Jump to ContentJump to Main Navigation
Show Summary Details
More options …

Regenerative Dentistry and Implant Therapy

1 Issue per year

Emerging Science

Open Access
See all formats and pricing
More options …

Wnt/β-catenin signaling for dental regeneration

Zhenhua Yang
  • Institute for Regenerative Medicine at Scott & White, Molecular and Cellular Medicine Department, College of Medicine, Texas A&M Health Science Center, Texas, USA
  • Department of Orthodontics, School of Stomatology, Fourth Military Medical University, Xi'an, Shaanxi 710032, China
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Fei Liu
  • Institute for Regenerative Medicine at Scott & White, Molecular and Cellular Medicine Department, College of Medicine, Texas A&M Health Science Center, Texas, USA
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2012-08-13 | DOI: https://doi.org/10.2478/scom-2012-0002

Wnt/β-catenin signaling for dental regeneration

Emerging regenerative strategies are promising to cure the irreversible damages to dental tissues, but the success of these strategies is constrained by the lack of insight on the molecular cues of regeneration, while recent advancements on the molecular controls of development of dental tissues provided valuable clues for identifying potential regenerative cues. Wnt/β-catenin signaling pathway is highly conserved in animals and regulates the differentiation, proliferation, death and function of many cell and tissue types. This pathway is essential for morphogenesis and homeostasis of multiple oral organs, including teeth, taste buds, salivary glands and oral mucosa. Following injury, this pathway is activated in salivary glands and teeth, which contributes to repair or regeneration of damaged tissues. Consistently, activation of the Wnt/β-catenin signaling pathway in mice prevents radiation-induced damages or promotes regeneration of these dental tissues. In this review we discuss our current understanding and potential application of Wnt/β-catenin signaling in dental regeneration.

Keywords: Wnt; β-catenin; Dental regeneration; Tooth; Taste bud; Salivary gland

  • Mikels AJ, Nusse R. Wnts as ligands: processing, secretion and reception. Oncogene 2006;25(57): 7461-8.CrossrefPubMedGoogle Scholar

  • Gordon MD, Nusse R. Wnt signaling: multiple pathways, multiple receptors, and multiple transcription factors. J Biol Chem 2006;281(32):22429-33.Google Scholar

  • Drees F, Pokutta S, Yamada S, Nelson WJ, Weis WI. Alpha-catenin is a molecular switch that binds E-cadherin-beta-catenin and regulates actin-filament assembly. Cell 2005;123(5):903-15.Google Scholar

  • Yamada S, Pokutta S, Drees F, Weis WI, Nelson WJ. Deconstructing the cadherin-catenin-actin complex. Cell 2005;123(5):889-901.Google Scholar

  • Liu C, Kato Y, Zhang Z, Do VM, Yankner BA, He X. beta-Trcp couples beta-catenin phosphorylation-degradation and regulates Xenopus axis formation. Proc Natl Acad Sci U S A 1999;96(11):6273-8.CrossrefGoogle Scholar

  • Brocardo M, Henderson BR. APC shuttling to the membrane, nucleus and beyond. Trends Cell Biol 2008;18(12):587-96.PubMedCrossrefGoogle Scholar

  • Tolwinski NS, Wieschaus E. Rethinking WNT signaling. Trends Genet 2004;20(4):177-81.PubMedCrossrefGoogle Scholar

  • Fiedler M, Mendoza-Topaz C, Rutherford TJ, Mieszczanek J, Bienz M. Dishevelled interacts with the DIX domain polymerization interface of Axin to interfere with its function in down-regulating beta-catenin. Proc Natl Acad Sci U S A 2011;108(5):1937-42.CrossrefGoogle Scholar

  • Taelman VF, Dobrowolski R, Plouhinec JL, Fuentealba LC, Vorwald PP, Gumper I, et al. Wnt signaling requires sequestration of glycogen synthase kinase 3 inside multivesicular endosomes. Cell 2010;143(7):1136-48.Google Scholar

  • Li VS, Ng SS, Boersema PJ, Low TY, Karthaus WR, Gerlach JP, et al. Wnt Signaling through Inhibition of beta-Catenin Degradation in an Intact Axin1 Complex. Cell 2012;149(6):1245-56.Google Scholar

  • Kramps T, Peter O, Brunner E, Nellen D, Froesch B, Chatterjee S, et al. Wnt/wingless signaling requires BCL9/legless-mediated recruitment of pygopus to the nuclear beta-catenin-TCF complex. Cell 2002;109(1):47-60.CrossrefGoogle Scholar

  • Bauer A, Chauvet S, Huber O, Usseglio F, Rothbacher U, Aragnol D, et al. Pontin52 and reptin52 function as antagonistic regulators of beta-catenin signalling activity. Embo J 2000;19(22):6121-30.CrossrefGoogle Scholar

  • Kawano Y, Kypta R. Secreted antagonists of the Wnt signalling pathway. J Cell Sci 2003;116(Pt 13):2627-34.Google Scholar

  • Jho EH, Zhang T, Domon C, Joo CK, Freund JN, Costantini F. Wnt/beta-catenin/Tcf signaling induces the transcription of Axin2, a negative regulator of the signaling pathway. Mol Cell Biol 2002;22(4):1172-83.CrossrefPubMedGoogle Scholar

  • Niida A, Hiroko T, Kasai M, Furukawa Y, Nakamura Y, Suzuki Y, et al. DKK1, a negative regulator of Wnt signaling, is a target of the beta-catenin/TCF pathway. Oncogene 2004;23(52):8520-6.PubMedCrossrefGoogle Scholar

  • Caldwell GM, Jones CE, Taniere P, Warrack R, Soon Y, Matthews GM, et al. The Wnt antagonist sFRP1 is downregulated in premalignant large bowel adenomas. Br J Cancer 2006;94(6):922-7.CrossrefGoogle Scholar

  • Goessling W, North TE, Loewer S, Lord AM, Lee S, Stoick-Cooper CL, et al. Genetic interaction of PGE2 and Wnt signaling regulates developmental specification of stem cells and regeneration. Cell 2009;136(6):1136-47.Google Scholar

  • He XC, Zhang J, Tong WG, Tawfik O, Ross J, Scoville DH, et al. BMP signaling inhibits intestinal stem cell self-renewal through suppression of Wnt-beta-catenin signaling. Nat Genet 2004;36(10):1117-21.PubMedCrossrefGoogle Scholar

  • Liu F, Chu EY, Watt B, Zhang Y, Gallant NM, Andl T, et al. Wnt/beta-catenin signaling directs multiple stages of tooth morphogenesis. Dev Biol 2008;313(1):210-24.Google Scholar

  • Jarvinen E, Salazar-Ciudad I, Birchmeier W, Taketo MM, Jernvall J, Thesleff I. Continuous tooth generation in mouse is induced by activated epithelial Wnt/beta-catenin signaling. Proc Natl Acad Sci U S A 2006;103(49):18627-32.CrossrefGoogle Scholar

  • Wang XP, O'Connell DJ, Lund JJ, Saadi I, Kuraguchi M, Turbe-Doan A, et al. Apc inhibition of Wnt signaling regulates supernumerary tooth formation during embryogenesis and throughout adulthood. Development 2009;136(11):1939-49.Google Scholar

  • Liu F, Dangaria S, Andl T, Zhang Y, Wright AC, Damek-Poprawa M, et al. beta-Catenin initiates tooth neogenesis in adult rodent incisors. J Dent Res 2010;89(9):909-14.PubMedCrossrefGoogle Scholar

  • Suomalainen M, Thesleff I. Patterns of Wnt pathway activity in the mouse incisor indicate absence of Wnt/beta-catenin signaling in the epithelial stem cells. Dev Dyn 2010;239(1):364-72.Google Scholar

  • Lohi M, Tucker AS, Sharpe PT. Expression of Axin2 indicates a role for canonical Wnt signaling in development of the crown and root during pre- and postnatal tooth development. Dev Dyn 2010;239(1):160-7.Google Scholar

  • Ling J, Du Y, Wei X, Ning Y, Xie N, Gu H, et al. Wnt/beta-catenin Signaling Participates in Cementoblast/Osteoblast Differentiation of Dental Follicle Cells. Connect Tissue Res 2012.PubMedGoogle Scholar

  • Han XL, Liu M, Voisey A, Ren YS, Kurimoto P, Gao T, et al. Post-natal effect of overexpressed DKK1 on mandibular molar formation. J Dent Res 2011;90(11):1312-7.CrossrefGoogle Scholar

  • Kim TH, Lee JY, Baek JA, Lee JC, Yang X, Taketo MM, et al. Constitutive stabilization of ss-catenin in the dental mesenchyme leads to excessive dentin and cementum formation. Biochem Biophys Res Commun 2011;412(4):549-55.Google Scholar

  • Zhu Y, Shang L, Chen X, Kong X, Liu N, Bai Y, et al. Deciduous dental pulp stem cells are involved in osteoclastogenesis during physiologic root resorption. J Cell Physiol 2012.Google Scholar

  • Krishnan V, Bryant HU, Macdougald OA. Regulation of bone mass by Wnt signaling. J Clin Invest 2006;116(5):1202-9.Google Scholar

  • Galli C, Passeri G, Macaluso GM. FoxOs, Wnts and oxidative stress-induced bone loss: new players in the periodontitis arena? J Periodontal Res 2011;46(4):397-406.PubMedCrossrefGoogle Scholar

  • Almeida M, Han L, Martin-Millan M, O'Brien CA, Manolagas SC. Oxidative stress antagonizes Wnt signaling in osteoblast precursors by diverting beta-catenin from T cell factor to forkhead box O-mediated transcription. J Biol Chem 2007;282(37):27298-305.Google Scholar

  • Stone LM, Finger TE, Tam PP, Tan SS. Taste receptor cells arise from local epithelium, not neurogenic ectoderm. Proc Natl Acad Sci U S A 1995;92(6):1916-20.CrossrefGoogle Scholar

  • Barlow LA, Northcutt RG. Embryonic origin of amphibian taste buds. Dev Biol 1995;169(1):273-85.Google Scholar

  • Vandenbeuch A, Clapp TR, Kinnamon SC. Amiloride sensitive channels in type I fungiform taste cells in mouse. BMC Neurosci 2008;9:1.CrossrefPubMedGoogle Scholar

  • Zhang Y, Hoon MA, Chandrashekar J, Mueller KL, Cook B, Wu D, et al. Coding of sweet, bitter, and umami tastes: different receptor cells sharing similar signaling pathways. Cell 2003;112(3):293-301.PubMedCrossrefGoogle Scholar

  • Kataoka S, Yang R, Ishimaru Y, Matsunami H, Sevigny J, Kinnamon JC, et al. The candidate sour taste receptor, PKD2L1, is expressed by type III taste cells in the mouse. Chem Senses 2008;33(3):243-54.PubMedCrossrefGoogle Scholar

  • Yang R, Ma H, Thomas SM, Kinnamon JC. Immunocytochemical analysis of syntaxin-1 in rat circumvallate taste buds. J Comp Neurol 2007;502(6):883-93.Google Scholar

  • Farbman AI. Renewal of taste bud cells in rat circumvallate papillae. Cell Tissue Kinet 1980;13(4):349-57.PubMedGoogle Scholar

  • Ichimori Y, Ueda K, Okada H, Honma S, Wakisaka S. Histochemical changes and apoptosis in degenerating taste buds of the rat circumvallate papilla. Arch Histol Cytol 2009;72(2):91-100.Google Scholar

  • Nguyen HM, Reyland ME, Barlow LA. Mechanisms of taste bud cell loss after head and neck irradiation. J Neurosci 2012;32(10):3474-84.PubMedCrossrefGoogle Scholar

  • Yamashita H, Nakagawa K, Hosoi Y, Kurokawa A, Fukuda Y, Matsumoto I, et al. Umami taste dysfunction in patients receiving radiotherapy for head and neck cancer. Oral Oncol 2009;45(3):e19-23.CrossrefPubMedGoogle Scholar

  • Liu F, Thirumangalathu S, Gallant NM, Yang SH, Stoick-Cooper CL, Reddy ST, et al. Wnt-beta-catenin signaling initiates taste papilla development. Nat Genet 2007;39(1):106-12.CrossrefPubMedGoogle Scholar

  • Iwatsuki K, Liu HX, Gronder A, Singer MA, Lane TF, Grosschedl R, et al. Wnt signaling interacts with Shh to regulate taste papilla development. Proc Natl Acad Sci U S A 2007;104(7):2253-8.CrossrefGoogle Scholar

  • Okubo T, Pevny LH, Hogan BL. Sox2 is required for development of taste bud sensory cells. Genes Dev 2006;20(19):2654-9.Google Scholar

  • Gaillard D, Barlow LA. Taste bud cells of adult mice are responsive to Wnt/beta-catenin signaling: implications for the renewal of mature taste cells. Genesis 2011;49(4):295-306.CrossrefPubMedGoogle Scholar

  • Nederfors T. Xerostomia and hyposalivation. Adv Dent Res 2000;14:48-56.PubMedCrossrefGoogle Scholar

  • Konings AW, Coppes RP, Vissink A. On the mechanism of salivary gland radiosensitivity. Int J Radiat Oncol Biol Phys 2005;62(4):1187-94.PubMedCrossrefGoogle Scholar

  • Coppes RP, Stokman MA. Stem cells and the repair of radiation-induced salivary gland damage. Oral Dis 2011;17(2):143-53.PubMedCrossrefGoogle Scholar

  • Lombaert IM, Knox SM, Hoffman MP. Salivary gland progenitor cell biology provides a rationale for therapeutic salivary gland regeneration. Oral Dis 2011;17(5):445-9.CrossrefPubMedGoogle Scholar

  • Patel N, Sharpe PT, Miletich I. Coordination of epithelial branching and salivary gland lumen formation by Wnt and FGF signals. Dev Biol 2011;358(1):156-67.Google Scholar

  • Haara O, Fujimori S, Schmidt-Ullrich R, Hartmann C, Thesleff I, Mikkola ML. Ectodysplasin and Wnt pathways are required for salivary gland branching morphogenesis. Development 2011;138(13):2681-91.Google Scholar

  • Hai B, Yang Z, Millar SE, Choi YS, Taketo MM, Nagy A, et al. Wnt/beta-catenin signaling regulates postnatal development and regeneration of the salivary gland. Stem Cells Dev 2010;19(11):1793-801.PubMedCrossrefGoogle Scholar

  • Hai B, Yang Z, Shangguan L, Zhao Y, Boyer A, Liu F. Concurrent transient activation of Wnt/beta-catenin pathway prevents radiation damage to salivary glands. Int J Radiat Oncol Biol Phys 2012;83(1):e109-16.Google Scholar

  • Sonis ST. Oral mucositis in cancer therapy. J Support Oncol 2004;2(6 Suppl 3):3-8.Google Scholar

  • Treister NS, Lerman MA. Acute oral ulcerations. J Am Dent Assoc 2007;138(4):499-501.Google Scholar

  • Zhao J, Kim KA, De Vera J, Palencia S, Wagle M, Abo A. R-Spondin1 protects mice from chemotherapy or radiation induced oral mucositis through the canonical Wnt/beta-catenin pathway. Proc Natl Acad Sci U S A 2009;106(7):2331-6.Google Scholar

  • Binnerts ME, Kim KA, Bright JM, Patel SM, Tran K, Zhou M, et al. R-Spondin1 regulates Wnt signaling by inhibiting internalization of LRP6. Proc Natl Acad Sci U S A 2007;104(37):14700-5.Google Scholar

  • de Lau W, Barker N, Low TY, Koo BK, Li VS, Teunissen H, et al. Lgr5 homologues associate with Wnt receptors and mediate R-spondin signalling. Nature 2011;476(7360):293-7.Google Scholar

  • Castilho RM, Squarize CH, Chodosh LA, Williams BO, Gutkind JS. mTOR mediates Wnt-induced epidermal stem cell exhaustion and aging. Cell Stem Cell 2009;5(3):279-89.PubMedCrossrefGoogle Scholar

  • Qiang YW, Hu B, Chen Y, Zhong Y, Shi B, Barlogie B, et al. Bortezomib induces osteoblast differentiation via Wnt-independent activation of beta-catenin/TCF signaling. Blood 2009;113(18):4319-30.PubMedCrossrefGoogle Scholar

About the article

Published Online: 2012-08-13

Published in Print: 2012-01-01

Citation Information: Stem Cells in Oral Medicine, Volume 1, Issue , Pages 3–8, ISSN (Online) 2084-7238, DOI: https://doi.org/10.2478/scom-2012-0002.

Export Citation

©2012 Versita Sp. z o.o.. This content is open access.

Comments (0)

Please log in or register to comment.
Log in