Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
JCR Impact Factor (IF) – 1.736
5-Year Impact Factor – 2.135
Index Copernicus  – 168.52
MEiN – 70 pts

ISSN 1899–5276 (print)
ISSN 2451-2680 (online)
Periodicity – monthly

Download original text (EN)

Advances in Clinical and Experimental Medicine

2019, vol. 28, nr 3, March, p. 397–406

doi: 10.17219/acem/76060

Publication type: review article

Language: English

Download citation:

  • BIBTEX (JabRef, Mendeley)
  • RIS (Papers, Reference Manager, RefWorks, Zotero)

Diseases of the oral cavity in light of the newest epigenetic research: Possible implications for stomatology

Jadwiga Jośko-Ochojska1,A,B,C,D,F, Katarzyna Rygiel1,D,E,F, Lidia Postek-Stefańska2,B,C,F

1 Department of Environmental Medicine and Epidemiology, Medical University of Silesia, Zabrze, Poland

2 Department of Pediatric Dentistry, Medical University of Silesia, Zabrze, Poland


Epigenetics is the study of inheritable changes in gene expression without changes in the underlying deoxyribonucleic acid (DNA) sequence. The main mechanisms of epigenetic regulation include DNA methylation, modifications in histones, and micro-ribonucleic acids (miRNA). Recent research evidence has shown that environmental and lifestyle factors dynamically interact with the genome, influencing epigenetic changes, from development to the later stages of life. This happens across a spectrum, from physiological to pathological conditions, such as genetic defects, developmental disorders, infectious or inflammatory processes, cancers, mental disorders, and substance abuse. Epigenetic studies have been conducted in various medical disciplines (e.g., oncology, internal medicine or psychiatry), adding valuable insight to standard medical approaches. However, in stomatology, epigenetic research is still in its infancy; thus, this review is aimed at presenting the role of epigenetic mechanisms in diseases of the oral cavity, including periodontal diseases, caries, developmental anomalies, and oral carcinoma. In addition, this paper reveals new insights into epigenetic biomarkers that can be helpful in the detection, early diagnosis, prognosis, and treatment of different oral diseases. Moreover, this review is focused on the possible clinical implications (diagnostic and therapeutic) of epigenetics, in the form of some noninvasive methods that can possibly be used in the future for the screening, work-up, outcome prediction and novel treatments of some dental diseases. Finally, this paper highlights that an epigenetic approach can be useful for designing novel interventions that will improve the management of oral malignancies or developmental abnormalities.

Key words

periodontal diseases, dental caries, epigenetics, developmental anomalies, oral squamous cell carcinoma

References (60)

  1. Jośko-Ochojska J. Inheritance of trauma. Epigenetic “letter” to future generations. In: Medical and Social Aspects of Trauma. Katowice, Poland: Śląski Uniwersytet Medyczny; 2016:41–73.
  2. Singh NN, Peer A, Nair S, Chaturvedi RK. Epigenetics: A possible answer to the undeciphered etiopathogenesis and behavior of oral lesions. J Oral Maxillofac Pathol. 2016;20(1):122–128.
  3. Williams SD, Hughes TE, Adler CJ, Brook AH, Townsend GC. Epigen­etics: A new frontier in dentistry. Aust Dent J. 2014;59(Suppl 1):23–33.
  4. Seo JY, Park YJ, Yi YA, et al. Epigenetics: General characteristics and implications for oral health. Restor Dent Endod. 2015;40(1):14–22.
  5. Packyanathan JS, Juneius CER. Role of epigenetic mechanisms in oral health: A review. Asian J Pharm. 2016;10(4):473–479.
  6. Mohsin AHB, Barshaik S. Epigenetics in dentistry: A literature review. J Clin Epigenet. 2017;3:1. doi: 10.21767/2472-1158.100035
  7. Barros SP, Offenbacher S. Modifiable risk factors in periodontal disease: Epigenetic regulation of gene expression in the inflammatory response. Periodontol 2000. 2014;64(1):95–110.
  8. Ari G, Cherukuri S, Namasivayam A. Epigenetics and periodontitis: A contemporary review. JCDR. 2016;10(11):ZE07–ZE09. doi: 10.7860/JCDR/2016/21025.8864
  9. de Faria Amormino SA, Arão TC, Saraiva AM, et al. Hypermethylation and low transcription of TLR2 gene in chronic periodontitis. Hum Immunol. 2013;74(9):1231–1236.
  10. Kowalski P, Rubin M, Kleer C. E-cadherin expression in primary carcinomas of the breast and its distant metastases. Breast Cancer Res. 2003;5(6):R217–R222. doi: 10.1186/bcr651
  11. Nagarakanti S. Differential expression of E-cadherin and cytokeratin 19 and net proliferative rate of gingival keratinocytes in oral epithelium in periodontal health and disease. J Periodontol. 2007;78(11):2197–2202.
  12. Loo WT, Jin L, Cheung MN, Wang M, Chow LW. Epigenetic change in E-cadherin and COX-2 to predict chronic periodontitis. J Transl Med. 2010;8:110. doi: 10.1186/1479-5876-8-110
  13. Barnes PJ. Targeting the epigenome in the treatment of asthma and chronic obstructive pulmonary disease. Proc Am Thorac Soc. 2009;6 (8):693–696.
  14. Zhang S, Barros SP, Niculescu MD, Moretti AJ, Preisser JS, Offenbacher S. Alteration of PTGS2 promoter methylation in chronic periodontitis. J Dent Res. 2010;89(2):133–137.
  15. Lindroth AM, Park YJ. Epigenetic biomarkers: A step forward for understanding periodontitis. J Periodontal Implant Sci. 2013;43(3):111–120.
  16. Offenbacher S. Epigenetic regulation of TNFA expression in periodontal disease. J Periodontol. 2013;84(11):1606–1616.
  17. Schulz S, Immel UD, Just L, Schaller HG, Gläser C, Reichert S. Epigenetic characteristics in inflammatory candidate genes in aggressive periodontitis. Hum Immunol. 2016;77(1):71–75.
  18. Modesto A, Klein O, Tenuta LM, Gerlach RF, Vieira AR. Summary of the IADR cariology research, craniofacial biology, and mineralized tissue groups symposium, Iguaçu Falls, Brazil, June 2012: Gene-environment. Interactions and epigenetics in oral diseases: Enamel formation and its clinical impact on tooth defects, caries, and erosion. Dent 3000. 2013;1(1).
  19. Jośko-Ochojska J. Wpływ dramatycznych przeżyć i lęków matki ciężarnej na losy jej dziecka. In: Jośko-Ochojska J, ed. Lęk – nieodłączny towarzysz człowieka od poczęcia aż do śmierci. Katowice, Poland: Śląski Uniwersytet Medyczny (SUM) in Katowice; 2013:11–35.
  20. Al-Jewair TS, Leake JL. The prevalence and risks of early childhood caries (ECC) in Toronto, Canada. J Contemp Dent Pract. 2010;11(5):1–8.
  21. Hughes T, Bockmann M, Mihailidis S, et al. Genetic, epigenetic, and environmental influences on dentofacial structures and oral health: Ongoing studies of Australian twins and their families. Twin Res Hum Genet. 2013;16(1):43–51.
  22. Apostolou E, Hochedlinger K. Chromatin dynamics during cellular reprogramming. Nature. 2013;502(7472):462–471.
  23. Smith ZD, Meissner A. DNA methylation: Roles in mammalian development. Nat Rev Genet. 2013;14(3):204–220.
  24. Delgado-Calle J, Sañudo C, Sanchez-Verde L, Garcia-Renedo RJ, Arozamena J, Riancho JA. Epigenetic regulation of alkaline phosphatase in human cells of the osteoblastic lineage. Bone. 2011;49(4):830–838.
  25. Delgado-Calle J, Sañudo C, Bolado A, et al. DNA methylation contributes to the regulation of sclerostin expression in human osteocytes. J Bone Miner Res. 2012;27(4):926–937.
  26. Dawson MA, Kouzarides T. Cancer epigenetics: From mechanism to therapy. Cell. 2012;150(1):12–27.
  27. Yoshioka H, Minamizaki T, Yoshiko Y. The dynamics of DNA methylation and hydroxymethylation during amelogenesis. Histochem Cell Biol. 2015;144(5):471–478.
  28. Fernando S, Speicher DJ, Bakr MM, et al. Protocol for assessing maternal, environmental and epigenetic risk factors for dental caries in children. BMC Oral Health. 2015;15:167. doi: 10.1186/s12903-015-0143-2
  29. Hui T, Wang C, Chen D, Zheng L, Huang D, Ye L. Epigenetic regulation in dental pulp inflammation. Oral Dis. 2017;23(1):22–28.
  30. Hui T, AP, Zhao Y, et al. EZH2, a potential regulator of dental pulp inflammation and regeneration. J Endod. 2014;40(8):1132–1138.
  31. Huang GT, Garcia-Godoy F. Missing concepts in de novo pulp regeneration. J Dent Res. 2014;93(8):717–724.
  32. Huang GT. Dental pulp and dentin tissue engineering and regeneration: Advancement and challenge. Front Biosci (Elite Ed). 2011;3:788–800.
  33. Duncan HF, Smith AJ, Fleming GJ, Cooper PR. Histone deacetylase inhibitors epigenetically promote reparative events in primary dental pulp cells. Exp Cell Res. 2013;319(10):1534–1543.
  34. Qiu X, Xiao X, Li N, Li Y. Histone deacetylases inhibitors (HDACis) as novel therapeutic application in various clinical diseases. Prog Neuropsychopharmacol Biol Psychiatry. 2017;72:60–72.
  35. Paino F, La Noce M, Tirino V, et al. Histone deacetylase inhibition with valproic acid downregulates osteocalcin gene expression in human dental pulp stem cells and osteoblasts: Evidence for HDAC2 involvement. Stem Cells. 2014;32(1):279–289.
  36. Wyszynski DF. Cleft Lip and Palate: From Origin to Treatment. New York, NY: Oxford University Press (US); 2002.
  37. Plamondon JA, Harris MJ, Mager DL, Gagnier L, Juriloff DM. The clf2 gene has an epigenetic role in the multifactorial etiology of cleft lip and palate in the A/WySn mouse strain. Birth Defects Res A Clin Mol Teratol. 2011;91(8):716–727.
  38. Little J, Cardy A, Munger RG. Tobacco smoking and oral clefts: A meta-analysis. Bull World Health Organ. 2004;82(3):213–218.
  39. Grosen D, Petersen B, Skytthe A, et al. Risk of oral clefts in twins. Epidemiology. 2011;22(3):313–319.
  40. Kuriyama M, Udagawa A, Yoshimoto S, et al. DNA methylation changes during cleft palate formation induced by retinoic acid in mice. Cleft Palate Craniofac J. 2008;45(5):545–551.
  41. Conrad R, Barrier M, Ford LP. Role of miRNA and miRNA processing factors in development and disease. Birth Defects Res C Embryo Today. 2006;78(2):107–117.
  42. Seelan RS, Mukhopadhyay P, Pisano MM, Greene RM. Developmental epigenetics of the murine secondary palate. ILAR J. 2012;53(3–4):240–252.
  43. Warner DR, Bhattacherjee V, Yin X, et al. Functional interaction between Smad, CREB binding protein, and p68 RNA helicase. Biochem Biophys Res Commun. 2004;324(1):70–76.
  44. Ornoy A. Valproic acid in pregnancy: How much are we endangering the embryo and fetus? Reprod Toxicol. 2009;28(1):1–10.
  45. Pandorf CE, Haddad F, Wright C, Bodell PW, Baldwin KM. Differential epigenetic modifications of histones at the myosin heavy chain genes in fast and slow skeletal muscle fibers and in response to muscle unloading. Am J Physiol Cell Physiol. 2009;297(1):6–16.
  46. Desh H, Gray SL, Horton MJ, et al. Molecular motor MYO1C, acetyltransferase KAT6B and osteogenetic transcription factor RUNX2 expression in human masseter muscle contributes to development of malocclusion. Arch Oral Biol. 2014;59(6):601–607.
  47. Rowlerson A, Raoul G, Daniel Y, et al. Fiber-type differences in masseter muscle associated with different facial morphologies. Am J Orthod Dentofacial Orthop. 2005;127(1):37–46.
  48. Baar K. Epigenetic control of skeletal muscle fibre type. Acta Physiol (Oxf). 2010;199(4):477–487.
  49. Deng P, Chen QM, Hong C, Wang CY. Histone methyltransferases and demethylases: Regulators in balancing osteogenic and adipogenic differentiation of mesenchymal stem cells. Int J Oral Sci. 2015;7(4):197–204.
  50. Huh A, Horton MJ, Cuenco KT, et al. Epigenetic influence of KAT6B and HDAC4 in the development of skeletal malocclusion. Am J Orthod Dentofacial Orthop.2013; 144(4):568–576.
  51. Cho Y, Kim B, Bae H, et al. G. Direct gingival fibroblast/osteoblast transdifferentiation via epigenetics. J Dent Res. 2017;96(5):555–561. doi: 10.1177/0022034516686745
  52. Guttal KS, Naikmasur VG, Bhargava P, Bathi RJ. Frequency of developmental dental anomalies in the Indian population. Eur J Dent. 2010;4(3):263–269.
  53. Wang J, Sun K, Shen Y, et al. DNA methylation is critical for tooth agenesis: Implications for sporadic non-syndromic anodontia and hypodontia. Sci Rep. 2016;6:19162. doi: 10.1038/srep19162
  54. Townsend G, Richards L, Hughes T, Pinkerton S, Schwerdt W. Epigenetic influences may explain dental differences in monozygotic twin pairs. Aust Dent J. 2005;50(2):95–100.
  55. Suda N, Hattori M, Kosaki K, et al. Correlation between genotype and supernumerary tooth formation in cleidocranial dysplasia. Orthod Craniofac Res. 2010;13(4):197–202.
  56. Brook AH. Multilevel complex interactions between genetic, epigenetic and environmental factors in the etiology of anomalies of dental development. Arch Oral Biol. 2009;54(Suppl 1):3–17.
  57. Langevin SM, Butler RA, Eliot M, et al. Novel DNA methylation targets in oral rinse samples predict survival of patients with oral squamous cell carcinoma. Oral Oncol. 2014;50(11):1072–1080.
  58. Ribeiro IP, Caramelo F, Marques F, et al. WT1, MSH6, GATA5 and PAX5 as epigenetic oral squamous cell carcinoma biomarkers – a short report. Cell Oncol (Dordr). 2016;39(6):573–582.
  59. Sushma PS, Jamil K, Kumar PU, Satyanarayana U, Ramakrishna M, Triveni B. PTEN and p16 genes as epigenetic biomarkers in oral squamous cell carcinoma (OSCC): A study on south Indian population. Tumour Biol. 2016;37(6):7625–7632.
  60. Cheng JC, Chiang MT, Lee CH, et al. γ-Synuclein expression is a malignant index in oral squamous cell carcinoma. J Dent Res. 2016;95(4): 439–445.