644
Views
181
CrossRef citations to date
0
Altmetric
Reviews

Wnt signaling as a therapeutic target for bone diseases

, &
Pages 485-496 | Published online: 31 Mar 2009

Bibliography

  • Dennison E, Mohamed MA, Cooper C. Epidemiology of osteoporosis. Rheum Dis Clin North Am 2006;32(4):617-29
  • Services UDoHaH. Bone health and osteoporosis: a report of the surgeon general. Rockville, MD: U.S. Department of health and human servises, office of the surgeon general 2004
  • Rossouw JE, Anderson GL, Prentice RL, et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the women's health initiative randomized controlled trial. JAMA 2002;288(3):321-33
  • Drake MT, Clarke BL, Khosla S. Bisphosphonates: mechanism of action and role in clinical practice. Mayo Clin Proc 2008;83(9):1032-45
  • Vahle JL, Sato M, Long GG, et al. Skeletal changes in rats given daily subcutaneous injections of recombinant human parathyroid hormone (1–34) for 2 years and relevance to human safety. Toxicol Pathol 2002;30(3):312-21
  • van Staa TP, Dennison EM, Leufkens HG, Cooper C. Epidemiology of fractures in England and Wales. Bone 2001;29(6):517-22
  • Rodriguez-Merchan EC, Forriol F. Nonunion: general principles and experimental data. Clin Orthop Relat Res 2004;(419):4-12
  • Khosla S, Westendorf JJ, Oursler MJ. Building bone to reverse osteoporosis and repair fractures. J Clin Invest 2008;118(2):421-8
  • Westendorf JJ, Kahler RA, Schroeder TM. Wnt signaling in osteoblasts and bone diseases. Gene 2004;341:19-39
  • van Amerongen R, Mikels A, Nusse R. Alternative wnt signaling is initiated by distinct receptors. Sci Signal 2008;1(35):re9. Published online 2 September 2008, doi: 10.1126/scisignal.135re9
  • Mikels AJ, Nusse R. Purified Wnt5a protein activates or inhibits β-catenin-TCF signaling depending on receptor context. PLoS Biol 2006;4(4):e115. Published online 4 April 2006 doi:10.1371/journal.pbio.0040115
  • Gong Y, Slee RB, Fukai N, et al. LDL receptor-related protein 5 (LRP5) affects bone accrual and eye development. Cell 2001;107(4):513-23
  • Kato M, Patel MS, Levasseur R, et al. Cbfa1-independent decrease in osteoblast proliferation, osteopenia, and persistent embryonic eye vascularization in mice deficient in Lrp5, a Wnt coreceptor. J Cell Biol 2002;157(2):303-14
  • Holmen SL, Giambernardi TA, Zylstra CR, et al. Decreased BMD and limb deformities in mice carrying mutations in both Lrp5 and Lrp6. J Bone Miner Res 2004;19(12):2033-40
  • Little RD, Carulli JP, Del Mastro RG, et al. A mutation in the LDL receptor-related protein 5 gene results in the autosomal dominant high-bone-mass trait. Am J Hum Genet 2002;70(1):11-9
  • Boyden LM, Mao J, Belsky J, et al. High bone density due to a mutation in LDL-receptor-related protein 5. N Engl J Med 2002;346(20):1513-21
  • Akhter MP, Wells DJ, Short SJ, et al. Bone biomechanical properties in LRP5 mutant mice. Bone 2004;35(1):162-9
  • Babij P, Zhao W, Small C, et al. High bone mass in mice expressing a mutant LRP5 gene. J Bone Miner Res 2003;18(6):960-74
  • Yadav VK, Ryu JH, Suda N, et al. Lrp5 controls bone formation by inhibiting serotonin synthesis in the duodenum. Cell 2008;135(5):825-37
  • Glass DA 2nd, Bialek P, Ahn JD, et al. Canonical Wnt signaling in differentiated osteoblasts controls osteoclast differentiation. Dev Cell 2005;8(5):751-64
  • Hu H, Hilton MJ, Tu X, et al. Sequential roles of Hedgehog and Wnt signaling in osteoblast development. Development 2005;132(1):49-60
  • Hill TP, Spater D, Taketo MM, et al. Canonical Wnt/β-catenin signaling prevents osteoblasts from differentiating into chondrocytes. Dev Cell 2005;8(5):727-38
  • Day TF, Guo X, Garrett-Beal L, Yang Y. Wnt/β-catenin signaling in mesenchymal progenitors controls osteoblast and chondrocyte differentiation during vertebrate skeletogenesis. Dev Cell 2005;8(5):739-50
  • Rodda SJ, McMahon AP. Distinct roles for Hedgehog and canonical Wnt signaling in specification, differentiation and maintenance of osteoblast progenitors. Development 2006;133(16):3231-44
  • Takada I, Mihara M, Suzawa M, et al. A histone lysine methyltransferase activated by non-canonical Wnt signalling suppresses PPAR-γ transactivation. Nat Cell Biol 2007;9(11):1273-85
  • Bennett CN, Ouyang H, Ma YL, et al. Wnt10b increases postnatal bone formation by enhancing osteoblast differentiation. J Bone Miner Res 2007;22(12):1924-32
  • Bennett CN, Longo KA, Wright WS, et al. Regulation of osteoblastogenesis and bone mass by Wnt10b. Proc Natl Acad Sci USA 2005;102(9):3324-9
  • Hens JR, Wilson KM, Dann P, et al. TOPGAL mice show that the canonical Wnt signaling pathway is active during bone development and growth and is activated by mechanical loading in vitro. J Bone Miner Res 2005;20(7):1103-13
  • Silkstone D, Hong H, Alman BA. β-catenin in the race to fracture repair: in it to Wnt. Nat Clin Pract Rheumatol 2008;4(8):413-9
  • Willert K, Brown JD, Danenberg E, et al. Wnt proteins are lipid-modified and can act as stem cell growth factors. Nature 2003;423(6938):448-52
  • Clement-Lacroix P, Ai M, Morvan F, et al. Lrp5-independent activation of Wnt signaling by lithium chloride increases bone formation and bone mass in mice. Proc Natl Acad Sci USA 2005;102(48):17406-11
  • Chen Y, Whetstone HC, Lin AC, et al. Beta-catenin signaling plays a disparate role in different phases of fracture repair: Implications for therapy to improve bone healing. PLoS Med 2007;4(7):e249. Published online 31 July 2007, doi:10.1371/journal.pmed.0040249
  • Edwards CM, Edwards JR, Lwin ST, et al. Increasing Wnt signaling in the bone marrow microenvironment inhibits the development of myeloma bone disease and reduces tumor burden in bone in vivo. Blood 2008;111(5):2833-42
  • Livingstone C, Rampes H. Lithium: a review of its metabolic adverse effects. J Psychopharmacol 2006;20(3):347-55
  • Vestergaard P, Rejnmark L, Mosekilde L. Reduced relative risk of fractures among users of lithium. Calcif Tissue Int 2005;77(1):1-8
  • Zamani A, Omrani GR, Nasab MM. Lithium's effect on bone mineral density. Bone 2009;44(2):331-4
  • Wilting I, de Vries F, Thio BM, et al. Lithium use and the risk of fractures. Bone 2007;40(5):1252-8
  • Engler TA, Henry JR, Malhotra S, et al. Substituted 3-imidazo[1,2-a]pyridin-3-yl-4-(1,2,3,4-tetrahydro-[1,4]diazepino-[6,7,1-hi]indol-7-yl)pyrrole-2,5-diones as highly selective and potent inhibitors of glycogen synthase kinase-3. J Med Chem 2004;47(16):3934-7
  • Kulkarni NH, Onyia JE, Zeng Q, et al. Orally bioavailable gsk-3α/β dual inhibitor increases markers of cellular differentiation in vitro and bone mass in vivo. J Bone Miner Res 2006;21(6):910-20
  • Kulkarni NH, Wei T, Kumar A, et al. Changes in osteoblast, chondrocyte, and adipocyte lineages mediate the bone anabolic actions of PTH and small molecule GSK-3 inhibitor. J Cell Biochem 2007;102(6):1504-18
  • Ali A, Hoeflich KP, Woodgett JR. Glycogen synthase kinase-3: properties, functions, and regulation. Chem Rev 2001;101(8):2527-40
  • Zeng X, Tamai K, Doble B, et al. A dual-kinase mechanism for Wnt co-receptor phosphorylation and activation. Nature 2005;438(7069):873-7
  • Mao B, Wu W, Davidson G, et al. Kremen proteins are Dickkopf receptors that regulate Wnt/β-catenin signalling. Nature 2002;417(6889):664-7
  • Glinka A, Wu W, Delius H, et al. Dickkopf-1 is a member of a new family of secreted proteins and functions in head induction. Nature 1998;391(6665):357-62
  • Balemans W, Devogelaer JP, Cleiren E, et al. Novel LRP5 missense mutation in a patient with a high bone mass phenotype results in decreased DKK1-mediated inhibition of Wnt signaling. J Bone Miner Res 2007;22(5):708-16
  • Ai M, Holmen SL, Van Hul W, et al. Reduced affinity to and inhibition by DKK1 form a common mechanism by which high bone mass-associated missense mutations in LRP5 affect canonical Wnt signaling. Mol Cell Biol 2005;25(12):4946-55
  • Li J, Sarosi I, Cattley RC, et al. DKK1-mediated inhibition of Wnt signaling in bone results in osteopenia. Bone 2006;39(4):754-66
  • Morvan F, Boulukos K, Clement-Lacroix P, 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 2006;21(6):934-45
  • MacDonald BT, Joiner DM, Oyserman SM, et al. Bone mass is inversely proportional to Dkk1 levels in mice. Bone 2007;41(3):331-9
  • Ellwanger K, Saito H, Clement-Lacroix P, et al. Targeted disruption of the Wnt regulator Kremen induces limb defects and high bone density. Mol Cell Biol 2008;28(15):4875-82
  • Cheng SL, Shao JS, Cai J, et al. Msx2 exerts bone anabolism via canonical Wnt signaling. J Biol Chem 2008;283(29):20505-22
  • Wang FS, Ko JY, Lin CL, et al. Knocking down dickkopf-1 alleviates estrogen deficiency induction of bone loss. A histomorphological study in ovariectomized rats. Bone 2007;40(2):485-92
  • Wang FS, Ko JY, Yeh DW, et al. Modulation of Dickkopf-1 attenuates glucocorticoid induction of osteoblast apoptosis, adipocytic differentiation, and bone mass loss. Endocrinology 2008;149(4):1793-801
  • Diarra D, Stolina M, Polzer K, et al. Dickkopf-1 is a master regulator of joint remodeling. Nat Med 2007;13(2):156-63
  • Yaccoby S, Ling W, Zhan F, et al. Antibody-based inhibition of DKK1 suppresses tumor-induced bone resorption and multiple myeloma growth in vivo. Blood 2007;109(5):2106-11
  • Tian E, Zhan F, Walker R, et al. The role of the wnt-signaling antagonist DKK1 in the development of osteolytic lesions in multiple myeloma. N Engl J Med 2003;349(26):2483-94
  • Heath DJ, Chantry AD, Buckle CH, 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 2008; Published online 18 November 2008: doi: 10.1359/jbmr.081104
  • Glantschnig H, Hampton R, Wei N, et al. Fully human anti-DKK1 antibodies increase bone formation and resolve osteopenia in mouse models of estrogen-deficiency induced bone loss. J Bone Miner Res 2008;23:S60
  • Hamersma H, Gardner J, Beighton P. The natural history of sclerosteosis. Clin Genet 2003;63(3):192-7
  • Loots GG, Kneissel M, Keller H, et al. Genomic deletion of a long-range bone enhancer misregulates sclerostin in van Buchem disease. Genome Res 2005;15(7):928-35
  • Balemans W, Patel N, Ebeling M, et al. Identification of a 52 kb deletion downstream of the SOST gene in patients with van Buchem disease. J Med Genet 2002;39(2):91-7
  • Li X, Ominsky MS, Niu QT, et al. Targeted deletion of the sclerostin gene in mice results in increased bone formation and bone strength. J Bone Miner Res 2008;23(6):860-9
  • Winkler DG, Sutherland MK, Geoghegan JC, et al. Osteocyte control of bone formation via sclerostin, a novel BMP antagonist. Embo J 2003;22(23):6267-76
  • van Bezooijen RL, Roelen BA, Visser A, et al. Sclerostin is an osteocyte-expressed negative regulator of bone formation, but not a classical BMP antagonist. J Exp Med 2004;199(6):805-14
  • Pederson L, Ruan M, Westendorf JJ, et al. Regulation of bone formation by osteoclasts involves Wnt/BMP signaling and the chemokine sphingosine-1-phosphate. Proc Natl Acad Sci USA 2008;105(52):20764-9
  • Robling AG, Niziolek PJ, Baldridge LA, et al. Mechanical stimulation of bone in vivo reduces osteocyte expression of sost/sclerostin. J Biol Chem 2008;283(9):5866-75
  • Bellido T, Ali AA, Gubrij I, et al. Chronic elevation of parathyroid hormone in mice reduces expression of sclerostin by osteocytes: a novel mechanism for hormonal control of osteoblastogenesis. Endocrinology 2005;146(11):4577-83
  • Semenov M, Tamai K, He X. SOST is a ligand for LRP5/LRP6 and a Wnt signaling inhibitor. J Biol Chem 2005;280(29):26770-5
  • Li X, Zhang Y, Kang H, et al. Sclerostin binds to LRP5/6 and antagonizes canonical Wnt signaling. J Biol Chem 2005;280(20):19883-7
  • Ellies DL, Viviano B, McCarthy J, et al. Bone density ligand, sclerostin, directly interacts with LRP5 but not LRP5G171V to modulate Wnt activity. J Bone Miner Res 2006;21(11):1738-49
  • Caverzasio J. Wnt/LRP5-independent inhibition of osteoblastic cell differentiation by sclerostin. J Bone Miner Res 2008;23:S72
  • Grabenstaetter T, Sakane Y, Jacobi C, et al. SOST blocks GSK3-beta inhibitor-induced alkaline phosphatase activity. J Bone Miner Res 008;23:S251
  • Li X, Ominsky MS, Warmington KS, et al. Sclerostin antibody treatment increases bone formation, bone mass and bone strength in a rat model of postmenopausal osteoporosis. J Bone Miner Res 2008; published online 2 December 2008 doi:10.1359/jbmr.081206
  • Ominsky M, Stouch B, Doellgast G, et al. Administration of sclerostin monoclonal antibodies to female cynomolgus monkeys results in increased bone mineral density and bone strength. J Bone Miner Res 2006;21:S44
  • Padhi D, Stouch B, Jang G, et al. Anti-sclerostin antibody increases markers of bone formation in healthy postmenopausal women. J Bone Miner Res 2007;22(Suppl 1):S37
  • Kawano Y, Kypta R. Secreted antagonists of the Wnt signalling pathway. J Cell Sci 2003;116(Pt 13):2627-34
  • Bodine PV, Zhao W, Kharode YP, et al. The Wnt antagonist secreted frizzled-related protein-1 is a negative regulator of trabecular bone formation in adult mice. Mol Endocrinol 2004;18(5):1222-37
  • Wang FS, Lin CL, Chen YJ, et al. Secreted frizzled-related protein 1 modulates glucocorticoid attenuation of osteogenic activities and bone mass. Endocrinology 2005;146(5):2415-23
  • Moore WJ, Kern JC, Bhat R, et al. Modulation of wnt signaling through inhibition of secreted frizzled-related protein I (sFRP-1) with N-substituted piperidinyl diphenylsulfonyl sulfonamides. J Med Chem 2009;52(1):105-16
  • Li CH, Amar S. Inhibition of SFRP1 reduces severity of periodontitis. J Dent Res 2007;86(9):873-7
  • Bovolenta P, Esteve P, Ruiz JM, et al. Beyond Wnt inhibition: New functions of secreted Frizzled-related proteins in development and disease. J Cell Sci 2008;121(Pt 6):737-46
  • Nusslein-Volhard C, Wieschaus E. Mutations affecting segment number and polarity in Drosophila. Nature 1980;287(5785):795-801
  • De Ferrari GV, Papassotiropoulos A, Biechele T, et al. Common genetic variation within the low-density lipoprotein receptor-related protein 6 and late-onset alzheimer's disease. Proc Natl Acad Sci USA 2007;104(22):9434-9
  • Polakis P. The many ways of Wnt in cancer. Curr Opin Genet Dev 2007;17(1):45-51
  • Jenkins ZA, van Kogelenberg M, Morgan T, et al. Germline mutations in WTX cause a sclerosing skeletal dysplasia but do not predispose to tumorigenesis. Nat Genet 2009;41(1):95-100
  • Shao JS, Cheng SL, Pingsterhaus JM, et al. Msx2 promotes cardiovascular calcification by activating paracrine Wnt signals. J Clin Invest 2005;115(5):1210-20
  • Rajamannan NM, Nealis TB, Subramaniam M, et al. Calcified rheumatic valve neoangiogenesis is associated with vascular endothelial growth factor expression and osteoblast-like bone formation. Circulation 2005;111(24):3296-301
  • Loughlin J, Dowling B, Chapman K, et al. Functional variants within the secreted frizzled-related protein 3 gene are associated with hip osteoarthritis in females. Proc Natl Acad Sci USA 2004;101(26):9757-62
  • Lane NE, Nevitt MC, Lui LY, et al. Wnt signaling antagonists are potential prognostic biomarkers for the progression of radiographic hip osteoarthritis in elderly caucasian women. Arthritis Rheum 2007;56(10):3319-25
  • Zhu M, Tang D, Wu Q, et al. Activation of β-catenin signaling in articular chondrocytes leads to osteoarthritis-like phenotype in adult β-catenin conditional activation mice. J Bone Miner Res 2009;24(1):12-21
  • Holmen SL, Zylstra CR, Mukherjee A, et al. Essential role of beta-catenin in postnatal bone acquisition. J Biol Chem 2005;280(22):21162-8
  • Ahmed Y, Nouri A, Wieschaus E. Drosophila Apc1 and Apc2 regulate wingless transduction throughout development. Development 2002;129(7):1751-62
  • Ikeda S, Kishida S, Yamamoto H, Murai H, Koyama S, Kikuchi A. Axin, a negative regulator of the wnt signaling pathway, forms a complex with gsk-3beta and beta-catenin and promotes gsk-3beta-dependent phosphorylation of beta-catenin. Embo J 1998;17(5):1371-84
  • Yu HM, Jerchow B, Sheu TJ, et al The role of axin2 in calvarial morphogenesis and craniosynostosis. Development 2005;132(8):1995-2005
  • Li X, Liu P, Liu W, et al. Dkk2 has a role in terminal osteoblast differentiation and mineralized matrix formation. Nat Genet 2005;37(9):945-52
  • Albers J, Gebauer M, Schulze J, et al. Mice lacking the wnt receptor frizzled-9 display osteopenia caused by decreased bone formation. J Bone Miner Res 2008;23:S3
  • Kugimiya F, Kawaguchi H, Ohba S, et al. Gsk-3beta controls osteogenesis through regulating runx2 activity. PLoS ONE 2007;2(9):e837
  • Zylstra C, Wan C, VanKoevering K, et al. Osteoblast-specific deletion of Lrp6 reveals distinct roles for Lrp5 and Lrp6 in bone development. J Bone Miner Res 2008;23:S2
  • Galceran J, Farinas I, Depew MJ, Clevers H, Grosschedl R. Wnt3a-/--like phenotype and limb deficiency in Lef1(-/-)Tcf1(-/-) mice. Genes Dev 1999;13(6):709-17

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.