scholarly journals TheTreponema denticolaChymotrypsin-Like Protease Dentilisin Induces Matrix Metalloproteinase-2-Dependent Fibronectin Fragmentation in Periodontal Ligament Cells

2010 ◽  
Vol 79 (2) ◽  
pp. 806-811 ◽  
Author(s):  
Di Miao ◽  
J. Christopher Fenno ◽  
John C. Timm ◽  
Nam Eok Joo ◽  
Yvonne L. Kapila
Keyword(s):  
Periodontal Disease ◽  
Periodontal Ligament ◽  
Alveolar Bone ◽  
Inflammatory Responses ◽  
Tissue Homeostasis ◽  
Matrix Metalloproteinase 2 ◽  
Periodontal Ligament Cells ◽  
Treponema Denticola ◽  
Periodontal Pathogens ◽  
Culture Supernatants

ABSTRACTPeriodontal disease is a bacterially mediated chronic inflammatory disease that results in destruction of the periodontal ligament (PDL) and alveolar bone that surround and support the dentition. While their precise roles are not well understood, periodontal pathogens, includingTreponema denticola, are believed to initiate the destructive inflammatory responses and dysregulation of tissue homeostasis that characterize the disease. These responses are believed to result from both proinflammatory effects of acylated bacterial membrane components (lipopolysaccharides and lipoproteins) and degradative effects of secreted bacterial proteases. Host-derived matrix metalloproteinases (MMPs) are key enzymes both in tissue homeostasis and tissue destruction. MMP expression is modulated in part by specific proteolytic fragments of fibronectin (FN), which are associated with periodontal disease. FN is a predominant extracellular matrix component in the periodontium. We examined the ability ofTreponema denticolaand its acylated outer membrane PrtP protease complex to induce both activation of MMP-2 and generation of FN fragments in human PDL cell culture supernatants.T. denticolaparent and isogenic mutant strains, as well as MMP-2 small interfering RNA and specific inhibitors of MMP-2 and PrtP activity, were used to examine protein expression, gelatinolytic activity, and FN fragmentation in culture supernatants.T. denticolaand its purified protease induced both MMP-2 activation and FN fragmentation. Here, we demonstrate that PrtP proteolytic activity induces the activation of MMP-2 and that active MMP-2 is required for FN fragmentation. These results suggest a specific mechanism by which theT. denticolaprotease may disrupt homeostatic processes required for the maintenance of periodontal health.

scholarly journals Treponema denticola dentilisin triggered TLR2/MyD88 activation upregulates a tissue destructive program involving MMPs via Sp1 in human oral cells

2021 ◽  
Vol 17 (7) ◽  
pp. e1009311
Author(s):  
Sean Ganther ◽  
Allan Radaic ◽  
Erin Malone ◽  
Pachiyappan Kamarajan ◽  
Nai-Yuan Nicholas Chang ◽  
...  
Keyword(s):  
Periodontal Disease ◽  
Alveolar Bone ◽  
Nuclear Translocation ◽  
Inflammatory Responses ◽  
Oral Microbiome ◽  
Oral Disease ◽  
Periodontal Ligament Cells ◽  
Treponema Denticola ◽  
Host Immune Responses

Periodontal disease is driven by dysbiosis in the oral microbiome, resulting in over-representation of species that induce the release of pro-inflammatory cytokines, chemokines, and tissue-remodeling matrix metalloproteinases (MMPs) in the periodontium. These chronic tissue-destructive inflammatory responses result in gradual loss of tooth-supporting alveolar bone. The oral spirochete Treponema denticola (T. denticola), is consistently found at significantly elevated levels in periodontal lesions. Host-expressed Toll-Like Receptor 2 (TLR2) senses a variety of bacterial ligands, including acylated lipopolysaccharides and lipoproteins. T. denticola dentilisin, a surface-expressed protease complex comprised of three lipoproteins has been implicated as a virulence factor in periodontal disease, primarily due to its proteolytic activity. While the role of acylated bacterial components in induction of inflammation is well-studied, little attention has been given to the potential role of the acylated nature of dentilisin. The purpose of this study was to test the hypothesis that T. denticola dentilisin activates a TLR2-dependent mechanism, leading to upregulation of tissue-destructive genes in periodontal tissue. RNA-sequencing of periodontal ligament cells challenged with T. denticola bacteria revealed significant upregulation of genes associated with extracellular matrix organization and degradation including potentially tissue-specific inducible MMPs that may play novel roles in modulating host immune responses that have yet to be characterized within the context of oral disease. The Gram-negative oral commensal, Veillonella parvula, failed to upregulate these same MMPs. Dentilisin-induced upregulation of MMPs was mediated via TLR2 and MyD88 activation, since knockdown of expression of either abrogated these effects. Challenge with purified dentilisin upregulated the same MMPs while a dentilisin-deficient T. denticola mutant had no effect. Finally, T. denticola-mediated activation of TLR2/MyD88 lead to the nuclear translocation of the transcription factor Sp1, which was shown to be a critical regulator of all T. denticola-dependent MMP expression. Taken together, these data suggest that T. denticola dentilisin stimulates tissue-destructive cellular processes in a TLR2/MyD88/Sp1-dependent fashion.

scholarly journals Porphyromonas gingivalisandTreponema denticolaMixed Microbial Infection in a Rat Model of Periodontal Disease

2010 ◽  
Vol 2010 ◽  
pp. 1-10 ◽  
Author(s):  
Raj K. Verma ◽  
Sunethra Rajapakse ◽  
Archana Meka ◽  
Clayton Hamrick ◽  
Sheela Pola ◽  
...  
Keyword(s):  
Periodontal Disease ◽  
Rat Model ◽  
Alveolar Bone ◽  
Treponema Denticola ◽  
Periodontal Pathogens ◽  
Microbial Infection ◽  
Morphometric Measurements ◽  
Th2 Immune Response ◽  
Microbial Infections ◽  
Antibody Levels

Porphyromonas gingivalisandTreponema denticolaare periodontal pathogens that express virulence factors associated with the pathogenesis of periodontitis. In this paper we tested the hypothesis thatP. gingivalisandT. denticolaare synergistic in terms of virulence; using a model of mixed microbial infection in rats. Groups of rats were orally infected with eitherP. gingivalisorT. denticolaor mixed microbial infections for 7 and 12 weeks.P. gingivalisgenomic DNA was detected more frequently by PCR thanT. denticola. Both bacteria induced significantly high IgG, IgG2b, IgG1, IgG2a antibody levels indicating a stimulation of Th1 and Th2 immune response. Radiographic and morphometric measurements demonstrated that rats infected with the mixed infection exhibited significantly more alveolar bone loss than shaminfected control rats. Histology revealed apical migration of junctional epithelium, rete ridge elongation, and crestal alveolar bone resorption; resembling periodontal disease lesion. These results showed thatP. gingivalisandT. denticolaexhibit no synergistic virulence in a rat model of periodontal disease.

Comparison of Sampling Techniques For qPCR Quantification of Periodontal Pathogens

2018 ◽  
Vol 68 (12) ◽  
pp. 2853-2856 ◽  
Author(s):  
Igor Jelihovschi ◽  
Cristian Drochioi ◽  
Aida Corina Badescu ◽  
Raoul Vasile Lupusoru ◽  
Alexandra Elena Munteanu ◽  
...  
Keyword(s):  
Periodontal Disease ◽  
Periodontal Diseases ◽  
Pcr Analysis ◽  
Treponema Denticola ◽  
Subgingival Plaque ◽  
Periodontal Pathogens ◽  
Radiographic Evidence ◽  
Gingival Bleeding ◽  
As Species ◽  
Qpcr Quantification

The diagnosis of periodontal disease is mainly based on use of clinical and radiographic evidence. In this study we employed a quantitative PCR analysis of Aggregatibacter actinomycetemcomitans and Treponema denticola as species strongly involved in periodontal diseases, burden in periodontal pockets to detect the main sampling factors that interfere with qPCR results. From 22 patients with advanced periodontal disease, subgingival plaque was comparatively collected by paper points and periodontal Gracey curettes. Samples were collected from the same situs in presence of gingival bleeding and absence of bleeding. The concordance and agreement of results between samples were assessed. The present study demonstrates that subgingival plaque sampling with sterile absorbable paper points is often accompanied by gingival bleeding resulting in quantification biases of periodontal pathogens.

Bullet for periodontal disease in future: Chemically modified tetracyclines

2021 ◽  
pp. 1-7
Author(s):  
Shivani Sachdeva ◽  
Ameet Mani ◽  
Harish Saluja
Keyword(s):  
Chronic Periodontitis ◽  
Periodontal Ligament ◽  
Host Response ◽  
Alveolar Bone ◽  
Gastrointestinal Toxicity ◽  
Collagenolytic Activity ◽  
Periodontal Pathogens ◽  
Oral Biofilm ◽  
Chemically Modified ◽  
Chemically Modified Tetracyclines

Chronic periodontitis is nowadays popularly regarded as Dysbiosis, [1] which causes destruction of tissues rich in collagen like periodontal ligament, alveolar bone and gingival connective tissue. The oral biofilm comprises many periodontal pathogens better regarded as ‘triggers’ in causing chronic periodontitis. Since, not everyone will be affected in the same manner due to periodontal pathogens. Some might not elicit a host response while, the others might have exaggerated response. So, host modulation therapy came into existence to counteract the exaggerated host response. The chemically modified tetracyclines (CMTs) have emerged to inhibit the inflammatory response or to reduce the collagenolytic activity of host. Though a derivative of tetracyclines, it still lacks an antimicrobial action and hence, can be used for periodontitis for longer duration with no adverse effects of gastrointestinal toxicity which parent tetracyclines have.

scholarly journals Invasion of Oral and Aortic Tissues by Oral Spirochete Treponema denticola in ApoE−/−Mice Causally Links Periodontal Disease and Atherosclerosis

2014 ◽  
Vol 82 (5) ◽  
pp. 1959-1967 ◽  
Author(s):  
Sasanka S. Chukkapalli ◽  
Mercedes F. Rivera ◽  
Irina M. Velsko ◽  
Ju-Youn Lee ◽  
Hao Chen ◽  
...  
Keyword(s):  
Periodontal Disease ◽  
Alveolar Bone ◽  
Tissue Growth ◽  
Aortic Tissue ◽  
Treponema Denticola ◽  
Rapid Progression ◽  
Causative Role ◽  
Igg Antibody ◽  
Content Type ◽  
Periodontal Infection

ABSTRACTTreponema denticolais a predominantly subgingival oral spirochete closely associated with periodontal disease and has been detected in atherosclerosis. This study was designed to evaluate causative links between periodontal disease induced by chronic oralT. denticolainfection and atherosclerosis in hyperlipidemic ApoE−/−mice. ApoE−/−mice (n= 24) were orally infected withT. denticolaATCC 35404 and were euthanized after 12 and 24 weeks.T. denticolagenomic DNA was detected in oral plaque samples, indicating colonization of the oral cavity. Infection elicited significantly (P= 0.0172) higher IgG antibody levels and enhanced intrabony defects than sham infection.T. denticola-infected mice had higher levels of horizontal alveolar bone resorption than sham-infected mice and an associated significant increase in aortic plaque area (P≤ 0.05). Increased atherosclerotic plaque correlated with reduced serum nitric oxide (NO) levels and increased serum-oxidized low-density lipoprotein (LDL) levels compared to those of sham-infected mice.T. denticolainfection altered the expression of genes known to be involved in atherosclerotic development, including the leukocyte/endothelial cell adhesion gene (Thbs4), the connective tissue growth factor gene (Ctgf), and the selectin-E gene (Sele). Fluorescentin situhybridization (FISH) revealedT. denticolaclusters in both gingival and aortic tissue of infected mice. This is the first study examining the potential causative role of chronicT. denticolaperiodontal infection and vascular atherosclerosisin vivoin hyperlipidemic ApoE−/−mice.T. denticolais closely associated with periodontal disease and the rapid progression of atheroma in ApoE−/−mice. These studies confirm a causal link for active oralT. denticolainfection with both atheroma and periodontal disease.

Abstract 180: Increased Atherosclerosis Associated with Periodontal Disease Is Mediated by CD36

2012 ◽  
Vol 32 (suppl_1) ◽  
Author(s):  
Maria Febbraio ◽  
Paul M Brown
Keyword(s):  
Periodontal Disease ◽  
Alveolar Bone ◽  
Inflammatory Responses ◽  
Disease Risk ◽  
Plasma Cholesterol ◽  
Atherosclerotic Lesion ◽  
Pcr Analysis ◽  
Modified Ldl ◽  
Oxidatively Modified

We previously showed that inflammation, and not hyperlipidemia alone, was necessary for CD36 dependent atherogenesis. Chronic periodontal disease is characterized by a persistent inflammatory state and is epidemiologically associated with cardiovascular disease. We hypothesize that CD36 is an essential link between periodontal disease and atherosclerosis. Low density lipoprotein receptor knock out (LDLR KO) mice and CD36/LDLR double KO mice were infected with the periodontal disease associated bacteria, Porphyromonas gingivalis (Pg), by oral lavage and fed a Western diet for 12 weeks (n = 7-14/group). We assessed periodontal disease, risk factors associated with atherosclerosis, and lesion burden. We conducted studies in isolated macrophages to understand mechanistic differences between the groups. Wild type and CD36 KO macrophages equally phagocytosed bacteria. We measured the cemento-enamel junction of each molar to assess periodontal disease and found that it was significantly increased in infected mice compared with uninfected controls. Histological analysis showed neutrophil, osteoclast and macrophage infiltrates in the alveolar bone of infected mice. Differences in plasma cholesterol, triacylglycerol, insulin resistance and weight gain did not necessarily track with atherosclerosis burden, however blood neutrophils and cytokines were increased in infected LDLR KO mice compared with all other groups. Infected LDLR KO mice had significantly increased atherosclerotic lesion burden compared with uninfected LDLR KO mice, and all of the increased lesion was CD36 dependent. PCR analysis found no evidence for direct infection of atherosclerotic lesions by Pg. In vitro macrophage studies showed that heat killed Pg, lipopolysaccharide (LPS) derived from Pg, oxidatively modified LDL or plasma from infected mice, could not activate the NALP3 inflammasome. Combining heat killed Pg or Pg LPS with oxidatively modified LDL or plasma from infected mice, however, led to significant IL-1 beta secretion that was CD36 and NFkB dependent. Our data suggest that atherosclerosis associated with periodontal disease is mediated by cellular inflammatory responses involving both CD36 and Toll-like receptor.

scholarly journals IL-4 Modulates CCL11 and CCL20 Productions from IL-1β-Stimulated Human Periodontal Ligament Cells

2016 ◽  
Vol 38 (1) ◽  
pp. 153-159 ◽  
Author(s):  
Yoshitaka Hosokawa ◽  
Ikuko Hosokawa ◽  
Satoru Shindo ◽  
Kazumi Ozaki ◽  
Takashi Matsuo
Keyword(s):  
Periodontal Disease ◽  
Western Blot ◽  
Blot Analysis ◽  
Periodontal Ligament ◽  
Western Blot Analysis ◽  
Th17 Cells ◽  
Th2 Cells ◽  
Periodontal Ligament Cells ◽  
Human Periodontal Ligament Cells ◽  
Multifunctional Cytokine

Background/Aims: IL-4 is a multifunctional cytokine that is related with the pathological conditions of periodontal disease. However, it is uncertain whether IL-4 could control T cells migration in periodontal lesions. The aim of this study was to examine the effects of IL-4 on CCL11, which is a Th2-type chemokine, and CCL20, which is related with Th17 cells migration, productions from human periodontal ligament cells (HPDLCs). Methods: CCL20 and CCL11 productions from HPDLCs were monitored by ELISA. Western blot analysis was performed to detect phosphorylations of signal transduction molecules in HPDLCs. Results: IL-1β could induce both CCL11 and CCL20 productions in HPDLCs. IL-4 enhanced CCL11 productions from IL-1β-stimulated HPDLCs, though IL-4 inhibited CCL20 production. Western blot analysis showed that protein kinase B (Akt) and signal transducer and activator of transcription (STAT)6 pathways were highly activated in IL-4/IL-1β-stimulated HPDLCs. Akt and STAT6 inhibitors decreased CCL11 production, but enhanced CCL20 production in HPDLCs stimulated with IL-4 and IL-1β. Conclusions: These results mean that IL-4 enhanced Th2 cells migration in periodontal lesion to induce CCL11 production from HPDLCs. On the other hand, IL-4 inhibits Th17 cells accumulation in periodontally diseased tissues to inhibit CCL20 production. Therefore, IL-4 is positively related with the pathogenesis of periodontal disease to control chemokine productions in periodontal lesions.

Osteogenic Gene Expression by Human Periodontal Ligament Cells under Cyclic Tension

2007 ◽  
Vol 86 (12) ◽  
pp. 1212-1216 ◽  
Author(s):  
D.C. Wescott ◽  
M.N. Pinkerton ◽  
B.J. Gaffey ◽  
K.T. Beggs ◽  
T.J. Milne ◽  
...  
Keyword(s):  
Periodontal Ligament ◽  
Alveolar Bone ◽  
Mechanical Strain ◽  
Osteogenic Potential ◽  
Periodontal Ligament Cells ◽  
Orthodontic Appliances ◽  
Fiber Types ◽  
Pdl Cells ◽  
Array Technology ◽  
Osteogenic Gene Expression

The forces that orthodontic appliances apply to the teeth are transmitted through the periodontal ligament (PDL) to the supporting alveolar bone, leading to the deposition or resorption of bone, depending upon whether the tissues are exposed to a tensile or compressive mechanical strain. To evaluate the osteogenic potential of PDL cells, we applied a 12% uni-axial cyclic tensile strain to cultured human PDL cells and analyzed the differential expression of 78 genes implicated in osteoblast differentiation and bone metabolism by real-time RT-PCR array technology. Sixteen genes showed statistically significant changes in expression in response to alterations in their mechanical environment, including cell adhesion molecules and collagen fiber types. Genes linked to the osteoblast phenotype that were up-regulated included BMP2, BMP6, ALP, SOX9, MSX1, and VEGFA; those down-regulated included BMP4 and EGF. This study has expanded our knowledge of the transcriptional profile of PDL cells and identified several new mechanoresponsive genes.

Sphingomyelin Phosphodiesterase 3 Enhances Cytodifferentiation of Periodontal Ligament Cells

2016 ◽  
Vol 96 (3) ◽  
pp. 339-346 ◽  
Author(s):  
S. Miyauchi ◽  
J. Kitagaki ◽  
R. Masumoto ◽  
A. Imai ◽  
K. Kobayashi ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Periodontal Ligament ◽  
Type I Collagen ◽  
Alveolar Bone ◽  
Skeletal Development ◽  
Aggressive Periodontitis ◽  
Periodontal Ligament Cells ◽  
Type I ◽  
Phosphodiesterase 3 ◽  
Pdl Cells

Sphingomyelin phosphodiesterase 3 ( Smpd3), which encodes neutral sphingomyelinase 2 (nSMase2), is a key molecule for skeletal development as well as for the cytodifferentiation of odontoblasts and alveolar bone. However, the effects of nSMase2 on the cytodifferentiation of periodontal ligament (PDL) cells are still unclear. In this study, the authors analyzed the effects of Smpd3 on the cytodifferentiation of human PDL (HPDL) cells. The authors found that Smpd3 increases the mRNA expression of calcification-related genes, such as alkaline phosphatase (ALPase), type I collagen, osteopontin, Osterix (Osx), and runt-related transcription factor (Runx)-2 in HPDL cells. In contrast, GW4869, an inhibitor of nSMase2, clearly decreased the mRNA expression of ALPase, type I collagen, and osteocalcin in HPDL cells, suggesting that Smpd3 enhances HPDL cytodifferentiation. Next, the authors used exome sequencing to evaluate the genetic variants of Smpd3 in a Japanese population with aggressive periodontitis (AgP). Among 44 unrelated subjects, the authors identified a single nucleotide polymorphism (SNP), rs145616324, in Smpd3 as a putative genetic variant for AgP among Japanese people. Moreover, Smpd3 harboring this SNP did not increase the sphingomyelinase activity or mRNA expression of ALPase, type I collagen, osteopontin, Osx, or Runx2, suggesting that this SNP inhibits Smpd3 such that it has no effect on the cytodifferentiation of HPDL cells. These data suggest that Smpd3 plays a crucial role in maintaining the homeostasis of PDL tissue.

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