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- Khouly, Ismael, et al.
(författare)
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Global DNA Methylation in Dental Implant Failure Due to Peri-Implantitis: An Exploratory Clinical Pilot Study.
- 2022
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Ingår i: International journal of environmental research and public health. - : MDPI AG. - 1660-4601. ; 19:2
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Tidskriftsartikel (refereegranskat)abstract
- Peri-implantitis (PIT) is highly prevalent in patients with dental implants and is a challenging condition to treat due to the limited outcomes reported for non-surgical and surgical therapies. Therefore, epigenetic therapeutics might be of key importance to treat PIT. However, developing epigenetic therapeutics is based on understanding the relationship between epigenetics and disease. To date, there is still scarce knowledge about the relationship between epigenetic modifications and PIT, which warrants further investigations.The purpose of this study was to evaluate the level of global DNA methylation associated with implant failure (IF) due to PIT compared to periodontally healthy (PH) patients.A total of 20 participants were initially enrolled in this pilot, exploratory, single-blinded, cross-sectional clinical human study in two groups: 10 in the PH group and 10 in the IF group. In the participants who have completed the study, gingival tissue and bone samples were harvested from each participant and were used to perform global DNA methylation analysis. The percentage of global DNA methylation (5-mC%) was compared (1) between groups (PH and IF); (2) between the subgroups of gingival tissue and bone separately; (3) in the whole sample, comparing gingival tissue and bone; (4) within groups, comparing gingival tissue and bone. Demographic, periodontal, and peri-implant measurements as well as periodontal staging, were also recorded. All statistical comparisons were made at the 0.05 significance level.Out of the initially enrolled 20 patients, only 19 completed the study and, thus, were included in the final analysis; 10 patients in the PH group and 9 patients in the IF group, contributing to a total of 38 samples. One patient from the IF group was excluded from the study due to systemic disease. The mean implant survival time was 10.8 years (2.17-15.25 years). Intergroup comparison, stratified by group, indicated a similar 5-mC% between the PH and IF groups in both gingival tissue and bone (p = 0.599), only in bone (p = 0.414), and only in gingival tissue (p = 0.744). Intragroup comparison, stratified by the type of sample, indicated a significantly higher 5-mC% in gingival tissue samples compared to bone in both the PH and IF groups (p = 0.001), in the PH group (p = 0.019), and in the IF group (p = 0.009).Within the limitations of this study, higher global DNA methylation levels were found in gingival tissue samples compared to bone, regardless of the study groups. However, similar global DNA methylation levels were observed overall between the IF and PH groups. Yet, differences in the global DNA methylation levels between gingival tissues and bone, regardless of the study group, could reflect a different epigenetic response between various tissues within the same microenvironment. Further studies are necessary to elucidate the present findings and to evaluate the role of epigenetic modifications in IF due to PIT.
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| 2. |
- Kreisel, Katrin, 1991, et al.
(författare)
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DNA polymerase η contributes to genome-wide lagging strand synthesis.
- 2019
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Ingår i: Nucleic acids research. - : Oxford University Press (OUP). - 1362-4962 .- 0305-1048. ; 47:5, s. 2425-2435
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Tidskriftsartikel (refereegranskat)abstract
- DNA polymerase η (pol η) is best known for its ability to bypass UV-induced thymine-thymine (T-T) dimers and other bulky DNA lesions, but pol ηalso has other cellular roles. Here, we present evidence that pol η competes with DNA polymerases α and δfor the synthesis of the lagging strand genome-wide, where it also shows a preference for T-T in the DNA template. Moreover, we found that the C-terminus of pol η,which contains a PCNA-Interacting Protein motif is required for pol ηto function in lagging strand synthesis. Finally, we provide evidence that a pol η dependent signature is also found to be lagging strand specific in patients with skin cancer. Taken together, these findings provide insight into the physiological role of DNA synthesis by pol η and have implications for our understanding of how our genome is replicated to avoid mutagenesis, genome instability and cancer.
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| 3. |
- Larsson, Lena, 1969, et al.
(författare)
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Expression of TET2 enzyme indicates enhanced epigenetic modification of cells in periodontitis
- 2016
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Ingår i: European Journal of Oral Sciences. - : Wiley. - 0909-8836. ; 124:4, s. 329-333
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Tidskriftsartikel (refereegranskat)abstract
- DNA methylation is an important epigenetic mechanism involved in the regulation of gene expression, and a reduction in DNA methylation influences cell-cycle progression and cell differentiation in inflammatory cells. The aim of the present study was to analyze the DNA-methylation pattern at local and global/systemic levels in patients with periodontitis and gingivitis. Twenty-one subjects with generalized, severe periodontitis and 17 subjects with gingival inflammation but no attachment loss were recruited. Gingival biopsies and peripheral blood samples were collected and prepared for immunohistochemical analysis of 5-methylcytosine (5mC), 5-hydroxymethylcytosine (5hmC), ten-eleven translocation 2 (TET2), and DNA methyltransferase 1 (DNMT1). Whilst a similar pattern for 5mC and 5hmC DNA methylation was found in both types of lesions, a significantly larger proportion of TET2-positive cells was found in periodontitis lesions than in gingivitis lesions. Quantitative real-time PCR analysis showed no differences between gingivitis and periodontitis lesions regarding expression of TET2 and isocitrate dehydrogenase (IDH) genes, while the global level of 5hmC was significantly higher in blood than in tissue in patients with periodontitis. It is suggested that epigenetic changes are more common in periodontitis lesions than in gingivitis lesions and that such changes are tissue specific.
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| 4. |
- Thorbert-Mros, Sara, 1970, et al.
(författare)
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Interleukin-17-producing T cells and interleukin-17 mRNA expression in periodontitis and long-standing gingivitis lesions
- 2019
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Ingår i: Journal of Periodontology. - : Wiley. - 0022-3492 .- 1943-3670. ; 90:5, s. 516-521
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Tidskriftsartikel (refereegranskat)abstract
- Background T helper17 cells (Th17) are key targets in the evaluation of differences between "destructive" and "non-destructive" periodontal lesions. The aim of the present study was to analyze the density of interleukin-17 (IL-17) producing T cells and IL-17 mRNA expression in lesions representing severe periodontitis and longstanding gingivitis. Methods Two groups of patients were recruited. The gingivitis group consisted of 28 patients, 41-70 years old, with evident signs of gingival inflammation but no attachment loss. The periodontitis group consisted of 36 patients, 33-67 years of age. A gingival biopsy was obtained from one selected diseased site from each patient and prepared for immunohistochemical and reverse transcription, quantitative polymerase chain reaction (RT-qPCR) analysis. Results Although the density of CD3 positive cells (T cells) did not differ between the two types of lesions, the total number and density of cells positive for CD3+CD161 (IL-17-producing T-cells) were larger in periodontitis than in long-standing gingivitis lesions. About 30% of CD3-cells in periodontitis lesions were also positive for CD161. The corresponding figure for gingivitis samples was 15%. Analysis of covariance (ANCOVA) analysis revealed that differences between periodontitis and gingivitis samples remained after adjusting for smoking, age, and gender. In addition, males had larger proportions of IL-17 producing T cells than females in both groups. The IL-17 mRNA expression was higher in periodontitis than in gingivitis samples. Conclusion It is suggested that IL-17 producing T cells represent a significant feature in the detection of differences between destructive and non-destructive lesions.
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