogenesis in a mouse model of chronic lymphocytic leukemia, Blood. 13 (2009) 3031–3039.CrossRefGoogle Scholar
Ranheim, E.A., Kwan, H.C., Reya, T., Wang, Y.K., Weissman, I.L., Francke, U., Frizzled 9 knock-out mice have abnormal B-cell development, Blood. 6 (2005) 2487–2494.CrossRefGoogle Scholar
Zhao, C., Aviles, C., Abel, R.A., Almli, C.R., McQuillen, P., Pleasure, S.J., Hippocampal and visuospatial learning defects in mice with a deletion of frizzled 9, a gene in the Williams syndrome deletion interval, Development 12 (2005) 2917–2927.CrossRefGoogle Scholar
Church, V.L., Francis-West, P., Wnt signalling during limb development, Int J Dev Biol 7 (2002) 927–936.Google Scholar
Gong, Y., et al., LDL receptor-related protein 5 (LRP5) affects bone accrual and eye development, Cell 4 (2001) 513–523.CrossRefGoogle Scholar
Little, R.D., et al., A Mutation in the LDL Receptor–Related Protein 5 Gene Results in the Autosomal Dominant High–Bone-Mass Trait, American Journal of Human Genetic (2002) 11–19.CrossRefGoogle ScholarPubMed
Boyden, L.M., et al., High Bone Density Due to a Mutation in LDL-Receptor-Related Protein 5, N Engl J Med 20 (2002) 1513–1521.CrossRefGoogle Scholar
Balemans, W., et al., Identification of a 52 kb deletion downstream of the SOST gene in patients with van Buchem disease, J Med Genet 2 (2002) 91–97.CrossRefGoogle Scholar
Hamersma, H., Gardner, J., Beighton, P., The natural history of sclerosteosis, Clin Genet 3 (2003) 192–197.CrossRefGoogle Scholar
Roodman, G.D., Pathogenesis of myeloma bone disease, Leukemia. 3 (2009) 435–441.CrossRefGoogle Scholar
Pinzone, J.J., Hall, B.M., Thudi, N.K., Vonau, M., Qiang, Y.W., Rosol, T.J., Shaughnessy, J.D., Jr., The role of Dickkopf-1 in bone development, homeostasis, and disease, Blood. 3 (2009) 517–525.CrossRefGoogle Scholar
Qiang, Y.W., et al., Myeloma-derived Dickkopf-1 disrupts Wnt-regulated osteoprotegerin and RANKL production by osteoblasts: a potential mechanism underlying osteolytic bone lesions in multiple myeloma, Blood. 1 (2008) 196–207.CrossRefGoogle Scholar
Qian, J., et al., Dickkopf-1 (DKK1) is a widely expressed and potent tumor-associated antigen in multiple myeloma, Blood. 5 (2007) 1587–1594.CrossRefGoogle Scholar
Yaccoby, S., Ling, W., Zhan, F., Walker, R., Barlogie, B., Shaughnessy, J.D., Jr., Antibody-based inhibition of DKK1 suppresses tumor-induced bone resorption and multiple myeloma growth in vivo, Blood. 5 (2007) 2106–2111.CrossRefGoogle Scholar
Tian, E., Zhan, F., Walker, R., Rasmussen, E., Ma, Y., Barlogie, B., Shaughnessy, J.D., Jr., The role of the Wnt-signaling antagonist DKK1 in the development of osteolytic lesions in multiple myeloma, N Engl J Med. 26 (2003) 2483–2494.CrossRefGoogle Scholar
Holmen, S.L., et al., Decreased BMD and limb deformities in mice carrying mutations in both Lrp5 and Lrp6, J Bone Miner Res 12 (2004) 2033–2040.CrossRefGoogle Scholar
Bennett, C.N., et al., Wnt10b increases postnatal bone formation by enhancing osteoblast differentiation, J Bone Miner Res. 12 (2007) 1924–1932.CrossRefGoogle Scholar
Bennett, C.N., Longo, K.A., Wright, W.S., Suva, L.J., Lane, T.F., Hankenson, K.D., MacDougald, O.A., Regulation of osteoblastogenesis and bone mass by Wnt10b, Proc Natl Acad Sci U S A 9 (2005) 3324–3329.CrossRefGoogle Scholar
Li, X., et al., Targeted deletion of the sclerostin gene in mice results in increased bone formation and bone strength, J Bone Miner Res. 6 (2008) 860–869.CrossRefGoogle Scholar
Morvan, F., et al., Deletion of a single allele of the Dkk1 gene leads to an increase in bone formation and bone mass, J Bone Miner Res. 6 (2006) 934–945.CrossRefGoogle Scholar
Ellwanger, K., et al., Targeted disruption of the Wnt regulator Kremen induces limb defects and high bone density, Mol Cell Biol. 15 (2008) 4875–4882.CrossRefGoogle Scholar
Bodine, P.V., et al., The Wnt antagonist secreted frizzled-related protein-1 is a negative regulator of trabecular bone formation in adult mice, Mol Endocrinol 5 (2004) 1222–1237.CrossRefGoogle Scholar
MacDonald, B.T., Joiner, D.M., Oyserman, S.M., Sharma, P., Goldstein, S.A., He, X., Hauschka, P.V., Bone mass is inversely proportional to Dkk1 levels in mice, Bone. 3 (2007) 331–339.CrossRefGoogle Scholar
Smerdel-Ramoya, A., Zanotti, S., Stadmeyer, L., Durant, D., Canalis, E., Skeletal overexpression of connective tissue growth factor impairs bone formation and causes osteopenia, Endocrinology. 9 (2008) 4374–4381.CrossRefGoogle Scholar
Li, J., et al., Transgenic Mice Over-Expressing Dkk-1 in Osteoblasts Develop Osteoporosis, J Bone Miner Res (2004) S6.Google Scholar
Li, X., et al., Dkk2 has a role in terminal osteoblast differentiation and mineralized matrix formation, Nat Genet. 9 (2005) 945–952.CrossRefGoogle Scholar
Rawadi, G., Vayssiere, B., Dunn, F., Baron, R., Roman-Roman, S., BMP-2 controls alkaline phosphatase expression and osteoblast mineralization by a Wnt autocrine loop, J Bone Miner Res 10 (2003) 1842–1853.CrossRefGoogle Scholar
Yadav, V.K., et al., Lrp5 controls bone formation by inhibiting serotonin synthesis in the duodenum, Cell. 5 (2008) 825–837.CrossRefGoogle Scholar
Gordon, M.D., Nusse, R., Wnt signaling: multiple pathways, multiple receptors, and multiple transcription factors, J Biol Chem. 32 (2006) 22429–22433.CrossRefGoogle Scholar
Garrett, I.R., et al., Selective inhibitors of the osteoblast proteasome stimulate bone formation in vivo and in vitro, J Clin Invest. 11 (2003) 1771–1782.CrossRefGoogle Scholar
Lee, H.W., Suh, J.H., Kim, A.Y., Lee, Y.S., Park, S.Y., Kim, J.B., Histone deacetylase 1-mediated histone modification regulates osteoblast differentiation, Mol Endocrinol. 10 (2006) 2432–2443.CrossRefGoogle Scholar
Clement-Lacroix, P., et al., Lrp5-independent activation of Wnt signaling by lithium chloride increases bone formation and bone mass in mice, Proc Natl Acad Sci U S A. 48 (2005) 17406–17411.CrossRefGoogle Scholar
Heath, D.J., et al., Inhibiting Dickkopf-1 (Dkk1) removes suppression of bone formation and prevents the development of osteolytic bone disease in multiple myeloma, J Bone Miner Res. 3 (2009) 425–436.CrossRefGoogle Scholar
Fulciniti, M., et al., Anti-DKK1 mAb (BHQ880) as a potential therapeutic agent for multiple myeloma, Blood (2009) 5.Google ScholarPubMed
Frank-Kamenetsky, M., et al., Small-molecule modulators of Hedgehog signaling: identification and characterization of Smoothened agonists and antagonists, J Biol 2 (2002) 10.CrossRefGoogle Scholar
Sen, M., Chamorro, M., Reifert, J., Corr, M., Carson, D.A., Blockade of Wnt-5A/frizzled 5 signaling inhibits rheumatoid synoviocyte activation, Arthritis Rheum 4 (2001) 772–781.3.0.CO;2-L>CrossRefGoogle Scholar

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