Cell and Tissue Research

, Volume 363, Issue 2, pp 321–335 | Cite as

Wnt/β-catenin signaling in bone marrow niche

  • Ahmad Ahmadzadeh
  • Fatemeh Norozi
  • Saeid Shahrabi
  • Mohammad Shahjahani
  • Najmaldin Saki
Review

Abstract

The bone marrow (BM) niche is a specific physiological environment for hematopoietic and non-hematopoietic stem cells (HSCs). Several signaling pathways (including Wnt/β-catenin) regulate various aspects of stem cell growth, function and death in the BM niche. In addition, the canonical Wnt pathway is crucial for directing self-renewal and differentiation as important mechanisms in many types of stem cells. We review the role of the Wnt/β-catenin pathway in the BM niche and its importance in stem cells. Relevant literature was identified by a PubMed search (1997–2014) of English-language literature by using the following keywords: BM niche, Wnt/β-catenin signaling, osteoblast, osteoclast and bone disease. The Wnt/β-catenin pathway regulates the stability of the β-catenin proto-oncogene. The stabilized β-catenin then translocates to the nucleus, forming a β-catenin-TCF/LEF complex regulating the transcription of specific target genes. Stem cells require β-catenin to mediate their response to Wnt signaling for maintenance and transition from the pluripotent state during embryogenesis. In adult stem cells, Wnt signaling functions at various hierarchical levels to contribute to the specification of the diverse tissues. Aberrant Wnt/β-catenin signaling and its downstream transcriptional regulators are observed in several malignant stem cells and human cancers. Because Wnt signaling can maintain stem cells and cancer cells, the ability to modulate the Wnt pathway either positively or negatively may be of therapeutic relevance. The controlled activation of Wnt signaling might allow us to enhance stem and progenitor cell activity when regeneration is needed.

Keywords

Bone marrow niche Wnt/β-catenin Osteoblast Osteoclast Cellular senescence 

Notes

Acknowledgments

We wish to thank all our colleagues in Shafa Hospital and Allied Health Sciences School, Ahvaz Jundishapur University of Medical Sciences.

Authors’ contributions

N.S. and F.N. conceived the manuscript and revised it. N.S. and M.Sh. wrote the manuscript. A.A. prepared the figures.

Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interest.

References

  1. Ai M, Holmen SL, Van Hul W, Williams BO, Warman ML (2005) 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 25:4946–4955CrossRefPubMedCentralPubMedGoogle Scholar
  2. Albers J, Keller J, Baranowsky A, Beil FT, Catala-Lehnen P, Schulze J, Amling M, Schinke T (2013) Canonical Wnt signaling inhibits osteoclastogenesis independent of osteoprotegerin. J Cell Biol 200:537–549CrossRefPubMedCentralPubMedGoogle Scholar
  3. Anastas JN, Moon RT (2013) WNT signalling pathways as therapeutic targets in cancer. Nat Rev Cancer 13:11–26CrossRefPubMedGoogle Scholar
  4. Arioka M, Takahashi-Yanaga F, Sasaki M, Yoshihara T, Morimoto S, Hirata M, Mori Y, Sasaguri T (2014) Acceleration of bone regeneration by local application of lithium: Wnt signal-mediated osteoblastogenesis and Wnt signal-independent suppression of osteoclastogenesis. Biochem Pharmacol 90:397–405CrossRefPubMedGoogle Scholar
  5. Ashihara E, Kawata E, Nakagawa Y, Shimazaski C, Kuroda J, Taniguchi K, Uchiyama H, Tanaka R, Yokota A, Takeuchi M, Kamitsuji Y, Inaba T, Taniwaki M, Kimura S, Maekawa T (2009) Beta-catenin small interfering RNA successfully suppressed progression of multiple myeloma in a mouse model. Clin Cancer Res 15:2731–2738CrossRefPubMedGoogle Scholar
  6. Austin TW, Solar GP, Ziegler FC, Liem L, Matthews W (1997) A role for the Wnt gene family in hematopoiesis: expansion of multilineage progenitor cells. Blood 89:3624–3635PubMedGoogle Scholar
  7. Baek SH, Kioussi C, Briata P, Wang D, Nguyen HD, Ohgi KA, Glass CK, Wynshaw-Boris A, Rose DW, Rosenfeld MG (2003) Regulated subset of G1 growth-control genes in response to derepression by the Wnt pathway. Proc Natl Acad Sci U S A 100:3245–3250CrossRefPubMedCentralPubMedGoogle Scholar
  8. Baksh D, Tuan RS (2007) Canonical and non-canonical Wnts differentially affect the development potential of primary isolate of human bone marrow mesenchymal stem cells. J Cell Physiol 212:817–826CrossRefPubMedGoogle Scholar
  9. Barker N, Clevers H (2006) Mining the Wnt pathway for cancer therapeutics. Nat Rev Drug Discov 5:997–1014CrossRefPubMedGoogle Scholar
  10. Baron R, Kneissel M (2013) WNT signaling in bone homeostasis and disease: from human mutations to treatments. Nat Med 19:179–192CrossRefPubMedGoogle Scholar
  11. Baron R, Rawadi G, Roman-Roman S (2006) Wnt signaling: a key regulator of bone mass. Curr Top Dev Biol 76:103–127CrossRefPubMedGoogle Scholar
  12. Bellon M, Ko NL, Lee MJ, Yao Y, Waldmann TA, Trepel JB, Nicot C (2013) Adult T-cell leukemia cells overexpress Wnt5a and promote osteoclast differentiation. Blood 121:5045–5054CrossRefPubMedCentralPubMedGoogle Scholar
  13. Benhaj K, Akcali KC, Ozturk M (2006) Redundant expression of canonical Wnt ligands in human breast cancer cell lines. Oncol Rep 15:701–707PubMedGoogle Scholar
  14. Bitler BG, Nicodemus JP, Li H, Cai Q, Wu H, Hua X, Li T, Birrer MJ, Godwin AK, Cairns P, Zhang R (2011) Wnt5a suppresses epithelial ovarian cancer by promoting cellular senescence. Cancer Res 71:6184–6194CrossRefPubMedCentralPubMedGoogle Scholar
  15. Blank U, Karlsson G, Karlsson S (2008) Signaling pathways governing stem-cell fate. Blood 111:492–503CrossRefPubMedGoogle Scholar
  16. Boland GM, Perkins G, Hall DJ, Tuan RS (2004) Wnt 3a promotes proliferation and suppresses osteogenic differentiation of adult human mesenchymal stem cells. J Cell Biochem 93:1210–1230CrossRefPubMedGoogle Scholar
  17. Boyle WJ, Simonet WS, Lacey DL (2003) Osteoclast differentiation and activation. Nature 423:337–342CrossRefPubMedGoogle Scholar
  18. Calvi L, Adams G, Weibrecht K, Weber J, Olson D, Knight M, Martin R, Schipani E, Divieti P, Bringhurst F (2003) Osteoblastic cells regulate the haematopoietic stem cell niche. Nature 425:841–846CrossRefPubMedGoogle Scholar
  19. Camilli TC, Weeraratna AT (2010) Striking the target in Wnt-y conditions: intervening in Wnt signaling during cancer progression. Biochem Pharmacol 80:702–711CrossRefPubMedCentralPubMedGoogle Scholar
  20. Campisi J (2005a) Aging, tumor suppression and cancer: high wire-act! Mech Ageing Dev 126:51–58CrossRefPubMedGoogle Scholar
  21. Campisi J (2005b) Senescent cells, tumor suppression, and organismal aging: good citizens, bad neighbors. Cell 120:513–522CrossRefPubMedGoogle Scholar
  22. Campisi J, Fagagna FDA di (2007) Cellular senescence: when bad things happen to good cells. Nat Rev Mol Cell Biol 8:729–740Google Scholar
  23. Campisi J, Andersen JK, Kapahi P, Melov S (2011) Cellular senescence: a link between cancer and age-related degenerative disease? Semin Cancer Biol 21:354–359PubMedCentralPubMedGoogle Scholar
  24. Canepa ET, Scassa ME, Ceruti JM, Marazita MC, Carcagno AL, Sirkin PF, Ogara MF (2007) INK4 proteins, a family of mammalian CDK inhibitors with novel biological functions. IUBMB Life 59:419–426CrossRefPubMedGoogle Scholar
  25. Chim CS, Pang R, Fung TK, Choi CL, Liang R (2007) Epigenetic dysregulation of Wnt signaling pathway in multiple myeloma. Leukemia 21:2527–2536CrossRefPubMedGoogle Scholar
  26. Cho HH, Kim YJ, Kim SJ, Kim JH, Bae YC, Ba B, Jung JS (2006) Endogenous Wnt signaling promotes proliferation and suppresses osteogenic differentiation in human adipose derived stromal cells. Tissue Eng 12:111–121CrossRefPubMedGoogle Scholar
  27. Chotinantakul K, Leeanansaksiri W (2012) Hematopoietic stem cell development, niches, and signaling pathways. Bone Marrow Res 2012:270425CrossRefPubMedCentralPubMedGoogle Scholar
  28. Christodoulides C, Scarda A, Granzotto M, Milan G, Dalla Nora E, Keogh J, De Pergola G, Stirling H, Pannacciulli N, Sethi JK, Federspil G, Vidal-Puig A, Farooqi IS, O’Rahilly S, Vettor R (2006) WNT10B mutations in human obesity. Diabetologia 49:678–684CrossRefPubMedCentralPubMedGoogle Scholar
  29. Clevers H (2006) Wnt/beta-catenin signaling in development and disease. Cell 127:469–480CrossRefPubMedGoogle Scholar
  30. Clevers H, Nusse R (2012) Wnt/beta-catenin signaling and disease. Cell 149:1192–1205CrossRefPubMedGoogle Scholar
  31. Clines GA, Guise TA (2008) Molecular mechanisms and treatment of bone metastasis. Expert Rev Mol Med 10:e7CrossRefPubMedGoogle Scholar
  32. Clines GA, Mohammad KS, Bao Y, Stephens OW, Suva LJ, Shaughnessy JD Jr, Fox JW, Chirgwin JM, Guise TA (2007) Dickkopf homolog 1 mediates endothelin-1-stimulated new bone formation. Mol Endocrinol 21:486–498CrossRefPubMedCentralPubMedGoogle Scholar
  33. Conidi A, Berghe V van den, Huylebroeck D (2013) Aptamers and their potential to selectively target aspects of EGF, Wnt/beta-Catenin and TGFbeta-Smad family signaling. Int J Mol Sci 14:6690–6719Google Scholar
  34. Davidson KC, Adams AM, Goodson JM, McDonald CE, Potter JC, Berndt JD, Biechele TL, Taylor RJ, Moon RT (2012) Wnt/beta-catenin signaling promotes differentiation, not self-renewal, of human embryonic stem cells and is repressed by Oct4. Proc Natl Acad Sci U S A 109:4485–4490CrossRefPubMedCentralPubMedGoogle Scholar
  35. Day TF, Guo X, Garrett-Beal L, Yang Y (2005) Wnt/beta-catenin signaling in mesenchymal progenitors controls osteoblast and chondrocyte differentiation during vertebrate skeletogenesis. Dev Cell 8:739–750CrossRefPubMedGoogle Scholar
  36. De Boer J, Wang HJ, Van Blitterswijk C (2004) Effects of Wnt signaling on proliferation and differentiation of human mesenchymal stem cells. Tissue Eng 10:393–401CrossRefPubMedGoogle Scholar
  37. DeCarolis NA, Wharton KA Jr, Eisch AJ (2008) Which way does the Wnt blow? Exploring the duality of canonical Wnt signaling on cellular aging. BioEssays News Rev Mol Cell Dev Biol 30:102–106CrossRefGoogle Scholar
  38. Dreesen O, Brivanlou AH (2007) Signaling pathways in cancer and embryonic stem cells. Stem Cell Rev 3:7–17CrossRefPubMedGoogle Scholar
  39. Dufourcq P, Descamps B, Tojais NF, Leroux L, Oses P, Daret D, Moreau C, Lamaziere JM, Couffinhal T, Duplaa C (2008) Secreted frizzled-related protein-1 enhances mesenchymal stem cell function in angiogenesis and contributes to neovessel maturation. Stem Cells 26:2991–3001CrossRefPubMedGoogle Scholar
  40. Edwards CM, Zhuang J, Mundy GR (2008) The pathogenesis of the bone disease of multiple myeloma. Bone 42:1007–1013CrossRefPubMedCentralPubMedGoogle Scholar
  41. 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 21:1738–1749CrossRefPubMedGoogle Scholar
  42. Endo-Munoz L, Evdokiou A, Saunders NA (2012) The role of osteoclasts and tumour-associated macrophages in osteosarcoma metastasis. Biochim Biophys Acta 1826:434–442PubMedGoogle Scholar
  43. Fehrer C, Lepperdinger G (2005) Mesenchymal stem cell aging. Exp Gerontol 40:926–930CrossRefPubMedGoogle Scholar
  44. Feng J, Iwama A, Satake M, Kohu K (2009) MicroRNA-27 enhances differentiation of myeloblasts into granulocytes by post-transcriptionally downregulating Runx1. Br J Haematol 145:412–423CrossRefPubMedGoogle Scholar
  45. Fodde R, Brabletz T (2007) Wnt/beta-catenin signaling in cancer stemness and malignant behavior. Curr Opin Cell Biol 19:150–158CrossRefPubMedGoogle Scholar
  46. Frattini A, Vezzoni P, Villa A (2006) The genetics of dominant osteopetrosis. Drug Discov Today Dis Mech 2:503–509CrossRefGoogle Scholar
  47. Frisch BJ, Porter RL, Calvi LM (2008) Hematopoietic niche and bone meet. Curr Opin Support Palliat Care 2:211–217CrossRefPubMedCentralPubMedGoogle Scholar
  48. Galli C, Piemontese M, Lumetti S, Manfredi E, Macaluso GM, Passeri G (2013) GSK3b-inhibitor lithium chloride enhances activation of Wnt canonical signaling and osteoblast differentiation on hydrophilic titanium surfaces. Clin Oral Implants Res 24:921–927CrossRefPubMedGoogle Scholar
  49. Gerdes JM, Davis EE, Katsanis N (2009) The vertebrate primary cilium in development, homeostasis, and disease. Cell 137:32–45CrossRefPubMedCentralPubMedGoogle Scholar
  50. Glass DA 2nd, 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 8:751–764CrossRefPubMedGoogle Scholar
  51. Goessling W, North TE, Loewer S, Lord AM, Lee S, Stoick-Cooper CL, Weidinger G, Puder M, Daley GQ, Moon RT, Zon LI (2009) Genetic interaction of PGE2 and Wnt signaling regulates developmental specification of stem cells and regeneration. Cell 136:1136–1147CrossRefPubMedCentralPubMedGoogle Scholar
  52. 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, Boogaard MJ van den, 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 107:513–523Google Scholar
  53. Grant SF, Thorleifsson G, Reynisdottir I, Benediktsson R, Manolescu A, Sainz J, Helgason A, Stefansson H, Emilsson V, Helgadottir A, Styrkarsdottir U, Magnusson KP, Walters GB, Palsdottir E, Jonsdottir T, Gudmundsdottir T, Gylfason A, Saemundsdottir J, Wilensky RL, Reilly MP, Rader DJ, Bagger Y, Christiansen C, Gudnason V, Sigurdsson G, Thorsteinsdottir U, Gulcher JR, Kong A, Stefansson K (2006) Variant of transcription factor 7-like 2 (TCF7L2) gene confers risk of type 2 diabetes. Nat Genet 38:320–323CrossRefPubMedGoogle Scholar
  54. Gregory CA, Gunn WG, Reyes E, Smolarz AJ, Munoz J, Spees JL, Prockop DJ (2005) How Wnt signaling affects bone repair by mesenchymal stem cells from the bone marrow. Ann N Y Acad Sci 1049:97–106CrossRefPubMedGoogle Scholar
  55. Gu Z, Tan W, Feng G, Meng Y, Shen B, Liu H, Cheng C (2014) Wnt/beta-catenin signaling mediates the senescence of bone marrow-mesenchymal stem cells from systemic lupus erythematosus patients through the p53/p21 pathway. Mol Cell Biochem 387:27–37CrossRefPubMedGoogle Scholar
  56. Hall CL, Keller ET (2006) The role of Wnts in bone metastases. Cancer Metastasis Rev 25:551–558CrossRefPubMedGoogle Scholar
  57. Henriksen K, Gram J, Hoegh-Andersen P, Jemtland R, Ueland T, Dziegiel MH, Schaller S, Bollerslev J, Karsdal MA (2005) Osteoclasts from patients with autosomal dominant osteopetrosis type I caused by a T253I mutation in low-density lipoprotein receptor-related protein 5 are normal in vitro, but have decreased resorption capacity in vivo. Am J Pathol 167:1341–1348CrossRefPubMedCentralPubMedGoogle Scholar
  58. Herbst A, Kolligs FT (2007) Wnt signaling as a therapeutic target for cancer. Methods Mol Biol 361:63–91PubMedGoogle Scholar
  59. Hiyama A, Sakai D, Risbud MV, Tanaka M, Arai F, Abe K, Mochida J (2010) Enhancement of intervertebral disc cell senescence by WNT/beta-catenin signaling-induced matrix metalloproteinase expression. Arthritis Rheum 62:3036–3047CrossRefPubMedCentralPubMedGoogle Scholar
  60. Hoffman MD, Benoit DS (2013) Agonism of Wnt-beta-catenin signalling promotes mesenchymal stem cell (MSC) expansion. J Tissue Eng Regen Med, doi  10.1002/term.1736 PubMedCentralPubMedGoogle Scholar
  61. Hu H, Hilton MJ, Tu X, Yu K, Ornitz DM, Long F (2005) Sequential roles of Hedgehog and Wnt signaling in osteoblast development. Development 132:49–60CrossRefPubMedGoogle Scholar
  62. Iwasaki H, Suda T (2009) Cancer stem cells and their niche. Cancer Sci 100:1166–1172CrossRefPubMedGoogle Scholar
  63. Jamieson CH, Ailles LE, Dylla SJ, Muijtjens M, Jones C, Zehnder JL, Gotlib J, Li K, Manz MG, Keating A, Sawyers CL, Weissman IL (2004) Granulocyte-macrophage progenitors as candidate leukemic stem cells in blast-crisis CML. N Engl J Med 351:657–667CrossRefPubMedGoogle Scholar
  64. Jang HD, Shin JH, Park DR, Hong JH, Yoon K, Ko R, Ko CY, Kim HS, Jeong D, Kim N, Lee SY (2011) Inactivation of glycogen synthase kinase-3beta is required for osteoclast differentiation. J Biol Chem 286:39043–39050CrossRefPubMedCentralPubMedGoogle Scholar
  65. Jin L, Hope KJ, Zhai Q, Smadja-Joffe F, Dick JE (2006) Targeting of CD44 eradicates human acute myeloid leukemic stem cells. Nat Med 12:1167–1174CrossRefPubMedGoogle Scholar
  66. Johnson ML, Harnish K, Nusse R, Van Hul W (2004) LRP5 and Wnt signaling: a union made for bone. J Bone Miner Res 19:1749–1757CrossRefPubMedGoogle Scholar
  67. Jost E, Schmid J, Wilop S, Schubert C, Suzuki H, Herman JG, Osieka R, Galm O (2008) Epigenetic inactivation of secreted Frizzled-related proteins in acute myeloid leukaemia. Br J Haematol 142:745–753CrossRefPubMedGoogle Scholar
  68. Ju Z, Choudhury AR, Rudolph KL (2007) A dual role of p21 in stem cell aging. Ann N Y Acad Sci 1100:333–344CrossRefPubMedGoogle Scholar
  69. Kaarbo M, Klokk TI, Saatcioglu F (2007) Androgen signaling and its interactions with other signaling pathways in prostate cancer. Bioessays 29:1227–1238CrossRefPubMedGoogle Scholar
  70. Kanazawa A, Tsukada S, Sekine A, Tsunoda T, Takahashi A, Kashiwagi A, Tanaka Y, Babazono T, Matsuda M, Kaku K, Iwamoto Y, Kawamori R, Kikkawa R, Nakamura Y, Maeda S (2004) Association of the gene encoding wingless-type mammary tumor virus integration-site family member 5B (WNT5B) with type 2 diabetes. Am J Hum Genet 75:832–843CrossRefPubMedCentralPubMedGoogle Scholar
  71. Kapinas K, Kessler C, Ricks T, Gronowicz G, Delany AM (2010) miR-29 modulates Wnt signaling in human osteoblasts through a positive feedback loop. J Biol Chem 285:25221–25231CrossRefPubMedCentralPubMedGoogle Scholar
  72. Katagiri T, Takahashi N (2002) Regulatory mechanisms of osteoblast and osteoclast differentiation. Oral Dis 8:147–159CrossRefPubMedGoogle Scholar
  73. Kim JA, Kang YJ, Park G, Kim M, Park YO, Kim H, Leem SH, Chu IS, Lee JS, Jho EH, Oh IH (2009) Identification of a stroma-mediated Wnt/beta-catenin signal promoting self-renewal of hematopoietic stem cells in the stem cell niche. Stem Cells 27:1318–1329CrossRefPubMedGoogle Scholar
  74. Kim JH, Liu X, Wang J, Chen X, Zhang H, Kim SH, Cui J, Li R, Zhang W, Kong Y, Zhang J, Shui W, Lamplot J, Rogers MR, Zhao C, Wang N, Rajan P, Tomal J, Statz J, Wu N, Luu HH, Haydon RC, He TC (2013) Wnt signaling in bone formation and its therapeutic potential for bone diseases. Ther Adv Musculoskelet Dis 5:13–31CrossRefPubMedCentralPubMedGoogle Scholar
  75. Kobayashi Y, Maeda K, Uehara S, Yamashita T, Takahashi N (2011) Regulatory mechanism of osteoclastogenesis by Wnt signaling. Inflamm Regen 31:413–419CrossRefGoogle Scholar
  76. Konopleva MY, Jordan CT (2011) Leukemia stem cells and microenvironment: biology and therapeutic targeting. J Clin Oncol 29:591–599CrossRefPubMedGoogle Scholar
  77. Kosar M, Bartkova J, Hubackova S, Hodny Z, Lukas J, Bartek J (2011) Senescence-associated heterochromatin foci are dispensable for cellular senescence, occur in a cell type- and insult-dependent manner and follow expression of p16(ink4a). Cell Cycle 10:457–468CrossRefPubMedGoogle Scholar
  78. Kramer I, Halleux C, Keller H, Pegurri M, Gooi JH, Weber PB, Feng JQ, Bonewald LF, Kneissel M (2010) Osteocyte Wnt/beta-catenin signaling is required for normal bone homeostasis. Mol Cell Biol 30:3071–3085CrossRefPubMedCentralPubMedGoogle Scholar
  79. Larue L, Luciani F, Kumasaka M, Champeval D, Demirkan N, Bonaventure J, Delmas V (2009) Bypassing melanocyte senescence by beta-catenin: a novel way to promote melanoma. Pathol Biol 57:543–547CrossRefPubMedGoogle Scholar
  80. Lee E, Salic A, Kruger R, Heinrich R, Kirschner MW (2003) The roles of APC and Axin derived from experimental and theoretical analysis of the Wnt pathway. PLoS Biol 1:E10CrossRefPubMedCentralPubMedGoogle Scholar
  81. Li G, Xu J, Li Z (2012) Receptor for advanced glycation end products inhibits proliferation in osteoblast through suppression of Wnt, PI3K and ERK signaling. Biochem Biophys Res Commun 423:684–689CrossRefPubMedGoogle Scholar
  82. 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 37:945–952CrossRefPubMedGoogle Scholar
  83. Lien WH, Fuchs E (2014) Wnt some lose some: transcriptional governance of stem cells by Wnt/beta-catenin signaling. Genes Dev 28:1517–1532CrossRefPubMedCentralPubMedGoogle Scholar
  84. Ling L, Nurcombe V, Cool SM (2009) Wnt signaling controls the fate of mesenchymal stem cells. Gene 433:1–7CrossRefPubMedGoogle Scholar
  85. Liu N, Shi S, Deng M, Tang L, Zhang G, Liu N, Ding B, Liu W, Liu Y, Shi H, Liu L, Jin Y (2011) High levels of beta-catenin signaling reduce osteogenic differentiation of stem cells in inflammatory microenvironments through inhibition of the noncanonical Wnt pathway. J Bone Miner Res 26:2082–2095CrossRefPubMedGoogle Scholar
  86. Logan CY, Nusse R (2004) The Wnt signaling pathway in development and disease. Annu Rev Cell Dev Biol 20:781–810CrossRefPubMedGoogle Scholar
  87. Luis TC, Ichii M, Brugman MH, Kincade P, Staal FJ (2012) Wnt signaling strength regulates normal hematopoiesis and its deregulation is involved in leukemia development. Leukemia 26:414–421CrossRefPubMedCentralPubMedGoogle Scholar
  88. Luu HH, Zhang R, Haydon RC, Rayburn E, Kang Q, Si W, Park JK, Wang H, Peng Y, Jiang W (2004) Wnt/β-catenin signaling pathway as novel cancer drug targets. Curr Cancer Drug Targets 4:653–671CrossRefPubMedGoogle Scholar
  89. Ma L, Wang HY (2007) Mitogen-activated protein kinase p38 regulates the Wnt/cyclic GMP/Ca2+ non-canonical pathway. J Biol Chem 282:28980–28990CrossRefPubMedGoogle Scholar
  90. MacDonald BT, Tamai K, He X (2009) Wnt/β-catenin signaling: components, mechanisms, and diseases. Dev Cell 17:9–26CrossRefPubMedCentralPubMedGoogle Scholar
  91. Manolagas SC, Almeida M (2007) Gone with the Wnts: beta-catenin, T-cell factor, forkhead box O, and oxidative stress in age-dependent diseases of bone, lipid, and glucose metabolism. Mol Endocrinol 21:2605–2614CrossRefPubMedGoogle Scholar
  92. Mikami I, You L, He B, Xu Z, Batra S, Lee AY, Mazieres J, Reguart N, Uematsu K, Koizumi K, Jablons DM (2005) Efficacy of Wnt-1 monoclonal antibody in sarcoma cells. BMC Cancer 5:53CrossRefPubMedCentralPubMedGoogle Scholar
  93. Mikesch JH, Steffen B, Berdel WE, Serve H, Muller-Tidow C (2007) The emerging role of Wnt signaling in the pathogenesis of acute myeloid leukemia. Leukemia 21:1638–1647CrossRefPubMedGoogle Scholar
  94. Milat F, Ng KW (2009) Is Wnt signalling the final common pathway leading to bone formation? Mol Cell Endocrinol 310:52–62CrossRefPubMedGoogle Scholar
  95. Miller JR, Hocking AM, Brown JD, Moon RT (1999) Mechanism and function of signal transduction by the Wnt/beta-catenin and Wnt/Ca2+ pathways. Oncogene 18:7860–7872CrossRefPubMedGoogle Scholar
  96. Monroe DG, McGee-Lawrence ME, Oursler MJ, Westendorf JJ (2012) Update on Wnt signaling in bone cell biology and bone disease. Gene 492:1–18CrossRefPubMedCentralPubMedGoogle Scholar
  97. Moon RT, Kohn AD, De Ferrari GV, Kaykas A (2004) WNT and beta-catenin signalling: diseases and therapies. Nat Rev Genet 5:691–701CrossRefPubMedGoogle Scholar
  98. Moore KA, Lemischka IR (2006) Stem cells and their niches. Science 311:1880–1885CrossRefPubMedGoogle Scholar
  99. Nagasawa T (2006) Microenvironmental niches in the bone marrow required for B-cell development. Nat Rev Immunol 6:107–116CrossRefPubMedGoogle Scholar
  100. Neth P, Ries C, Karow M, Egea V, Ilmer M, Jochum M (2007) The Wnt signal transduction pathway in stem cells and cancer cells: influence on cellular invasion. Stem Cell Rev 3:18–29CrossRefPubMedGoogle Scholar
  101. Oh IH (2010) Microenvironmental targeting of Wnt/beta-catenin signals for hematopoietic stem cell regulation. Expert Opin Biol Ther 10:1315–1329CrossRefPubMedGoogle Scholar
  102. Pardal R, Clarke MF, Morrison SJ (2003) Applying the principles of stem-cell biology to cancer. Nat Rev Cancer 3:895–902CrossRefPubMedGoogle Scholar
  103. Park I-K, Morrison SJ, Clarke MF (2004) Bmi1, stem cells, and senescence regulation. J Clin Invest 113:175CrossRefPubMedCentralPubMedGoogle Scholar
  104. Pederson L, Ruan M, Westendorf JJ, Khosla S, Oursler MJ (2008) Regulation of bone formation by osteoclasts involves Wnt/BMP signaling and the chemokine sphingosine-1-phosphate. Proc Natl Acad Sci U S A 105:20764–20769CrossRefPubMedCentralPubMedGoogle Scholar
  105. Qiang YW, Shaughnessy JD Jr, Yaccoby S (2008) Wnt3a signaling within bone inhibits multiple myeloma bone disease and tumor growth. Blood 112:374–382CrossRefPubMedCentralPubMedGoogle Scholar
  106. Qiang YW, Chen Y, Brown N, Hu B, Epstein J, Barlogie B, Shaughnessy JD Jr (2010) Characterization of Wnt/beta-catenin signalling in osteoclasts in multiple myeloma. Br J Haematol 148:726–738CrossRefPubMedCentralPubMedGoogle Scholar
  107. Rahim F, Hajizamani S, Mortaz E, Ahmadzadeh A, Shahjahani M, Shahrabi S, Saki N (2014) Molecular regulation of bone marrow metastasis in prostate and breast cancer. Bone Marrow Res 2014:405920CrossRefPubMedCentralPubMedGoogle Scholar
  108. Rattis FM, Voermans C, Reya T (2004) Wnt signaling in the stem cell niche. Curr Opin Hematol 11:88–94CrossRefPubMedGoogle Scholar
  109. 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 18:1842–1853CrossRefPubMedGoogle Scholar
  110. Reya T, Clevers H (2005) Wnt signalling in stem cells and cancer. Nature 434:843–850CrossRefPubMedGoogle Scholar
  111. Rich JN (2007) Cancer stem cells in radiation resistance. Cancer Res 67:8980–8984CrossRefPubMedGoogle Scholar
  112. Rizo A, Vellenga E, de Haan G, Schuringa JJ (2006) Signaling pathways in self-renewing hematopoietic and leukemic stem cells: do all stem cells need a niche? Hum Mol Genet 15:R210–R219CrossRefPubMedGoogle Scholar
  113. Rodier F, Campisi J (2011) Four faces of cellular senescence. J Cell Biol 192:547–556CrossRefPubMedCentralPubMedGoogle Scholar
  114. Roodman GD (2004) Mechanisms of bone metastasis. N Engl J Med 350:1655–1664CrossRefPubMedGoogle Scholar
  115. Rosenbluh J, Wang X, Hahn WC (2014) Genomic insights into WNT/beta-catenin signaling. Trends Pharmacol Sci 35:103–109CrossRefPubMedCentralPubMedGoogle Scholar
  116. Rybchyn MS, Slater M, Conigrave AD, Mason RS (2011) An Akt-dependent increase in canonical Wnt signaling and a decrease in sclerostin protein levels are involved in strontium ranelate-induced osteogenic effects in human osteoblasts. J Biol Chem 286:23771–23779CrossRefPubMedCentralPubMedGoogle Scholar
  117. Saki N, Abroun S, Hagh MF, Asgharei F (2011) Neoplastic bone marrow niche: hematopoietic and mesenchymal stem cells. Cell J 13:131PubMedCentralPubMedGoogle Scholar
  118. Salazar VS, Zarkadis N, Huang L, Watkins M, Kading J, Bonar S, Norris J, Mbalaviele G, Civitelli R (2013) Postnatal ablation of osteoblast Smad4 enhances proliferative responses to canonical Wnt signaling through interactions with beta-catenin. J Cell Sci 126:5598–5609CrossRefPubMedCentralPubMedGoogle Scholar
  119. Sanaa E, Jérôme L, Annelise B, Ali T (2014) Mesenchymal stem cells: pivotal players in hematopoietic stem cell microenvironment. J Stem Cell Res Ther 4:2Google Scholar
  120. Schaniel C, Sirabella D, Qiu J, Niu X, Lemischka IR, Moore KA (2011) Wnt-inhibitory factor 1 dysregulation of the bone marrow niche exhausts hematopoietic stem cells. Blood 118:2420–2429CrossRefPubMedCentralPubMedGoogle Scholar
  121. Schuettpelz LG, Link DC (2011) Niche competition and cancer metastasis to bone. J Clin Invest 121:1253–1255CrossRefPubMedCentralPubMedGoogle Scholar
  122. Sharma M, Jamieson C, Johnson M, Molloy MP, Henderson BR (2012) Specific armadillo repeat sequences facilitate beta-catenin nuclear transport in live cells via direct binding to nucleoporins Nup62, Nup153, and RanBP2/Nup358. J Biol Chem 287:819–831CrossRefPubMedCentralPubMedGoogle Scholar
  123. Shim JH, Greenblatt MB, Zou W, Huang Z, Wein MN, Brady N, Hu D, Charron J, Brodkin HR, Petsko GA, Zaller D, Zhai B, Gygi S, Glimcher LH, Jones DC (2013) Schnurri-3 regulates ERK downstream of WNT signaling in osteoblasts. J Clin Invest 123:4010–4022CrossRefPubMedCentralPubMedGoogle Scholar
  124. Sims NA, Vrahnas C (2014) Regulation of cortical and trabecular bone mass by communication between osteoblasts, osteocytes and osteoclasts. Arch Biochem Biophys 561:22–28CrossRefPubMedGoogle Scholar
  125. Singh M, Piekorz RP (2013) Senescence-associated lysosomal alpha-L-fucosidase (SA-alpha-Fuc): a sensitive and more robust biomarker for cellular senescence beyond SA-beta-Gal. Cell Cycle 12:1996CrossRefPubMedCentralPubMedGoogle Scholar
  126. Suda T, Arai F (2008) Wnt signaling in the niche. Cell 132:729–730CrossRefPubMedGoogle Scholar
  127. Tian E, Zhan F, Walker R, Rasmussen E, Ma Y, Barlogie B, Shaughnessy JD Jr (2003) The role of the Wnt-signaling antagonist DKK1 in the development of osteolytic lesions in multiple myeloma. N Engl J Med 349:2483–2494CrossRefPubMedGoogle Scholar
  128. Toledo EM, Colombres M, Inestrosa NC (2008) Wnt signaling in neuroprotection and stem cell differentiation. Prog Neurobiol 86:281–296CrossRefPubMedGoogle Scholar
  129. Tothova Z, Kollipara R, Huntly BJ, Lee BH, Castrillon DH, Cullen DE, McDowell EP, Lazo-Kallanian S, Williams IR, Sears C, Armstrong SA, Passegue E, DePinho RA, Gilliland DG (2007) FoxOs are critical mediators of hematopoietic stem cell resistance to physiologic oxidative stress. Cell 128:325–339CrossRefPubMedGoogle Scholar
  130. Valencia A, Roman-Gomez J, Cervera J, Such E, Barragan E, Bolufer P, Moscardo F, Sanz GF, Sanz MA (2009) Wnt signaling pathway is epigenetically regulated by methylation of Wnt antagonists in acute myeloid leukemia. Leukemia 23:1658–1666CrossRefPubMedGoogle Scholar
  131. Verkaar F, Zaman GJ (2011) New avenues to target Wnt/beta-catenin signaling. Drug Discov Today 16:35–41CrossRefPubMedGoogle Scholar
  132. Vermeulen L, De Sousa EMF, Heijden M van der, Cameron K, Jong JH de, Borovski T, Tuynman JB, Todaro M, Merz C, Rodermond H, Sprick MR, Kemper K, Richel DJ, Stassi G, Medema JP (2010) Wnt activity defines colon cancer stem cells and is regulated by the microenvironment. Nat Cell Biol 12:468–476Google Scholar
  133. Vormer TL, Wojciechowicz K, Dekker M, Vries S de, Wal A van der, Delzenne-Goette E, Naik SH, Song JY, Dannenberg JH, Hansen JB, Te Riele H (2014) RB family tumor suppressor activity may not relate to active silencing of E2F target genes. Cancer Res 74:5266–5276Google Scholar
  134. Wagner W, Horn P, Castoldi M, Diehlmann A, Bork S, Saffrich R, Benes V, Blake J, Pfister S, Eckstein V, Ho AD (2008) Replicative senescence of mesenchymal stem cells: a continuous and organized process. PLoS One 3:e2213CrossRefPubMedCentralPubMedGoogle Scholar
  135. Wan Y, Zhao W, Jiang Y, Liu D, Meng G, Cai Y (2014) Beta-catenin is a valuable marker for differential diagnosis of osteoblastoma and osteosarcoma. Hum Pathol 45:1459–1465CrossRefPubMedGoogle Scholar
  136. Wang T, Xu Z (2010) miR-27 promotes osteoblast differentiation by modulating Wnt signaling. Biochem Biophys Res Commun 402:186–189CrossRefPubMedGoogle Scholar
  137. Wang Y, Li YP, Paulson C, Shao JZ, Zhang X, Wu M, Chen W (2014) Wnt and the Wnt signaling pathway in bone development and disease. Front Biosci (Landmark edition) 19:379–407CrossRefGoogle Scholar
  138. Watt FM, Hogan B (2000) Out of Eden: stem cells and their niches. Science 287:1427–1430CrossRefPubMedGoogle Scholar
  139. Wend P, Holland JD, Ziebold U, Birchmeier W (2010) Wnt signaling in stem and cancer stem cells. Semin Cell Dev Biol 21:855–863CrossRefPubMedGoogle Scholar
  140. Westendorf JJ, Kahler RA, Schroeder TM (2004) Wnt signaling in osteoblasts and bone diseases. Gene 341:19–39CrossRefPubMedGoogle Scholar
  141. Wu JY, Scadden DT, Kronenberg HM (2009) Role of the osteoblast lineage in the bone marrow hematopoietic niches. J Bone Miner Res 24:759–764CrossRefPubMedCentralPubMedGoogle Scholar
  142. Xu M, Yu Q, Subrahmanyam R, Difilippantonio MJ, Ried T, Sen JM (2008) Beta-catenin expression results in p53-independent DNA damage and oncogene-induced senescence in prelymphomagenic thymocytes in vivo. Mol Cell Biol 28:1713–1723CrossRefPubMedCentralPubMedGoogle Scholar
  143. Yaccoby S, Ling W, Zhan F, Walker R, Barlogie B, Shaughnessy JD Jr (2007) Antibody-based inhibition of DKK1 suppresses tumor-induced bone resorption and multiple myeloma growth in vivo. Blood 109:2106–2111CrossRefPubMedCentralPubMedGoogle Scholar
  144. Yao H, Ashihara E, Maekawa T (2011) Targeting the Wnt/beta-catenin signaling pathway in human cancers. Expert Opin Ther Targets 15:873–887CrossRefPubMedGoogle Scholar
  145. Yavropoulou MP, Yovos JG (2007) The role of the Wnt signaling pathway in osteoblast commitment and differentiation. Hormones (Athens) 6:279–294CrossRefGoogle Scholar
  146. Yeung J, Esposito MT, Gandillet A, Zeisig BB, Griessinger E, Bonnet D, So CW (2010) Beta-catenin mediates the establishment and drug resistance of MLL leukemic stem cells. Cancer Cell 18:606–618CrossRefPubMedGoogle Scholar
  147. Yin T, Li L (2006) The stem cell niches in bone. J Clin Invest 116:1195–1201CrossRefPubMedCentralPubMedGoogle Scholar
  148. Yin JJ, Mohammad KS, Kakonen SM, Harris S, Wu-Wong JR, Wessale JL, Padley RJ, Garrett IR, Chirgwin JM, Guise TA (2003) A causal role for endothelin-1 in the pathogenesis of osteoblastic bone metastases. Proc Natl Acad Sci U S A 100:10954–10959CrossRefPubMedCentralPubMedGoogle Scholar
  149. Yoon JC, Ng A, Kim BH, Bianco A, Xavier RJ, Elledge SJ (2010) Wnt signaling regulates mitochondrial physiology and insulin sensitivity. Genes Dev 24:1507–1518CrossRefPubMedCentralPubMedGoogle Scholar
  150. Zhang DY, Wang HJ, Tan YZ (2011) Wnt/beta-catenin signaling induces the aging of mesenchymal stem cells through the DNA damage response and the p53/p21 pathway. PLoS One 6:e21397CrossRefPubMedCentralPubMedGoogle Scholar
  151. Zhang DY, Pan Y, Zhang C, Yan BX, Yu SS, Wu DL, Shi MM, Shi K, Cai XX, Zhou SS, Wang JB, Pan JP, Zhang LH (2013a) Wnt/beta-catenin signaling induces the aging of mesenchymal stem cells through promoting the ROS production. Mol Cell Biochem 374:13–20CrossRefPubMedGoogle Scholar
  152. Zhang R, Oyajobi BO, Harris SE, Chen D, Tsao C, Deng HW, Zhao M (2013b) Wnt/beta-catenin signaling activates bone morphogenetic protein 2 expression in osteoblasts. Bone 52:145–156CrossRefPubMedCentralPubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Ahmad Ahmadzadeh
    • 1
  • Fatemeh Norozi
    • 1
  • Saeid Shahrabi
    • 2
  • Mohammad Shahjahani
    • 1
  • Najmaldin Saki
    • 1
  1. 1.Health Research Institute, Research Center of Thalassemia & HemoglobinopathyAhvaz Jundishapur University of Medical SciencesAhvazIran
  2. 2.Department of Biochemistry and Hematology, Faculty of MedicineSemnan University of Medical SciencesSemnanIran

Personalised recommendations