The role of Dickkopf-1 in bone development, homeostasis, and disease

Blood

Volumn 113, Issue 3, 2009, Pages 517-525

  Pinzone, Joseph J ^a,b,g   Hall, Brett M ^c,d   Thudi, Nanda K ^c   Vonau, Martin ^a   Qiang, Ya Wei ^e   Rosol, Thomas J ^b,c   Shaughnessy Jr , John D ^e,f  

^a Department of Internal Medicine ^*  (United States)

^b Department of Internal Medicine   (United States)

^c OHIO STATE UNIVERSITY   (United States)

^d THE RESEARCH INSTITUTE AT NATIONWIDE CHILDREN S HOSPITAL   (United States)

^e UNIVERSITY OF ARKANSAS FOR MEDICAL SCIENCES   (United States)

^f UNIVERSITY OF ARKANSAS MEDICAL CENTER   (United States)

^g THE OHIO STATE UNIVERSITY WEXNER MEDICAL CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BORTEZOMIB; DICKKOPF 1 PROTEIN; DICKKOPF 1 PROTEIN ANTIBODY; LITHIUM CHLORIDE; NEUTRALIZING ANTIBODY; UNCLASSIFIED DRUG; WNT3A PROTEIN; DKK1 PROTEIN, HUMAN; SIGNAL PEPTIDE;

ADIPOGENESIS; APOPTOSIS; ARTICLE; AUTOLOGOUS STEM CELL TRANSPLANTATION; BONE DEVELOPMENT; BONE DISEASE; BONE MASS; BONE METASTASIS; CELL FUNCTION; HEMATOPOIETIC STEM CELL; HOMEOSTASIS; HUMAN; MULTIPLE MYELOMA; NEOPLASM; NONHUMAN; OSSIFICATION; OSTEOBLAST; PRIORITY JOURNAL; PROTEIN EXPRESSION; ANIMAL; BONE; PATHOPHYSIOLOGY; PHYSIOLOGY; REVIEW;

ANIMALS; BONE AND BONES; BONE DEVELOPMENT; BONE DISEASES; HOMEOSTASIS; HUMANS; INTERCELLULAR SIGNALING PEPTIDES AND PROTEINS;

EID: 60249086335     PISSN: 00064971     EISSN: 15280020     Source Type: Journal    
DOI: 10.1182/blood-2008-03-145169     Document Type: Article

References (100)

1. Clevers H. Wnt/beta-catenin signaling in development and disease. Cell. 2006;127:469-480.
2. Yamamoto H, Sakane H, Yamamoto H, Michiue T, Kikuchi A. Wnt3a and Dkk1 regulate distinct internalization pathways of LRP6 to tune the activation of beta-catenin signaling. Dev Cell. 2008;15: 37-48.
3. Glinka A, Wu W, Delius H, Monaghan AP, Blumenstock C, Niehrs C. Dickkopf-1 is a member of a new family of secreted proteins and functions in head induction. Nature. 1998;391:357-362.
4. Mao B, Wu W, Davidson G, et al. Kremen proteins are Dickkopf receptors that regulate Wnt/ beta-catenin signalling. Nature. 2002;417:664-667.
5. Kim KA, Wagle M, Tran K, et al. R-spondin family members regulate the wnt pathway by a common mechanism. Mol Biol Cell. 2008;19:2588-2596.
6. Semenov M, Tamai K, He X. SOST is a ligand for LRP5/LRP6 and a Wnt signaling inhibitor. J Biol Chem. 2005;280:26770-26775.
7. Itasaki N, Jones CM, Mercurio S, et al. Wise, a context-dependent activator and inhibitor of Wnt signalling. Development. 2003;130:4295-4305.
8. Hoang B, Moos M Jr, Vukicevic S, Luyten FP. Primary structure and tissue distribution of FRZB, a novel protein related to Drosophila frizzled, suggest a role in skeletal morphogenesis. J Biol Chem. 1996;271:26131-26137.
9. Hsieh JC, Kodjabachian L, Rebbert ML, et al. A new secreted protein that binds to Wnt proteins and inhibits their activities. Nature. 1999;398:431-436.
10. Baksh D, Tuan RS. Canonical and non-canonical Wnts differentially affect the development potential of primary isolate of human bone marrow mesenchymal stem cells. J Cell Physiol. 2007; 212:817-826.
11. Hu H, Hilton MJ, Tu X, Yu K, Ornitz DM, Long F. Sequential roles of Hedgehog and Wnt signaling in osteoblast development. Development. 2005; 132:49-60.
12. Baksh D, Boland GM, Tuan RS. Cross-talk between Wnt signaling pathways in human mesenchymal stem cells leads to functional antagonism during osteogenic differentiation. J Cell Biochem. 2007;101:1109-1124.
13. Boland GM, Perkins G, Hall DJ, Tuan RS. Wnt 3a promotes proliferation and suppresses osteogenic differentiation of adult human mesenchymal stem cells. J Cell Biochem. 2004;93:1210-1230.
14. Etheridge SL, Spencer GJ, Heath DJ, Genever PG. Expression profiling and functional analysis of wnt signaling mechanisms in mesenchymal stem cells. Stem Cells. 2004;22:849-860.
15. Day TF, Guo X, Garrett-Beal L, Yang Y. Wnt/betacatenin signaling in mesenchymal progenitors controls osteoblast and chondrocyte differentiation during vertebrate skeletogenesis. Dev Cell. 2005;8:739-750.
16. Ross SE, Hemati N, Longo KA, et al. Inhibition of adipogenesis by Wnt signaling. Science. 2000; 289:950-953.
17. 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;21:934-945.
18. Takada I, Mihara M, Suzawa M, et al. A histone lysine methyltransferase activated by non-canonical Wnt signalling suppresses PPAR-gamma transactivation. Nat Cell Biol. 2007;9:1273-1285.
19. Christodoulides C, Laudes M, Cawthorn WP, et al. The Wnt antagonist Dickkopf-1 and its receptors are coordinately regulated during early human adipogenesis. J Cell Sci. 2006;119:2613-2620.
20. Cheng SL, Shao JS, Cai J, Sierra OL, Towler DA. Msx2 exerts bone anabolism via canonical Wnt signaling. J Biol Chem. 2008;283:20505-20522.
21. Enomoto-Iwamoto M, Kitagaki J, Koyama E, et al. The Wnt antagonist Frzb-1 regulates chondrocyte maturation and long bone development during limb skeletogenesis. Dev Biol. 2002;251:142-156.
22. 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. 1997;236:502-504.
23. Chen Y, Whetstone HC, Youn A, et al. Beta-catenin signaling pathway is crucial for bone morphogenetic protein 2 to induce new bone formation. J Biol Chem. 2007;282:526-533.
24. Grotewold L, Ruther U. The Wnt antagonist Dickkopf- 1 is regulated by Bmp signaling and c-Jun and modulates programmed cell death. EMBO J. 2002;21:966-975.
25. Mukhopadhyay M, Shtrom S, Rodriguez-Esteban C, et al. Dickkopf1 is required for embryonic head induction and limb morphogenesis in the mouse. Dev Cell. 2001;1:423-434.
26. Zuzarte-Luis V, Montero JA, Rodriguez-Leon J, Merino R, Rodriguez-Rey JC, Hurle JM. A new role for BMP5 during limb development acting through the synergic activation of Smad and MAPK pathways. Dev Biol. 2004;272:39-52.
27. Knobloch J, Shaughnessy JD Jr, Ruther U. Thalidomide induces limb deformities by perturbing the Bmp/Dkk1/Wnt signaling pathway. FASEB J. 2007;21:1410-1421.
28. Gong Y, Slee RB, Fukai N, et al. LDL receptorrelated protein 5 (LRP5) affects bone accrual and eye development. Cell. 2001;107:513-523.
29. Baron R, Rawadi G. Targeting the Wnt/beta-catenin pathway to regulate bone formation in the adult skeleton. Endocrinology. 2007;148:2635-2643.
30. Glass DA, 2nd Bialek P, Ahn JD, et al. Canonical Wnt signaling in differentiated osteoblasts controls osteoclast differentiation. Dev Cell. 2005;8: 751-764.
31. Glass DA, 2nd Karsenty G. In vivo analysis of Wnt signaling in bone. Endocrinology. 2007;148: 2630-2634.
32. 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;19:2033-2040.
33. MacDonald BT, Adamska M, Meisler MH. Hypomorphic expression of Dkk1 in the doubleridge mouse: dose dependence and compensatory interactions with Lrp6. Development. 2004;131: 2543-2552.
34. Macdonald BT, Joiner DM, Oyserman SM, et al. Bone mass is inversely proportional to Dkk1 levels in mice. Bone. 2007;41:331-339.
35. 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;157:303-314.
36. Babij P, Zhao W, Small C, et al. High bone mass in mice expressing a mutant LRP5 gene. J Bone Miner Res. 2003;18:960-974.
37. 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-bonemass trait. Am J Hum Genet. 2002;70:11-19.
38. 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;346:1513-1521.
39. Mao B, Wu W, Li Y, et al. LDL-receptor-related protein 6 is a receptor for Dickkopf proteins. Nature. 2001;411:321-325.
40. Ai M, Holmen SL, Van Hul W, Williams BO, Warman ML. 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;25:4946-4955.
41. Brunkow ME, Gardner JC, Van Ness J, et al. Bone dysplasia sclerosteosis results from loss of the SOST gene product, a novel cystine knotcontaining protein. Am J Hum Genet. 2001;68: 577-589.
42. Semenov MV, He X. LRP5 mutations linked to high bone mass diseases cause reduced LRP5 binding and inhibition by SOST. J Biol Chem. 2006;281:38276-38284.
43. Balemans W, Piters E, Cleiren E, et al. The binding between sclerostin and LRP5 is altered by DKK1 and by high-bone mass LRP5 mutations. Calcif Tissue Int. 2008 Jun 3. [Epub ahead of print].
44. 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;28:4875-4882.
45. Wang FS, Ko JY, Lin CL, Wu HL, Ke HJ, Tai PJ. Knocking down dickkopf-1 alleviates estrogen deficiency induction of bone loss: a histomorphological study in ovariectomized rats. Bone. 2007; 40:485-492.
46. Hurson CJ, Butler JS, Keating DT, et al. Gene expression analysis in human osteoblasts exposed to dexamethasone identifies altered developmental pathways as putative drivers of osteoporosis. BMC Musculoskelet Disord. 2007;8:12.
47. Wang FS, Ko JY, Yeh DW, Ke HC, Wu HL. Modulation of Dickkopf-1 attenuates glucocorticoid induction of osteoblast apoptosis, adipocytic differentiation, and bone mass loss. Endocrinology. 2008;149:1793-1801.
48. 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:e249.
49. Diarra D, Stolina M, Polzer K, et al. Dickkopf-1 is a master regulator of joint remodeling. Nat Med. 2007;13:156-163.
50. Forget MA, Turcotte S, Beauseigle D, et al. The Wnt pathway regulator DKK1 is preferentially expressed in hormone-resistant breast tumours and in some common cancer types. Br J Cancer. 2007;96:646-653.
51. Qian J, Xie J, Hong S, et al. Dickkopf-1 (DKK1) is a widely expressed and potent tumor-associated antigen in multiple myeloma. Blood. 2007;110: 1587-1594.
52. Hall CL, Bafico A, Dai J, Aaronson SA, Keller ET. Prostate cancer cells promote osteoblastic bone metastases through Wnts. Cancer Res. 2005;65: 7554-7560.
53. Thudi NK, Martin CK, Nadella MV, et al. Zoledronic acid decreased osteolysis but not bone metastasis in a nude mouse model of canine prostate cancer with mixed bone lesions. Prostate. 2008;68:1116-1125.
54. Schwaninger R, Rentsch CA, Wetterwald A, et al. Lack of noggin expression by cancer cells is a determinant of the osteoblast response in bone metastases. Am J Pathol. 2007;170:160-175.
55. Voorzanger-Rousselot N, Goehrig D, Journe F, et al. Increased Dickkopf-1 expression in breast cancer bone metastases. Br J Cancer. 2007;97: 964-970.
56. Yamabuki T, Takano A, Hayama S, et al. Dikkopf-1 as a novel serologic and prognostic biomarker for lung and esophageal carcinomas. Cancer Res. 2007;67:2517-2525.
57. Gonzalez-Sancho JM, Aguilera O, Garcia JM, et al. The Wnt antagonist DICKKOPF-1 gene is a downstream target of beta-catenin/TCF and is downregulated in human colon cancer. Oncogene. 2005;24:1098-1103.
58. Kuphal S, Lodermeyer S, Bataille F, Schuierer M, Hoang BH, Bosserhoff AK. Expression of Dickkopf genes is strongly reduced in malignant melanoma. Oncogene. 2006;25:5027-5036.
59. Hall CL, Kang S, MacDougald OA, Keller ET. Role of Wnts in prostate cancer bone metastases. J Cell Biochem. 2006;97:661-672.
60. Hall CL, Daignault SD, Shah RB, Pienta KJ, Keller ET. Dickkopf-1 expression increases early in prostate cancer development and decreases during progression from primary tumor to metastasis. Prostate. 2008;68:1396-1404.
61. Bu G, Lu W, Liu CC, et al. Breast cancer-derived Dickkopf1 inhibits osteoblast differentiation and osteoprotegerin expression: implication for breast cancer osteolytic bone metastases. Int J Cancer. 2008;123:1034-1042.
62. Yin JJ, Mohammad KS, Kakonen SM, et al. A causal role for endothelin-1 in the pathogenesis of osteoblastic bone metastases. Proc Natl Acad Sci U S A. 2003;100:10954-10959.
63. Clines GA, Mohammad KS, Bao Y, et al. Dickkopf homolog 1 mediates endothelin-1-stimulated new bone formation. Mol Endocrinol. 2007;21:486-498.
64. Granchi D, Baglio SR, Amato I, Giunti A, Baldini N. Paracrine inhibition of osteoblast differentiation induced by neuroblastoma cells. Int J Cancer. 2008;123:1526-1535.
65. Hideshima T, Mitsiades C, Tonon G, Richardson PG, Anderson KC. Understanding multiple myeloma pathogenesis in the bone marrow to identify new therapeutic targets. Nat Rev Cancer. 2007;7:585-598.
66. 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;349:2483-2494.
67. Qiang YW, Barlogie B, Rudikoff S, Shaughnessy JD Jr. Dkk1-induced inhibition of Wnt signaling in osteoblast differentiation is an underlying mechanism of bone loss in multiple myeloma. Bone. 2008;42:669-680.
68. Qiang YW, Chen Y, Stephens O, et al. Myelomaderived Dickkopf-1 disrupts Wnt-regulated osteoprotegerin and RANKL production by osteoblasts: a potential mechanism underlying osteolytic bone lesions in multiple myeloma. Blood. 2008;112: 196-207.
69. Giuliani N, Colla S, Morandi F, et al. Myeloma cells block RUNX2/CBFA1 activity in human bone marrow osteoblast progenitors and inhibit osteoblast formation and differentiation. Blood. 2005; 106:2472-2483.
70. Giuliani N, Rizzoli V. Myeloma cells and bone marrow osteoblast interactions: role in the development of osteolytic lesions in multiple myeloma. Leuk Lymphoma. 2007;48:2323-2329.
71. Kyle RA, Therneau TM, Rajkumar SV, et al. Prevalence of monoclonal gammopathy of undetermined significance. N Engl J Med. 2006;354: 1362-1369.
72. Kyle RA, Therneau TM, Rajkumar SV, et al. A long-term study of prognosis in monoclonal gammopathy of undetermined significance. N Engl J Med. 2002;346:564-569.
73. Kaiser M, Mieth M, Liebisch P, et al. Serum concentrations of DKK-1 correlate with the extent of bone disease in patients with multiple myeloma. Eur J Haematol. 2008;80:490-494.
74. Hadjidakis DJ, Androulakis II. Bone remodeling. Ann N Y Acad Sci. 2006;1092:385-396.
75. Steeve KT, Marc P, Sandrine T, Dominique H, Yannick F. IL-6, RANKL, TNF-alpha/IL-1: interrelations in bone resorption pathophysiology. Cytokine Growth Factor Rev. 2004;15:49-60.
76. Adams GB, Scadden DT. The hematopoietic stem cell in its place. Nat Immunol. 2006;7:333-337.
77. Fleming HE, Janzen V, Lo Celso C, et al. Wnt signaling in the niche enforces hematopoietic stem cell quiescence and is necessary to preserve self-renewal in vivo. Cell Stem Cell. 2008;2:274-283.
78. Gregory CA, Singh H, Perry AS, Prockop DJ. The Wnt signaling inhibitor dickkopf-1 is required for reentry into the cell cycle of human adult stem cells from bone marrow. J Biol Chem. 2003;278: 28067-28078.
79. Matushansky I, Hernando E, Socci ND, et al. Derivation of sarcomas from mesenchymal stem cells via inactivation of the Wnt pathway. J Clin Invest. 2007;117:3248-3257.
80. Lee N, Smolarz AJ, Olson S, et al. A potential role for Dkk-1 in the pathogenesis of osteosarcoma predicts novel diagnostic and treatment strategies. Br J Cancer. 2007;97:1552-1559.
81. Kumar S, Dispenzieri A, Lacy MQ, et al. Impact of lenalidomide therapy on stem cell mobilization and engraftment post-peripheral blood stem cell transplantation in patients with newly diagnosed myeloma. Leukemia. 2007;21:2035-2042.
82. Colla S, Zhan F, Xiong W, et al. The oxidative stress response regulates DKK1 expression through the JNK signaling cascade in multiple myeloma plasma cells. Blood. 2007;109:4470-4477.
83. Shaughnessy JD Jr, Barlogie B. Interpreting the molecular biology and clinical behavior of multiple myeloma in the context of global gene expression profiling. Immunol Rev. 2003;194:140-163.
84. Yaccoby S, Ling W, Zhan F, Walker R, Barlogie B, Shaughnessy JD Jr. Antibody-based inhibition of DKK1 suppresses tumor-induced bone resorption and multiple myeloma growth in vivo. Blood. 2007;109:2106-2111.
85. Qiang YW, Shaughnessy JD Jr., Yaccoby S. Wnt3a signaling within bone inhibits multiple myeloma bone disease and tumor growth. Blood. 2008;112:374-382.
86. 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;111:2833-2842.
87. Edwards CM. Wnt signaling: bone's defense against myeloma. Blood. 2008;112:216-217.
88. Holmen SL, Zylstra CR, Mukherjee A, et al. Essential role of beta-catenin in postnatal bone acquisition. J Biol Chem. 2005;280:21162-21168.
89. Spencer GJ, Utting JC, Etheridge SL, Arnett TR, Genever PG. Wnt signalling in osteoblasts regulates expression of the receptor activator of NFkappaB ligand and inhibits osteoclastogenesis in vitro. J Cell Sci. 2006;119:1283-1296.
90. Gunn WG, Conley A, Deininger L, Olson SD, Prockop DJ, Gregory CA. A crosstalk between myeloma cells and marrow stromal cells stimulates production of DKK1 and interleukin-6: a potential role in the development of lytic bone disease and tumor progression in multiple myeloma. Stem Cells. 2006;24:986-991.
91. Kishimoto T. Interleukin-6: from basic science to medicine-40 years in immunology. Annu Rev Immunol. 2005;23:1-21.
92. Fulciniti M, Tassone P, Hideshima T, et al. Anti-DKK1 mAb (BHQ880) as a potential therapeutic for multiple myeloma. Blood. 2007;110:Abstract 551.
93. Richardson PG, Barlogie B, Berenson J, et al. A phase 2 study of bortezomib in relapsed, refractory myeloma. N Engl J Med. 2003;348:2609-2617.
94. Garrett IR, Chen D, Gutierrez G, et al. Selective inhibitors of the osteoblast proteasome stimulate bone formation in vivo and in vitro. J Clin Invest. 2003;111:1771-1782.
95. Zangari M, Esseltine D, Lee CK, et al. Response to bortezomib is associated to osteoblastic activation in patients with multiple myeloma. Br J Haematol. 2005;131:71-73.
96. Oyajobi BO, Garrett IR, Gupta A, et al. Stimulation of new bone formation by the proteasome inhibitor, bortezomib: implications for myeloma bone disease. Br J Haematol. 2007;139:434-438.
97. Gaur T, Lengner CJ, Hovhannisyan H, et al. Canonical WNT signaling promotes osteogenesis by directly stimulating Runx2 gene expression. J Biol Chem. 2005;280:33132-33140.
98. Nishio Y, Dong Y, Paris M, O'Keefe RJ, Schwarz EM, Drissi H. Runx2-mediated regulation of the zinc finger Osterix/Sp7 gene. Gene. 2006;372: 62-70.
99. Duplomb L, Dagouassat M, Jourdon P, Heymann D. Concise review: embryonic stem cells: a new tool to study osteoblast and osteoclast differentiation. Stem Cells. 2007;25:544-552.
100. Huang W, Yang S, Shao J, Li YP. Signaling and transcriptional regulation in osteoblast commitment and differentiation. Front Biosci. 2007;12: 3068-3092.