epidermal-growth-factor and Periodontitis

Topics: Alveolar Bone Loss; Animals; Biomarkers; Bone Resorption; Collagen; Collagen Type I; Endothelial Growth Factors; Epidermal Growth Factor; Extracellular Matrix Proteins; Gingival Crevicular Fluid; Gingivitis; Glycosaminoglycans; Growth Substances; Humans; Intercellular Signaling Peptides and Proteins; Lymphokines; Osteocalcin; Peptides; Periodontal Diseases; Periodontal Index; Periodontitis; Platelet-Derived Growth Factor; Protein Isoforms; Proteoglycans; Transforming Growth Factor alpha; Transforming Growth Factor beta; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors

Periodontal disease is a chronic progressive inflammatory process leading to damage of tooth-supporting tissues. This comparative study assessed the effect of PhotoBioModulation (PBM) versus conventional therapy, and investigated biomarkers involved in the healing process. The test group comprised twenty systemically-healthy non-smoking subjects with chronic periodontitis with the presence of two matched contro-lateral premolar sites (probing depth > 5 mm); twenty subjects without chronic periodontitis (CP) served as control group. Patients were treated at baseline, either with scaling and root planing (SRP group) or with a procedure entailing SRP supported by PBM (PBM group). The laser used was a diode laser operating at 645 nm wavelength, 10 J/cm2, and 0.5 W/cm2 with a 600 μm fiber optic. Crevicular fluid levels of bradykinin (BK), vascular endothelial growth factor (VEGF), and epidermal growth factor z (EGF) were determined at both sites. Crevicular fluid specimens from both groups were analyzed with the ELISA TEST. Clinical differences in analyzed outcomes were observed in favor of PBM treatment. Taking average values as 100%, the reduction in BK concentration was 47.68% with SRP and 68.43% with PBM on day 3; the VEGF concentration decreased by 35.73% with SRP and 48.59% with PBM on day 7; the EGF concentration increased by 55.58% with SRP and by 58.11% with PBM on day 21.Clinical parameters improved significantly in both groups (pooled mean values of probing depth decreased from 5.6 to 4.5 mm; gingival index from 1.92 to 1.1; and bleeding on probing from 49.67 to 23.23) but did not vary significantly between the PBM and the SRP group. The results confirmed that PBM have beneficial effects in the early phases of the healing process playing a role in modulation of BK, EGF, and VEGF in gingival crevicular fluid levels; both groups had significant clinical improvement over control but there was no significant difference between them, only a trend for PBM group. The overall results of the study suggest a potential benefit of PBM in conjunction with SRP in treating chronic periodontitis.

Topics: Adult; Biomarkers; Bradykinin; Epidermal Growth Factor; Female; Gingival Crevicular Fluid; Humans; Low-Level Light Therapy; Male; Middle Aged; Periodontitis; Vascular Endothelial Growth Factor A

Many pathogens are known to modulate epithelial physical barriers, particularly tight-junction (TJ) proteins, to enter host cells and/or tissues. Growth factors have been implicated in the regulation of TJ proteins. The aim of this study is to determine differences in the levels of TJ proteins, growth factors, and their receptors in relation to bacterial invasion in diseased gingival tissues obtained from patients with periodontitis.. The presence of bacteria and expression of junctional adhesion molecule (JAM)-A, occludin, epidermal growth factor (EGF), keratinocyte growth factor (KGF), insulin-like growth factor-I (IGF-I), EGF receptor, KGF receptor, and IGF-1 receptor (IGF-1R) were evaluated in gingival tissues from healthy (n = 10) and diseased (n = 10) sites in patients with periodontitis by in situ hybridization and immunohistochemistry.. The bacterial invasion of gingival tissue was increased in periodontal lesions compared with healthy sites. Although the levels of JAM-A and occludin were not significantly different between the healthy and diseased sites, aberrant cytoplasmic expression of JAM-A and occluding was often observed in the lesions. In addition, more leukocytes expressing JAM-A or occludin were observed within the disease-associated epithelia. Compared with the healthy sites, the differential expression of KGF, IGF-I, and IGF-1R was observed in the periodontal lesions. The levels of TJ proteins showed positive correlations with those of growth factors.. The aberrant expression of growth factors and TJ proteins may contribute to increased bacterial invasion and disease progression in periodontal lesions.

Topics: Adult; Bacteria; Bacterial Load; Cell Adhesion Molecules; Cytoplasm; Disease Progression; Epidermal Growth Factor; Epithelial Attachment; ErbB Receptors; Female; Fibroblast Growth Factor 7; Gingiva; Humans; Insulin-Like Growth Factor I; Intercellular Signaling Peptides and Proteins; Leukocytes; Male; Middle Aged; Occludin; Periodontitis; Receptor, IGF Type 1; Receptors, Cell Surface; Receptors, Growth Factor; Tight Junction Proteins

Porphyromonas gingivalis is a Gram-negative bacterium associated with the development of periodontitis. The evolutionary success of this pathogen results directly from the presence of numerous virulence factors, including peptidylarginine deiminase (PPAD), an enzyme that converts arginine to citrulline in proteins and peptides. Such posttranslational modification is thought to affect the function of many different signaling molecules. Taking into account the importance of tissue remodeling and repair mechanisms for periodontal homeostasis, which are orchestrated by ligands of the epidermal growth factor receptor (EGFR), we investigated the ability of PPAD to distort cross talk between the epithelium and the epidermal growth factor (EGF) signaling pathway. We found that EGF preincubation with purified recombinant PPAD, or a wild-type strain of P. gingivalis, but not with a PPAD-deficient isogenic mutant, efficiently hindered the ability of the growth factor to stimulate epidermal cell proliferation and migration. In addition, PPAD abrogated EGFR-EGF interaction-dependent stimulation of expression of suppressor of cytokine signaling 3 and interferon regulatory factor 1. Biochemical analysis clearly showed that the PPAD-exerted effects on EGF activities were solely due to deimination of the C-terminal arginine. Interestingly, citrullination of two internal Arg residues with human endogenous peptidylarginine deiminases did not alter EFG function, arguing that the C-terminal arginine is essential for EGF biological activity. Cumulatively, these data suggest that the PPAD-activity-abrogating EGF function in gingival pockets may at least partially contribute to tissue damage and delayed healing within P. gingivalis-infected periodontia.

Topics: Arginine; Bacteroidaceae Infections; Cell Movement; Cell Proliferation; Cells, Cultured; Epidermal Growth Factor; Epithelium; ErbB Receptors; Fibroblasts; Humans; Hydrolases; Interferon Regulatory Factor-1; Periodontitis; Periodontium; Porphyromonas gingivalis; Protein-Arginine Deiminases; Suppressor of Cytokine Signaling 3 Protein; Suppressor of Cytokine Signaling Proteins; Wound Healing

Evidence of the role of cytokines produced by resident and inflammatory cells during inflammation is well established. The aim of this study was to quantify in healthy and diseased human gingiva the area fraction (AA%) occupied by collagen fibers and the amount of cytokines such as interleukin (IL)-1beta, IL-4, IL-6, tumor necrosis factor (TNF)-alpha, transforming growth factor (TGF)-beta, and epidermal growth factor (EGF) to investigate a possible correlation between such cytokines, collagen degradation, and the gingival index.. Gingival tissue specimens from 6 healthy controls (group 1), 6 patients with mild gingival inflammation (group 2), 6 patients with moderate gingival inflammation (group 3), and 6 patients with severe gingival inflammation (group 4) were cultured for 72 hours, and the cytokines present in the culture media were quantified using an enzyme-linked immunosorbent assay (ELISA). Paraffin gingival sections from the 24 subjects were stained with sirius red F3Ba for visualization of collagen fibers, then the area fraction (AA%) occupied by the gingival fibers was determined by automated image analysis.. The present study revealed significant differences (P < 0.05) between means of AA% in group 1 (53%), group 2 (41%), group 3 (39.5%), and group 4 (35%) for collagen fibers. Compared to controls, there were significant increases of IL-1beta (groups 3 and 4), IL-6, and TNF-alpha (group 3); a significant decrease of IL-4 (groups 2, 3, and 4) and TGF-beta (groups-2 and, 3); and no change of EGF. The collagen AA% was significantly correlated with the amounts of IL-4 and TGF-beta, and significantly inversely correlated with the amounts of IL-1beta for all 3 inflamed groups and IL-6 and TNF-alpha for groups 2 and 3.. The present study showed that EGF was not changed in inflamed gingival tissue and that IL-1beta and IL-4 were particularly and intensively correlated with collagen loss. These 2 cytokines could be markers of clinical severity during active periodontitis.

Topics: Adolescent; Adult; Analysis of Variance; Case-Control Studies; Child; Culture Techniques; Cytokines; Disease Progression; Enzyme-Linked Immunosorbent Assay; Epidermal Growth Factor; Fibrillar Collagens; Gingivitis; Humans; Interleukins; Periodontal Index; Periodontitis; Transforming Growth Factor beta; Tumor Necrosis Factor-alpha

Saliva provides a natural reservoir of growth factors whose purposes have remained elusive. Animal studies suggest that saliva-derived growth factors play a role in systemic and oral wound healing. In the current study, salivary concentrations of epidermal growth factor (EGF) were monitored in patients before and after oral and juxtaoral surgery.. Whole resting saliva was collected from a group of patients with parotid gland tumors requiring surgical resection. Another group of patients a history of periodontal disease requiring surgical intervention also provided whole salivary samples. Healthy age- and sex-matched persons served as controls.. Salivary EGF levels were elevated in both groups of patients within 24 hours after surgery. In the periodontitis patients, a second smaller peak was assayed noted between 36 and 48 hours. After this, EGF concentrations returned to levels comparable to healthy controls in both experimental groups.. Although the local cells have the ability to synthesize and secrete growth factors at a site of injury, these results suggest that surgery stimulates increased synthesis and secretion of growth factors in the saliva as well. This increased level of saliva-derived growth factor may also aid in promoting wound healing.

Topics: Adult; Aged; Analysis of Variance; Case-Control Studies; Epidermal Growth Factor; Female; Follow-Up Studies; Humans; Linear Models; Logistic Models; Male; Middle Aged; Parotid Neoplasms; Periodontitis; Saliva; Spectrophotometry; Wound Healing

Numerous data strongly suggest the involvement of cytokines and the matrix metalloproteinase collagenase (MMP-1) in the pathogenesis of periodontitis. Recently, we have demonstrated that, upon culturing under the influence of IL-1 alpha + EGF, a large amount of inactive procollagenase (MMP-1) is stored in the extracellular matrix of periosteal tissue. We now show that this endogenous reservoir of proenzyme can be operative after activation with plasmin and is able to induce a rapid and almost complete breakdown of the collagenous extracellular matrix. The level of collagen degradation following activation showed a strong correlation with the amount of proenzyme that was incorporated in the tissue. The highest level of degradation (70% of the total amount of collagenous proteins) was found with the IL-1 alpha + EGF-treated explants, followed by those treated with IL-1 alpha alone (35%). Explants cultured with EGF or in the absence of cytokines, containing only small amounts of procollagenase, showed little collagen breakdown following plasmin activation (7%). Inhibition of metalloproteinases by EDTA, or blockage of plasmin by PMSF, prevented the degradation in all explants irrespective of the amount of proenzyme present in the tissue. Our findings demonstrate that endogenous proenzyme stored in a native connective tissue matrix can be activated at a later time interval which results in a massive breakdown of the tissue. This study shows a possible pathway of collagenase-induced breakdown without recent de novo synthesis of the enzyme. Such a sequence may be operative in chronic inflammatory diseases, such as periodontitis, where production of procollagenase under the influence of cytokines spans a longer time period, whereas breakdown is often characterized by a cyclic behaviour.

Topics: Analysis of Variance; Animals; Collagen; Collagenases; Connective Tissue; Culture Techniques; Cytokines; Enzyme Activation; Enzyme Induction; Enzyme Precursors; Epidermal Growth Factor; Extracellular Matrix; Fibrinolysin; Hydroxyproline; Interleukin-1; Matrix Metalloproteinase 1; Periodontitis; Periosteum; Rabbits; Recombinant Proteins; Statistics, Nonparametric