Epigenetiğin Odontogenez ve Dental Hastalıkların Patogenezindeki Rolü

Yıl 2025, Cilt: 11 Sayı: 3, 315 - 327, 31.12.2025

Irmak Tümay , Yeliz Güven

Öz

Tüm canlı organizmaların hücrelerinde bulunan ve genetik bilginin temel yapı taşı olan deoksiribonükleik asidin (DNA) temel yapısı ve işlevi ile ilgili bilgilerin, gen düzenlemesi ve hastalık gelişimindeki tüm mekanizmaları açıklamada yeterli olmadığı görülmektedir. Çevresel faktörlerin, beslenmenin, stresin, toksinlerin ve yaşam tarzı gibi dış etkenlerin gen ifadesi üzerindeki etkilerini inceleyen epigenetik bilimi, genomik yapı ve gen ifadesinin daha iyi anlaşılmasını sağlamada önemli bir rol üstlenmektedir. Alzheimer, Parkinson, kanser, yaşlanma, infertilite gibi sağlık sorunlarının patogenezlerinde epigenetik mekanizmaların etkileri ile ilgili son dönemde birçok araştırma gerçekleştirilmiş olmasına karşın, diş hekimliği ile ilgili epigenetik araştırmaların henüz başlangıç aşamasında olduğu görülmektedir. Diş hekimliğinde epigenetik değişimler, özellikle dişlerin ve çenelerin gelişim sürecinde gen ekspresyonunda oynadıkları roller nedeniyle mine defektleri, dental anomaliler, çürük, ortodontik anomaliler, pulpa iltihabı, periodontal hastalık gelişimi gibi pek çok alanda etkisini gösterebilmektedir. Ayrıca kök hücreler ve rejeneratif diş hekimliği alanında epigenetik mekanizmaların yönlendirilmesiyle doku mühendisliğinde yeni yaklaşımlar geliştirilmektedir. Epigenetik mekanizmalar ve ağız hastalıklarının gelişimi ile ilgili henüz doğrudan bir neden-sonuç ilişkisi kurmak mümkün olmamakla birlikte, olası epigenetik değişimlerin belirlenmesi hastalık patogenezinin aydınlatılmasına katkı sunacağı gibi hastalıkların önlenmesi, kişiselleştirilmiş tedavi yaklaşımlarının geliştirilmesi ve diş hekimliğinde yenilikçi yaklaşımların önünün açılması açısından da büyük bir potansiyel taşımaktadır. Bu derlemede öncelikle epigenetik bilimi ile ilgili temel kavramlar açıklandıktan sonra diş hekimliğinin farklı alanlarındaki epigenetik çalışmalar güncel literatürler eşliğinde değerlendirilmiştir.

Anahtar Kelimeler

Diş anomalileri , Diş Hekimliği , Epigenomik , Gen ekspresyonunun düzenlenmesi

The Role of Epigenetics in Odontogenesis and the Pathogenesis of Dental Diseases

Öz

The structure and function of deoxyribonucleic acid (DNA), the fundamental carrier of genetic information in all living cells, are often insufficient to fully explain gene regulation and the mechanisms involved in disease development. Epigenetics, the science that explores how environmental factors such as nutrition, stress, toxins, and lifestyle influence gene expression, plays a significant role in enhancing the understanding of genomic structure and gene expression. Although significant progress has been made in uncovering the role of epigenetic mechanisms in the pathogenesis of various systemic conditions such as Alzheimer’s disease, Parkinson’s disease, cancer, aging, and infertility, epigenetic research in the field of dentistry is still in its early stages. Epigenetic changes in dentistry can influence a wide range of areas, including enamel defects, dental anomalies, caries, orthodontic anomalies, and the development of periodontal diseases and pulpitis, particularly due to their roles in gene expression during tooth and jaw development. Furthermore, the manipulation of epigenetic mechanisms in stem cell research and regenerative dentistry opens promising avenues for novel tissue engineering approaches. While a direct causal relationship between epigenetic alterations and oral diseases has yet to be clearly established, the identification of such changes could enhance understanding of disease pathogenesis, aid in prevention strategies, and support the development of personalized treatment modalities. This review first introduces the basic principles of epigenetics and then evaluates current epigenetic research across various subfields of dentistry based on the existing literature.

Anahtar Kelimeler

Tooth abnormalities , Dentistry , Epigenomics , Gene expression regulation

Kaynakça

• Cacabelos R, Tellado I, Cacabelos P. The epigenetic machinery in the life cycle and pharmacoepigenetics. In: Cacabelos R, editor. Pharmacoepigenetics. London: Academic Press; 2019. p. 1-100.
• Hamilton JP. Epigenetics: principles and practice. Dig Dis. 2011;29(2):130-5.
• Tığlı H, Özgür E, Tığlı H. A clinical perspective on the role of epigenetics in human diseases. Istanbul Gelisim Univ J Health Sci. 2020;4(10):10722. doi:10.38079/igusabder.653270
• Lodish HF. Molecular Cell Biology: New York: W.H. Freeman; 2000.
• Rodenhiser D, Mann M. Epigenetics and human disease: translating basic biology into clinical applications. CMAJ. 2006;174(3):341-8.
• Ducasse M, Brown MA. Epigenetic aberrations and cancer. Mol Cancer. 2006;5:60.
• Szyf M. The early life social environment and DNA methylation: DNA methylation mediating the long-term impact of social environments early in life. Epigenetics. 2011;6(8):971-8.
• Moore LD, Le T, Fan G. DNA methylation and its basic function. Neuropsychopharmacology. 2013;38(1):23-38.
• Liu Y, Zhang X, Blumenthal RM, Cheng X. A common mode of recognition for methylated CpG. Trends Biochem Sci. 2013;38:177-83.
• Gopinathan G, Diekwisch TGH. Epigenetics and early development. J Dev Biol. 2022;10(2):23.
• Nafee TM, Farrell WE, Carroll WD, Fryer AA, Ismail KM. Epigenetic control of fetal gene expression. BJOG. 2008;115(2):158-68.
• Weber M, Schübeler D. Genomic patterns of DNA methylation: targets and function of an epigenetic mark. Curr Opin Cell Biol. 2007;19(3):273-80.
• Okano M, Bell DW, Haber DA, Li E. DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development. Cell. 1999;99(3):247-57.
• Chen BF, Chan WY. The de novo DNA methyltransferase DNMT3A in development and cancer. Epigenetics. 2014;9(5):669-77.
• Kim JK, Samaranayake M, Pradhan S. Epigenetic mechanisms in mammals. Cell Mol Life Sci. 2009;66(4):596-612.
• Newell-Price J, Clark AJ, King P. DNA methylation and silencing of gene expression. Trends Endocrinol Metab. 2000;11(4):142-8.
• Yaykasli K, Hatipoglu O, Kaya E, Yaykasli E. Epigenetic mechanisms and cancer. Duzce Med J. 2012;14(3):58-68.
• Varol N. Akut lösemilerde Socs-1 geninin metilasyon analizi [Yüksek Lisans Tezi]. Ankara: Ankara Üniversitesi; 2007. Turkish.
• Wang YA, Kamarova Y, Shen KC ve ark. DNA methyltransferase-3a interacts with p53 and represses p53-mediated gene expression. Cancer Biol Ther. 2005;4(10):1138-43.
• Suzuki M, Yamada T, Kihara-Negishi F ve ark. Site-specific DNA methylation by a complex of PU.1 and Dnmt3a/b. Oncogene. 2006;25(17):2477-88.
• Hervouet E, Vallette FM, Cartron PF. Dnmt3/ transcription factor interactions as crucial players in targeted DNA methylation. Epigenetics. 2009;4(7):487-99.
• Goll MG, Kirpekar F, Maggert KA ve ark. Methylation of tRNAAsp by the DNA methyltransferase homolog Dnmt2. Science. 2006;311(5760):395-8.
• Lachner M, O'Sullivan RJ, Jenuwein T. An epigenetic road map for histone lysine methylation. J Cell Sci. 2003;116:2117-24.
• Abu-Hanna J, Patel JA, Anastasakis E ve ark. Therapeutic potential of inhibiting histone 3 lysine 27 demethylases: a review of the literature. Clin Epigenetics. 2022;14:98.
• Greer EL, Shi Y. Histone methylation: a dynamic mark in health, disease and inheritance. Nat Rev Genet. 2012;13(5):343-57.
• Tran TQ, Lowman XH, Kong M. Molecular Pathways: Metabolic control of histone methylation and gene expression in cancer. Clin Cancer Res. 2017;23(15):4004-9.
• Fraser P, Bickmore W. Nuclear organization of the genome and the potential for gene regulation. Nature. 2007;447(7143):413-7.
• Margueron R, Reinberg D. Chromatin structure and the inheritance of epigenetic information. Nat Rev Genet. 2010;11(4):285-96.
• Bustin S. Molecular biology of the cell, sixth edition. Int J Mol Sci. 2015;16(12):28123-5. doi:10.3390/ijms161226074
• Mattick JS, Makunin IV. Non-coding RNA. Hum Mol Genet. 2006;15 Spec No 1:R17-29.
• Birney E, Stamatoyannopoulos JA, Dutta A ve ark. Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project. Nature. 2007;447(7146):799-816.
• Carninci P, Kasukawa T, Katayama S ve ark. The transcriptional landscape of the mammalian genome. Science. 2005;309(5740):1559-63.
• Bayarsaihan D. Epigenetic mechanisms in inflammation. J Dent Res. 2011;90(1):9-17.
• Kaikkonen MU, Lam MT, Glass CK. Non-coding RNAs as regulators of gene expression and epigenetics. Cardiovasc Res. 2011;90(3):430-40.
• Akkaya Z, Dinçer P. A new era in treatment approaches: non-coding RNAs and diseases. Marmara Med J. 2015;26(1):5-10.
• Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004;116(2):281- 97.
• Kloosterman WP, Plasterk RH. The diverse functions of microRNAs in animal development and disease. Dev Cell. 2006;11(4):441-50.
• Gay I, Cavender A, Peto D ve ark. Differentiation of human dental stem cells reveals a role for microRNA-218. J Periodontal Res. 2014;49(1):110-20.
• Seo JY, Park YJ, Yi YA ve ark. Epigenetics: general characteristics and implications for oral health. Restor Dent Endod. 2015;40(1):14-22.
• Borrell LN, Papapanou PN. Analytical epidemiology of periodontitis. J Clin Periodontol. 2005;32 Suppl 6:132-58.
• Takashiba S, Naruishi K. Gene polymorphisms in periodontal health and disease. Periodontol 2000. 2006;40:94-106.
• Burt B. Position paper: epidemiology of periodontal diseases. J Periodontol. 2005;76(8):1406-19.
• Adcock IM, Tsaprouni L, Bhavsar P, Ito K. Epigenetic regulation of airway inflammation. Curr Opin Immunol. 2007;19(6):694-700.
• Gomez RS, Dutra WO, Moreira PR. Epigenetics and periodontal disease: future perspectives. Inflamm Res. 2009;58(10):625-9.
• Yu SL. Diagnostic potential of miR-200 family members in gingival crevicular fluid for chronic periodontitis: correlation with clinical parameters and therapeutic implications. BMC Oral Health. 2023;23:532.
• Almiñana-Pastor PJ, Alpiste-Illueca FM, Micó- Martinez P, García-Giménez JL, García-López E, López-Roldán A. MicroRNAs in gingival crevicular fluid: an observational case-control study of differential expression in periodontitis. Noncoding RNA. 2023;9(6):67.
• 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.
• Proffit WR, Fields HW, Sarver DM. Contemporary orthodontics. 4th ed. St. Louis: Mosby Elsevier; 2007.
• Carlson DS. Theories of craniofacial growth in the postgenomic era. Semin Orthod. 2005;11(3):119-27.
• Shirinian M, Yazbek S, Genno P. Insights in orthodontic genetic and epigenetic knowledge and its translation in clinical practice. Semin Orthod. 2023;29(3):260-3.
• Šidlauskas M, Šalomskienė L, Andriuškevičiūtė I ve ark. Heritability of mandibular cephalometric variables in twins with completed craniofacial growth. Eur J Orthod. 2016;38(5):493-502.
• Ghafari JG, Haddad RV, Saadeh ME. Class III malocclusion—The evidence on diagnosis and treatment. In: Artese F, Turpin D, Ngan P, editors. Evidence-based orthodontics. Oxford: Wiley-Blackwell; 2011. p. 247-80.
• 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):1-5.
• Jeremias F, Koruyucu M, Küchler EC ve ark. Genes expressed in dental enamel development are associated with molarincisor hypomineralization. Arch Oral Biol. 2013;58(10):1434-42.
• Silva MJ, Mohandas N, Craig JM ve ark. DNA methylation in childhood dental caries and hypomineralization. J Dent. 2022;117:103913.
• Yoshioka H, Minamizaki T, Yoshiko Y. The dynamics of DNA methylation and hydroxymethylation during amelogenesis. Histochem Cell Biol. 2015;144(5):471-8.
• Tynior W, Ilczuk-Rypuła D, Hudy D, Strzelczyk JK. Is aberrant DNA methylation a key factor in molar incisor hypomineralization? Curr Issues Mol Biol. 2022;44(7):2868-78.
• Salatino S, Cuber P, Tynior W ve ark. Harnessing nanopore sequencing to investigate the epigenomic landscape in molar incisor hypomineralization—A pilot study. Int J Mol Sci. 2025;26:3401.
• Alghadeer A, Hanson-Drury S, Patni AP ve ark. Single-cell census of human tooth development enables generation of human enamel. Dev Cell. 2023;58(20):2163-2180.e9. doi:10.1016/j. devcel.2023.07.013.
• Li H, Cui D, Zheng L ve ark. Bisphenol A exposure disrupts enamel formation via EZH2-Mediated H3K27me3. J Dent Res. 2021;100(8):847-57.
• Blankenship-Sefczek EC, Goodman AH, Hubbe M, Hunter JP, Guatelli-Steinberg D. Nutritional supplementation, tooth crown size, and trait expression in individuals from Tezonteopan, Mexico. PLoS One. 2024;19(6):e0305123.
• Duncan HF, Smith AJ, Fleming GJ, Cooper PR. Histone deacetylase inhibitors induced differentiation and accelerated mineralization of pulp-derived cells. J Endod. 2012;38(3):339-45.
• Xuan K, Li B, Guo H ve ark. Deciduous autologous tooth stem cells regenerate dental pulp after implantation into injured teeth. Sci Transl Med. 2018;10(455)eaaf3227.
• Nayak A, Viale-Bouroncle S, Morsczeck C, Müller S. The SUMO-specific isopeptidase SENP3 regulates MLL1/MLL2 methyltransferase complexes and controls osteogenic differentiation. Mol Cell. 2014;55(1):47-58.
• Li Y, He P, Zheng L, Zhou X. Histone-modifying enzymes: Roles in odontogenesis and beyond. Oral Dis. 2024;30(6):3710-8.
• Townsend GC, 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.
• Wang J, Sun K, Shen Y ve ark. DNA methylation is critical for tooth agenesis: implications for sporadic non-syndromic anodontia and hypodontia. Sci Rep. 2016;6:19162.
• Pohl S, Akamp T, Smeda M ve ark. Understanding dental pulp inflammation: from signaling to structure. Front Immunol. 2024;15:1474466.
• Kearney M, Cooper PR, Smith AJ, Duncan HF. Epigenetic approaches to the treatment of dental pulp inflammation and repair: Opportunities and Obstacles. Front Genet. 2018;9:311.
• Lod S, Johansson T, Abrahamsson KH, Larsson L. The influence of epigenetics in relation to oral health. Int J Dent Hyg. 2014 Feb;12(1):48-54.
• Seo JY, Park YJ, Yi YA ve ark. Epigenetics: general characteristics and implications for oral health. Restor Dent Endod. 2015 Feb;40(1):14- 22.