Porphyromonas gingivalis oral infection exacerbates the development and severity of collagen-induced arthritis

Abstract Introduction Clinical studies suggest a direct influence of periodontal disease (PD) on serum inflammatory markers and disease assessment of patients with established rheumatoid arthritis (RA). However, the influence of PD on arthritis development remains unclear. This investigation was undertaken to determine the contribution of chronic PD to immune activation and development of joint inflammation using the collagen-induced arthritis (CIA) model. Methods DBA1/J mice orally infected with Porphyromonas gingivalis were administered with collagen II (CII) emulsified in complete Freund’s adjuvant (CFA) or incomplete Freund’s adjuvant (IFA) to induce arthritis. Arthritis development was assessed by visual scoring of paw swelling, caliper measurement of the paws, mRNA expression, paw micro-computed tomography (micro-CT) analysis, histology, and tartrate resistant acid phosphatase for osteoclast detection (TRAP)-positive immunohistochemistry. Serum and reactivated splenocytes were evaluated for cytokine expression. Results Mice induced for PD and/or arthritis developed periodontal disease, shown by decreased alveolar bone and alteration of mRNA expression in gingival tissues and submandibular lymph nodes compared to vehicle. P. gingivalis oral infection increased paw swelling and osteoclast numbers in mice immunized with CFA/CII. Arthritis incidence and severity were increased by P. gingivalis in mice that received IFA/CII immunizations. Increased synovitis, bone erosions, and osteoclast numbers in the paws were observed following IFA/CII immunizations in mice infected with P gingivalis. Furthermore, cytokine analysis showed a trend toward increased serum Th17/Th1 ratios when P. gingivalis infection was present in mice receiving either CFA/CII or IFA/CII immunizations. Significant cytokine increases induced by P. gingivalis oral infection were mostly associated to Th17-related cytokines of reactivated splenic cells, including IL-1β, IL-6, and IL-22 in the CFA/CII group and IL-1β, tumor necrosis factor-α, transforming growth factor-β, IL-6 and IL-23 in the IFA/CII group. Conclusions Chronic P. gingivalis oral infection prior to arthritis induction increases the immune system activation favoring Th17 cell responses, and ultimately accelerating arthritis development. These results suggest that chronic oral infection may influence RA development mainly through activation of Th17-related pathways.http://deepblue.lib.umich.edu/bitstream/2027.42/112639/1/13075_2013_Article_4062.pd

Common Polymorphisms in IFI16 and AIM2 Genes Are Associated With Periodontal Disease

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142266/1/jper0663-sup-0009.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/142266/2/jper0663-sup-0008.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/142266/3/jper0663-sup-0010.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/142266/4/jper0663-sup-0005.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/142266/5/jper0663.pd

Genome-wide association study of biologically informed periodontal complex traits offers novel insights into the genetic basis of periodontal disease

Genome-wide association studies (GWAS) of chronic periodontitis (CP) defined by clinical criteria alone have had modest success to-date. Here, we refine the CP phenotype by supplementing clinical data with biological intermediates of microbial burden (levels of eight periodontal pathogens) and local inflammatory response (gingival crevicular fluid IL-1β) and derive periodontal complex traits (PCTs) via principal component analysis. PCTs were carried forward to GWAS (∼2.5 million markers) to identify PCT-associated loci among 975 European American adult participants of the Dental ARIC study. We sought to validate these findings for CP in the larger ARIC cohort (n = 821 participants with severe CP, 2031—moderate CP, 1914—healthy/mild disease) and an independent German sample including 717 aggressive periodontitis cases and 4210 controls. We identified six PCTs with distinct microbial community/IL-1β structures, although with overlapping clinical presentations. PCT1 was characterized by a uniformly high pathogen load, whereas PCT3 and PCT5 were dominated by Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis, respectively. We detected genome-wide significant signals for PCT1 (CLEC19A, TRA, GGTA2P, TM9SF2, IFI16, RBMS3), PCT4 (HPVC1) and PCT5 (SLC15A4, PKP2, SNRPN). Overall, the highlighted loci included genes associated with immune response and epithelial barrier function. With the exception of associations of BEGAIN with severe and UBE3D with moderate CP, no other loci were associated with CP in ARIC or aggressive periodontitis in the German sample. Although not associated with current clinically determined periodontal disease taxonomies, upon replication and mechanistic validation these candidate loci may highlight dysbiotic microbial community structures and altered inflammatory/immune responses underlying biological sub-types of CP

Salivary Biomarkers in a Biofilm Overgrowth Model

The purpose of this study was to determine whether baseline salivary inflammatory biomarkers could discriminate between different clinical levels of disease and/or predict clinical progression over a 3-week stent-induced biofilm overgrowth (SIBO) period

Effects of enamel matrix derivative and transforming growth factor-β1 on human osteoblastic cells

<p>Abstract</p> <p>Background</p> <p>Extracellular matrix proteins are key factors that influence the regenerative capacity of tissues. The objective of the present study was to evaluate the effects of enamel matrix derivative (EMD), TGF-β1, and the combination of both factors (EMD+TGF-β1) on human osteoblastic cell cultures.</p> <p>Methods</p> <p>Cells were obtained from alveolar bone of three adult patients using enzymatic digestion. Effects of EMD, TGF-β1, or a combination of both were analyzed on cell proliferation, bone sialoprotein (BSP), osteopontin (OPN) and alkaline phosphatase (ALP) immunodetection, total protein synthesis, ALP activity and bone-like nodule formation.</p> <p>Results</p> <p>All treatments significantly increased cell proliferation compared to the control group at 24 h and 4 days. At day 7, EMD group showed higher cell proliferation compared to TGF-β1, EMD + TGF-β1 and the control group. OPN was detected in the majority of the cells for all groups, whereas fluorescence intensities for ALP labeling were greater in the control than in treated groups; BSP was not detected in all groups. All treatments decreased ALP levels at 7 and 14 days and bone-like nodule formation at 21 days compared to the control group.</p> <p>Conclusions</p> <p>The exposure of human osteoblastic cells to EMD, TGF-β1 and the combination of factors <it>in vitro </it>supports the development of a less differentiated phenotype, with enhanced proliferative activity and total cell number, and reduced ALP activity levels and matrix mineralization.</p

Tumor Necrosis Factorâ α and Porphyromonas gingivalis Lipopolysaccharides Decrease Periostin in Human Periodontal Ligament Fibroblasts

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141843/1/jper0694.pd

Oral biofilm dysbiosis during experimental periodontitis

ObjectivesWe have previously characterized the main osteoimmunological events that occur during ligature periodontitis. This study aims to determine the polymicrobial community shifts that occur during disease development.MethodsPeriodontitis was induced in C57BL/6 mice using the ligature-induced periodontitis model. Healthy oral mucosa swabs and ligatures were collected every 3 days from 0 to 18 days post-ligature placement. Biofilm samples were evaluated by 16SrRNA gene sequencing (Illumina MiSeq) and QIIME. Time-course changes were determined by relative abundance, diversity, and rank analyses (PERMANOVA, Bonferroni-adjusted).ResultsMicrobial differences between health and periodontal inflammation were observed at all phylogenic levels. An evident microbial community shift occurred in 25 genera during the advancement of “gingivitis” (3–6 days) to periodontitis (9–18 days). From day 0 to 18, dramatic changes were identified in Streptococcus levels, with an overall decrease (54.04%–0.02%) as well an overall increase of Enterococcus and Lactobacillus (23.7%–73.1% and 10.1%–70.2%, respectively). Alpha-diversity decreased to its lowest at 3 days, followed by an increase in diversity as disease advancement. Beta-diversity increased after ligature placement, indicating that bone loss develops in response to a greater microbial variability (p = 0.001). Levels of facultative and strict anaerobic bacteria augmented over the course of disease progression, with a total of eight species significantly different during the 18-day period.ConclusionThe data supports that murine gingival inflammation and alveolar bone loss develop in response to microbiome shifts. Bacterial diversity increased during progression to bone loss. These findings further support the utilization of the periodontitis ligature model for microbial shift analysis under different experimental conditions.The shift in microbiome community during periodontitis development in a murine model. Gingival inflammation and bone loss in murine periodontitis develops in response to microbiome shifts, marked by a decrease in alpha diversity in the initial stages, followed by an increase in alpha and beta diversities as disease progresses.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/175239/1/omi12389-sup-0001-tableS1.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/175239/2/omi12389.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/175239/3/omi12389_am.pd