Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0031099 (periodontitis)
 12,489 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Rheumatoid arthritis and periodontitis are inflammatory diseases modulated by proinflammatory cytokines [e.g. interleukin (IL-1) 1 and tumour necrosis factor alpha], which activate local fibroblasts to do the following: (1) proliferate, (2) induce gene expression and (3) produce destructive metalloproteinases. Hypoxia-inducible factor 1 (HIF-1) is a heterodimeric transcription factor (composed of HIF-1alpha and HIF-1beta/aryl hydrocarbon receptor nuclear transporter) that is modulated by hypoxia. HIF-1 binds to and induces several genes containing an HIF-1 consensus-binding site, including vascular endothelial growth factor and several glycolytic enzymes. Through differential screening of a human synovial fibroblast cDNA library, we identified HIF-1alpha as a clone up-regulated by IL-1. The mRNA for HIF-1alpha subunit was increased 3-4-fold by Northern blot analysis after cells had been incubated for 3 h in the presence of IL-1. In addition, IL-1 increased the binding of the heterodimer HIF-1 to the HIF consensus sequence. These results suggest that HIF-1 might have a role in inflammation, possibly in attempting to re-establish homoeostasis.
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PMID:Interleukin 1 induces hypoxia-inducible factor 1 in human gingival and synovial fibroblasts. 1092 58

Periodontitis is a chronic inflammatory disease of the highly vascularised supporting tissues of the teeth. Little is known about the vascular changes in untreated advanced periodontitis. Using confocal immunofluorescence microscopy and morphometry, we defined and quantified vascular remodelling in this lesion. In the connective tissue subjacent to the altered epithelium lining of the periodontal pocket, there was a significant increase in the numerical density of vascular profiles, primarily accounted for by vessels > or = 25 microm in diameter. In addition, vascular basement membranes were thickened and there was accumulation of non-vascular basement membrane remnants. We investigated the distribution of major angiogenic growth factors in periodontitis using immunohistochemistry. Basic fibroblast growth factor, although consistently associated with blood vessels, showed no regional variation in its distribution. In contrast, there was a marked regional variation in the intensity of immunostaining for vascular endothelial growth factor, with significantly reduced staining of the pocket epithelium. The changes in the vascularity of the periodontal connective tissues in untreated advanced periodontitis may be, in part, a consequence of altered expression of angiogenic activity by the epithelium. In turn, this may reflect the epithelial response to microbial flora in the microenvironment of the periodontal pocket.
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PMID:Vascular remodelling in chronic inflammatory periodontal disease. 1104 66

Differential gene expression was examined in human neutrophils stimulated with lipopolysaccharide from Porphyromonas gingivalis (P. gingivalis-LPS) using RNA fingerprinting by arbitrarily primed polymerase chain reaction (RAP-PCR). LPS from Escherichia coli (E. coli-LPS) was used as control. More than 200 differently expressed transcripts were found in 8 subjects showing differential regulation at the transcriptional level. Densitometric analyses revealed that 42-100 genes were upregulated, while 53-116 genes were downregulated by P. gingivalis-LPS compared with E. coli-LPS. The results of sequencing identification showed the presence of supervillin (SVIL) and vascular endothelial growth factor (VEGF) genes in the clones which were upregulated by P. gingivalis-LPS. Consequently, semiquantitative analyses proved that the level of mRNA for SVIL and VEGF were significantly higher in P. gingivalis-LPS-stimulated neutrophils than in other bacterial (E. coli, Actinobacillus actinomycetemcomitans, Prevotella intermedia) LPS- or synthetic lipid A-stimulated neutrophils. Our findings suggest that an elevated mRNA expression for SVIL could be associated with impaired function of neutrophils when stimulated by P. gingivalis-LPS. Further, the VEGF mRNA over-expression might be related to the pathogenesis of P. gingivalis-associated periodontitis. The RAP-PCR technique used in this study enabled us to identify a number of P. gingivalis-LPS regulated genes which hitherto have not been reported.
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PMID:Elevated mRNA expression for supervillin and vascular endothelial growth factor in human neutrophils stimulated with lipopolysaccharide from Porphyromonas gingivalis. 1145 14

Tooth eruption requires the presence of the dental follicle, a loose connective tissue sac that surrounds each unerupted tooth. The follicle appears to regulate many of the cellular and molecular events of eruption, including the formation of osteoclasts needed to resorb alveolar bone to form an eruption pathway. To that end, the expression of the tumour necrosis factor-alpha (TNF-alpha) gene was examined in the dental follicle as a possible regulator of osteoclastogenesis. TNF-alpha was expressed slightly in the dental follicle of the first mandibular molar of the rat beginning at day 3 postnatally, but maximal expression was seen at day 9, a time that correlates with a slight burst of osteoclast formation seen at day 10 postnatally. In vitro, TNF-alpha was not expressed constitutively in the follicle cells but incubating them with interleukin 1alpha resulted in a strong expression of TNF-alpha after only 0.5h. TNF-alpha itself enhanced monocyte chemotactic protein 1 (MCP-1) and vascular endothelial growth factor (VEGF) gene expression. It also slightly decreased the expression of osteoprotegerin after 3-h incubation but this returned to the control level at 6h. MCP-1 and VEGF could aid in recruiting mononuclear cells (osteoclast precursors) to the dental follicle. In addition to the potential role of TNF-alpha in tooth eruption, this study suggests that the periodontal ligament derived from the dental follicle might have the capacity to synthesize TNF-alpha, and thereby contribute to the destructive events of periodontitis.
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PMID:Expression of tumour necrosis factor-alpha in the rat dental follicle. 1261 41

Diabetic patients are susceptible to severe inflammatory periodontitis manifesting as swollen gingiva with bleeding, but the underlying mechanism is not well understood. Our purpose was to determine the effect of a high glucose (HG) condition on the interleukin-6/soluble interleukin-6 receptor (IL-6/sIL-6R)-induced activation of signaling and vascular endothelial growth factor (VEGF) expression in human gingival fibroblasts (HGFs). In this study, HGFs were cultured for at least two passages under a normal glucose (NG; 5.5 mM) condition or high glucose (25 mM) condition. Importantly, the HG condition significantly induced expression of gp130 mRNA in HGFs compared with levels in control cells. Consistent with the expression of its mRNA, the HG condition also increased the expression of gp130 protein, and phosphorylation of the tyrosine residue by gp130 was enhanced significantly by IL-6/sIL-6R stimulation. Furthermore, the HG condition enhanced the IL-6/sIL-6R-induced phosphorylation of p44/42 MAPK and led to subsequent activation of CCAAT/enhancer binding protein in nuclei. In contrast, there was no significant difference in phosphorylation of JNK between the HG and NG condition. Interestingly, HGFs increased IL-6/sIL-6R-induced VEGF165 mRNA expression and VEGF165 secretion under the HG condition compared with levels under the NG condition. In contrast, the induction of VEGF165 secretion was partially inhibited by PD98059 (selective p44/42 MAPK inhibitor) under the HG condition. In addition, the VEGF165 secretion was completely inhibited by the combination of PD98059 and SP600125 (JNK inhibitor). Our findings suggest that the HG condition indirectly increases VEGF expression via activation of gp130-mediated p44/42 MAPK-CCAAT/enhancer binding protein signaling in HGFs. Thus, elevated VEGF secretion in HGFs under the HG condition may play a role in the development of the severe periodontitis observed in diabetic patients.
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PMID:High glucose enhances interleukin-6-induced vascular endothelial growth factor 165 expression via activation of gp130-mediated p44/42 MAPK-CCAAT/enhancer binding protein signaling in gingival fibroblasts. 1467 17

Enamel matrix derivative, obtained from developing porcine teeth, is composed mainly of amelogenin proteins and used topically in periodontal surgery for advanced periodontitis to regenerate lost connective tissues. The primary objective of this study was to investigate the effects of enamel matrix derivative on skin wound healing. Secondly, in vitro effects of enamel matrix derivative on dermal fibroblasts and microvascular endothelial cells were examined. Full-thickness, circular 2-cm skin wounds in white 16-week-old rabbits were treated thrice weekly with enamel matrix derivative (30 mg/ml) in the vehicle propylene glycol alginate or with vehicle alone. Enamel matrix derivative treatment increased the amount of granulation tissue and accelerated time to complete epithelialization by 3 days (p < 0.001) compared to vehicle treatment. In cultured fibroblasts, vascular endothelial growth factor levels in conditioned media were increased more than fivefold (p < 0.001) with enamel matrix derivative treatment (0.1mg/ml) over control, measured by specific enzyme-linked immunosorbent assay. Enamel matrix derivative also increased release of matrix metalloproteinase-2 more than threefold from fibroblasts (p < 0.001) and from endothelial cells (p < 0.001). Thus, enamel matrix derivative significantly accelerated wound closure in rabbits, possibly by increasing levels of growth factors and proteinases important for granulation tissue formation and remodeling.
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PMID:Effects of a topical enamel matrix derivative on skin wound healing. 1497 71

Today, implant-supported prostheses are widely accepted as a reliable treatment modality, but failures in longitudinal studies have been shown. In some cases, peri-implantitis with a progressive periodontal bone loss takes place, and mechanical or load factors and biological or plaque-induced lesions have been claimed as main etiologic factors. We compared five cases of peri-implantitis, with five cases of healthy peri-implant tissues and five cases of aggressive periodontitis in order to give new findings on the osseointegration loss process. Biopsy specimens from the peri-implant tissues including oral (O), sulcular, and junctional epithelium and the underlying and supracrestal connective tissue, were taken in all cases for histological and immunohistochemical analysis. T lymphocytes were the most prominent cell in the peri-implantitis (PG) and aggressive periodontitis (AG) groups, but not in the peri-implant healthy group (HG). CD1a-positive cells (Langerhans and immature dendritic cells) were observed more frequently in the O than in the sulcular-junctional (S-J) epithelium: they were located in the basal and parabasal layers, without any differences between the three groups. Vascular proliferation analysed by immunoreactivity for CD34, Factor VIII, and vascular endothelial growth factor was more prominent in the PG comparing with HG and AG in the S-J area. Apoptosis, analysed by bcl2 and p53 immunoreactivity, was similar in the three groups. In conclusion, we suggest that the osseointegration loss process is due to an inflammatory process similar to that observed in aggressive periodontitis according to the number of T lymphocytes, but not to the vascular proliferation.
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PMID:Immunohistochemical analysis of soft tissues in implants with healthy and peri-implantitis condition, and aggressive periodontitis. 1535 97

Growth factors such as platelet-derived growth factor (PDGF) exert potent effects on wound healing including the regeneration of tooth-supporting structures. This investigation examined the effect of the local delivery of PDGF-BB when combined with reconstructive periodontal surgery on local wound fluid (WF) levels of PDGF-AB, vascular endothelial growth factor (VEGF), and bone collagen telopeptide (ICTP) in humans with advanced periodontitis. Sixteen patients exhibiting localized periodontal osseous defects were randomized to one of three groups (beta-TCP carrier alone, beta-TCP + 0.3 mg/mL of recombinant human PDGF-BB [rhPDGF-BB], or beta-TCP + 1.0 mg/mL of rhPDGF-BB) and monitored for 6 months. WF was harvested and analyzed for PDGF-AB, VEGF, and ICTP WF levels. Teeth contralateral to the target lesions served as controls. Increased levels of VEGF in the WF was observed for all surgical treatment groups with the 1.0 mg/mL rhPDGF-BB group showing the most pronounced difference at 3 weeks in the AUC analysis versus control (p < 0.0001). PDGF-AB WF levels were increased for the carrier alone group compared to both rhPDGFBB groups. Low-dose rhPDGF-BB application elicited increases in ICTP at days 3-5 in the wound healing process, suggesting a promotion of bone turnover at early stages of the repair process (p < 0.02). These results demonstrate contrasting inducible expression patterns of PDGF-AB, VEGF, and ICTP during periodontal wound healing in humans.
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PMID:Effect of rhPDGF-BB delivery on mediators of periodontal wound repair. 1684 42

The periodontal vasculature is profoundly affected during the progression of periodontitis, and several specific bacteria are believed to be involved in this inflammatory disease. Eikenella corrodens is one of the common bacteria detected in periodontitis diseased lesions; however, the function of this organism in periodontitis is not well understood. In this study, we investigated the E. corrodens-induced endothelial cell alteration and inflammation process that leads to leukocyte infiltration in inflamed regions. Soluble products from E. corrodens (EcSP) induced the gene expression and protein production of vascular endothelial growth factor in oral epithelial cells and human umbilical vein endothelial cells (HUVEC). Direct stimulation by EcSP also activated endothelial cell proliferation. Moreover, EcSP induced ERK1/2 (p44/42) and p38 mitogen-activated protein kinase (MAPK) phosphorylation within 10-30 min in HUVEC, as demonstrated by Western blot analysis and up-regulated intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), E-selectin and interleukin-8 (IL-8) production demonstrated by reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay. The specific p38 MAPK inhibitor SB203580 reduced the expression of ICAM-1, VCAM-1 and IL-8, whereas the blockade of p44/42 by MAPK kinase (MEK1) inhibitor, PD98059, inhibited only IL-8 expression. Our results indicate that E. corrodens can trigger a cascade of events that induce inflammatory responses in periodontal tissue via the MAPK cascade and may promote chronic periodontitis without bacteria-cell contact.
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PMID:Soluble products from Eikenella corrodens induce cell proliferation and expression of interleukin-8 and adhesion molecules in endothelial cells via mitogen-activated protein kinase pathways. 1724 Nov 69

It has been demonstrated that diabetes mellitus (DM) may have an inductive effect on the vascular endothelial growth factor (VEGF) levels of periodontium during periodontal disease. The aim of this study is to confirm this phenomenon, investigating whether it is also valid for diabetic periodontitis patients under good metabolic control. Sixteen type II DM patients, all with a glycosylated hemoglobin (HbA1c) value less than 7 (test), and 15 systemically healthy (control) chronic periodontitis patients were included in the study. The VEGF concentrations in the gingival supernatants and gingival crevicular fluid (GCF) samples of the study groups were measured by enzyme-linked immunosorbent assay. The data were analyzed by Student's t test in statistical means. The VEGF levels were significantly higher in the gingival supernatants of the test group (55.89 +/- 8.11 pg/ml) than that of the control group (24.81 +/- 2.04 pg/ml; p < 0.01). However, there was no statistically significant difference in the VEGF levels of GCF between the study groups (38.96 +/- 4.89 pg/ml in the test and 32.20 +/- 4.02 pg/ml in the control group; p > 0.05). Our study confirms that DM affects the VEGF levels of periodontal soft tissues in periodontal disease, and our results also suggest that this effect may not be influenced by the metabolic control of DM.
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PMID:Vascular endothelial growth factor (VEGF) levels of gingiva and gingival crevicular fluid in diabetic and systemically healthy periodontitis patients. 1727 64


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