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Query: UMLS:C0031099 (periodontitis)
 12,489 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bacteroides forsythus is a gram-negative anaerobic bacterium associated with periodontitis. The bspA gene encoding a cell surface associated leucine-rich repeat protein (BspA) involved in adhesion to fibronectin and fibrinogen was recently cloned from this bacterium in our laboratory. We now describe the construction of a BspA-defective mutant of B. forsythus. This is the first report describing the generation of a specific gene knockout mutant of B. forsythus, and this procedure should be useful in establishing the identity of virulence-associated factors in these organisms.
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PMID:Development of a gene inactivation system for Bacteroides forsythus: construction and characterization of a BspA mutant. 1140 17

The purpose of this in vitro study was to observe and evaluate the effects of fibronectin(FN) on the growth of periodontal ligament cells(PDLC) on different root surfaces. Cell culture and scanning electronic microscopic techniques were used. The results showed that the growth pattern of PDLC on normal root surfaces were better than that of periodontitis. FN can significantly enhanced the attachment and proliferation of PDL cells on normal root surfaces. On the other hand, only the enhancement of attachment by FN was observed on the periodontitis root surfaces. It may be concluded that FN can promote the growth of PDLC and FN may play different effects on the attachment and proliferation of PDLC.
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PMID:[The effects of fibronectin on the attachment and proliferation of periodontal ligament cells]. 1221 7

Porphyromonas gingivalis is a predominant periodontal pathogen, which expresses a number of potential virulence factors involved in the pathogenesis of periodontitis. Among them, fimbriae are a critical factor to mediate the bacterial interaction with host tissues, which promotes the bacterial adhesion to and invasion of the targeted sites. Fimbriae are capable of binding to human salivary components, commensal bacteria, and a variety of host cells including macrophages, epithelial cells, and fibroblasts. Human extracellular matrix (ECM) proteins such as vitronectin and fibronectin play important roles in cellular signal transduction via binding to receptor integrins. Fimbriae showed significant binding affinity to ECM proteins and clearly inhibited the molecular interactions between vitronectin/fibronectin and their receptor alphavbeta3 and alpha5beta1 integrins overexpressed on Chinese hamster ovary (CHO) cell strain. P. gingivalis fimbriae are likely to interrupt the cellular signaling via ECM proteins/integrins in periodontal regions. Fimbriae are also thought to be critically important in invasive events of the organism to host cells. The fimA genes, encoding FimA (a subunit of fimbriae), of P. gingivalis strains are classified into 5 types, I to V. Recent clinical investigations demonstrated the close relationship between the organisms with type II fimA and periodontitis development. Recombinant FimA (rFimA) proteins of types I to V were generated to compare their adhesion/invasion abilities to human gingival fibroblasts (HGF) and a human epithelial cell line (HEp-2 cells), respectively. There were no significant differences in the adhesion ability of microspheres (MS) coated with these rFimAs to HGF; however, the adhesion of type II rFimA-MS to HEp-2 cells was significantly greater than that of other rFimA types. It was also observed that the type II rFimA-MS markedly invaded the epithelial cells and accumulated around the nuclei. Collectively, these findings suggest that fimbriae of P. gingivalis, especially type II, are involved in the initiation and progression of human periodontitis.
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PMID:Molecular interaction of Porphyromonas gingivalis with host cells: implication for the microbial pathogenesis of periodontal disease. 1259 2

Previously, we revealed that hepatocyte growth factor (HGF) or an HGF-like factor secreted by periodontal ligament fibroblasts (PLF) and gingival fibroblasts cultured in the presence of serum was a major chemoattractant for gingival epithelial cells, and suggested that it might play a role in epithelial invasion. However, our recent study showed that serum-free culture of PLF and gingival fibroblasts produced potent chemoattractants other than HGF for gingival epithelial cells. To identify these chemoattractants, PLF-conditioned medium (PLF-CM) from serum-free cultures was obtained, concentrated, and separated by gel filtration column chromatography, and the chemotactic activity for gingival epithelial cells of each eluted fraction was monitored by a modified Boyden chamber assay. The chemoattractant activity was eluted at a molecular mass of around 600 kDa, which would include laminin and fibronectin, but not HGF, determined by ELISA. The chemotactic activity was reduced by treatment with antilaminin and/or antifibronectin polyclonal antibodies. Western blots using both antibodies revealed that the PLF-CM contained laminin- and fibronectin-like molecules. Along with HGF, these large glycoprotein molecules produced by PLF may be involved in the pathogenesis and progression of periodontitis by inducing the apical migration of epithelial cells.
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PMID:Laminin- and fibronectin-like molecules produced by periodontal ligament fibroblasts under serum-free culture are potent chemoattractants for gingival epithelial cells. 1260 12

Treatment options for crescentic glomerulonephritis include the use of steroids, cytotoxic therapy, and, in severe cases, intravenous immunoglobulins and plasmapheresis. Injury and lysis of capillary glomerular basement membrane, which is made up of type IV collagen, laminin, fibronectin, and proteoglycans, by serine proteinases and matrix metalloproteinases (MMPs) likely is an important participant in the pathogenesis of crescentic glomerulonephritis. Tetracycline derivatives inhibit not only the activity of MMPs, but also their production, and have been investigated for the treatment of disorders in which the MMP system becomes amplified, such as degenerative osteoarthritis, periodontitis, cancer, and abdominal aortic aneurysm. We report an interesting case of crescentic glomerulonephritis in a young man who was treated with cyclophosphamide and prednisone. The patient developed steroid-induced acne that was treated with long-term oral doxycycline therapy. During the period the patient was administered doxycycline, proteinuria decreased by 70% and recurred when doxycycline was stopped. To our knowledge, this is the first report of possible benefits of a metalloproteinase inhibitor (doxycycline) in glomerulonephritis in humans. Future studies are urgently required to explore the option of metalloproteinase inhibitors in the treatment of proliferative glomerulonephritis.
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PMID:Doxycycline decreases proteinuria in glomerulonephritis. 1290 Aug 22

The gingipains are cell surface Arg- and Lys-specific proteinases of the bacterium Porphyromons gingivalis, which has been associated with periodontitis, a disease that results in the destruction of the teeth-s supporting tissues. The proteinases are encoded by three genes designated rgpA, rgpB and kgp. Arg-specific proteolytic activity is encoded by rgpA/B and the Lys-specific activity by kgp. RgpA and Kgp are polyproteins comprising proteinases with C-terminal adhesin domains that are proteolytically processed. After processing, the domains remain non-covalently associated as complexes on the cell surface. RgpB is also a cell surface proteinase but does not associate with adhesin domains. Using gene knockout P. gingivalis mutants, the proteolytic processing of the gingipain domains has been shown to involve the gingipains themselves as well as C-terminal processing by a carboxypeptidase. A motif in the C-terminal domain of each protein/polyprotein has been identified that is suggested to be involved in attachment to LPS on the cell surface. RgpB lacks a C-terminal adhesin binding motif found in the catalytic domains of RgpA and Kgp. This adhesin binding motif is proposed to be responsible for the non-covalent association of the RgpA and Kgp catalytic domains into the cell surface complexes with the processed adhesin domains. The RgpA-Kgp proteinase-adhesin complexes, through the adhesin domains A1 and A3, have been implicated in colonization of P. gingivalis by binding to other bacteria in subgingival plaque and also binding to crevicular epithelial cells. The RgpA-Kgp complexes also bind to fibrinogen, laminin, collagen type V, fibronectin and hemoglobin. Amino acid sequences likely to be involved in binding to these host proteins have been identified in adhesin domains A1 and A3. It is proposed that these adhesins target the proteolytic activity to host cell surface matrix proteins and receptors. The continual cycle of binding and degradation of the surface proteins/receptors on epithelial, fibroblast and endothelial cells by the RgpA-Kgp complexes in the gingival tissue leading to cell death would contribute to inflammation, tissue destruction and vascular disruption (bleeding). P. gingivalis has an obligate growth requirement for iron and protoporphyrin IX, which it preferentially utilizes in the form of hemoglobin. Kgp proteolytic activity is essential for rapid hydrolysis of hemoglobin and it is suggested therefore that a major role of the RgpA-Kgp complexes is in vascular disruption and the binding and rapid degradation of hemoglobin for heme assimilation by P. gingivalis. The RgpA-Kgp complexes also have a major role in the evasion and dysregulation of the host-s immune response. It is proposed that host pro-inflammatory cytokines and cellular receptors close to the infection site may be rapidly and efficiently degraded by the gingipains while the proteinases at lower concentrations distally could result in the promotion of an inflammatory response through activation of proteinase-activated receptors and cytokine release. The culmination of this dysregulation would be tissue destruction and bone resorption. In animal models of disease the RgpA-Kgp complex when used as a vaccine to produce a high titre antibody response protects against challenge with P. gingivalis. Using recombinant domains of RgpA and Kgp as vaccines, it has been demonstrated that the A1 and A3 domains confer protection.
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PMID:Porphyromonas gingivalis gingipains: the molecular teeth of a microbial vampire. 1468 27

The immunologic cross-reactivity between human fibronectin and Actinobacillus actinomycetemcomitans GroEL was examined. Analyses by SDS-PAGE/Western immunoblotting and ELISA showed that a polyclonal antibody directed against the purified GroEL protein of A. actinomycetemcomitans, but not against the Escherichia coli GroEL, cross-reacts with human fibronectin. No antigenic cross-reactivity was observed between anti-A. actinomycetemcomitans GroEL antibody and type IV collagen, another important constituent of the basement membrane. A comparative analysis of the amino acid sequences of A. actinomycetemcomitans GroEL and human fibronectin revealed eight instances of four-amino acid sequence homology between the two proteins. Six of these tetrapeptide sequences were also shared with E. coli GroEL, suggesting that the remaining two tetrapeptides, GQLI (Glycine-Glutamine-Leucine-Isoleucine) and TGLE (Threonine-Glycine-Leucine-Glutamic acid), may be associated with the epitope that the anti-A. actinomycetemcomitans GroEL antibody specifically recognizes. Reactivity between TGLE, but not GQLI, with anti-A. actinomycetemcomitans GroEL antibody was confirmed by a biospecific interaction analysis using a biosensor technology. Although additional investigations are required, the observed phenomenon may lead to an autoimmune response and thus contribute to tissue destruction during periodontitis.
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PMID:Antigenic cross-reactivity and sequence homology between Actinobacillus actinomycetemcomitans GroEL protein and human fibronectin. 1487 54

Porphyromonas gingivalis is a pathogen associated with adult periodontitis. It produces dipeptidyl aminopeptidase IV (DPPIV), which may act as a virulence factor by contributing to the degradation of connective tissue. We investigated the molecular mechanism by which DPPIV contributes to the destruction of connective tissue. DPPIV itself did not show gelatinase or collagenase activity toward human type I collagen, but it promoted the activity of the host-derived matrix metalloproteinase 2 (MMP-2) (gelatinase) and MMP-1 (collagenase). DPPIV bound to fibronectin and mediated the adhesion of P. gingivalis to fibronectin. Mutant DPPIV with catalytic Ser mutagenized to Ala (DPPSA) did not accelerate the degradation of collagen and gelatin by MMPs but retained fibronectin-binding activity. The adhesion of human gingival fibroblasts and NIH 3T3 cells to fibronectin was inhibited by DPPIV. Strain 4351ADPPSA exhibited an intermediate level of virulence in mice, between that of the strain expressing wild-type DPPIV (4351ADPP) and that of the strain harboring only the plasmid vector (4351AVEC). It is suggested that both activity promoting the degradation of collagen and gelatin and binding to fibronectin are required for full virulence. These results reveal novel biological functions of DPPIV and suggest a pathological role in the progression of periodontitis.
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PMID:Molecular mechanism for connective tissue destruction by dipeptidyl aminopeptidase IV produced by the periodontal pathogen Porphyromonas gingivalis. 1584 67

Porphyromonas gingivalis, a pathogen associated with periodontitis, bound to fibrinogen, fibronectin, hemoglobin, and collagen type V with a similar profile to that of its major virulence factor, the cell surface RgpA-Kgp proteinase-adhesin complex. Using peptide-specific, purified Abs in competitive inhibition ELISAs and epitope mapping assays, we have identified potential adhesin binding motifs (ABMs) of the RgpA-Kgp complex responsible for binding to host proteins. The RgpA-Kgp complex and synthetic ABM and proteinase active site peptides conjugated to diphtheria toxoid, when used as vaccines, protected against P. gingivalis-induced periodontal bone loss in the murine periodontitis model. The most efficacious peptide and protein vaccines were found to induce a high-titer IgG1 Ab response. Furthermore, mice protected in the lesion and periodontitis models had a predominant P. gingivalis-specific IL-4 response, whereas mice with disease had a predominant IFN-gamma response. The peptide-specific Abs directed to the ABM2 sequence (EGLATATTFEEDGVA) protected against periodontal bone loss and inhibited binding of the RgpA-Kgp complex to fibrinogen, fibronectin, and collagen type V. Furthermore, the peptide-specific Abs directed to the ABM3 sequence (GTPNPNPNPNPNPNPGT) protected against periodontal bone loss and inhibited binding to hemoglobin. However, the most protective Abs were those directed to the active sites of the RgpA and Kgp proteinases. The results suggest that when the RgpA-Kgp complex, or functional binding motif or active site peptides are used as a vaccine, they induce a Th2 response that blocks function of the RgpA-Kgp complex and protects against periodontal bone loss.
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PMID:An immune response directed to proteinase and adhesin functional epitopes protects against Porphyromonas gingivalis-induced periodontal bone loss. 1614 46

Interleukin-1beta (IL-1beta) mediates destruction of matrix collagens in diverse inflammatory diseases including arthritis, periodontitis, and pulmonary fibrosis by activating fibroblasts, cells that interact with matrix proteins through integrin-based adhesions. In vitro, IL-1beta signaling is modulated by focal adhesions, supramolecular protein complexes that are enriched with tyrosine kinases and phosphatases. We assessed the importance of tyrosine phosphatases in regulating cell-matrix interactions and IL-1beta signaling. In human gingival fibroblasts plated on fibronectin, IL-1beta enhanced the maturation of focal adhesions as defined by morphology and enrichment with paxillin and alpha-actinin. IL-1beta also induced activation of ERK and recruitment of phospho-ERK to focal complexes/adhesions. Treatment with the potent tyrosine phosphatase inhibitor pervanadate, in the absence of IL-1beta, recapitulated many of these responses indicating the importance of tyrosine phosphatases. Immunoblotting of collagen bead-associated complexes revealed that the tyrosine phosphatase, SHP-2, was also enriched in focal complexes/adhesions. Depletion of SHP-2 by siRNA or by homologous recombination markedly altered IL-1beta-induced ERK activation and maturation of focal adhesions. IL-1beta-induced tyrosine phosphorylation of SHP-2 on residue Y542 promoted focal adhesion maturation. Association of Gab1 with SHP-2 in focal adhesions correlated temporally with activation of ERK and was abrogated in cells expressing mutant (Y542F) SHP-2. We conclude that IL-1beta mediated maturation of focal adhesions is dependent on tyrosine phosphorylation of SHP-2 at Y542, leading to recruitment of Gab1, a process that may influence the downstream activation of ERK.
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PMID:Tyrosine phosphatase SHP-2 regulates IL-1 signaling in fibroblasts through focal adhesions. 1625 12


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