Mediators of Periodontal Osseous Destruction and Remodeling: Principles and Implications for Diagnosis and Therapy

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142298/1/jper1377.pd

Expression of Extracellular Matrix Proteins in Human Periodontal Ligament Cells During Mineralization In Vitro

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142249/1/jper0320.pd

Dexamethasone and Basic‐Fibroblast Growth Factor Regulate Markers of Mineralization in Cementoblasts In Vitro

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142252/1/jper1550.pd

Epigenetic adaptations of the masticatory mucosa to periodontal inflammation

Background: In mucosal barrier interfaces, flexible responses of gene expression to long-term environmental changes allow adaptation and fine-tuning for the balance of host defense and uncontrolled not-resolving inflammation. Epigenetic modifications of the chromatin confer plasticity to the genetic information and give insight into how tissues use the genetic information to adapt to environmental factors. The oral mucosa is particularly exposed to environmental stressors such as a variable microbiota. Likewise, persistent oral inflammation is the most important intrinsic risk factor for the oral inflammatory disease periodontitis and has strong potential to alter DNA-methylation patterns. The aim of the current study was to identify epigenetic changes of the oral masticatory mucosa in response to long-term inflammation that resulted in periodontitis. Methods and results: Genome-wide CpG methylation of both inflamed and clinically uninflamed solid gingival tissue biopsies of 60 periodontitis cases was analyzed using the Infinium MethylationEPIC BeadChip. We validated and performed cell-type deconvolution for infiltrated immune cells using the EpiDish algorithm. Effect sizes of DMPs in gingival epithelial and fibroblast cells were estimated and adjusted for confounding factors using our recently developed “intercept-method”. In the current EWAS, we identified various genes that showed significantly different methylation between periodontitis-inflamed and uninflamed oral mucosa in periodontitis patients. The strongest differences were observed for genes with roles in wound healing (ROBO2, PTP4A3), cell adhesion (LPXN) and innate immune response (CCL26, DNAJC1, BPI). Enrichment analyses implied a role of epigenetic changes for vesicle trafficking gene sets. Conclusions: Our results imply specific adaptations of the oral mucosa to a persistent inflammatory environment that involve wound repair, barrier integrity, and innate immune defense

Genetic Association of a Gain-of-Function IFNGR1 Polymorphism and the Intergenic Region LNCAROD/DKK1 With Behcet's Disease

Objective. Behçet’s disease is a complex systemic inflammatory vasculitis of incompletely understood etiology. This study was undertaken to investigate genetic associations with Behçet’s disease in a diverse multiethnic population.Methods. A total of 9,444 patients and controls from 7 different populations were included in this study. Genotyping was performed using an Infinium ImmunoArray- 24 v.1.0 or v.2.0 BeadChip. Analysis of expression data from stimulated monocytes, and epigenetic and chromatin interaction analyses were performed.Results. We identified 2 novel genetic susceptibility loci for Behçet’s disease, including a risk locus in IFNGR1(rs4896243) (odds ratio [OR] 1.25; P = 2.42 × 10−9) and within the intergenic region LNCAROD/DKK1 (rs1660760) (OR 0.78; P = 2.75 × 10−8). The risk variants in IFNGR1 significantly increased IFNGR1 messenger RNA expression in lipopolysaccharide- stimulated monocytes. In addition, our results replicated the association (P 30 genetic susceptibility loci with a suggestive level of association (P < 5 × 10−5), which will require replication. Finally, functional annotation of genetic susceptibility loci in Behçet’s disease revealed their possible regulatory roles and suggested potential causal genes and molecular mechanisms that could be further investigated.Conclusion. We performed the largest genetic association study in Behçet’s disease to date. Our findings reveal novel putative functional variants associated with the disease and replicate and extend the genetic associations in other loci across multiple ancestries

Evaluation Of Gingival Crevicular Fluid And Peri-Implant Sulcus Fluid Levels Of Periostin: A Preliminary Report

BackgroundPeriostin is a protein present in alveolar bone and periodontal ligament whose function is related to response to external forces. The aims of this study are to detect levels of periostin in peri-implant sulcular fluid (PISF) and gingival crevicular fluid (GCF) and to evaluate the relationship between periostin, pyridinoline cross-linked carboxyterminal telopeptide of Type I collagen (ICTP), and C-terminal cross-linked telopeptide of Type I collagen (CTX) levels and clinical inflammatory symptoms and duration of functional loading. MethodsThe study population comprised nine women and four men with mean age 43.23 12.48. Twenty bone-level designed dental implants (DIs) placed in molar or premolar sites, without any signs of peri-implant bone loss and with a restoration in function for at least 12 months, were included in the study with 20 contralateral natural teeth (NT) as controls. Clinical parameters and restoration dates of the implants were recorded. PISF, GCF, ICTP, CTX, and periostin levels were evaluated using enzyme-linked immunosorbent assay. ResultsICTP, CTX, and periostin levels were similar between DI and NT groups. There were no statistically significant differences between PISF and GCF values. When implants were grouped as healthy (gingival index [GI]=0) and inflamed (GI0), ICTP levels and PISF volume were lower in healthy implants compared with the inflamed group. Both periostin and CTX levels were negatively correlated with functioning time, suggesting less bone remodeling around DIs at later stages of functioning. ConclusionFindings of this study suggest collagen breakdown products may be used as markers to evaluate peri-implant metabolism.Wo