Pathology Of Periodontitis Research Articles

Uncovering periodontitis-associated markers through the aggregation of transcriptomics information from diverse sources.

Periodontitis, a common chronic inflammatory disease, significantly impacted oral health. To provide novel biological indicators for the diagnosis and treatment of periodontitis, we analyzed public microarray datasets to identify biomarkers associated with periodontitis. The Gene Expression Omnibus (GEO) datasets GSE16134 and GSE106090 were downloaded. We performed differential analysis and robust rank aggregation (RRA) to obtain a list of differential genes. To obtain the core modules and core genes related to periodontitis, we evaluated differential genes through enrichment analysis, correlation analysis, protein-protein interaction (PPI) network and competing endogenous RNA (ceRNA) network analysis. Potential biomarkers for periodontitis were identified through comparative analysis of dual networks (PPI network and ceRNA network). PPI network analysis was performed in STRING. The ceRNA network consisted of RRA differentially expressed messenger RNAs (RRA_DEmRNAs) and RRA differentially expressed long non-coding RNAs (RRA_DElncRNAs), which regulated each other's expression by sharing microRNA (miRNA) target sites. RRA_DEmRNAs were significantly enriched in inflammation-related biological processes, osteoblast differentiation, inflammatory response pathways and immunomodulatory pathways. Comparing the core ceRNA module and the core PPI module, C1QA, CENPK, CENPU and BST2 were found to be the common genes of the two core modules, and C1QA was highly correlated with inflammatory functionality. C1QA and BST2 were significantly enriched in immune-regulatory pathways. Meanwhile, LINC01133 played a significant role in regulating the expression of the core genes during the pathogenesis of periodontitis. The identified biomarkers C1QA, CENPK, CENPU, BST2 and LINC01133 provided valuable insight into periodontitis pathology.

Identifying MS4A6A+ macrophages as potential contributors to the pathogenesis of nonalcoholic fatty liver disease, periodontitis, and type 2 diabetes mellitus

PurposeConcrete epidemiological evidence has suggested the mutually-contributing effect respectively between nonalcoholic fatty liver disease (NAFLD), type 2 diabetes mellitus (T2DM), and periodontitis (PD); however, their shared crosstalk mechanism remains an open issue. MethodThe NAFLD, PD, and T2DM-related datasets were obtained from the NCBI GEO repository. Their common differentially expressed genes (DEGs) were identified and the functional enrichment analysis performed by the DAVID platform determined relevant biological processes and pathways. Then, the STRING database established a PPI network of such DEGs and topological analysis through Cytoscape 3.7.1 software along with the machine-learning analysis by the least absolute shrinkage and selection operator (LASSO) algorithm screened out hub characteristic genes. Their efficacy was validated by external datasets using the receiver operating characteristic (ROC) curve, and gene expression and location of the most robust one was determined using single-cell sequencing and immunohistochemical staining. Finally, the promising drugs were predicted through the CTD database, and the CB-DOCK 2 and Pymol platform mimicked molecular docking. ResultIntersection of differentially expressed genes from three datasets identified 25 shared DEGs of the three diseases, which were enriched in MHC II-mediated antigen presenting process. PPI network and LASSO machine-learning analysis determined 4 feature genes, of which the MS4A6A gene mainly expressed by macrophages was the hub gene and key immune cell type. Molecular docking simulation chosen fenretinide as the most promising medicant for MS4A6A+ macrophages. ConclusionMS4A6A+ macrophages were suggested to be important immune-related mediators in the progression of NAFLD, PD, and T2DM pathologies.

Mendelian Randomisation Study on Association of Gut Microbiota and Periodontitis

ObjectiveSeveral studies have demonstrated the possible association between gut microbiota and periodontitis. The mechanism by which gut microbiota contribute to periodontitis remains unknown. MethodsA 2-sample Mendelian randomisation (MR) study was conducted using publicly available Genome-Wide Association Studies (GWAS) data of European ancestry. The relationships between gut microbiota and tooth loss and periodontitis were assessed using summary-level data. Moreover, inverse variance weighted (IVW), MR-Egger, weighted median, and simple Mendelian were used. The results were further validated using sensitivity analyses. ResultsA total of 211 gut microbiota were studied, including 9 phyla, 16 classes, 20 orders, 35 families, and 131 genera. The IVW method identified 16 bacterial genera related to the risk of periodontitis and tooth loss. Lactobacillaceae was associated with an increased risk of periodontitis (odds ratio [OR], 1.40, 95% confidence interval [CI], 1.03–1.91, P<.001) and tooth loss (OR, 1.12; 95% CIs, 1.02–1.24, P = .002), whereas Lachnospiraceae UCG008 was linked to a lower risk of tooth loss (P = .041). There was no heterogeneity and horizontal pleiotropy in the sensitivity analysis. ConclusionsSeveral microorganisms were identified to be linked to the risk of periodontitis. Furthermore, the findings improved our understanding of gut microbiota and periodontitis pathology.

Circ_0138960 contributes to lipopolysaccharide-induced periodontal ligament cell dysfunction.

Periodontitis is a common oral inflammatory disease, and lipopolysaccharide (LPS) is a key risk factor in periodontitis pathology. Here, we used LPS-induced periodontal ligament cells (PDLCs) to explore the molecular mechanism of periodontitis. Cell viability, proliferation, and apoptosis were analyzed by Cell Counting Kit-8, 5-ethynyl-20-deoxyuridine (EDU), and flow cytometry assays, respectively. Apart from that, their targeting relationship was validated using dual-luciferase reporter and RNA-pull down. Circular RNA_0138960 (circ_0138960) was notably upregulated in periodontitis sufferers (p < .001) and LPS-disposed PDLCs (p < .05). LPS exposure dampened PDLC proliferation, and promoted apoptosis and inflammation (p < .05). Circ_0138960 acted as a microRNAsponge for miR-518a-5p to affect histone deacetylase 6 (HDAC6) expression. Circ_0138960 absence-mediated protective effects in LPS-induced PDLCs were largely abrogated via silencing miR-518a-5p or HDAC6 overexpression (p < .05). Circ_0138960 promoted LPS-induced dysfunction in PDLCs by targeting miR-518a-5p/HDAC6 axis, which provided novel potential therapeutic targets for periodontitis.

Molecular Mechanisms Leading from Periodontal Disease to Cancer.

Periodontitis is prevalent in half of the adult population and raises critical health concerns as it has been recently associated with an increased risk of cancer. While information about the topic remains somewhat scarce, a deeper understanding of the underlying mechanistic pathways promoting neoplasia in periodontitis patients is of fundamental importance. This manuscript presents the literature as well as a panel of tables and figures on the molecular mechanisms of Porphyromonas gingivalis and Fusobacterium nucleatum, two main oral pathogens in periodontitis pathology, involved in instigating tumorigenesis. We also present evidence for potential links between the RANKL–RANK signaling axis as well as circulating cytokines/leukocytes and carcinogenesis. Due to the nonconclusive data associating periodontitis and cancer reported in the case and cohort studies, we examine clinical trials relevant to the topic and summarize their outcome.

Long non‐coding RNAs: Emerging roles in periodontitis

Periodontitis is a major burden of public health, affecting 20%-50% of the global population. It is a complex inflammatory disease characterized by the destruction of supporting structures of the teeth, leading to tooth loss and the emergence or worsening of systematic diseases. Understanding the molecular mechanisms underlying the physiopathology of periodontitis is beneficial for targeted therapeutics. Long non-coding RNAs (lncRNAs), transcripts made up of more than 200 nucleotides, have emerged as novel regulators of many biological and pathological processes. Recently, an increasing number of dysregulated lncRNAs have been found to be implicated in periodontitis. In this review, an overview of lncRNAs, including their biogenesis, characteristics, function mechanisms and research approaches, is provided. And we summarize recent research reports on the emerging roles of lncRNAs in regulating proliferation, apoptosis, inflammatory responses, and osteogenesis of periodontal cells to elucidate lncRNAs related physiopathology of periodontitis. Furthermore, we have highlighted the underlying mechanisms of lncRNAs in periodontitis pathology by interacting with microRNAs. Finally, the potential clinical applications, current challenges, and prospects of lncRNAs as diagnostic and prognostic biomarkers and therapeutic targets for periodontitis disease are discussed.

Increased Sphingosine-1-Phosphate Serum Concentrations in Subjects with Periodontitis: A Matter of Inflammation.

PurposePeriodontitis is an inflammatory disease of the oral cavity with an alarmingly high prevalence within the adult population. The signaling lipid sphingosine-1-phosphate (S1P) plays a crucial role in inflammatory and immunomodulatory responses. In addition to cardiovascular disease, sepsis and tumor entities, S1P has been recently identified as both mediator and biomarker in osteoporosis. We hypothesized that S1P may play a role in periodontitis as an inflammation-prone bone destructive disorder. The goal of our study was to evaluate associations between periodontitis and S1P serum concentrations in the Study of Health in Pomerania (SHIP)-Trend cohort. In addition, we investigated the expression of S1P metabolizing enzymes in inflamed gingival tissue.Patients and MethodsWe analyzed data from 3371 participants (51.6% women) of the SHIP-Trend cohort. Periodontal parameters and baseline characteristics were assessed. Serum S1P was measured by liquid chromatography tandem mass spectrometry. The expression of S1P metabolizing enzymes was determined by immunofluorescence staining of human gingival tissue.ResultsS1P serum concentrations were significantly increased in subjects with both moderate and severe periodontitis, assessed as probing depth and clinical attachment loss. In contrast, no significant association of S1P was seen with caries variables (number and percentage of decayed or filled surfaces). S1P concentrations significantly increased with increasing high-sensitivity C-reactive protein (hs-CRP) levels. Interestingly, inflamed compared to normal human gingival tissue exhibited elevated expression levels of the S1P-generating enzyme sphingosine kinase 1 (SphK1).ConclusionWe report an intriguingly significant association of various periodontal parameters with serum levels of the inflammatory lipid mediator S1P. Our data point towards a key role of S1P during periodontitis pathology. Modulation of local S1P levels or its signaling properties may represent a potential future therapeutic strategy to prevent or to retard periodontitis progression and possibly reduce periodontitis-related tooth loss.

Targeting TSP-1 decreased periodontitis by attenuating extracellular matrix degradation and alveolar bone destruction

An important factor in periodontitis pathogenesis relates to a network of interactions of various cytokines. Thrombospondin-1 (TSP-1) is upregulated in several inflammatory diseases. We previously found that Porphyromonas gingivalis lipopolysaccharide (P. gingivalis LPS)-induced TSP-1 production, and that TSP-1 simultaneously and effectively elevated inflammatory cytokines in THP-1 macrophages. This suggests that TSP-1 plays an important role in the pathology of periodontitis. However, the function of TSP-1 on oral cells is largely unknown. This study aimed to elucidate the underlying molecular mechanisms of TSP-1 in human periodontal fibroblasts (hPDLFs). We demonstrated that TSP-1 is highly expressed in the gingival crevicular fluid of patients with chronic periodontitis and in the inflammatory gingival tissues of rats. TSP-1 overexpression or treatment with recombinant human TSP-1(rTSP-1) promoted the expression of MMP-2, MMP-9 and RANKL/OPG in hPDLFs, while anti-TSP-1 inhibited cytokines production from P. gingivalis LPS-treated hPDLFs. Additional experiments showed that SB203580 (a special p38MAPK inhibitor) inhibited MMP-2, MMP-9 and RANKL/OPG expression induced by rTSP-1. Thus, TSP-1 effectively promoted P. gingivalis LPS-induced periodontal tissue (extracellular matrix (ECM) and alveolar bone) destruction by the p38MAPK signalling pathway, indicating that it may be a potential therapeutic target against periodontitis.

Treatment challenges and delivery systems in immunomodulation and probiotic therapies for periodontitis

ABSTRACT Introduction: Periodontitis is a widespread illness that arises due to disrupted interplay between the oral microbiota and the host immune response. In some cases, conventional therapies can provide temporary remission, although this is often followed by disease relapse. Recent studies of periodontitis pathology have promoted the development of new therapeutics to improve treatment options, together with local application using advanced drug delivery systems. Areas covered: This paper provides a critical review of the status of current treatment approaches to periodontitis, with a focus on promising immunomodulation and probiotic therapies. These are based on delivery of small molecules, peptides, proteins, DNA or RNA, and probiotics. The key findings on novel treatment strategies and formulation of advanced delivery systems, such as nanoparticles and nanofibers, are highlighted. Expert opinion: Multitarget therapy based on antimicrobial, immunomodulatory, and probiotic active ingredients incorporated into advanced delivery systems for application to the periodontal pocket can improve periodontitis treatment outcomes. Translation of such adjuvant therapy from laboratory to patient is expected in the future.

Cannabinoid type-2 receptor agonist, inverse agonist, and anandamide regulation of inflammatory responses in IL-1β stimulated primary human periodontal ligament fibroblasts.

The aim of this study is to understand the role of cannabinoid type 2 receptor (CB2R) during periodontal inflammation and to identify anti-inflammatory agents for the development of drugs to treat periodontitis (PD). Cannabinoid type 2 receptor is found in periodontal tissue at sites of inflammation/infection. Our previous study demonstrated anti-inflammatory responses in human periodontal ligament fibroblasts (hPDLFs) via CB2R ligands. Anandamide (AEA), HU-308 (agonist), and SMM-189 (inverse agonist) were tested for effects on IL-1β-stimulated cytokines, chemokines, and angiogenic and vascular markers expressed by hPDLFs using Mesoscale Discovery V-Plex Kits. Signal transduction pathways (p-c-Jun, p-ERK, p-p-38, p-JNK, p-CREB, and p-NF-kB) were investigated using Cisbio HTRF kits. ACTOne and Tango™ -BLA functional assays were used to measure cyclic AMP (cAMP) and β-arrestin activity. IL-1β stimulated hPDLF production of 18/39 analytes, which were downregulated by the CB2R agonist and the inverse agonist. AEA exhibited pro-inflammatory and anti-inflammatory effects. IL-1β increased phosphoproteins within the first hour except p-JNK. CB2R ligands attenuated p-p38 and p-NFĸB, but a late rise in p-38 was seen with HU-308. As p-ERK levels declined, a significant increase in p-ERK was observed later in the time course by synthetic CB2R ligands. P-JNK was significantly affected by SMM-189 only, while p-CREB was elevated significantly by CB2R ligands at 180minutes. HU-308 affected both cAMP and β-arrestin pathway. SMM-189 only stimulated cAMP. The findings that CB2R agonist and inverse agonist may potentially regulate inflammation suggest that development of CB2R therapeutics could improve on current treatments for PD and other oral inflammatory pathologies.

CLINICO-BIOCHEMICAL AND MORPHOLOGICAL CHARACTERISTICS OF PERIODONTAL DISEASE IN INDIVIDUALS OF THE CONTROL GROUP

Periodontal diseases are widespread all over the world. In this connection, the questions relating to the prevalence of these diseases, and the subtle mechanisms occurring in tissues in norm at the subcellular level it is important to investigate for a correct assessment of biochemical changes occurring in the pathology ofperiodontitis. The article analyzes the biochemical changes in the periodontal tissues with intact tooth rows and periodontium. Material for biochemical analysis obtained from 36 patients, while removing the first premolars with the aim of orthodontic treatment.

Rat as laboratory animal model in periodontology

For ethical reason, initiation and progression of periodontal disease as well as certain types of periodontal treatment cannot be studied in humans. Instead, numerous studies in this field have been carried out in laboratory animals. Animal models are needed to objectively evaluate the pathogenesis of human periodontal disease and its various treatment modalities. A number of animal models have been used in studying etiology and pathology of periodontitis. The primate model is recommended because the pathogenesis in primate model closely resembles that in humans. In addition, the dog model is used frequently because of ease of ligature placement as well as the natural occurrence of periodontal disease. However, ease of handling, inexpensive, short study time, low variation among strains and controlled microflora, relatively disease resistant, make the rat model extremely versatile and suited for a wide range of research endeavors. Rats are used mainly for research in toxicity, nutrition, behavior, and cancer. Normal oral structure and physiology and the pathogenesis of periodontal diseases have been studied more extensively in the rat than in any other rodents. Rats are used extensively to study the effects of drugs on the gingiva because their tissue overgrowth is similar to that of humans. The purpose of this review is to evaluate rats as models for studying various aspects of periodontal disease, including disease process and its treatment handling, advantages and limitations of these models.

Inhibitory Effects of Portulaca Oleracea Ethanol Extract and Glechoma Hederacea Ethanol Extract on the Periodontitis

Both Portulaca oleracea (PO) and Glechoma hederacea (GH) have been used as traditional medicine due to the multiple pharmacological activities. However, the effects of PO and GH in the pathology of periodontitis is still elusive. In this study, we examined anti-microbial activity of PO ethanol extract (POEE) and GH ethanol extract (GHEE) in vitro, and physiological effects of POEE and GHEE on the cell inflammatory responses and the severity of periodontitis were determined using the rat periodontitis model. Our results indicate that POEE and GHEE had no effects on the proliferation of streptococcus mutans and on LPS-mediated inflammatory responses in gingival fibroblast cells. Notably, ingestion of POEE and GHEE resulted in attenuating the severity of periodontitis and population change of immune cells. These data suggests that PO and GH should be considered as candidates for relieving the severity of periondontitis.

Lipid Peroxidation Levels and Total Oxidant/Antioxidant Status in Serum and Saliva From Patients With Chronic and Aggressive Periodontitis. Oxidative Stress Index: A New Biomarker for Periodontal Disease?

In this study, levels of malondialdehyde (MDA), which is a significant product of lipid peroxidation (LPO), total oxidant status (TOS), total antioxidant capacity (TAOC), and the oxidative stress index (OSI), a novel value as a marker of periodontal disease activity, are investigated in serum and saliva from patients with chronic (CP) and generalized aggressive (GAgP) periodontitis. A total of 98 patients (33 with CP, 35 patients with GAgP, and 30 periodontally healthy controls) enrolled in the study. After clinical measurements and sample collection, the MDA level, TOS, and TAOC were measured by high-performance liquid chromatography and a novel automatic colorimetric method. The OSI was calculated as [(TOS/TAOC) × 100]. Although the salivary MDA levels and serum and salivary TOS and OSI values were significantly higher in the periodontitis groups than in the control group (P <0.05), the serum and salivary TAOC levels were significantly lower, and no significant difference in serum MDA levels was found (P >0.05). Furthermore, oxidative stress parameters were higher in the GAgP group than in the CP group (except the serum and salivary MDA levels and serum TAOC). Significant positive and negative correlations were observed between periodontal parameters and the MDA levels and TOS, TAOC, and OSI values (except serum MDA) (P <0.05). The present findings suggest that an increased TOS and decreased TAOC, rather than LPO, play important roles in the pathology of periodontitis and are closely associated with clinical periodontal status. Furthermore, the OSI may be a useful and practical parameter for evaluating periodontal disease activity.

Cytokines and chemokines are differentially expressed in patients with periodontitis: Possible role for TGF-β1 as a marker for disease progression

Periodontitis is a chronic inflammatory disease characterized by destruction of periodontal tissue ultimately leading to bone destruction and has been associated with other inflammatory diseases, such as atherosclerosis. Attachment loss of periodontal tissue is primarily caused by host cell-derived immune responses against subgingival biofilm. The aim of the present study was to determine the cytokine profile in serum, saliva and gingival crevicular fluid (GCF) patients with periodontitis and healthy controls. We show that periodontitis patients exhibit higher numbers of periodontal pathogens and their immune responses are significantly altered. The levels of IL-6 in saliva and GCF were significantly suppressed, and while CXCL8 was not altered in serum, its expression levels were significantly suppressed in saliva and elevated in GCF. The T-cell-derived cytokine IL-2 did not differ between patients and controls in serum and saliva, but there was a significant suppression in GCF of patients. Interestingly, TGF-β1 levels were significantly elevated in serum, saliva and GCF in patients compared to controls. Furthermore, by using cultured gingival fibroblasts stimulated with wild type and proteinase mutant strains of Porphyromonas gingivalis, we show that the suppression of CXCL8 and IL-6, and the induction of TGF-β1 is primarily mediated by the proteolytic activity of lysine-specific proteinases. These results indicate that P. gingivalis is a major contributor to the altered immune responses and the pathology of periodontitis. Furthermore, the ease of sampling and analyzing cytokine expression profiles, including TGF-β1, in saliva and GCF may serve to predict the progression of periodontitis and associated systemic inflammatory diseases.

Beneficial Effects of Hormone Replacement Therapy on Periodontitis Are Vitamin D Associated

Possible synergism between female sex hormones and vitamin D on periodontitis pathology has not been assessed. Here, the authors investigate effects of estrogen, progesterone, and vitamin D on periodontitis in a population-based sample and use cell studies to explore mechanistic explanations of the population-based findings. The epidemiologic analysis uses cross-sectional data from the continuous National Health and Nutrition Examination Survey 2001 to 2004. The cross sections include 1,230 women aged 40 to 85 years who received a periodontal examination, responded to questions regarding hormone replacement therapy (HRT), and provided a blood sample for serum vitamin D assessments. For mechanistic cell culture studies, human monocytes were cultured with or without lipopolysaccharide (LPS), estradiol, progesterone, and/or 1,25-dihydroxyvitamin D3; and transcriptional activity of interleukin (IL)-6, IL-1β, B lymphocyte chemoattractant (BLC), and regulated on activation normal T-cell expressed and secreted (RANTES) was assessed. HRT use (versus none) was associated with higher attachment levels and more teeth only among participants who were vitamin D sufficient (>20 ng/mL). The odds ratio for having moderate/severe periodontitis among users of HRT versus participants who did not use HRT was 0.69 among participants who were vitamin D sufficient and 1.19 in participants who were vitamin D deficient. LPS-induced IL-6, IL-1β, and BLC expression was attenuated in human monocytes treated with estrogen and progesterone. Downregulation of IL-6 expression by estrogen and progesterone was potentiated when vitamin D was included. LPS-induced IL-6 and RANTES expression was decreased, and BLC expression was totally reversed, by vitamin D treatment. The association between HRT and clinical periodontal measures was strongest among women with high vitamin D levels. This association is plausibly mediated via an anti-inflammatory transcriptional mechanism.

Endotoxins—the Invisible Companion in Biomaterials Research

Metal implants and polymeric devices for the application in the clinical treatment of orthopedic tissue injuries are increasingly coated with bioactive biomaterials derived from natural substances to induce desirable biological effects. Many metals and polymers used in biomaterials research show high affinity for endotoxins, which are abundant in the environment. Endotoxin contamination is indicated in the pathology of periodontitis and aseptic implant loosening, but may also affect the evaluation of a biomaterial's bioactivity by inducing strong inflammatory reactions. In this review, we discuss the high affinity of three commonly used implant biomaterials for endotoxins and how the contamination can affect the outcome of the orthopedic fixation. The chemical nature of bacterial endotoxins and some of the clinical health implications are described, as this knowledge is critically important to tackle the issues associated with the measurement and removal of endotoxins from medical devices. Commonly used methods for endotoxin testing and removal from natural substances are examined and the lack of standard guidelines for the in vitro evaluation of biomaterials is discussed.

Aggregatibacter actinomycetemcomitans Leukotoxin: A Powerful Tool with Capacity to Cause Imbalance in the Host Inflammatory Response

Aggregatibacter actinomycetemcomitans has been described as a member of the indigenous oral microbiota of humans, and is involved in the pathology of periodontitis and various non-oral infections. This bacterium selectively kills human leukocytes through expression of leukotoxin, a large pore-forming protein that belongs to the Repeat in Toxin (RTX) family. The specificity of the toxin is related to its prerequisite for a specific target cell receptor, LFA-1, which is solely expressed on leukocytes. The leukotoxin causes death of different leukocyte populations in a variety of ways. It activates a rapid release of lysosomal enzymes and MMPs from neutrophils and causes apoptosis in lymphocytes. In the monocytes/macrophages, the toxin activates caspase-1, a cysteine proteinase, which causes a proinflammatory response by the activation and secretion of IL-1β and IL-18. A specific clone (JP2) of A. actinomycetemcomitans with enhanced leukotoxin expression significantly correlates to disease onset in infected individuals. Taken together, the mechanisms by which this toxin kills leukocytes are closely related to the pathogenic mechanisms of inflammatory disorders, such as periodontitis. Therapeutic strategies targeting the cellular and molecular inflammatory host response in periodontal diseases might be a future treatment alternative.

Development of a Database and Ontology for Pathogenic Pathways in Periodontitis

It is getting familiar that pathway information greatly contributes to elucidate the molecular basis of human disease with large-scale biological data. We developed a pathway database for molecular pathology in periodontitis named 'Pathogenic Pathway Database for Periodontitis'. Periodontitis is an inflammation disease in periodontal tissue and associated with an increased health risk of angina, myocardial infarction, and fetal cardiovascular events. Despite accumulation of biomedical research on periodontitis pathology at the molecular level, there has been no systematization for biological pathways in periodontitis. We checked 185 reference papers and extracted causal relationships among molecules as well as pathways representing molecular etiology. We also built an ontology that systematizes conceptual terms associated with the pathways. Besides pathways, our ontology provides cellular and tissue specific contextual information that is required to represent pathology at the cellular and tissue specific levels. We implemented in our database an integrated viewer for the association between pathways and ontology. Pathogenic Pathway Database for Periodontitis is freely available at http://bio-omix.tmd.ac.jp/disease/perio/.

Lipid peroxidation levels and total oxidant status in serum, saliva and gingival crevicular fluid in patients with chronic periodontitis

Increased levels of reactive oxygen species lead to oxidative stress. Recent data suggest increased lipid peroxidation (LPO) levels and oxidative stress in periodontitis. Malondialdehyde (MDA), a significant LPO product, increases in oxidative stress. In this study, MDA levels and total oxidant status (TOS) in serum, saliva and gingival crevicular fluid (GCF) were investigated in patients with chronic periodontitis (CP). Thirty-six CP patients and 28 periodontally healthy controls were included in the study. Following clinical measurements and samplings, MDA and TOS levels were measured by high-performance liquid chromatography and a novel automatic colorimetric method, respectively. While the saliva and GCF MDA levels, and serum, saliva and GCF TOS values were significantly higher in the CP group than the control group (p<0.05), no significant difference in serum MDA levels was found (p>0.05). Strong positive correlations were observed between periodontal parameters and MDA and TOS levels (p<0.05). The results revealed that LPO significantly increased locally in the periodontal pocket/oral environment, while TOS displayed both systemic and local increases in periodontitis. The findings suggest that increased LPO and TOS may play an important role in the pathology of periodontitis, and are closely related to the clinical periodontal status.