Abstract
The aim of this study is to investigate the potential role and the association of PAX9, WNT10a, and AXIN2 genes during the development of hypodontia. A total of 40 participants from both genders were divided equally into two groups. The study group consisted of healthy unrelated individuals with isolated hypodontia and the control group consisted of unrelated healthy individuals with full dentition. The mean age for the study group was 17 ± 7 and it was 16.5 ± 6 for the control group. RNA was isolated from saliva samples, and cDNA was synthesized accordingly. PAX9, WNT10a, AXIN2, and GAPDH primers were added to the mastermix and QPCR was performed. Gene expression was calculated according to the 2−ΔΔCt method as the expression of our target genes was normalized to the reference gene. Our results showed a significant lower expression of PAX9 in the study group p = 0.018. Whilst WNT10a was significantly up-regulated in the study group p = 0.005, AXIN2 showed no statistical significance between groups p = 0.69. Our results indicate the potential role of the overexpression of WNT10a in the development of hypodontia.
Similar content being viewed by others
References
Arte S, Parmanen S, Pirinen S, Alaluusua S, Nieminen P (2013) Candidate gene analysis of tooth agenesis identifies novel mutations in six genes and suggests significant role for WNT and EDA signaling and allele combinations. PLoS ONE 8(8):e73705
Arzoo PS, Klar J, Bergendal B, Norderyd J, Dahl N (2014) WNT10A mutations account for ¼ of population-based isolated oligodontia and show phenotypic correlations. Am J Med Genet A 164(2):353–359
Arzoo PS, Klar J, Bergendal B, Norderyd J, Dahl N (2014) WNT10A mutations account for ¼ of population-based isolated oligodontia and show phenotypic correlations. Am J Med Genet A 164:353–359
Bondemark L, Tsiopa J (2007) Prevalence of ectopic eruption, impaction, retention and agenesis of the permanent second molar. Angle Orthod 77:773–778
Brook AH (2009) Multilevel complex interactions between genetic, epigenetic and environmental factors in the aetiology of anomalies of dental development. Arch Oral Biol 1(54):S3-17
Cho SY, Lee CK, Chan JC (2004) Congenitally missing maxillary permanent canines: report of 32 cases from an ethnic Chinese population. Int J Paediatr Dent 14:446–460
Dhanrajani PJ (2002) Hypodontia: etiology, clinical features, and management. Quintessence Int 33(4):294–302
Flores-Mir C (2005) More women in Europe and Australia have dental agenesis than their counterparts in North America. Evid Based Dent 6:22–23
Forgie AH, Thind BS, Larmour CJ, Mossey PA, Stirrups DR (2005) Management of hypodontia: restorative considerations. Quintessence Int 36:437–445
Graber LW (1978) Congenital absence of teeth: a review with emphasis on inheritance patterns. J Am Dent Assoc 96:266–275
Hu BR, Fairey AS, Madhav A, Yang D, Li M, Groshen S, Stephens C, Kim PH, Virk N, Wang L, Martin SE (2016) AXIN2 expression predicts prostate cancer recurrence and regulates invasion and tumor growth. Prostate 76(6):597–608
Johannsdottir B, Wisth PJ, Magnusson TE (1997) Prevalence of malocclusion in 6-year-old Icelandic children. Acta Odontol Scand 55:398–402
Kist R, Watson M, Wang X, Cairns P, Miles C, Reid DJ, Peters H (2005) Reduction of Pax9 gene dosage in an allelic series of mouse mutants causes hypodontia and oligodontia. Hum Mol Genet 14(23):3605–17
Kratochwil K, Galceran J, Tontsch S, Roth W, Grosschedl R (2002) FGF4, a direct target of LEF1 and Wnt signaling, can rescue the arrest of tooth organogenesis in Lef1−/− mice. Genes Dev 16(24):3173–3185
Lammi L, Arte S, Somer M, Järvinen H, Lahermo P, Thesleff I, Pirinen S, Nieminen P (2004) Mutations in AXIN2 cause familial tooth agenesis and predispose to colorectal cancer. Am J Hum Genet 74:1043–1050
Larmour CJ, Mossey PA, Thind BS, Forgie AH, Stirrups DR (2005) Hypodontia: a retrospective review of prevalence and etiology. Part I Quintessence Int 36:263–270
Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2−ΔΔCT method. Methods 25(4):402–8
Matalova E, Fleischmannova J, Sharpe PT, Tucker AS (2008) Tooth agenesis: from molecular genetics to molecular dentistry. J Dent Res 87:617–623
Muller TP, Hill IN, Peterson AC, Blayney JR (1970) A survey of congenitally missing permanent teeth. J Am Dent Assoc 81:101–107
Näsman M, Forsberg CM, Dahllöf G (1997) Long-term dental development in children after treatment for malignant disease. Eur J Orthod 19(2):151–159
Nieminen P (2009) Genetic basis of tooth agenesis. J Exp Zool B Mol Dev Evol 312(4):320–342
Nordgarden H, Jensen JL, Storhaug K (2002) Reported prevalence of congenitally missing teeth in two Norvegian countries. Community Dent Health 19:258–261
Ockeloen CW, Khandelwal KD, Dreesen K, Ludwig KU, Sullivan R, Van Rooij IA, Thonissen M, Swinnen S, Phan M, Conte F, Ishorst N (2016) Novel mutations in LRP6 highlight the role of WNT signaling in tooth agenesis. Genet Med 18(11):1158
Rakhshan V (2015) Congenitally missing teeth (hypodontia): a review of the literature concerning the etiology, prevalence, risk factors, patterns and treatment. Dent Res J 12(1):1
Rolling S, Poulsen S (2001) Oligodontia in Danish school children. Acta Odontol Scand 59:111–112
Ruiz-Heiland G, Lenz S, Bock N, Ruf S (2019) Prevalence of WNT10A gene mutations in non-syndromic oligodontia. Clin Oral Investig 23(7):3103–3113
Salama FS, Abdel-Megid FY (1994) Hypodontia of primary and permanent teeth in a sample of Saudi children. Egypt Dent J 40:625–632
Schmid S, Bieber M, Zhang F, Zhang M, He B, Jablons D, Teng NN (2011) Wnt and hedgehog gene pathway expression in serous ovarian cancer. Int J Gynecol cancer. 21(6):975–980
Šerý O, Bonczek O, Hloušková A, Černochová P, Vaněk J, Míšek I, Krejčí P, Izakovičová HL (2015) A screen of a large Czech cohort of oligodontia patients implicates a novel mutation in the PAX 9 gene. Eur J Oral Sci 123(2):65–71
Tamura M, Nemoto E (2016) Role of the Wnt signaling molecules in the tooth. Jpn Dent Sci Rev 52(4):75–83
Thind BS, Stirrups DR, Forgie AH, Larmour CJ, Mossey PA (2005) Management of hypodontia: orthodontic considerations. Quintessence Int 36:345–353
Thompson GW, Popovich F (1974) Probability of congenitally missing teeth: results in 1,191 children in Burlington Growth Centre in Toronto. Community Dent Oral Epidemiol 2:26–32
van den Boogaard MJ, Créton M, Bronkhorst Y, van der Hout A, Hennekam E, Lindhout D, Cune M, van Amstel HK (2012) Mutations in WNT10A are present in more than half of isolated hypodontia cases. J Med Genet 49(5):327–331
Wei Z, Zhong M, Guo Y, Wang Y, Ren M, Wang Z (2013) Expression of β-catenin and AXIN2 in ameloblastomas. Contemp Oncol 17(3):250
Wu R, Zhai Y, Fearon ER, Cho KR (2001) Diverse mechanisms of β-catenin deregulation in ovarian endometrioid adenocarcinomas. Cancer res 61(22):8247–8255
Yang J, Wang SK, Choi M, Reid BM, Hu Y, Lee YL, Herzog CR, Kim-Berman H, Lee M, Benke PJ, Kent Lloyd KC (2015) Taurodontism, variations in tooth number, and misshapened crowns in Wnt10a null mice and human kindreds. Mol Genet Genomic Med 3(1):40–58
Ynham A (1990) Panoramic radiographic survey of hypodontia in Australian defence force recruits. Austr Dent J 35:19–22
Funding
This study was self-funded.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflicts of interest
There are no conflicts of interest. All authors declare that they have no conflict of interest.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Kashoura, Y., Serakinci, N., Beleva, N. et al. WNT signaling pathway genes expression profile in isolated hypodontia. Appl Nanosci 13, 1085–1092 (2023). https://doi.org/10.1007/s13204-021-01850-3
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s13204-021-01850-3