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Volume 38 , Issue 4
July/August 2018
Pages 476–477

Editorial Epigenetics: A Missing Link Between Periodontitis and Peri-implantitis?

Alberto Monje, DDS, MS/Farah Asa’ad, BDS, MSc, PhD/Lena Larsson, PhD/William V. Giannobile, DDS, DMedSc/Hom-Lay Wang, DDS, MS, PhD

DOI: 10.11607/prd.2018.4.e

Current or past history of periodontal disease is a potential risk factor for the initiation and progression of peri-implantitis.^1–8 Peri-implantitis can display bursts of activity associated with the release of cytokines and/or chemokines that evoke an inflammatory cascade, leading to destruction of bone and soft tissues surrounding the implant. A primary etiologic factor, as in periodontitis, is the microbial biofilm. Mounting evidence also supports a potential complex of factors driving pathologic mechanisms around oral implants, such as surface characteristics of the implant material, occlusion, and excess cement.

Microbiologic data suggest that after full-mouth extraction, there is a substantial reduction of the putative periodontal microbial load.^9,10 In contrast, edentulous individuals possessing multiple implants—often as a consequence of severe periodontal disease—display higher rates of peri-implantitis.^11,12 Indeed, peri-implantitis lesions are more than twice as large and contain significantly greater proportions, numbers, and densities of CD138-, CD68-, and MPO-positive cells than periodontitis lesions.¹³ Nevertheless, these striking features of the lesions are in disagreement with the expression of Th17-related cytokines in mucositis sites, which seem to be similar around periodontal and peri-implant alveolar bone defects.¹⁴ These differing lines of evidence suggest more information is required to understand the pathologic mechanisms—both parallels and contrasts—between peri-implantitis and periodontitis.

Epigenetics, different from genetics, is a stably heritable phenotype resulting from changes in a chromosome without alternations in the DNA sequence.¹⁵ Three major epigenetic mechanisms (DNA methylation, histone modifications, and microRNAs) have been shown to influence DNA expression via chromatin remodeling, which modifies gene expression.^16,17 While it seems that in the field of periodontology histone modification and DNA methylation mostly entail the expression level of cytokines, chemokines, and toll-like receptors of the oral epithelia, microRNAs have been shown to be more involved in the expression of osteogenic and osteoclast-related genes.^18,19 Major disease risk factors, such as smoking and diabetes, alter epigenetics by down-regulating the gene expression of bone matrix proteins.²⁰ Epidrugs have been successfully implemented in the treatment of alveolar bone loss in an experimental periodontitis murine model.²¹ Accordingly, it could be speculated that epigenetic changes during periodontitis in patients possessing implants may tilt the balance of susceptibility in the pathway from mucositis to peri-implantitis by suppressing specific transcription factors for osteogenesis or by activating certain transcription factors for osteoclastogenesis.

Emerging data are being accumulated that recognize that specific materials, including titanium, may evoke differing responses of biomaterial surfaces on cells derived from the periodontium that are modulated due to material surface energy, composition, or topography.²² Epigenetic modifications might be sustained in periodontal tissues even subsequent to nonsurgical periodontal therapy. As such, these epigenetically altered tissues subsequent to tooth extraction may differ from those not exposed to epigenetic cues such as histone deacetylation or DNA hypermethlyation.^23,24 This connection could be the missing link between periodontitis and peri-implantitis and could serve as a rationale for why patients with a history of periodontal disease, even with enhanced oral hygiene measures, should have more intense monitoring. This theory needs to be tested, given the very limited information available on epigenetic mechanisms and the initiation and progression of peri-implantitis. Future investigations may help shed light on this field of epigenetics in relation to oral disease to advance a better understanding of pathogenesis of periodontitis and periimplantitis.

Alberto Monje, DDS, MS

Barcelona, Spain

Farah Asa’ad, BDS, MSc, PhD

Milan, Italy

Lena Larsson, PhD

Ann Arbor, Michigan, USA

William V. Giannobile, DDS, DMedSc

Ann Arbor, Michigan, USA

Hom-Lay Wang, DDS, MS, PhD

Ann Arbor, Michigan, USA

Acknowledgments

The authors reported no conflicts of interest in relation to the publication of this editorial.

References

1. Lindhe J, Meyle J, Group D of European Workshop on Periodontology. Peri-implant diseases: Consensus Report of the Sixth European Workshop on Periodontology. J Clin Periodontol 2008;35(suppl):s282–s285.

2. Nevins M, Langer B. The successful use of osseointegrated implants for the treatment of the recalcitrant periodontal patient. J Periodontol 1995;66:150–157.

3. Sbordone L, Barone A, Ciaglia RN, Ramaglia L, Iacono VJ. Longitudinal study of dental implants in a periodontally compromised population. J Periodontol 1999;70:1322–1329. 4. Fardal O, Johannessen AC, Olsen I. Severe, rapidly progressing peri-implantitis. J Clin Periodontol 1999;26:313–317.

5. Mengel R, Schröder T, Flores-de-Jacoby L. Osseointegrated implants in patients treated for generalized chronic periodontitis and generalized aggressive periodontitis: 3- and 5-year results of a prospective long-term study. J Periodontol 2001;72:977–989.

6. Wennström JL, Ekestubbe A, Gröndahl K, Karlsson S, Lindhe J. Implant-supported single-tooth restorations: A 5-year prospective study. J Clin Periodontol 2005;32:567–574.

7. Baelum V, Ellegaard B. Implant survival in periodontally compromised patients. J Periodontol 2004;75:1404–1412.

8. Quirynen M, Abarca M, Van Assche N, Nevins M, van Steenberghe D. Impact of supportive periodontal therapy and implant surface roughness on implant outcome in patients with a history of periodontitis. J Clin Periodontol 2007;34:805–815.

9. Quirynen M, Van Assche N. Microbial changes after full-mouth tooth extraction, followed by 2-stage implant placement. J Clin Periodontol 2011;38:581–589.

10. Kocar M, Seme K, Hren NI. Characterization of the normal bacterial flora in periimplant sulci of partially and completely edentulous patients. Int J Oral Maxillofac Implants 2010;25:690–698.

11. Renvert S, Lindahl C, Persson GR. Occurrence of cases with peri-implant mucositis or peri-implantitis in a 21-26 years follow-up study. J Clin Periodontol 2018;45:233–240.

12. Derks J, Schaller D, Håkansson J, Wennström JL, Tomasi C, Berglundh T. Effectiveness of implant therapy analyzed in a Swedish population: Prevalence of peri-implantitis. J Dent Res 2016;95:43–49.

13. Carcuac O, Berglundh T. Composition of human peri-implantitis and periodontitis lesions. J Dent Res 2014;93:1083–1088.

14. Teixeira MK, Lira-Junior R, Telles DM, Lourenço EJV, Figueredo CM. Th17-related cytokines in mucositis: Is there any difference between peri-implantitis and periodontitis patients? Clin Oral Implants Res 2017;28:816–822.

15. Berger SL, Kouzarides T, Shiekhattar R, Shilatifard A. An operational definition of epigenetics. Genes Dev 2009;23:781–783.

16. Martins MD, Jiao Y, Larsson L, et al. Epigenetic modifications of histones in periodontal disease. J Dent Res 2016;95:215–222.

17. Larsson L, Castilho RM, Giannobile WV. Epigenetics and its role in periodontal diseases: A state-of-the-art review. J Periodontol 2015;86:556–568.

18. Wang Z, Wu G, Feng Z, et al. Microarcoxidized titanium surfaces functionalized with microRNA-21-loaded chitosan/hyaluronic acid nanoparticles promote the osteogenic differentiation of human bone marrow mesenchymal stem cells. Int J Nanomedicine 2015;10:6675–6687.

19. Ding X, Zhou L, Wang J, et al. The effects of hierarchical micro/nanosurfaces decorated with TiO2 nanotubes on the bioactivity of titanium implants in vitro and in vivo. Int J Nanomedicine 2015;10:6955–6973.

20. Razzouk S, Sarkis R. Smoking and diabetes. Epigenetics involvement in osseointegration. N Y State Dent J 2013;79:27–30.

21. Cantley MD, Bartold PM, Marino V, et al. Histone deacetylase inhibitors and periodontal bone loss. J Periodontal Res 2011;46:697–703.

22. Larsson L, Pilipchuk SP, Giannobile WV, Castilho RM. When epigenetics meets bioengineering: A material characteristics and surface topography perspective [epub ahead of print 25 Jul 2017]. J Biomed Mater Res B Appl Biomater doi: 10.1002/jbm.b.33953.

23. Barros SP, Offenbacher S. Epigenetics: Connecting environment and genotype to phenotype and disease. J Dent Res 2009;88:400–408.

24. Asa’ad F, Bollati V, Pagni G, et al. Evaluation of DNA methylation of inflammatory genes following treatment of chronic periodontitis: A pilot case-control study. J Clin Periodontol 2017;44:905–914.

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