Minireview: Targeting the Wnt/β-catenin pathway to regulate bone formation in the adult skeleton

Endocrinology

Volumn 148, Issue 6, 2007, Pages 2635-2643

  Baron, Roland ^a   Rawadi, Georges ^b  

^a YALE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b Galapagos   (France)

Author keywords

[No Author keywords available]

Indexed keywords

6 BROMO INDIRUBIN 3' OXIME; ANTISENSE OLIGONUCLEOTIDE; CATENIN; DKK PROTEIN; GENE PRODUCT; GLYCOGEN SYNTHASE KINASE 3 INHIBITOR; LITHIUM; LOW DENSITY LIPOPROTEIN RECEPTOR RELATED PROTEIN 5; LY 603281318; MONOCLONAL ANTIBODY; PROTEIN INHIBITOR; SCLEROSTIN; UNCLASSIFIED DRUG; WNT PROTEIN; BETA CATENIN; BONE DENSITY CONSERVATION AGENT; BONE MORPHOGENETIC PROTEIN; DKK1 PROTEIN, HUMAN; GLYCOGEN SYNTHASE KINASE 3; GLYCOGEN SYNTHASE KINASE 3 BETA; LIPOPROTEIN RECEPTOR RELATED PROTEIN 5; LIPOPROTEIN RECEPTOR RELATED PROTEIN 6; LIPOPROTEIN RECEPTOR-RELATED PROTEIN 6; LOW DENSITY LIPOPROTEIN RECEPTOR; LOW DENSITY LIPOPROTEIN RECEPTOR RELATED PROTEIN; SIGNAL PEPTIDE; SOST PROTEIN, HUMAN;

BIOLOGY; BONE MASS; BONE METABOLISM; DRUG BIOAVAILABILITY; DRUG MECHANISM; GENE TARGETING; HUMAN; NONHUMAN; NORRIE DISEASE; OSSIFICATION; OSTEOPOROSIS; PRIORITY JOURNAL; PROTEIN FUNCTION; PROTEIN STRUCTURE; SHORT SURVEY; SKELETON; ADULT; ANIMAL; BIOLOGICAL MODEL; BONE; BONE DEVELOPMENT; BONE DISEASE; CHEMISTRY; DRUG ANTAGONISM; DRUG DESIGN; GENETIC MARKER; GENETICS; METABOLISM; PHYSIOLOGY; REVIEW; SIGNAL TRANSDUCTION; SYNTHESIS;

ADULT; ANIMALS; BETA CATENIN; BONE AND BONES; BONE DENSITY CONSERVATION AGENTS; BONE DISEASES; BONE MORPHOGENETIC PROTEINS; DRUG DESIGN; GENETIC MARKERS; GLYCOGEN SYNTHASE KINASE 3; HUMANS; INTERCELLULAR SIGNALING PEPTIDES AND PROTEINS; LDL-RECEPTOR RELATED PROTEINS; MODELS, BIOLOGICAL; OSTEOGENESIS; RECEPTORS, LDL; SIGNAL TRANSDUCTION; WNT PROTEINS;

EID: 34250823973     PISSN: 00137227     EISSN: 00137227     Source Type: Journal    
DOI: 10.1210/en.2007-0270     Document Type: Short Survey

References (93)

1. Aubin JE, Triffitt JT 2002 Mesenchymal stem cells and osteoblast differentiation. In: Bilezikian JP, Raisz LG, Rodan G, eds. Principles of bone biology. Chap 4. New York: Academic Press; 59-82
2. Khosla S 2001 The OPG/RANKL/RANK system. Endocrinology 142:5050-5055
3. Suda T, Takahashi N, Udagawa N, Jimi E, Gillespie MT, Martin TJ 1999 Modulation of osteoclast differentiation and function by the new members of the tumor necrosis factor receptor and ligand families. Endocr Rev 20:345-357
4. Simonet WS, Lacey DL, Dunstan CR, Kelley M, Chang MS, Luthy R, Nguyen HQ, Wooden S, Bennett L, Boone T, Shimamoto G, DeRose M, Elliott R, Colombero A, Tan HL, Trail G, Sullivan J, Davy E, Bucay N, Renshaw-Gegg L, Hughes TM, Hill D, Pattison W, Campbell P, Sander S, Van G, Tarpley J, Derby P, Lee R, Boyle WJ 1997 Osteoprotegerin: a novel secreted protein involved in the regulation of bone density. Cell 89:309-319
5. Deaton DN, Tavares FX 2005 Design of cathepsin K inhibitors for osteoporosis. Curr Top Med Chem 5:1639-1675
6. Zaidi M, Troen B, Moonga BS, Abe E 2001 Cathepsin K, osteoclastic resorption, and osteoporosis therapy. J Bone Miner Res 16:1747-1749
7. Zhao C, Irie N, Takada Y, Shimoda K, Miyamoto T, Nishiwaki T, Suda T, Matsuo K 2006 Bidirectional ephrinB2-EphB4 signaling controls bone homeostasis. Cell Metab 4:111-121
8. Chen D, Zhao M, Mundy GR 2004 Bone morphogenetic proteins. Growth Factors 22:233-241
9. Chung U-i, Schipani E, McMahon AP, Kronenberg HM 2001 Indian hedgehog couples chondrogenesis to osteogenesis in endochondral bone development. J Clin Invest 107:295-304
10. Long F, Chung U-i, Ohba S, McMahon J, Kronenberg HM, McMahon AP 2004 Ihh signaling is directly required for the osteoblast lineage in the endochondral skeleton. Development 131:1309-1318
11. Wan M, Cao X 2005 BMP signaling in skeletal development. Biochem Biophys Res Commun 328:651-657
12. Ducy P, Zhang R, Geoffroy V, Ridall AL, Karsenty G 1997 Osf2/Cbfa1: a transcriptional activator of osteoblast differentiation. Cell 89:747-754
13. Otto F, Thornell AP, Crompton T, Denzel A, Gilmour KC, Rosewell IR, Stamp GW, Beddington RS, Mundlos S, Olsen BR, Selby PB, Owen MJ 1997 Cbfa1, a candidate gene for cleidocranial dysplasia syndrome, is essential for osteoblast differentiation and bone development. Cell 89:765-771
14. Mundlos S, Otto F, Mundlos C, Mulliken JB, Aylsworth AS, Albright S, Lindhout D, Cole WG, Henn W, Knoll JH, Owen MJ, Mertelsmann R, Zabel BU, Olsen BR 1997 Mutations involving the transcription factor CBFA1 cause cleidocranial dysplasia. Cell 89:773-779
15. Nakashima K, Zhou X, Kunkel G, Zhang Z, Deng JM, Behringer RR, de Crombrugghe B 2002 The novel zinc finger-containing transcription factor osterix is required for osteoblast differentiation and bone formation. Cell 108:17-29
16. Mundlos S 1999 Cleidocranial dysplasia: clinical and molecular genetics. J Med Genet 36:177-182
17. Doecke JD, Day CJ, Stephens AS, Carter SL, van Daal A, Kotowicz MA, Nicholson GC, Morrison NA 2006 Association of functionally different RUNX2 P2 promoter alleles with BMD. J Bone Miner Res 21:265-273
18. Vaughan T, Pasco JA, Kotowicz MA, Nicholson GC, Morrison NA 2002 Alleles of RUNX2/CBFA1 gene are associated with differences in bone mineral density and risk of fracture. J Bone Miner Res 17:1527-1534
19. Boyden LM, Mao J, Belsky J, Mitzner L, Farhi A, Mitnick MA,WuD, Insogna K, Lifton RP 2002 High bone density due to a mutation in LDL-receptor-related protein 5. N Engl J Med 346:1513-1521
20. Gong Y, Slee RB, Fukai N, Rawadi G, Roman-Roman S, Reginato AM, Wang H, Cundy T, Glorieux FH, Lev D, Zacharin M, Oexle K, Marcelino J, Suwairi W, Heeger S, Sabatakos G, Apte S, Adkins WN, Allgrove J, Arslan-Kirchner M, Batch JA, Beighton P, Black GC, Boles RG, Boon LM, Borrone C, Brunner HG, Carle GF, Dallapiccola B, De Paepe A, Floege B, Halfhide ML, Hall B, Hennekam RC, Hirose T, Jans A, Juppner H, Kim CA, Keppler-Noreuil K, Kohlschuetter A, LaCombe D, Lambert M, Lemyre E, Letteboer T, Peltonen L, Ramesar RS, Romanengo M, Somer H, Steichen-Gersdorf E, Steinmann B, Sullivan B, Superti-Furga A, Swoboda W, van den Boogaard MJ, Van Hul W, Vikkula M, Votruba M, Zabel B, Garcia T, Baron R, Olsen BR, Warman ML 2001 LDL receptor-related protein 5 (LRP5) affects bone accrual and eye development. Cell 107:513-523
21. Little RD, Carulli JP, Del Mastro RG, Dupuis J, Osborne M, Folz C, Manning SP, Swain PM, Zhao S, Eustace B, Lappe MM, Spitzer L, Zweier S, Braunschweiger K, Benchekroun Y, Hu X, Adair R, Chee L, FitzGerald MG, Tulig C, Caruso A, Tzellas N, Bawa A, Franklin B, McGuire S, Nogues X, Gong G, Allen KM, Anisowicz A, Morales AJ, Lomedico PT, Recker SM, Eerdewegh PV, Recker RR, Johnson ML 2002 A mutation in the LDL receptor-related protein 5 gene results in the autosomal dominant high-bone-mass trait. Am J Hum Genet 70:11-19
22. Staehling-Hampton K, Proll S, Paeper BW, Zhao L, Charmley P, Brown A, Gardner JC, Galas D, Schatzman RC, Beighton P, Papapoulos S, Hamersma H, Brunkow ME 2002 A 52-kb deletion in the SOST-MEOX1 intergenic region on 17q12-q21 is associated with van Buchem disease in the Dutch population. Am J Med Genet 110:144-152
23. Balemans W, Ebeling M, Patel N, Van Hul E, Olson P, Dioszegi M, Lacza C, Wuyts W, Van Den Ende J, Willems P, Paes-Alves AF, Hill S, Bueno M, Ramos FJ, Tacconi P, Dikkers FG, Stratakis C, Lindpaintner K, Vickery B, Foernzler D, Van Hul W 2001 Increased bone density in sclerosteosis is due to the deficiency of a novel secreted protein (SOST). Hum Mol Genet 10:537-543
24. Balemans W, Patel N, Ebeling M, Van Hul E, Wuyts W, Lacza C, Dioszegi M, Dikkers FG, Hildering P, Willems PJ, Verheij JB, Lindpaintner K, Vickery B, Foernzler D, Van Hul W 2002 Identification of a 52 kb deletion downstream of the SOST gene in patients with van Buchem disease. J Med Genet 39:91-97
25. Clevers H 2006 Wnt/β-catenin signaling in development and disease. Cell 127:469-480
26. Wehrli M, Dougan ST, Caldwell K, O'Keefe L, Schwartz S, Vaizel-Ohayon D, Schejter E, Tomlinson A, DiNardo S 2000 arrow encodes an LDL-receptor-related protein essential for Wingless signalling. Nature [Erratum (2001) 410:847] 407:527-530
27. Jeon H, Meng W, Takagi J, Eck MJ, Springer TA, Blacklow SC 2001 Implications for familial hypercholesterolemia from the structure of the LDL receptor YWTD-EGF domain pair. Nat Struct Biol 8:499-504
28. Zeng X, Tamai K, Doble B, Li S, Huang H, Habas R, Okamura H, Woodgett J, He X 2005 A dual-kinase mechanism for Wnt co-receptor phosphorylation and activation. Nature 438:873-877
29. Davidson G, Wu W, Shen J, Bilic J, Fenger U, Stannek P, Glinka A, Niehrs C 2005 Casein kinase 1 couples Wnt receptor activation to cytoplasmic signal transduction. Nature 438:867-872
30. Hay E, Faucheu C, Suc-Royer I, Touitou R, Stiot V, Vayssiere B, Baron R, Roman-Roman S, Rawadi G 2005 Interaction between LRP5 and Frat1 mediates the activation of the Wnt canonical pathway. J Biol Chem 280:13616-13623
31. Chen HJ, Lin CM, Lin CS, Perez-Olle R, Leung CL, Liem RK 2006 The role of microtubule actin cross-linking factor 1 (MACF1) in the Wnt signaling pathway. Genes Dev 20:1933-1945
32. Kato M, Patel MS, Levasseur R, Lobov I, Chang BH, Glass 2nd DA, Hartmann C, Li L, Hwang TH, Brayton CF, Lang RA, Karsenty G, Chan L 2002 Cbfa1-independent decrease in osteoblast proliferation, osteopenia, and persistent embryonic eye vascularization in mice deficient in Lrp5, a Wnt coreceptor. J Cell Biol 157:303-314
33. Wei W, Lu Q, Chaudry GJ, Leppla SH, Cohen SN 2006 The LDL receptor-related protein LRP6 mediates internalization and lethality of anthrax toxin. Cell 124:1141-1154
34. Van Wesenbeeck L, Cleiren E, Gram J, Beals RK, Benichou O, Scopelliti D, Key L, Renton T, Bartels C, Gong Y, Warman ML, De Vernejoul MC, Bollerslev J, Van Hul W 2003 Six novel missense mutations in the LDL receptor-related protein 5 (LRP5) gene in different conditions with an increased bone density. Am J Hum Genet 72:763-771
35. Kiel DP, Ferrari SL, Cupples LA, Karasik D, Manen D, Imamovic A, Herbert AG, Dupuis J 2006 Genetic variation at the low-density lipoprotein receptor-related protein 5 (LRP5) locus modulates Wnt signaling and the relationship of physical activity with bone mineral density in men. Bone 40:587-596
36. Koller DL, Ichikawa S, Johnson ML, Lai D, Xuei X, Edenberg HJ, Conneally PM, Hui SL, Johnston CC, Peacock M, Foroud T, Econs MJ 2005 Contribution of the LRP5 gene to normal variation in peak BMD in women. J Bone Miner Res 20:75-80
37. Ferrari SL, Deutsch S, Antonarakis SE 2005 Pathogenic mutations and polymorphisms in the lipoprotein receptor-related protein 5 reveal a new biological pathway for the control of bone mass. Curr Opin Lipidol 16:207-214
38. Hartikka H, Makitie O, Mannikko M, Doria AS, Daneman A, Cole WG, Ala-Kokko L, Sochett EB 2005 Heterozygous mutations in the LDL receptor-related protein 5 (LRP5) gene are associated with primary osteoporosis in children. J Bone Miner Res 20:783-789
39. Urano T, Shiraki M, Ezura Y, Fujita M, Sekine E, Hoshino S, Hosoi T, Orimo H, Emi M, Ouchi Y, Inoue S 2004 Association of a single-nucleotide polymorphism in low-density lipoprotein receptor-related protein 5 gene with bone mineral density. J Bone Miner Metab 22:341-345
40. Clement-Lacroix P, Ai M, Morvan F, Roman-Roman S, Vayssiere B, Belleville C, Estrera K, Warman ML, Baron R, Rawadi G 2005 Lrp5-independent activation of Wnt signaling by lithium chloride increases bone formation and bone mass in mice. Proc Natl Acad Sci USA 102:17406-17411
41. Babij P, Zhao W, Small C, Kharode Y, Yaworsky PJ, Bouxsein ML, Reddy PS, Bodine PV, Robinson JA, Bhat B, Marzolf J, Moran RA, Bex F 2003 High bone mass in mice expressing a mutant LRP5 gene. J Bone Miner Res 18:960-974
42. Bennett CN, Longo KA, Wright WS, Suva LJ, Lane TF, Hankenson KD, MacDougald OA 2005 Regulation of osteoblastogenesis and bone mass by Wnt10b. Proc Natl Acad Sci USA 102:3324-3329
43. Bodine PV, Zhao W, Kharode YP, Bex FJ, Lambert AJ, Goad MB, Gaur T, Stein GS, Lian JB, Komm BS 2004 The Wnt antagonist secreted frizzled-related protein-1 is a negative regulator of trabecular bone formation in adult mice. Mol Endocrinol 18:1222-1237
44. Glass 2nd DA, Bialek P, Ahn JD, Starbuck M, Patel MS, Clevers H, Taketo MM, Long F, McMahon AP, Lang RA, Karsenty G 2005 Canonical Wnt signaling in differentiated osteoblasts controls osteoclast differentiation. Dev Cell 8:751-764
45. Holmen SL, Zylstra CR, Mukherjee A, Sigler RE, Faugere MC, Bouxsein ML, Deng L, Clemens TL, Williams BO 2005 Essential role of β-catenin in postnatal bone acquisition. J Biol Chem 280:21162-21168
46. Morvan F, Boulukos K, Clement-Lacroix P, Roman Roman S, Suc-Royer I, Vayssiere B, Ammann P, Martin P, Pinho S, Pognonec P, Mollat P, Niehrs C, Baron R, Rawadi G 2006 Deletion of a single allele of the Dkk1 gene leads to an increase in bone formation and bone mass. J Bone Miner Res 21:934-945
47. Li J, Sarosi I, Cattley RC, Pretorius J, Asuncion F, Grisanti M, Morony S, Adamu S, Geng Z, Qiu W, Kostenuik P, Lacey DL, Simonet WS, Bolon B, Qian X, Shalhoub V, Ominsky MS, Zhu Ke H, Li X, Richards WG 2006 Dkk1-mediated inhibition of Wnt signaling in bone results in osteopenia. Bone 39:754-766
48. Nakanishi T, Yamaai T, Asano M, Nawachi K, Suzuki M, Sugimoto T, Takigawa M 2001 Overexpression of connective tissue growth factor/hypertrophic chondrocyte-specific gene product 24 decreases bone density in adult mice and induces dwarfism. Biochem Biophys Res Commun 281:678-681
49. Cao J, Morony S, Warmington K, Pretorius J, McDorman K, Paszty C 2004 Transgenic overexpression of WIF-1, a secreted Wnt antagonist expressed in bone, causes decreased bone mineral density and increased susceptibility to bone fracture in mice: a role for WIF-1 in bone biology. J Bone Miner Res 19:S55
50. Hill TP, Taketo MM, Birchmeier W, Hartmann C 2006 Multiple roles of mesenchymal β-catenin during murine limb patterning. Development 133:1219-1229
51. Hill TP, Spater D, Taketo MM, Birchmeier W, Hartmann C 2005 Canonical Wnt/β-catenin signaling prevents osteoblasts from differentiating into chondrocytes. Dev Cell 8:727-738
52. Day TF, Guo X, Garrett-Beal L, Yang Y 2005 Wnt/β-catenin signaling in mesenchymal progenitors controls osteoblast and chondrocyte differentiation during vertebrate skeletogenesis. Dev Cell 8:739-750
53. Rawadi G, Vayssiere B, Dunn F, Baron R, Roman-Roman S 2003 BMP-2 controls alkaline phosphatase expression and osteoblast mineralization by a Wnt autocrine loop. J Bone Miner Res 18:1842-1853
54. Kalajzic I, Staal A, Yang WP, Wu Y, Johnson SE, Feyen JH, Krueger W, Maye P, Yu F, Zhao Y, Kuo L, Gupta RR, Achenie LE, Wang HW, Shin DG, Rowe DW 2005 Expression profile of osteoblast lineage at defined stages of differentiation. J Biol Chem 280:24618-24626
55. Roman-Roman S, Garcia T, Jackson A, Theilhaber J, Rawadi G, Connolly T, Spinella-Jaegle S, Kawai S, Courtois B, Bushnell S, Auberval M, Call K, Baron R 2003 Identification of genes regulated during osteoblastic differentiation by genome-wide expression analysis of mouse calvaria primary osteoblasts in vitro. Bone 32:474-482
56. Vaes BL, Dechering KJ, van Someren EP, Hendriks JM, van de Ven CJ, Feijen A, Mummery CL, Reinders MJ, Olijve W, van Zoelen EJ, Steegenga WT 2005 Microarray analysis reveals expression regulation of Wnt antagonists in differentiating osteoblasts. Bone 36:803-811
57. Li X, Liu P, Liu W, Maye P, Zhang J, Zhang Y, Hurley M, Guo C, Boskey A, Sun L, Harris SE, Rowe DW, Ke HZ, Wu D 2005 Dkk2 has a role in terminal osteoblast differentiation and mineralized matrix formation. Nat Genet 37:945-952
58. Diarra D, Stolina M, Polzer K, Zwerina J, Ominsky MS, Dwyer D, Korb A, Smolen J, Hoffmann M, Scheinecker C, van der Heide D, Landewe R, Lacey D, Richards WG, Schett G 2007 Dickkopf-1 is a master regulator of joint remodeling. Nat Med 13:156-163
59. Tian E, Zhan F, Walker R, Rasmussen E, Ma Y, Barlogie B, Shaughnessy Jr JD 2003 The role of the Wnt-signaling antagonist DKK1 in the development of osteolytic lesions in multiple myeloma. N Engl J Med 349:2483-2494
60. Harwood AJ 2001 Regulation of GSK-3: a cellular multiprocessor. Cell 105:821-824
61. Doble BW, Woodgett JR 2003 GSK-3: tricks of the trade for a multi-tasking kinase. J Cell Sci 116:1175-1186
62. Vestergaard P, Rejnmark L, Mosekilde L 2005 Reduced relative risk of fractures among users of lithium. Calcif Tissue Int 77:1-8
63. Kulkarni NH, Onyia JE, Zeng Q, Tian X, Liu M, Halladay DL, Frolik CA, Engler T, Wei T, Kriauciunas A, Martin TJ, Sato M, Bryant HU, Ma YL 2006 Orally bioavailable GSK-3α/β dual inhibitor increases markers of cellular differentiation in vitro and bone mass in vivo. J Bone Miner Res 21:910-920
64. Poole KE, van Bezooijen RL, Loveridge N, Hamersma H, Papapoulos SE, Lowik CW, Reeve J 2005 Sclerostin is a delayed secreted product of osteocytes that inhibits bone formation. FASEB J 19:1842-1844
65. Holmen SL, Robertson SA, Zylstra CR, Williams BO 2005 Wnt-independent activation of β-catenin mediated by a Dkk1-Fz5 fusion protein. Biochem Biophys Res Commun 328:533-539
66. Bafico A, Liu G, Yaniv A, Gazit A, Aaronson SA 2001 Novel mechanism of Wnt signalling inhibition mediated by Dickkopf-1 interaction with LRP6/Arrow. Nat Cell Biol 3:683-686
67. Brott BK, Sokol SY 2002 Regulation of Wnt/LRP signaling by distinct domains of Dickkopf proteins. Mol Cell Biol 22:6100-6110
68. Mao B, Wu W, Li Y, Hoppe D, Stannek P, Glinka A, Niehrs C 2001 LDL-receptor-related protein 6 is a receptor for Dickkopf proteins. Nature 411:321-325
69. Semenov MV, Tamai K, Brott BK, Kuhl M, Sokol S, He X 2001 Head inducer Dickkopf-1 is a ligand for Wnt coreceptor LRP6. Curr Biol 11:951-961
70. Li L, Mao J, Sun L, Liu W, Wu D 2002 Second cysteine-rich domain of Dickkopf-2 activates canonical Wnt signaling pathway via LRP-6 independently of dishevelled. J Biol Chem 277:5977-5981
71. Gregory CA, Perry AS, Reyes E, Conley A, Gunn WG, Prockop DJ 2005 Dkk-1-derived synthetic peptides and lithium chloride for the control and recovery of adult stem cells from bone marrow. J Biol Chem 280:2309-2323
72. Davidson G, Mao B, del Barco Barrantes I, Niehrs C 2002 Kremen proteins interact with Dickkopf1 to regulate anteroposterior CNS patterning. Development 129:5587-5596
73. Mao B, Wu W, Davidson G, Marhold J, Li M, Mechler BM, Delius H, Hoppe D, Stannek P, Walter C, Glinka A, Niehrs C 2002 Kremen proteins are Dickkopf receptors that regulate Wnt/β-catenin signalling. Nature 417:664-667
74. Mao B, Niehrs C 2003 Kremen2 modulates Dickkopf2 activity during Wnt/LRP6 signaling. Gene 302:179-183
75. Krupnik VE, Sharp JD, Jiang C, Robison K, Chickering TW, Amaravadi L, Brown DE, Guyot D, Mays G, Leiby K, Chang B, Duong T, Goodearl AD, Gearing DP, Sokol SY, McCarthy SA 1999 Functional and structural diversity of the human Dickkopf gene family. Gene 238:301-313
76. Barrantes Idel B, Montero-Pedrazuela A, Guadano-Ferraz A, Obregon MJ, Martinez de Mena R, Gailus-Durner V, Fuchs H, Franz TJ, Kalaydjiev S, Klempt M, Holter S, Rathkolb B, Reinhard C, Morreale de Escobar G, Bernal J, Busch DH, Wurst W, Wolf E, Schulz H, Shtrom S, Greiner E, Hrabe de Angelis M, Westphal H, Niehrs C 2006 Generation and characterization of dickkopf3 mutant mice. Mol Cell Biol 26:2317-2326
77. Mukhopadhyay M, Shtrom S, Rodriguez-Esteban C, Chen L, Tsukui T, Gomer L, Dorward DW, Glinka A, Grinberg A, Huang SP, Niehrs C, Belmonte JC, Westphal H 2001 Dickkopf1 is required for embryonic head induction and limb morphogenesis in the mouse. Dev Cell 1:423-434
78. Roodman GD 2006 New potential targets for treating myeloma bone disease. Clin Cancer Res 12:6270s-6273s
79. Wang FS, Ko JY, Lin CL, Wu HL, Ke HJ, Tai PJ 2006 Knocking down dickkopf-1 alleviates estrogen deficiency induction of bone loss. A histomorphological study in ovariectomized rats. Bone 40:485-492
80. Guise TA, Mohammad KS, Clines G, Stebbins EG, Wong DH, Higgins LS, Vessella R, Corey E, Padalecki S, Suva L, Chirgwin JM 2006 Basic mechanisms responsible for osteolytic and osteoblastic bone metastases. Clin Cancer Res 12:6213s-6216s
81. Hall CL, Bafico A, Dai J, Aaronson SA, Keller ET 2005 Prostate cancer cells promote osteoblastic bone metastases through Wnts. Cancer Res 65:7554-7560
82. Yaccoby S, Ling W, Zhan F, Walker R, Barlogie B, Shaughnessy Jr JD 2006 Antibody-based inhibition of DKK1 suppresses tumor-induced bone resorption and multiple myeloma growth in-vivo. Blood 109:2906-2911
83. Pacifici M, Koyama E, Shibukawa Y,WuC, Tamamura Y, Enomoto-Iwamoto M, Iwamoto M 2006 Cellular and molecular mechanisms of synovial joint and articular cartilage formation. Ann NY Acad Sci 1068:74-86
84. Ellies DL, Viviano B, McCarthy J, Rey JP, Itasaki N, Saunders S, Krumlauf R 2006 Bone density ligand, Sclerostin, directly interacts with LRP5 but not LRP5G171V to modulate Wnt activity. J Bone Miner Res 21:1738-1749
85. Semenov M, Tamai K, He X 2005 SOST is a ligand for LRP5/LRP6 and a Wnt signaling inhibitor. J Biol Chem 280:26770-26775
86. Semenov MV, He X 2006 LRP5 mutations linked to high bone mass diseases cause reduced LRP5 binding and inhibition by SOST. J Biol Chem 281:38276-38284
87. Brunkow ME, Gardner JC, Van Ness J, Paeper BW, Kovacevich BR, Proll S, Skonier JE, Zhao L, Sabo PJ, Fu Y, Alisch RS, Gillett L, Colbert T, Tacconi P, Galas D, Hamersma H, Beighton P, Mulligan J 2001 Bone dysplasia sclerosteosis results from loss of the SOST gene product, a novel cystine knot-containing protein. Am J Hum Genet 68:577-589
88. Bellido T, Ali AA, Gubrij I, Plotkin LI, Fu Q, O'Brien CA, Manolagas SC, Jilka RL 2005 Chronic elevation of parathyroid hormone in mice reduces expression of sclerostin by osteocytes: a novel mechanism for hormonal control of osteoblastogenesis. Endocrinology 146:4577-4583
89. Keller H, Kneissel M 2005 SOST is a target gene for PTH in bone. Bone 37:148-158
90. Robling AG, Bellido T, Turner CH 2006 Mechanical stimulation in vivo reduces osteocyte expression of sclerostin. J Musculoskelet Neuronal Interact 6:354
91. Winkler DG, Sutherland MK, Geoghegan JC, Yu C, Hayes T, Skonier JE, Shpektor D, Jonas M, Kovacevich BR, Staehling-Hampton K, Appleby M, Brunkow ME, Latham JA 2003 Osteocyte control of bone formation via sclerostin, a novel BMP antagonist. EMBO J 22:6267-6276
92. Ominsky M, Warmongton KS, Asuncion FJ, Tan HL, Grisanti MS, Geng Z, Stephens P, Henry A, Lawson A, Lightwood D, Perkins V, Kirby P, Moore A, Popplewell A, Robinson M, Li X, Kostenuik PJ, Simonet WS, Lacey DL, Paszty C 2006 Sclerostin monoclonal antibody treatment increases bone strength in aged osteopenic ovariectomized rats. J Bone Miner Res 21:S44
93. Ominsky M, Stouch B, Doellgast G, Gong J, Gao Y, Haldankar R, Winters A, Chen Q, Graham K, Zhou L, Hale M, Henry A, Lightwood D, Moore A, Popplewell A, Robinson M, Vlasseros F, Jolette J, Smith SY, Kostenuik PJ, Simonet WS, Lacey DL, Paszty C 2006 Administration of sclerostin monoclonal antibodies to female Cynomologous monkeys results in increased bone formation, bone mineral density, and bone strength. J Bone Miner Res 21:S44