lipoteichoic-acid and Periodontitis

The signaling network involved in the pathogenesis of periodontal disease is not yet fully understood. This review aims to describe possible mechanisms through which the bacterial modulators may be linked directly or indirectly to the process of alveolar bone loss in periodontitis. From the late 1970s to present, new paradigm shifts have been developed regarding our understanding of pathological bone remodeling in periodontal disease. Upcoming evidence suggests that in periodontal disease the local immune response is exacerbated and involves the existence of signaling pathways that have been shown to modulate bone-cell function leading to alveolar bone loss. Those complex signaling pathways have been observed not only between bacteria but also between bacteria and the gingival surface of the host. More specifically, it has been shown that bacteria, through their secretion molecules, may interact indirectly and directly with immune-type cells of the host, resulting in the production of osteolytic agents that enhance bone resorption. Further research is required to provide a clear understanding of the role of these molecules in the pathogenesis of periodontal disease, and the availability of new technologies, such as next-generation sequencing and metagenomic analysis, may be useful tools in achieving this.

Topics: Alveolar Bone Loss; Antigens, Bacterial; Autoimmunity; Bacteria; Bacterial Physiological Phenomena; Bone Remodeling; Cytokines; Humans; Lipopeptides; Lipopolysaccharides; Lipoproteins; Osteoclasts; Osteolysis; Periodontal Diseases; Periodontal Pocket; Periodontitis; Teichoic Acids

Periodontitis is an inflammatory disease associated with severe alveolar bone loss and is dominantly induced by lipopolysaccharide from Gram-negative bacteria; however, the role of Gram-positive bacteria in periodontal bone resorption remains unclear. In this study, we examined the effects of lipoteichoic acid (LTA), a major cell-wall factor of Gram-positive bacteria, on the progression of inflammatory alveolar bone loss in a model of periodontitis. In coculture of mouse primary osteoblasts and bone marrow cells, LTA induced osteoclast differentiation in a dose-dependent manner. LTA enhanced the production of PGE

Topics: Alveolar Bone Loss; Animals; Bone Marrow Cells; Cell Differentiation; Cell Wall; Cells, Cultured; Cyclooxygenase 2; Gram-Positive Bacteria; Inflammation; Lipopolysaccharides; Male; Mice; Osteoblasts; Osteoclasts; Periodontitis; Prostaglandins E; RAW 264.7 Cells; Teichoic Acids

Topics: Enzyme-Linked Immunosorbent Assay; Humans; Lipopeptides; Lipopolysaccharide Receptors; Lipopolysaccharides; Periodontal Ligament; Periodontitis; Polymerase Chain Reaction; Stem Cells; Teichoic Acids; Toll-Like Receptor 2

To study the reactivity of lipopolysaccharide (LPS) and lipoteichoic acid (LTA) with the cationically charged agents cetylpyridinium chloride, stannous fluoride, and the non-cationic agent triclosan. We also assessed the effect of these agents to inhibit LPS and LTA binding to cellular Toll-like Receptors (TLRs) in vitro.. The ability of these antimicrobials to bind with LPS and/or LTA was assessed in both the Limulus amebocyte lysate and BODIPY-TR-cadaverine dye assays. Mass spectroscopy was then used to confirm that stannous fluoride directly binds with LPS and to determine stoichiometry. Lastly, we looked for possible inhibitory effects of these antimicrobial agents on the ability of fluorescently conjugated LPS to bind to TLR4 expressed on HEK 293 cells.. Cetylpyridinium chloride (CPC) and stannous salts including stannous fluoride interfered with LPS and LTA reactivity in both dye assays, while triclosan had no effect. Mass spectroscopy revealed direct binding of stannous fluoride with E. Coli LPS at 1:1 stoichiometric ratios. In the cellular assay, cetylpyridinium chloride and stannous fluoride, but not triclosan, inhibited LPS binding to TLR4.. These results support a potential mechanism of action for stannous fluoride and CPC formulated in oral products in which these ingredients bind bacterial toxins and potentially render them less toxic to the host. These results may influence home care recommendations for patients at risk for plaque-related diseases.

Topics: Anti-Infective Agents, Local; Cetylpyridinium; HEK293 Cells; Humans; Lipopolysaccharides; Mouthwashes; Periodontitis; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Teichoic Acids; Tin Fluorides; Toll-Like Receptors; Toothpastes; Triclosan; Virulence

This study tested the hypothesis that in vitro cleavage of C3 could be triggered with similar case in serum samples from patients with adult periodontitis (n = 26) as in samples from periodontally healthy subjects (n = 13). A lipoteichoic acid, a lipopolysaccharide and an aggregated IgG served as activators of complement. On the average, the periodontitis group generated significantly (p < 0.01) more C3d activation fragments than did the healthy group, as judged from rocket immunoelectrophoresis measurements. Cleavage of C4 and factor B were then assayed through immunoblotting, without prior purification of the sera. C4c fragments were seen in all activated samples, the healthy group causing significantly (p < 0.05) more C4 conversion than did the periodontitis group. Cleavage of factor B, taken as a measure of soluble amplification convertase formation, was about equal between the groups. We inferred therefore that the 2 groups produced comparable amounts of C3b. The results suggested, however, that periodontitis sera favour breakdown of the opsonin C3b, most likely by activating the regulatory proteins factor H and I. Lipoteichoic acid, causing moderate depletion of C4 and factor B, produced significantly (p < 0.01) more C3d fragments than the other two activators examined. It may be that complement activation is down-regulated in periodontitis sera, perhaps at the expense of adequate local opsonic function.

Topics: Adult; Analysis of Variance; Blood Protein Electrophoresis; Blotting, Western; Case-Control Studies; Complement Activation; Complement C3d; Down-Regulation; Female; Humans; Immunoelectrophoresis, Two-Dimensional; Immunoglobulin G; Lipopolysaccharides; Male; Periodontitis; Regression Analysis; Teichoic Acids

IgG antibody levels to lipoteichoic acid (LTA), prepared from Streptococcus mutans cells, were determined by enzyme-linked immunosorbent assay in serum samples from 149 subjects. An extract from Bacteroides gingivalis and lipopolysaccharide from Escherichia coli 055:B5 served as control antigens. The reference group comprised 28 systemically and periodontally healthy adults. The main test groups were: 52 persons with gingivitis only, and 69 patients with periodontitis. Within those groups, 37 patients had insulin-dependent diabetes mellitus, another 20 patients were prospective or renal transplant recipients. The periodontitis patient group showed significantly (p less than 0.05) higher mean antibody value and higher frequency of extreme antibody responses to both LTA and B. gingivalis than the gingivitis group. LPS did not discriminate between the groups. Multiple regression analysis with gingivitis scores as the dependent variable selected plaque scores, anti-LTA antibody values and general health status as significant (p less than 0.05) regressors. The variance in radiographical alveolar bone loss was significantly (p less than 0.05) explained by age and by antibody values to B. gingivalis and to LTA. The patients with extreme immunological responsiveness to LTA or to B. gingivalis had about twice as much alveolar bone loss as those with normal serological reactivity. The results support the contention that LTA modulates the progression of periodontitis in humans.

Topics: Adolescent; Adult; Antigen-Antibody Reactions; Bone Resorption; Diabetes Mellitus, Type 1; Enzyme-Linked Immunosorbent Assay; Gingivitis; Humans; Immunoglobulin G; Immunosuppression Therapy; Kidney Failure, Chronic; Lipopolysaccharides; Middle Aged; Periodontitis; Teichoic Acids