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Background: Dental implant loss is the worst problem. Today, implant failure is precisely characterized, however the underlying reasons vary by instance. Multiple implant failures indicate genetic risk factors., Methods: This cross-sectional study included 80 subjects (15 peri-implantitis patients, 35 successful implants and 30 healthy controls); their mean age was 44.22±10.936 years). Blood samples and peri-implant sulcular fluid (PISF) were collected from all subjects (patients with peri-implantitits, successful implants and healthy controls) attending the Department of Oral and Maxillofacial Surgery in the Dental College Teaching Hospital/Baghdad University, and Shahid Ghazi Al-Hariri Hospital/Medical City Baghdad, Iraq. The blood sample is used for the detection of gene polymorphism of Interleukin-10 conducted by a polymerase chain reaction. While the PISF is used to measure IL-10 level by enzyme-linked immunosorbent assay (ELISA)., Results: In the peri-implantitis group, CC genotypes had higher PISF for IL-10 than TC and TT genotypes (P<0.05). IL-10 genetic polymorphism indicated an odds ratio of genotype related to peri-implantitis, with the C/C genotype having a 0.4-fold greater risk (P=0.0035). In the peri-implantitis group, the T/C genotype had a 1.3-fold greater risk (P<0.05) and the T/T genotype had a one-fold increased risk., Conclusions: The polymorphisms of IL-10 rs1800896 evaluated were not predictive of the failure of dental implants. However, a significant association between peri-implant disease and IL-10 level could be observed.

Objective: The present study was performed to identify key biomarkers associated with immune cell infiltration in peri-implantitis through bioinformatic analyses., Methods: Six peri-implantitis soft tissue samples and six healthy gingiva samples were obtained from GSE106090, and were used to identify immune-associated differentially expressed genes (DEGs) in peri-implantitis. The candidate biomarkers associated with immune cell infiltration were examined by immunohistochemical staining., Results: We identified 2089 upregulated and 2173 downregulated genes. Upregulated DEGs were significantly associated with immune response. Ten key candidate biomarkers were identified in the PPI network, including IL1B, TLR2, TLR4, CCL4, CXCL8, IL10, IL6, CD4, CCL3, and PTPRC. The expression level of the 10 genes increased in peri-implantitis soft tissue samples compared with healthy gingiva samples. The proportion of CD4 + T cells, iTreg, and Tfh in infiltration immune cells increased in peri-implantitis soft tissue samples and were positively correlated with the expression level of candidate biomarkers TLR4, CCL3, CXCL8, and IL1B. Immunohistochemistry showed that there were more lymphocytes in peri-implantitis soft tissue samples, with an increased expression level of TLR4, CCL3, CXCL8, and IL1B., Conclusion: Identification of four novel diagnostic biomarkers was helpful for revealing the molecular mechanisms and could serve as a risk predictor for the immune microenvironment in peri-implantitis., (© 2023 The Authors. Oral Diseases published by Wiley Periodicals LLC.)

Purpose: To investigate whether genetic variations in cytokine genes involved in the pathogenesis of peri-implantitis are associated with the occurrence of peri-implantitis, an issue that remains controversial and may vary according to the population evaluated., Materials and Methods: A cross-sectional analytical study was carried out on 102 Caucasian Portuguese individuals who were divided into two groups: (1) 43 individuals with peri-implantitis and (2) 59 individuals with good peri-implant health. Samples from the buccal mucosa were obtained, and genetic analysis was performed using the real-time polymerase chain reaction (PCR) technique for IL-1A and IL-1B and PCR for IL-1RN., Results: The IL-1A-889 C/T polymorphism presented with a higher prevalence of the less common allele (T allele) in patients with peri-implantitis (27.9%) than in healthy patients (16.9%), but without statistical significance (P &#61; .060). For the IL-1B&#43;3954 C/T and IL-1RN (variable number of tandem repeats [VNTR]) polymorphisms, analysis revealed that the allele and genotype frequencies did not differ significantly between groups. There was a significant association between a history of periodontitis and peri-implantitis (P &#61; .020)., Conclusions: The evaluated genetic polymorphisms had no influence on the occurrence of peri-implantitis in the study population. Further research into genetic variations in different populations is needed to elucidate the role of genetic factors in the onset and progression of peri-implant disease.

Purpose: To analyse the relative expression and diagnostic potential of lncRNA XIST (XIST) in peri-implantitis, and explore the related mechanism of XIST in peri-implantitis., Materials and Methods: XIST expression in saliva of patients with peri-implantitis was detected by qRT-PCR. The diagnostic significance of XIST in peri-implantitis was assessed by ROC curve. Clinical indicators of the included patients were collected and the correlation between XIST levels and peri-implant indicators was determined by Pearson correlation analysis. Bioinformatic prediction and luciferase reporter assay confirmed the targeting relationship of XIST with downstream factors., Results: Salivary XIST levels were obviously higher in patients with peri-implantitis than in the healthy control group, and the AUC value for identifying patients was 0.8742 with a sensitivity and specificity of 83.5% and 81.4%. Patients in the peri-implantitis group had higher levels of plaque index (PLI), sulcus bleeding index (SBI) and probing depth (PD) than those in the healthy control group, and the expression of XIST was positively correlated with PLI, SBI, and PD levels. In addition, miR-150-5p was confirmed to be a potential downstream target of XIST., Conclusion: XIST was overexpressed in the saliva of patients with peri-implantitis and correlated with the severity of the disease. XIST has high diagnostic significance for detecting peri-implantitis.

Background: In literature, the levels of miRNA-146a and miRNA-155 are increased in periodontitis. Limited data are available regarding the expression of miRNA-146a and miR-NA-155 in diseased human peri-implant tissue. Therefore, the objective of this study was to explore the expression of miRNA-146a and miRNA-155 in human gingival peri-implant tissue affected by peri-implantitis., Methods: After recording the clinical parameters, human peri-implant pocket tissues were harvested from sites diagnosed with peri-implantitis (n = 15 cases) in addition to healthy peri-implant sulcus tissues (n = 15 controls). The levels of miRNA-146a and miRNA-155 were assessed using real-time qPCR., Results: Cases exhibited a significantly higher mean expression of miRNA-155 (5.2-fold increase) and miRNA-146a (2.8-fold increase) than controls. MiRNA-155 and miRNA-146a demonstrated an appropriate sensitivity (87.5% and 87.5%, respectively) and specificity (73.3% and 66.7%, respectively) in discriminating cases from controls. A moderate correlation (r = 0.544, p = 0.029) was found between miRNA-155 and miRNA-146a levels in the case group., Conclusions: The expressions of miRNA-146a and miR-NA-155 are different between healthy and peri-implantitis affected tissues. Both miRNAs might potentially able to discriminate healthy from peri-implantitis affected tissues., (© 2024. The Author(s).)

Background: Peri-implantitis (PI) is a frequent inflammatory disorder characterised by progressive loss of the supporting bone. Not all patients with recognised risk factors develop PI. The aim of this study is to evaluate the presence of single nucleotide polymorphisms (SNP) of inflammatory and bone metabolism related proteins in a population treated with dental implants from the Basque Country (Spain)., Methods: We included 80 patients with diagnosis of PI and 81 patients without PI, 91 women and 70 men, with a mean age of 60.90 years. SNPs of BMP-4, BRINP3, CD14, FGF-3, FGF-10, GBP-1, IL-1α, IL-1β, IL-10, LTF, OPG and RANKL proteins were selected. We performed a univariate and bivariate analysis using IBM SPSS® v.28 statistical software., Results: Presence of SNPs GBP1 rs7911 (p = 0.041) and BRINP3 rs1935881 (p = 0.012) was significantly more common in patients with PI. Patients with PI who smoked (> 10 cig/day) showed a higher presence of OPG rs2073617 SNP (p = 0.034). Also, BMP-4 rs17563 (p = 0.018) and FGF-3 rs1893047 (p = 0.014) SNPs were more frequent in patients with PI and Type II diabetes mellitus., Conclusions: Our findings suggest that PI could be favoured by an alteration in the osseointegration of dental implants, based on an abnormal immunological response to peri-implant infection in patients from the Basque Country (Spain)., (© 2024. The Author(s).)

Background: Peri-implantitis and periodontitis have similar immunological bioprocesses and inflammatory phenotypes. In the inflammatory process, the adaptive immune cells can drive the development of disease. This research investigated the differences and diagnostic significance of peri-implantitis and periodontitis in adaptive immune responses., Methods: We acquired four GEO datasets of gene expressions in surrounding tissues in healthy person, healthy implant, periodontitis, and peri-implantitis patients. The structural characteristics and enrichment analyses of differential expression genes were examined. The adaptive immune landscapes in peri-implantitis and periodontitis were then evaluated using single sample gene set enrichment analysis. The STRING database and Cytoscape were used to identify adaptive hub genes, and the ROC curve was used to verify them. Finally, qRT-PCR method was used to verify the expression level of Hub gene in activated T cells on the titanium-containing or titanium-free culture plates., Results: At the transcriptome level, the data of healthy implant, peri-implantitis and periodontitis were highly dissimilar. The peri-implantitis and periodontitis both exhibited adaptive immune response. Except for the activated CD4 + T cells, there was no significant difference in other adaptive immune cells between peri-implantitis and periodontitis. In addition, correlation analysis showed that CD53, CYBB, and PLEK were significantly positively linked with activated CD4 + T cells in the immune microenvironment of peri-implantitis, making them effective biomarkers to differentiate it from periodontitis., Conclusions: Peri-implantitis has a uniquely immunogenomic landscape that differs from periodontitis. This study provides new insights and ideas into the activated CD4 + T cells and hub genes that underpin the immunological bioprocess of peri-implantitis., (© 2024 The Authors. Immunity, Inflammation and Disease published by John Wiley & Sons Ltd.)

Objective: Periimplantitis (PI) is a complex multifactorial chronic disease caused by interactions between bacteria, host immune-inflammatory responses, and genetic or environmental factors that modify buccal eutrophism. In daily clinical practice, an increase in the prevalence of PI (8%) determined the need to establish the PI causes and set optimal therapeutic strategies. The interleukin family (IL-1), a group of cytokines, triggers and perpetuates peri-implantitis. Therefore, they could be used as biomarkers for diagnosis and treatment. This systematic review aimed to analyze the correlation between IL-1 allelic polymorphism (IL-1A -889, IL-1β -511, IL-1β +3954) and the PI disease., Materials and Methods: Selected databases were PubMed, Scopus, and Cochrane Library. The search strategy included the following terms: "dental implants"; "periimplantitis"; "interleukin-IL-1"; "polymorphism"; "perimplant bone loss". Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. A meta-analysis was conducted on five of 40 review articles. p-values, confidence intervals (CI), and Odds ratios (OR) were assessed. In 4 articles, the p-value was lower than 0.05, confirming the statistical significance of the result., Results: The prevalence of the selected studies reported the existence of a causal association between polymorphisms of IL-1 and the onset of peri-implantitis, especially for IL-1 allelic variants associated with further polymorphic genes encoding for IL-6, tumor necrosis factor-alpha (TNF-α), matrix metalloproteinases (MMP)-8, IL-1Na, IL-8, IL-18, osteopontin (OPN). In addition, the presence of the IL-1 polymorphism and PI is particularly higher in smokers, diabetes, and autoimmune disease patients., Conclusions: The detection of salivary biomarkers is, therefore, a diagnostic tool with a high potential to intercept the PI early and act with appropriate and non-invasive treatment. Due to the continued technological innovation in biomarkers and diagnostic sciences, further studies are needed to investigate the role of these biochemical mediators. The results of studies and the recent technological innovation in biomarkers and diagnostic sciences will allow further research to investigate the role of these biochemical mediators.

Early diagnosis of peri-implantitis (PI) is crucial to understand its pathological progression and prevention. This study is committed to investigating the signature genes, relevant signaling pathways and their associations with immune cells in PI. We analyzed differentially expressed genes (DEGs) from a PI dataset in the gene expression omnibus database. Functional enrichment analysis was conducted for these DEGs. Weighted Gene Co-expression Network Analysis was used to identify specific modules. Least absolute shrinkage and selection operator and support vector machine recursive feature elimination were ultimately applied to identify the signature genes. These genes were subsequently validated in an external dataset. And the immune cells infiltration was classified using CIBERSORT. A total of 180 DEGs were screened from GSE33774. Weighted Gene Co-expression Network Analysis revealed a significant association between the MEturquoise module and PI (cor = 0.6, P < .0001). Least absolute shrinkage and selection operator and support vector machine recursive feature elimination algorithms were applied to select the signature genes, containing myeloid-epithelial-reproductive tyrosine kinase, microfibrillar-associated protein 5, membrane-spanning 4A 4A, tribbles homolog 1. In the validation on the external dataset GSE106090, all these genes achieved area under curve values exceeding 0.95. GSEA analysis showed that these genes were correlated with the NOD-like receptor signaling pathway, metabolism of xenobiotics by cytochrome P450, and arachidonic acid metabolism. CIBERSORT revealed elevated levels of macrophage M2 and activated mast cells in PI. This study provides novel insights into understanding the molecular mechanisms of PI and contributes to advancements in its early diagnosis and prevention., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objectives: This study aimed to reveal critical genes regulating peri-implantitis during its development and construct a diagnostic model by using random forest (RF) and artificial neural network (ANN)., Methods: GSE-33774, GSE106090, and GSE57631 datasets were obtained from the GEO database. The GSE33774 and GSE106090 datasets were analyzed for differential expression and functional enrichment. The protein-protein interaction networks (PPI) and RF screened vital genes. A diagnostic model for peri-implantitis was established using ANN and validated on the GSE33774 and GSE57631 datasets. A transcription factor-gene interaction network and a transcription factor-micro-RNA (miRNA) regulatory network were also established., Results: A total of 124 differentially expressed genes (DEGs) involved in the regulation of peri-implantitis were screened. Enrichment analysis showed that DEGs were mainly associated with immune receptor activity and cytokine receptor activity and were mainly involved in processes such as leukocyte and neutrophil migration. The PPI and RF screened six essential genes, namely, CD38, CYBB, FCGR2A, SELL, TLR4, and CXCL8. The receiver operating characteristic curve (ROC) indicated that the ANN model had an excellent diagnostic performance. FOXC1, GATA2, and NF-κB1 may be essential transcription factors in peri-implantitis, and hsa-miR-204 may be a key miRNA., Conclusions: The diagnostic model of peri-implantitis constructed by RF and ANN has high confidence, and CD38, CYBB, FCGR2A, SELL, TLR4, and CXCL8 are potential diagnostic markers. FOXC1, GATA2, and NF-κB1 may be essential transcription factors in peri-implantitis, and hsa-miR-204 plays a vital role as a critical miRNA.

Background: Peri-implantitis is similar to periodontitis, but there are some differences. For the effective control of peri-implantitis, it is necessary to clarify its similarities and differences with periodontitis in terms of gene expression., Methods: This cross-sectional study included 20 participants (10 healthy subjects and 10 patients with periodontitis and peri-implantitis). Gingival tissue samples (10 healthy, 10 periodontitis, and 10 peri-implantitis tissues) were collected, RNAs were extracted, and RNA sequencing and analysis were performed., Results: Differentially expressed gene (DEG) analysis identified 757 upregulated and 159 downregulated genes common between periodontitis and peri-implantitis. Periodontitis tissues uniquely showed 186 overexpressed and 22 suppressed genes compared with peri-implantitis and healthy tissues, while peri-implantitis had 1974 and 642, respectively. Each common and unique differential gene set showed distinct enriched biological features between periodontitis and peri-implantitis after the pathway enrichment analysis. The expression pattern of selected DEGs focused on the representability of the disease was validated by RT-qPCR., Conclusions: Although periodontitis and peri-implantitis showed common gene expression that was clearly differentiated from healthy conditions, there were also unique gene patterns that were differentially expressed only in peri-implantitis. These findings will help elucidate the mechanisms involved in the progression of peri-implantitis., (© 2023 American Academy of Periodontology.)

Objective: The goal of the study was to examine the genetic correlation of cluster of differentiation 14 (CD14) gene polymorphisms with peri-implantitis (PI) predisposition in a Chinese Han population., Methods: In the case-control study, blood samples were collected from PI patients and healthy individuals (n = 120/group), who were admitted to the Affiliated Hospital of Yangzhou University from 2021 to 2023. One-way analysis of variance (ANOVA) was applied to compare differences of continuous variables among different groups. Genotype and allele distributions of CD14 gene rs2569190 and rs2915863 polymorphisms were analyzed between groups via χ 2 test., Results: A high percentage of rs2569190 GG genotype or G allele carriers were identified in PI group compared with control group (p < .01). Rs2569190 GG genotype carriers had high risk to develop PI (odds ratio: 2.545, 95% confidence interval: 1.257-5.156, p = .009). The rs2569190 AA genotype carriers had the lowest values of gingival index, plaque index, calculus index, peri-implant pocket depth, and clinical attachment level, which were the highest in cases with GG genotype., Conclusion: Rs2569190 polymorphism of CD14 gene was significantly associated with PI predisposition in the Chinese Han population, and the GG genotype and G allele were risk factors for the development of PI., (© 2024 The Authors. Immunity, Inflammation and Disease published by John Wiley & Sons Ltd.)

Background: N6-methyladenosine (m6A) RNA modification and its regulatory enzymes play important roles in the modulation of inflammation by regulating inflammation-related gene expression. Dysregulation of m6A has been associated with inflammatory diseases, including periodontitis. This study aimed to investigate the potential role of m6A modification and its master regulatory enzyme METTL3 in patients with peri‑implantitis., Materials and Methods: Peri-implant soft tissues from 20 subjects (10 healthy controls and 10 patients with peri‑implantitis) were enrolled in this study. Quantitative reverse transcription PCR (RT-qPCR) was used to detect METTL3 gene expression and western blotting was used to detect METTL3 protein expression. The m6A mRNA levels were measured using an m6A-RNA methylation quantification kit. Protein-protein interaction networks and in silico functional analyses were conducted using various bioinformatics tools., Results: m6A mRNA levels significantly increased in the peri‑implantitis group. Higher METTL3 mRNA and protein levels were observed in the peri‑implantitis group. High METTL3 expression might influence elevated levels of m6A RNA methylation. In addition, in silico functional analysis indicated that the METTL3 gene and protein were associated with inflammatory pathways., Conclusions: Our data provide evidence, for the first time, that dysregulation of m6A modification is associated with peri‑implantitis and may represent a strong risk factor for this inflammatory disease., Competing Interests: Declaration of Competing Interest Authors do not have conflicting interest, (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Objective: Titanium particles have been shown in in-vitro studies to lead to the activation of specific pathways, this work aims to systematically review in- vivo studies examining peri-implant and periodontal tissues at the transcriptome, proteome, epigenome and genome level to reveal implant material-related processes favoring peri-implantitis development investigated in animal and human trials., Methods: Inquiring three literature databases (Medline, Embase, Cochrane) a systematic search based on a priori defined PICOs was conducted: '-omics' studies comparing molecular signatures in healthy and infected peri-implant sites and/or healthy and periodontitis-affected teeth in animals/humans. After risk of bias assessments, lists of differentially expressed genes and results of functional enrichment analyses were compiled whenever possible., Results: Out of 2187 screened articles 9 publications were deemed eligible. Both healthy and inflamed peri-implant tissues showed distinct gene expression patterns compared to healthy/diseased periodontal tissues in animal (n = 4) or human studies (n = 5), with immune response, bone metabolism and oxidative stress being affected the most. Due to the lack of available re-analyzable data and inconsistency in methodology of the eligible studies, integrative analyses on differential gene expression were not applicable CONCLUSION: The differences of transcriptomic signatures in between peri-implant lesions compared to periodontal tissue might be related to titanium particles arising from dental implants and are in line with the in-vitro data recently published by our group. Nevertheless, limitations emerge from small sample sizes of included studies and insufficient publication of re-analyzable data., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Peri-implantitis is an irreversible infectious disease that occurs with high incidence. Exploring the immune responses of peri-implantitis is key to developing targeted treatment strategies. However, there is limited research on the immune response of peri-implantitis., Methods: This study performed a weighted gene co-expression network analysis to identify the peri-implantitis related gene network and conducted a functional enrichment analysis of the gene network. Thereafter, the candidate hub genes were selected by constructing a protein-protein interaction network and drawing an upset plot. The hub genes were identified through their significant associations with disease condition and validated using quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analysis. Using the gene set variation analysis, the hub genes were further used to explore infiltrating immunocytes and immune factors in peri-implantitis. Finally, the immunocytes and immune factor related hub genes were intersected to obtain the therapeutic target, which was validated using histological staining., Results: The peri-implantitis related gene network was enriched in innate and adaptive immune response. Subsequently, interleukin (IL)1B, IL10, ITGAM, ITGB1, STAT3, and TLR4 were identified as hub genes. Plasmacytoid dendritic cells, macrophages, myeloid-derived suppressor cells, natural killer T cells, and immature B cells were positively and significantly related to the hub genes IL1B, TLR4, ITGAM, and ITGB1 (correlation coefficient > 0.80). While immune factors CXCL10, IL6, and CXCL12 and hub genes IL10 and IL1B held the highest degree in the immune factors network. IL1B may be a promising therapeutic target., Conclusion: This study provides new insights into the hub genes, immunocytes, and immune factors underlying peri-implantitis immunological bioprocess., (© 2023 American Academy of Periodontology.)

Objectives: Limited information is available about the biological characterization of peri-implant soft tissue at the transcriptional level. The aim of this study was to investigate the effect of dental implant on the soft tissue in vivo by using paired samples and compare the differences between peri-implant soft tissue and periodontal gingiva at the transcriptional level., Methods: Paired peri-implant soft tissue and periodontal gingiva tissue from 6 patients were obtained, and the pooled RNAs were analyzed by deep sequencing. Venn diagram was used to further screen out differentially expressed genes in every pair of samples. Annotation and enrichment analysis was performed. Further verification was done by quantitative real-time PCR., Results: Totally 3549 differentially expressed genes (DEGs) were found between peri-implant and periodontal groups. The Venn diagram further identified 185 DEGs in every pair of samples, of which the enrichment analysis identified significant enrichment for cellular component was associated with external side of plasma membrane, for molecular function was protein binding, for biological process was immune system process, and for KEGG pathway was cytokine-cytokine receptor interaction. Among the DEGs, CST1, SPP1, AQP9, and SFRP2 were verified to be upregulated in peri-implant soft tissue., Conclusions: Peri-implant soft tissue showed altered expressions of several genes related to the cell-ECM interaction compared to periodontal gingiva., Clinical Relevance: Compared to periodontal gingiva, altered cell-ECM interactions in peri-implant may contribute to the susceptibility of peri-implant diseases. At the transcriptional level, periodontal gingiva is generally considered the appropriate control for peri-implantitis, except regarding the cell-ECM interactions., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

This case-control study evaluated the gene expression levels of interleukin (IL)-4, macrophage inflammatory protein type 1 alpha (MIP-1α), and metalloproteinase (MMP)-9, factors involved in the formation of giant cells in healthy peri-implant tissue and peri-implantitis. Thirty-five subjects (15 healthy and 20 with peri-implantitis), who met the inclusion and exclusion criteria, were included in this study. The peri-implant tissue biopsies were subjected to total RNA extraction, DNAse treatment, and cDNA synthesis. Subsequently, the reaction of real-time PCR was performed to evaluate the gene expression levels of IL-4, MIP-1α, and MMP-9 concerning the reference gene. IL-4 gene expression showed higher (18-fold) values in the Peri-Implantitis Group of Patients when compared with the Healthy (Control) Group (p<0.0001). Although MIP- 1α and MMP-9 gene expression levels were higher in diseased implants, they showed no significant differences (p=0.06 and p=0.2337), respectively. Within the limitations of this study, the results showed that in tissues affected by peri-implantitis, only levels of Il-4 were increased when compared with tissues in the control group.

Objective: Since peri-implantitis differs clinically and histopathologically from periodontitis, implant wear debris is considered to play a role in the destructive processes. This work aims to systematically review if titanium particles affect oral-related cells through changes in molecular signatures (e.g., transcriptome, proteome, epigenome), thereby promoting peri-implantitis., Methods: Leveraging three literature databases (Medline, Embase, Cochrane) a systematic search based on a priori defined PICOs was conducted: '-omics' studies examining titanium exposure in oral-related cells. After risk of bias assessments, lists of differentially expressed genes, proteins, and results of functional enrichment analyses were compiled. The significance of overlapping genes across multiple studies was assessed via Monte Carlo simulation and their ranking was verified using rank aggregation., Results: Out of 2104 screened articles we found 12 eligible publications. A significant overlap of gene expression in oral-related cells exposed to titanium particles was found in four studies. Furthermore, changes in biological processes like immune/inflammatory or stress response as well as toll-like receptor (TLR) and mitogen-activated protein kinase (MAPK) signaling pathways were linked to titanium in transcriptome and proteome studies. Epigenetic changes caused by titanium were detected but inconsistent., Conclusion: An influence of titanium implant wear debris on the development and progression of peri-implantitis is plausible but needs to be proven in further studies. Limitations arise from small sample sizes of included studies and insufficient publication of re-analyzable data., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objectives: Peri-implantitis was an inflammatory progress on the tissue around the implant. The Osteoprotegerin G1181C (rs2073618) polymorphism was reported to be related to the increased risk of the peri-implantitis, whereas another found no relationship. The present study was conducted to research the relationship between Osteoprotegerin rs2073618 polymorphism and peri-implantitis susceptibility., Materials and Methods: The meta-analysis was performed according to the Preferred Reporting Items for Systematic reviews. Electronic databases including PubMed, Web of science, Springer Link and Embase (updated to April 15, 2022) were retrieved. The cohort study, case-control study or cross-sectional study focusing on the Osteoprotegerin rs2073618 polymorphism and peri-implantitis were retrieved. The data included basic information of each study and the genotype and allele frequencies of the cases and controls., Results: Three studies were finally included, including 160 cases and 271 controls. Allelic model, homozygote model, recessive model, dominant model, and heterozygous model were established to assess the relationship between OPG rs2073618 polymorphism and peri-implantitis susceptibility. The Osteoprotegerin rs2073618 polymorphism was significantly associated with peri-implantitis in Recessive model and Homozygote model., Conclusion: OPG rs2073618 polymorphism in Recessive model and Homozygote model was highly likely related to the risk of peri-implantitis. PROSPERO registration number: CRD42022320812., (© 2022. The Author(s).)

Background: Peri-implant mucositis and peri-implantitis cases increase in number with the increase of implant applications. Peri-implant mucositis and peri-implantitis are defined as inflammatory diseases with inflammation and loss in soft and hard tissue, similar to the other periodontal diseases. As observed in many diseases, genetic predisposition factors also affect the progress of periodontitis and peri-implantitis., Aim: This study examines if there is any solid genetic predisposition causing periodontitis and peri-implantitis formation in Turkish patients., Patients & Methods: In order to evaluate single nucleotide polymorphism (SNP), Interleukin-8 (IL-8) and N-formyl-L-methionyl-L-leucyl-phenylalanine (fMLP), playing a role in the chemotaxis of neutrophils, and Fc Gamma Receptor IIA (FcγRIIA) and Fc Gamma Receptor IIIA (FcγRIIIA), playing a role in the antigen-antibody complexes and phagocytosis, were selected. Thirty-two Turkish non-smoking subjects, having periodontitis, thirty-three Turkish non-smoking subjects, having peri-implantitis and thirty-three Turkish non-smoking healthy subjects were selected. In total 98 adults participated in our study. Collected saliva samples from the participants were used for DNA isolation. SNPs were determined in these subgroups of the study by means of genotype-specific polymerase chain reactions., Results: When IL-8 A-251T, FcγRIIa -H131 and FcγRIIIa -V158 polymorphism were evaluated, no significant difference was found between periodontitis, peri-implantitis and healthy groups. However, this study observed that fMLP Receptor (FPR1) gene polymorphism creates a significant difference in individuals at higher risk of periodontitis or peri-implantitis., Conclusion: Results show that individuals with the G genotype have a higher risk of periodontitis, while individuals with G / C genotype have higher risk of peri-implantitis., Competing Interests: None

Background: Ageing is associated with increased incidence of peri-implantitis but the roles of ageing-associated biological mechanisms in the occurrence of peri-implantitis are not known. This study is aimed at performing integrative bioinformatic analysis of publically available datasets to uncover molecular mechanisms related to ageing and peri-implantitis., Methods: Gene expression datasets related to ageing and peri-implantitis (PI) were sought, and differentially expressed genes (DEGs) were analysed. Ageing-related genes were also identified from the "Aging Atlas" database. Using intersection analysis, an age-related-PI gene set was identified. Functional enrichment analysis for enriched GO biological process and KEGG pathways, protein-protein interaction (PPI) network analysis, correlation analysis, and immune cell infiltration analysis to determine high-abundance immune cells were performed. Least absolute shrinkage and selection operator (LASSO) logistic regression identified key age-related-PI genes. Transcription factor-gene and drug-gene interactions and enriched KEGG pathways for the key age-related-PI genes were determined., Results: A total of 52 genes were identified as age-related-PI genes and found enriched in several inflammation-associated processes including myeloid leukocyte activation, acute inflammatory response, mononuclear cell differentiation, B cell activation, NF-kappa B signalling, IL-17 signalling, and TNF signalling. LYN, CDKN2A, MAPT, BTK, and PRKCB were hub genes in the PPI network. Immune cell infiltration analysis showed activated dendritic cells, central memory CD4 T cells, immature dendritic cells, and plasmacytoid dendritic cells were highly abundant in PI and ageing. 7 key age-related PI genes including ALOX5AP, EAF2, FAM46C, GZMK, MAPT, RGS1, and SOSTDC1 were identified using LASSO with high predictive values and found to be enriched in multiple neurodegeneration-associated pathways, MAPK signalling, and Fc epsilon RI signalling. MAPT and ALOX5AP were associated with multiple drugs and transcription factors and interacted with other age-related genes to regulate multiple biological pathways., Conclusion: A suite of bioinformatics analysis identified a 7-signature gene set highly relevant to cooccurrence of ageing and peri-implantitis and highlighted the role of neurodegeneration, autoimmune, and inflammation related pathways. MAPT and ALOX5AP were identified as key candidate target genes for clinical translation., Competing Interests: The author declares no competing interests., (Copyright © 2022 Zhaojun Tian.)

Periodontitis is a disease characterized by tooth-associated microbial biofilms that drive chronic inflammation and destruction of periodontal-supporting tissues. In some individuals, disease progression can lead to tooth loss. A similar condition can occur around dental implants in the form of peri-implantitis. The immune response to bacterial challenges is not only influenced by genetic factors, but also by environmental factors. Epigenetics involves the study of gene function independent of changes to the DNA sequence and its associated proteins, and represents a critical link between genetic and environmental factors. Epigenetic modifications have been shown to contribute to the progression of several diseases, including chronic inflammatory diseases like periodontitis and peri-implantitis. This review aims to present the latest findings on epigenetic influences on periodontitis and to discuss potential mechanisms that may influence peri-implantitis, given the paucity of information currently available., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: To compare miRNA expression levels and predict relevant target genes and signaling pathways in peri-implantitis and periodontitis., Background: There are many differences between periodontitis and peri-implantitis. An understanding of the similarities and differences in the transcriptional patterns of these diseases, as well as the molecular mechanisms, is beneficial for the development of management strategies., Materials and Methods: Rat models of periodontitis (PD, n = 6) and peri-implantitis (PI, n = 5) were established by ligation. Implantation without ligation (PIC, n = 5) and normal rats (PDC, n = 6) were used as controls. Micro-CT was used to confirm the successful establishment of the model. Gingiva was harvested for miRNA transcriptome sequencing, and the results were confirmed by qRT-PCR. miRNA target genes were predicted with miRTarBase. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed., Results: Sixty-nine miRNAs were differentially expressed in PI vs. PD, 105 were differentially expressed in PI vs. PIC, and 70 were differentially expressed in PD vs. PDC (log 2 FC ≥1 and padj <0.05). The upregulated genes in all three comparisons were mostly involved in the biological process response to stimulus, whereas most of the downregulated genes were involved in nervous system development (p < .01). The upregulated genes in PI vs. PD and PI vs. PIC were involved in Toll-like receptor signaling and RIG-I-like signaling. The upregulated genes in PI vs. PD were involved in T- and B-cell receptor signaling, apoptosis, and osteoclast differentiation. Focal adhesion was downregulated in all three comparisons, and adherens junction was downregulated in PI vs. PD and PD vs. PDC (p < .1)., Conclusion: This study showed differences in the miRNA expression profiles between peri-implantitis and periodontitis and annotated the possible target genes and molecular mechanisms; this study could lay a foundation for the development of management strategies., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: Peri-implantitis is a condition resulting in destructive inflammation in the peri-implant soft tissue barrier. Clinically, it demonstrates vast clinical differences to periodontitis that suggest distinct inflammatory mechanisms. Implant-derived titanium particles (i-TiPs) frequently found around diseased implants appear to alter the microenvironment and confer resistance to antibiotic treatments. Studies in orthopedic implants have demonstrated potent inflammatory responses to i-TiPs involving a variety of cell types in aseptic conditions. Nonetheless, the genetic programs of cells surveilling and supporting the peri-implant soft tissue barrier in response to the combined challenges of biomaterial degradation products and oral bacteria are poorly defined. Thus, we studied gene expression specific to oral peri-implant inflammatory disease., Methods: Peri-implant tissues were collected from healthy or diseased implants ( N = 10) according to the 2018 classification criteria. Following RNA extraction and purification, a gene-level view of the transcriptome was obtained via a next-generation transcriptome-wide microarray profiling workflow (Clariom S; Applied Biosystems) that covers >20,000 well-annotated genes. A discovery analysis assessed global differential expression of genes and identified pathways in peri-implant health versus disease., Results: Genes involved in the endosomal-lysosomal pathway, such as actin polymerization, were strongly upregulated in diseased tissues ( P < .05), proposing increased intracellular activities in response to bacteria and i-TiPs. Cellular respiration pathways involved in oxidative stress were highly transcribed in all peri-implant samples, suggesting that implant-specific factors may trigger a constant state of oxidative stress., Conclusion: Within the limitations of this discovery study, expressive upregulation of genes in the endosomal-lysosomal and oxidative stress pathway suggests that inflammation related to receptor-driven responses to extracellular signals, such as i-TiPs and pathogens, may have a crucial role in peri-implantitis. Results warrant external replication in validation cohorts., Knowledge Transfer Statement: Our findings regarding physiologic processes affected by peri-implantitis could advance knowledge of the mechanisms and consequences of the disease. Understanding the cellular programs that partake in peri-implant inflammation has the potential to translate to novel treatment strategies for patients with peri-implantitis.

Objective: Peri-implantitis (PI) is one of the main reasons for dental implant failure. Until now, the etiology and pathogenesis of PI remain unclear., Methods: In this study, we used differentially expressed genes (DEGs) analysis and gene function enrichment analysis to assess the expression profile of peri-implant bone tissue and gingiva in PI public data from the Gene Expression Omnibus (GEO) database. Then, we used gingival tissues from patients with PI and healthy individual to construct gene coexpression networks to reveal the biological functions of the genes in PI using RNA sequencing data. Afterward, key gene modules were selected to reveal the critical biological process or signaling pathway using Hallmark's gene enrichment and expression analysis of the related pathway members in PI., Results: DEGs were enriched in the formation of cellular responses to external stimuli in bone tissue. Cytokine production, lymphocyte activation, immune response-regulating signaling pathway, and blood vessel development were the top GO biology process or pathways of the DEGs in gingival tissue. Weighted gene coexpression network analysis (WGCNA) of RNA-seq data was used to assess the results of correlation analysis between modules and traits and correlation analysis between modules and functions. kMEpurple, kMEgreen, and kMEred modules were selected as the key gene modules. Signaling pathways and gene expression analysis were performed on selected modules, such as IL2/STAT5 signaling pathway, TNF α signaling pathway via NF κ B, and angiogenesis were enriched in kMEpurple module. Hedgehog signaling pathway, Wnt β -catenin signaling pathway, and IL2/STAT5 signaling pathway were enriched in kMEgreen module. Peroxisome, IL2/STAT5 signaling pathway, and epithelial-mesenchymal transformation process were enriched in kMEred module. All the enrichment results of key modules contained IL2/STAT5 signaling pathway . Conclusion . Differential gene and enrichment analysis based on public data showed differences in gene expression patterns and biological process between bone and gingival tissues in PI. This spatial-temporal heterogeneity is reflected in the formation of cellular responses to external stimuli, which was enriched in bone tissue, but cytokine production, lymphocyte activation, immune response regulating signaling pathway, and blood vessel development were enriched in gingival tissue. WGCNA and Hallmark gene sets enrichment analysis of the gingival tissue expression profile and showed that IL2-mediated activation of immune cells could be a critical mechanism in PI. As a new clinical treatment alternative, we suggest that IL2/STAT5 pathway blockers could be helpful in the treatment of PI., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Li Tang et al.)

Objective: With our study we aimed at investigating the levels of high mobility group box chromosomal protein-1 (HMGB-1), tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-1β in periimplant crevicular fluid (PICF) of smokers and never-smokers, with and without periimplantitis, and correlate these levels with the clinical and radiographic periimplant parameters., Subjects and Methods: Sixty participants (n=15/group) were recruited and divided into 4 groups: cigarette smokers with periimplantitis (CSPI); cigarette smokers without periimplantitis (CSNPI); never-smokers with periimplantitis (NSPI); and never-smokers without periimplantitis (NSNPI). Clinical and radiographic periimplant parameters, including plaque scores (PS), bleeding on probing (BOP), probing depth (PD) and crestal bone level (CBL), were assessed. Crevicular levels of HMGB-1, TNF-α, and IL-1β were quantified using human enzyme linked immunosorbent assay. p-values were generated using Kruskal-Wallis' test for comparison between the study groups, while correlations between HMGB-1, TNF-α, IL-1β levels and clinical variables were analyzed using Spearman rank correlation coefficient analysis., Results: Bleeding on probing was least in NSNPI and CSNPI followed by CSPI and NSPI (p<0.05). The highest PD and CBL was recorded for CSPI and NSPI groups, while the least PD and CBL were recorded among non-periimplantitis groups. HMGB-1 and IL-1β were found to be significantly highest in CSPI groups followed by NSPI and CSNPI groups with no statistically significant difference between CSPI and NSPI groups (p<0.05). CSPI groups reported the highest TNF-α levels in the PICF in comparison to other groups (p<0.05). A significant negative correlation was observed between plaque scores (p=0.0187) and CBL (p=0.0049) in NSNPI and CSPI groups with HMGB-1, respectively. A significant positive correlation was seen for HMGB-1 in groups CSPI (p=0.0023) and NSPI (p=0.0018) for BOP. In CSPI group, a significant positive correlation was observed between TNF-α and PD (p=0.0443). On correlating IL-1β, a significant positive correlation was observed for CBL in CSPI (p=0.0006) and NSPI (p=0.0275) groups, respectively., Conclusions: HMGB-1 could play a significant role in periimplant inflammatory response and inflammation. Higher crevicular fluid HMGB-1 levels are indicative of a possible surrogate biomarker for peri-implantitis.

Background and Objectives : The histopathological and clinical conditions for transforming peri-implant mucositis into peri-implantitis (PI) are not fully clarified. We aim to uncover molecular mechanisms and new potential biomarkers of PI. Materials and Methods : Raw GSE33774 and GSE57631 datasets were obtained from the Gene Expression Omnibus (GEO) database. The linear models for microarray data (LIMMA) package in R software completes differentially expressed genes (DEGs). We conducted a weighted gene co-expression network analysis (WGCNA) on the top 25% of altered genes and identified the key modules associated with the clinical features of PI. Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed using the R software. We constructed a protein-protein interaction (PPI) network through the STRING database. After that we used Cytohubba plug-ins of Cytoscape to screen out the potential hub genes, which were subsequently verified via receiver operating characteristic (ROC) curves in another dataset, GSE178351, and revalidation of genes through the DisGeNET database. Results : We discovered 632 DEGs (570 upregulated genes and 62 downregulated genes). A total of eight modules were screened by WGCNA, among which the turquoise module was most correlated with PI. The Cytohubba plug-ins were used for filtering hub genes, which are highly linked with PI development, from the candidate genes in the protein-protein interaction (PPI) network. Conclusions : We found five key genes from PI using WGCNA. Among them, ICAM1, CXCL1, and JUN are worthy of further study of new target genes, providing the theoretical basis for further exploration of the occurrence and development mechanism of PI.

Background: Scientific evidence indicates that biological complications in dental implants tend to be concentrated in a subset of individuals, which seems to imply that the host response may play a determining role in implant success. Over the last few decades, several polymorphisms have been studied. Polymorphisms in the interleukin (IL) 1 gene cluster have been associated with periodontitis. There are some similar features in the sequence of immunopathological events in peri-implant and periodontal infections. We aimed to investigate if individuals carrying the genetic single nucleotide polymorphism (SNP) in the IL-1A (rs1800587) and IL-1B (rs1143634) genes are more susceptible to develop peri-implantitis., Methods: A cross-sectional analytic pilot study was conducted in 20 Caucasian Portuguese subjects divided into two groups: 10 subjects with peri-implantitis and 10 subjects with peri-implant health (control group). Samples containing cells from the buccal mucosa were stored at -20 °C and later submitted to the DNA extraction process. Genetic analysis was performed using the polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analysis. Data were analyzed by using descriptive and inferential statistical methodologies., Results: For the IL-1A (-889) gene polymorphism, it was observed that the mutated allele was present in a higher percentage in the peri-implantitis group compared to the control group (30% vs 15% respectively, Fisher's exact test, p  = 0.45). For the IL-1B (+3954) gene polymorphism, it was also observed that the altered allele was present in a higher percentage in the disease group compared to the control group (35% vs 10% respectively, Fisher's exact test, p  = 0.13). The positive genotype (at least one allele with nucleotide sequence changed in both genes) was detected in six patients, five belonging to the disease group and one to the health group., Conclusions: Regarding IL-1 gene polymorphisms, there was no statistically significant difference between the health and disease group, however a trend should be highlighted, showing a potential link between the IL-1 genotype and peri-implantitis. More studies are needed to clarify the role of genetic polymorphisms in the development of peri-implantitis., Competing Interests: The authors declare there are no competing interests., (©2022 Cardoso et al.)

Peri-implantitis is a plaque-associated condition characterized by mucosal inflammation and subsequent progressive loss of supporting bone; it is caused by bacterial biofilm, but the host response triggered by bacterial stimulation promotes the release of cells and mediators that culminate in tissue destruction. The Aryl-hydrocarbon Receptor (AhR) is associated with IL-22 production by Th22 and Th17 CD4+ Th cells. The presence of IL-6 may promote the Th22 phenotype. The present case-control study evaluated the gene expression of AhR, IL-22, and IL-6 in the peri-implant tissues of healthy and peri-implantitis patients. Tissue biopsies were collected from thirty-five volunteers (15 healthy and 20 with peri-implantitis). A real-time PCR reaction was utilized to assess the AhR, IL-22, and IL-6 gene expression levels relative to the reference gene (GAPDH). The results were analyzed using the Mann-Whitney test with a significance level of 5%. Higher levels of gene expression of AhR and IL-6 were detected in peri-implantitis tissues. The IL-22 gene expression levels did not differ between groups. In conclusion, higher gene expression levels for AhR and IL-6 were detected in the soft tissues of peri-implantitis patients. IL-22 did not vary between conditions, which may indicate the loss of the immunomodulatory role of IL-22 in periimplantitis.

Purpose: To perform a systematic review and meta-analysis on the presence of inflammatory polymorphisms in patients with peri-implantitis (PI). PI is the main complication associated to dental implant therapy. Although its main risk factors are history of periodontitis, poor plaque control and lack of regular maintenance, genetic susceptibility could also be a determinant factor for its appearance. Single nucleotide polymorphisms (SNP) are small mutations of the DNA that alter the osseointegration of implants. Inflammatory proteins participate in both destruction of the extracellular matrix and reabsorption of the alveolar bone., Methods: A bibliographical research was made in PubMed, Scopus and Web of Science (keywords: "single nucleotide polymorphism", "polymorphism", "periimplantitis", "SNP" and "implant failure")., Results: There is a statistically significant association of peri-implant bone loss with the homozygotic model of IL-1β (- 511) (OR: 2.255; IC: 1.040-4.889)., Conclusions: Associations between inflammatory polymorphisms and PI must be taken with caution due to the heterogeneous methodological design, sample size and diagnostic criteria of the studies. Thus, more well-designed studies are needed that analyze the relationship between these and more SNP and PI., (© 2022. The Author(s).)

Background: 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., Aim: 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., Material and Methods: 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., Results: 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)., Conclusions: 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.

Objectives: To investigate potential genetic biomarkers of peri-implantitis and target genes for the therapy of peri-implantitis by bioinformatics analysis of publicly available data., Methods: The GSE33774 microarray dataset was downloaded from the Gene Expression Omnibus (GEO). The differentially expressed genes (DEGs) between peri-implantitis and healthy gingival tissues were identified using the GEO2R tool. GO enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed using the DAVID database and the Metascape tool, and the results were expressed as a bubble diagram. The protein-protein interaction network of DEGs was constructed using the Search Tool for the Retrieval of Interacting Genes (STRING) and visualized using Cytoscape. The hub genes were screened by the cytoHubba plugin of Cytoscape. The potential target genes associated with peri-implantitis were obtained from the DisGeNET database and the Open Targets Platform. The intersecting genes were identified using the Venn diagram web tool., Results: Between the peri-implantitis group and the healthy group, 205 DEGs were investigated including 140 upregulated genes and 65 downregulated genes. These DEGs were mainly enriched in functions such as the immune response, inflammatory response, cell adhesion, receptor activity, and protease binding. The results of KEGG pathway enrichment analysis revealed that DEGs were mainly involved in the cytokine-cytokine receptor interaction, pathways in cancer, and the PI3K-Akt signaling pathway. The intersecting genes, including IL6 , TLR4 , FN1 , IL1β , CXCL8 , MMP9 , and SPP1 , were revealed as potential genetic biomarkers and target genes of peri-implantitis., Conclusions: This study provides supportive evidence that IL6 , TLR4 , FN1 , IL1β , CXCL8 , MMP9 , and SPP1 might be used as potential target biomarkers for peri-implantitis which may provide further therapeutic potentials for peri-implantitis., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Xiaogen Zhang et al.)

Peri-implant disease is an inflammatory disease and is related to genetic heterogeneity. Considering the genetic association of epidermal growth factor ( EGF ) gene polymorphisms with the susceptibility of periodontitis, its genetic association with peri-implantitis risk in a Chinese Han population was explored. Three hundred individuals who underwent dental implants were recruited, and divided into healthy implant group and peri-implantitis group. The genotype and allele distribution of EGF gene rs2237051 and rs4444903 polymorphisms were analyzed via direct sequencing and the frequencies were compared between the two groups using chi-square test. No significant difference was detected for the clinical information between healthy implant group and peri-implantitis group, including lifestyle habits platform type and position, peri-implant phenotype, brushing time, dental floss, and mouth washing frequencies. Individuals with peri-implantitis had poor periodontal status. The GG genotype and G allele of rs2237051 showed significant increasing trend in peri-implantitis group compared with the healthy implant group. Compared with the AA genotype carriers, rs2237051 GG genotype carriers showed lower risk to suffer from peri-implantitis (OR = 0.236, 95%CI = 0.089-0.624), and possessed low values of gingival index, plaque index and calculus index, peri-implant pocket depth (PPD) and clinical attachment level (CAL). But there was no significant difference for the rs4444903 genotype distributions between the case and control groups. In summary, EGF rs2237051 polymorphism showed close association with the genetic background of peri-implantitis. Rs2237051 GG genotype and G allele might be protective factors for the onset of peri-implantitis.

Background: This bioinformatics study aimed to reveal potential cross-talk genes, related pathways, and transcription factors between periimplantitis and rheumatoid arthritis (RA)., Methods: The datasets GSE33774 (seven periimplantitis and eight control samples) and GSE106090 (six periimplantitis and six control samples) were included from the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO). A differential expression analysis ( p < 0.05 and |logFC (fold change)| ≥ 1) and a functional enrichment analysis ( p < 0.05) were performed. Based on this, a protein-protein interaction (PPI) network was constructed by Cytoscape. RA-related genes were extracted from DisGeNET database, and an overlap between periimplantitis-related genes and these RA-related genes was examined to identify potential cross-talk genes. Gene expression was merged between two datasets, and feature selection was performed by Recursive Feature Elimination (RFE) algorithm. For the feature selection cross-talk genes, support vector machine (SVM) models were constructed. The expression of these feature genes was determined from GSE93272 for RA. Finally, a network including cross-talk genes, related pathways, and transcription factors was constructed., Results: Periimplantitis datasets included 138 common differentially expressed genes (DEGs) including 101 up- and 37 downregulated DEGs. The PPI interwork of periimplantitis comprised 1,818 nodes and 2,517 edges. The RFE method selected six features, i.e., MERTK, CD14, MAPT, CCR1, C3AR1, and FCGR2B, which had the highest prediction. Out of these feature genes, CD14 and FCGR2B were most highly expressed in periimplantitis and RA. The final activated pathway-gene network contained 181 nodes and 360 edges. Nuclear factor (NF) kappa B signaling pathway and osteoclast differentiation were identified as potentially relevant pathways., Conclusions: This current study revealed FCGR2B and CD14 as the most relevant potential cross-talk genes between RA and periimplantitis, which suggests a similarity between RA and periimplantitis and can serve as a theoretical basis for future research., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Li, Zhou, Xu, Wang, Li, Pelekos, Ziebolz, Schmalz and Qin.)

Background: Pro-inflammatory cytokines interleukin-1 (IL-1) and tumor necrosis factor α (TNFα) play important roles in host immune response and bone metabolism during dental implant osseointegration. Whether the functional polymorphisms in IL-1α, IL-1β and TNFα were associated with peri-implant disease was unclear, and we performed the present meta-analysis for this purpose., Methods: Eligible studies investigating IL-1α C-889T, IL-1β C+3954T and C-511T, TNFα G-308A, composite genotype of IL-1α C-889T and IL-1β C+3954T for association with peri-implant disease, including peri-implantitis (PI), marginal bone loss (MBL) and implant failure/loss (IF/IL), were searched on several literature databases prior to April 30, 2021. Odds ratio (OR) and corresponding 95% confidence interval (CI) were calculated for each polymorphism in different genetic models and for composite genotype comparing carriers to non-carriers., Results: Twenty-seven studies (1324 cases with peri-implant disease and 1808 controls with healthy implants) were included. There was significant correlation between IL-1α C-889T and peri-implant disease in all genetic models. IL-1β C+3954T was associated with peri-implant disease risk in allelic (OR = 1.66, 95%CI 1.17-2.35, p = 0.004) and dominant model (OR = 1.74, 95%CI 1.19-2.53, p = 0.004), and in subgroups of Asians, Caucasians, non-smokers, IF/IL and PI. TT genotype of IL-1β C-511T increased the risk of peri-implant disease (OR = 1.68, 95%CI 1.15-2.43, p = 0.007) and MBL (OR = 4.33, 95%CI 1.72-10.9, p = 0.002) compared to CC+CT genotypes. We did not observed a significant association between TNFα G-308A and peri-implant diseases in overall or subgroups analysis. Carriers of positive composite genotype of IL-1α C-889T and IL-1β C+3954T had 1.95-fold (95%CI 1.35-2.80, p<0.001) risk of peri-implant disease and 1.76-fold (95%CI 1.05-2.95, p = 0.032) risk of IF/IL than non-carriers., Conclusion: Functional polymorphisms of IL-1α (C-889T), IL-1β (C+3954T, C-511T) and composite genotype of IL-1 can be used as predictive markers for peri-implant disease, whereas TNFα G-308A polymorphism was not associated with peri-implant disease., Competing Interests: The authors have declared that no competing interests exist.

Objective: Chronic periodontitis (CP), aggressive periodontitis (AP), and peri-implantitis (PI) are chronic inflammatory diseases. Tumor necrosis factor-α (TNF-a) is an effective immune inflammatory mediator. Several studies have been conducted to explore the association between the TNF-α (G-308A) polymorphism and susceptibility to CP, AP, and PI. Our objective was to examine whether the TNF-α (G-308A) polymorphism is related to these diseases., Methods: We conducted a meta-analysis to investigate the association between the TNF-α (G-308A) polymorphism and CP, AP, and PI. The PubMed, Embase, CNKI, and Web of Science electronic databases were searched for studies published from inception to August 11, 2020; the reference lists of included studies were also searched. The included studies were assessed in the following genetic models: dominant model, recessive model, allelic model, heterozygous model, and homozygous model., Results: Forty articles (50 comparisons) with 2243 CP, 824 AP, 615 PI, 795 healthy peri-implant, and 3575 healthy controls were considered for the TNF-α (G-308A) polymorphism in this meta-analysis. Variant A of TNF-α (G-308A) was associated with increased AP risk in the general population, especially in Asians, and this polymorphism was significantly associated with elevated risk of CP in Asians and Caucasians. There was no association between the A allele and PI risk. None of the contrasts of the genetic model yielded a significant finding in Latin Americans. Different genotyping methods may affect the association between the TNF-α (G-308A) polymorphism and these diseases., Conclusion: These findings supported that variant A of the TNF-α (G-308A) polymorphism may contribute to CP and AP susceptibility, particularly in Asians and Caucasians. More efforts and further studies with larger sample sizes will be required to validate the risk of CP, AP, and PI., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Peri-implantitis (PI) is a multifactorial condition caused by the interactions of pathogens and the host immune response. Previous studies have demonstrated a relationship between PI and specific gene polymorphisms, particularly cytokine genes involved in the pathogenesis of PI. This study aimed to evaluate the frequency of single nucleotide polymorphisms (SNPs) of interleukin-10 (IL-10), interleukin 1ß (IL-1ß), and tumor necrosis factor-α (TNF-α) genes in PI patients and healthy controls. A total of 50 patients with PI and 89 periodontally healthy controls were recruited for this study. Venous blood samples (5 cc) were collected, and DNA was extracted. After DNA purification, the relevant gene segments were amplified by polymerase chain reaction (PCR). Restriction fragment length polymorphism (RFLP) and electrophoresis were performed to assess the polymorphisms of the related genes. The analysis revealed that allele and genotype frequencies of IL-10 ─ 819 C/T, IL-10 ─ 592 C/A, and IL-1ß + 3954 C/T significantly differed between PI patients and healthy controls. The analysis revealed no significant association between TNF-α ─ 857 G/A and TNF-α ─ 308 G/A polymorphisms and PI. Our results indicated that specific gene polymorphisms of IL-10 ─ 819 C/T, IL-10 ─ 592 C/A, and IL-1ß + 3954 C/T may play a role in the pathogenesis of PI, and increase its risk of occurrence.

This study compared the gene expression of the immunoinflammatory markers interleukin (IL)-6, IL-1ß, and tumor necrosis factor alpha (TNF-α), the matrix metalloproteinases (MMP)-1, -2, -8, and -9, and the tissue inhibitors of matrix metalloproteases (TIMP)-1 and -2 in the gingival tissue of individuals with periodontal and peri-implant disease. The study population included individuals with four periodontal statuses: periodontal health (PH group, n = 20); periodontitis (P group, n = 20); peri-implant health (PIH group, n = 20), and peri-implantitis (PI group, n = 20). Gingival biopsies were collected from one tooth per patient according to the inclusion criteria of each group. The mRNA levels of IL-6, IL-1ß, TNF-α, MMP-1, MMP-2, MMP-8, MMP-9, TIMP-1, and TIMP-2 were evaluated by qPCR. The levels of IL-1ß were significantly higher in the PI group when compared to the other groups ( p < 0.05), while the levels of IL-6 were significantly higher in the groups with periodontal and peri-implant disease when compared with the healthy groups ( p < 0.05); however, the levels of IL-6 did not differ between the PI and P groups ( p > 0.05). For all other studied biomarkers, no significant differences were observed between groups ( p > 0.05). IL-6 and IL-1ß presented higher levels of mRNA in diseased periodontal and peri-implant tissues. However, the expression of metalloproteinases and their inhibitors did not differ between the different periodontal statuses.

Background: Peri-implantitis is an inflammation that occurs around the implant, resulting in varying degrees of inflammatory damage to the soft and hard tissues. The characteristic criterion is the loss of the supporting bone in an inflammatory environment. However, the specific mechanisms and biomarkers involved in peri-implantitis remain to be further studied. Recently, competing endogenous RNAs (ceRNA) and immune microenvironment have been found to play a more important role in the inflammatory process. In our study, we analyzed the expression of immune related microRNAs (miRNAs), long noncoding RNAs (lncRNAs) and message RNAs (mRNAs) in peri-implantitis by analyzing GSE33774 and GSE57631., Methods: In this study, we explored the expression profile data of immune-related lncRNAs, miRNAs and mRNAs, and constructed immune-related ceRNA network involved in the pathogenesis of peri-implantitis. In addition, the CIBERSORT was used to evaluate the content of immune cells in normal tissues and peri-implantitis to detect the immune microenvironment of peri-implantitis., Results: In the analysis, 14 DElncRNAs, 16 DEmiRNAs, and 18 DEmRNAs were used to establish an immune related ceRNA network and the immune infiltration patterns associated with peri-implantitis was discovered. Through the mutual verification of the two datasets, we found that GSK3B and miR-1297 may have important significance in the immune microenvironment and pathogenesis of peri-implantitis and GSK3B was closely related to four types of immune cells, especially with the highest correlation with resting mast cells (P = 0.0003)., Conclusions: Through immune-related ceRNA network, immune-related genes (IRGs) and immune cell infiltration can further comprehensively understand the pathogenesis of peri-implantitis, which built up an immunogenomic landscape with clinical significance for peri-implantitis.

Aim: The purpose of this review was to evaluate the expression patterns of miRNAs in periodontal and peri-implant diseases, while identifying potential miRNAs with the greatest diagnostic ability as an oral fluid biomarker., Materials and Methods: Human and animal studies were included when evaluating expression of miRNAs between health and different forms/stages of diseases, in which microarray and/or real-time polymerase chain reaction (RT-PCR) was carried out to detect fold changes in gene expression. After full-text analysis, 43 articles were considered for a qualitative assessment, and 16 miRNAs were selected to perform meta-analysis., Results: Based on human studies, results showed an overall upregulation of most of the evaluated miRNAs in periodontitis, with miRNA-142-3p and miRNA-146a being the most conclusive on both microarray and RT-PCR values and potentially serving as diagnostic biomarkers for disease activity. Conversely, miR-155 was the only miRNA revealing a statistically significant difference (SSD) ( p < 0.05*) in experimental periodontitis models from RT-PCR values. Scarce scientific evidence is available from peri-implant diseases, however, most explored miRNAs in peri-implantitis were downregulated except for miR-145., Conclusions: Although our results revealed that a distinct differential expression of specific miRNAs can be noted between the state of health and disease, future research remains necessary to explore the functional role of specific miRNAs and their potential as therapeutic targets in periodontal and peri-implant diseases. MeSH Terms: periodontitis, peri-implantitis, epigenomics, microarray analysis, real-time polymerase chain reaction, microRNAs., Clinical Relevance: Scientific background: Although most research identified different expression levels of miRNAs in periodontal and peri-implant diseases compared to their counterparts, their actual role in the pathogenesis of these conditions remains unclear. Therefore, we aimed to present a systematic review and meta-analysis on the expression patterns of miRNAs in periodontitis and peri-implantitis, while identifying potential miRNAs with the greatest diagnostic ability as an oral fluid biomarker., Principal Findings: In periodontitis-related studies, miRNA-142-3p and miRNA-146a were the most conclusive on both microarray and RT-PCR values. Scarce scientific evidence is available from peri-implant diseases., Practical Implications: Both miRNA-142-3p and miRNA-146a might serve as future diagnostic biomarkers for disease activity in periodontitis. Yet, future research remains necessary to explore the functional role of specific miRNAs and their potential as therapeutic targets in periodontal and peri-implant diseases.

Background and Objective: Peri-implantitis is a biofilm-mediated infectious disease that results in progressive loss of implant-supporting bone. As compared to its analogue periodontitis, peri-implantitis is generally known to be more aggressive, with comparatively rapid progression and less predictable treatment outcomes, especially when advanced. An understanding of molecular mechanisms underpinning the similarities and differences between peri-implantitis and periodontitis is essential to develop novel management strategies. This study aimed to compare long non-coding RNAs (lncRNAs) and messenger RNA (mRNA) expression profiles between peri-implantitis and periodontitis., Methods: Inflamed soft tissue from peri-implantitis and periodontitis lesions, and healthy gingival tissue controls were analyzed by microarray. Cluster graphs, gene ontology (GO) analysis, and pathway analysis were performed. Quantitative real-time PCR was employed to verify microarray results. The expression levels of RANKL and OPG in the three tissue types were also evaluated, using qRT-PCR. Coding non-coding (CNC) network analyses were performed., Results: Microarray analyses revealed 1079 lncRNAs and 1003 mRNAs as differentially expressed in peri-implantitis when compared to periodontitis. The cyclooxygenase-2 pathway was the most up-regulated biological process in peri-implantitis as compared to periodontitis, whereas hemidesmosome assembly was the most down-regulated pathway. Osteoclast differentiation was relatively up-regulated, and RANKL/OPG ratio was higher in peri-implantitis than in periodontitis., Conclusions: The study demonstrated that peri-implantitis and periodontitis exhibit significantly different lncRNA and mRNA expression profiles, suggesting that osteoclast differentiation-related pathways are comparatively more active in peri-implantitis. These data highlight potential molecular targets for periodontitis and peri-implantitis therapy development., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Peri-implantitis is similar to periodontitis in both symptoms and treatment; however, their level of similarity remains controversial. Here, we compared multiple cases of periodontitis and peri-implantitis through transcriptome and methylome profiling, and analyzed the effects of smoking as a typical risk factor. Human gingival tissues were obtained from 20 patients with periodontitis or peri-implantitis via periodontal surgical procedures. Total RNA and genomic DNA were isolated, and transcriptome and methylome datasets were generated. Comprehensive analysis of differential gene expression, DNA methylation, and protein-protein interactions indicated that periodontitis and peri-implantitis share biological similarities; however, hierarchical clustering between the two disease groups revealed distinct molecular characteristics. These differences might be related to structural differences in natural tooth-bone and implant-bone. Additionally, smoking differentially affected periodontitis and peri-implantitis in terms of host-defense mechanism impairment. Within the limitations of this study, the results provide evidence that peri-implantitis is distinct from periodontitis and that smoking potentially affects disease progression. Our study provides a foundation for the rational design of a large-scale study in the future for a more comprehensive analysis that includes microbiome and clinical data., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objectives: The purpose of this study was to investigate whether the genetic variations which could regulate inflammatory responses were associated with the risk of peri-implantitis., Materials and Methods: We evaluated three genetic variants including tumor necrosis factor-alpha (TNF-α) - 308G/A, interleukin-1 alpha (IL-1A) - 889C/T, and IL-1 beta (IL-1B) + 3954C/T, as risk factors for peri-implantitis, in a total of 144 patients with peri-implantitis and 174 healthy controls in a Chinese non-smoking population., Results: Logistic regression analyses revealed that subjects carrying the T allele of IL-1A - 889C/T and IL-1B + 3954C/T had a significant 2.27-2.47-fold (CT, OR [95% CI] = 2.27 [1.12-4.58], p = 0.021; TT, OR [95% CI] = 2.47 [1.32-4.69], p = 0.006) and 1.9-1.99-fold (CT, OR [95% CI] = 1.99 [1-3.93], p = 0.041; TT, OR [95% CI] = 1.9 [1.08-3.43], p = 0.03) increased risk of peri-implantitis, respectively, when using the CC genotype as a reference point. And subjects carrying the TT genotype of IL-1A - 889C/T or IL-1B + 3954C/T also had significantly higher periodontal variables including peri-implant pocket depth (PPD), bleeding on probing (BOP), gingival index (GI), plaque index (PI), calculus index (CI), and clinical attachment level (CAL) (p < 0.05). However, no associations were found between the TNF-α - 308G/A polymorphism and the risk of peri-implantitis., Conclusions: Our results suggest that the IL-1A - 889C/T or IL-1B + 3954C/T genetic polymorphisms were associated with the risk of peri-implantitis and periodontal status., Clinical Relevance: Genetic polymorphisms are constant and can be measured before disease onset, thus it could be of great benefit for treatment planning and prognosis in an early stage.

The interactome - the network of protein-protein interactions (PPIs) within a cell or organism - is technically difficult to assess. Bioinformatic tools can, not only, identify potential PPIs that can be later experimentally validated, but also be used to assign functional meaning to PPIs. Saliva's potential as a non-invasive diagnostic fluid is currently being explored by several research groups. But, in order to fully attain its potential, it is necessary to achieve the full characterization of the mechanisms that take place within this ecosystem. The onset of omics technologies, and specifically of proteomics, delivered a huge set of data that is largely underexplored. Quantitative information relative to proteins within a given context (for example a given disease) can be used by computational algorithms to generate information regarding PPIs. These PPIs can be further analyzed concerning their functional meaning and used to identify potential biomarkers, therapeutic targets, defense and pathogenicity mechanisms. We describe a computational pipeline that can be used to identify and analyze PPIs between human and microbial proteins. The pipeline was tested within the scenario of human PPIs of systemic (Zika Virus infection) and of oral conditions (Periodontal disease) and also in the context of microbial interactions (Candida-Streptococcus) and showed to successfully predict functionally relevant PPIs. The pipeline can be applied to different scientific areas, such as pharmacological research, since a functional meaningful PPI network can provide insights on potential drug targets, and even new uses for existing drugs on the market., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Periodontitis and peri-implantitis are multifactorial diseases characterized by alveolar bone destruction mediated by the host response to a microbial challenge. Alveolar bone resorption mediated by epigenetics could be one of the mechanisms responsible for this destruction of alveolar bone. The relationship between epigenetic modifications and bone metabolism has been thoroughly investigated in bone remodeling, cancer, and rheumatoid arthritis, but evidence is low regarding the relationship between epigenetic modifications and alveolar bone loss related to periodontal and peri-implant diseases. Therefore, we conducted a review of the pertinent literature based on a priori-formulated focused questions and a screening strategy, in an attempt to comprehend the role of different epigenetic mechanisms in alveolar bone loss and to determine the current state with respect to their possible therapeutic applications in regenerative medicine. The review showed that the roles of DNA methylation, histone modifications, and non-coding RNAs in bone loss have been investigated. The results indicate that epigenetic mechanisms can participate in periodontal and peri-implant alveolar bone breakdown, suggesting their potential as therapeutic targets in alveolar bone regeneration. However, there is still only preliminary information regarding the possible therapeutic utility of these epigenetic mechanisms, suggesting a need for basic and translational research to assess the potential of such mechanisms in promoting alveolar bone regeneration., (© 2019 Eur J Oral Sci.)

Implant loss is the most serious complication of dental implants. Although the problems and causes behind the implant failure are clearly defined today, determination of the underlying causes of failure varies by the case. The clusterization phenomenon of implant loss (multiple implant failures) implies the existence of genetic risk factors. Inflammation has a critical effect on osseointegration and implant success. Peri-implantitis is an inflammatory disease of tissue supporting the tooth or implant. Inflammation leads to loss of support tissue, particularly bone, resulting in failure of implants. A single nucleotide polymorphism (SNP) of pro-inflammatory mediator genes may affect their expression levels or amino acid sequence, and, consequently, the host inflammatory response. Since the end of the past century, many studies have been conducted to investigate the association of SNP with implant failure and related conditions. Involvement of several groups of genes-including interleukins, tumor necrosis factor-α, matrix metalloproteinases, and growth factors involved in immune regulation, inflammatory response, and bone metabolism-has been explored. Some have been found to be associated with implant loss and considered potential genetic risk factors for implant failure. In this review, we summarize results of recent studies of impact of genetic factors on dental implant failure.

Purpose: To evaluate the gene expression levels of semaphorins 3A, 3B, 4A, and 4D in both healthy and diseased implants., Materials and Methods: Subjects with peri-implantitis presented clinical attachment loss, probing depth ≥ 5 mm, bleeding on probing and/or suppuration, and radiographic bone loss > 4 mm. Peri-implant tissue biopsy specimens were sampled for analysis of the mRNA expression levels for semaphorins 3A, 3B, 4A, and 4D. A real-time polymerase chain reaction was performed, and the gene expression levels of semaphorins in relation to the housekeeping gene were analyzed by using the nonparametric Mann-Whitney test (P < .05)., Results: Thirty-five subjects (16 men, 19 women; mean age: 54.12 ± 2.34 years) with implant-supported restorations, using screw-shaped dental implants with internal or external hexagon were enrolled in this study. Higher levels of semaphorins 3A and 4D were detected in the peri-implantitis compared with the healthy tissues (P = .0011 and P = .0404, respectively), whereas Sem4A levels were significantly higher in the control group (P < .0001). Differences between groups in the expression levels of Sem3B were not significant., Conclusion: Advanced peri-implantitis lesions showed higher levels of gene expression for Sem3A and Sem4D and lower levels of Sem4A in comparison to tissues obtained from a healthy dental implant.

Background and Objective: Peri-implantitis (PI) is an inflammatory condition that affects the tissues surrounding dental implants. Although the pathogenesis of PI is not fully understood, evidence suggests that the etiology is multifactorial and may include a genetic component. The aim of this study was to investigate the role of genetics in the development of peri-implantitis., Material and Methods: Four-week-old C57BL/6J, C3H/HeJ and A/J male mice had their left maxillary molars extracted. Implants were placed in the healed extraction sockets. Upon osseointegration, ligatures were placed around the implant head for 1 or 4 weeks to induce PI. Micro-computed tomography scanning was used to measure volumetric bone loss. Histological analyses were also performed to evaluate collagen organization and the presence of neutrophils and osteoclasts., Results: Radiographically, comparing the ligature-treated mice, C57BL/6J displayed the greatest amount of bone loss, followed by C3H/HeJ and A/J mice at 1 and 4 weeks. Histologically, at 1 week, C57BL/6J mice presented with the highest numbers of neutrophils and osteoclasts. At 4 weeks, C57BL/6J mice presented with the most active bone remodeling compared with the other two strains., Conclusion: There were significant differences in the severity of peri-implantitis among the different mouse strains, suggesting that the genetic framework can affect implant survival and success. Future work is needed to dissect the genetic contribution to the development of peri-implantitis., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

In chronic periodontitis and peri-implantitis, cells of the innate and adaptive immune systems are involved directly in the lesions within the tissues of the patient. Absence of a periodontal ligament around implants does not prevent a biologic process similar to that of periodontitis from affecting osseointegration. Our first focus is on factors in the biology of individuals that are responsible for the susceptibility of such individuals to chronic periodontitis and to peri-implantitis. Genetic factors are of significant importance in susceptibility to these diseases. Genetic factors of the host affect the composition of the oral microbiome in the same manner that they influence other microbiomes, such as those of the intestines and of the lungs. Our second focus is on the central role of stem cells in tissue regeneration, in the functioning of innate and adaptive immune systems, and in metabolism of bone. Epithelial cell rests of Malassez (ERM) are stem cells of epithelial origin that maintain the periodontal ligament as well as the cementum and alveolar bone associated with the ligament. The tissue niche within which ERM are found extends into the supracrestal areas of collagen fiber-containing tissues of the gingivae above the bony alveolar crest. Maintenance and regeneration of all periodontal tissues involves the activity of a variety of stem cells. The success of dental implants indicates that important groups of stem cells in the periodontium are active to enable that biologic success. Successful replantation of avulsed teeth and auto-transplantation of teeth is comparable to placing dental implants, and so must also involve periodontal stem cells. Biology of teeth and biology of implants represents the biology of the various stem cells that inhabit specialized niches within the periodontal tissues. Diverse biologic processes must function together successfully to maintain periodontal health. Osseointegration of dental implants does not involve formation of cementum or collagen fibers inserted into cementum - indicating that some stem cells are not active around dental implants or their niches are not available. Investigation of these similarities and differences between teeth and implants will help to develop a better understanding of the biology and physiologic functioning of the periodontium.

Peri-implantitis, which is characterized by dense inflammatory infiltrates and increased osteoclast activity, can lead to alveolar bone destruction and implantation failure. miRNAs participate in the regulation of various inflammatory diseases, such as periodontitis and osteoporosis. Therefore, the present study aimed to investigate the differential expression of miRNAs in canine peri-implantitis and to explore the functions of their target genes. An miRNA sequence analysis was used to identify differentially expressed miRNAs in peri-implantitis. Under the criteria of a fold-change >1.5 and P <0.01, 8 up-regulated and 30 down-regulated miRNAs were selected for predictions of target genes and their biological functions. Based on the results of Gene Ontology (GO) and KEGG pathway analyses, these miRNAs may fine-tune the inflammatory process in peri-implantitis through an intricate mechanism. The results of quantitative real-time PCR (qRT-PCR) revealed that let-7g, miR-27a , and miR-145 may play important roles in peri-implantitis and are worth further investigation. The results of the present study provide insights into the potential biological effects of the differentially expressed miRNAs, and specific enrichment of target genes involved in the mitogen-activated protein kinase (MAPK) signaling pathway was observed. These findings highlight the intricate and specific roles of miRNAs in inflammation and osteoclastogenesis, both of which are key aspects of peri-implantitis, and thus may contribute to future investigations of the etiology, underlying mechanism, and treatment of peri-implantitis., (© 2017 The Author(s).)