scholarly journals Evolution of Periodontal Disease: Immune Response and RANK/RANKL/OPG System

2017 ◽  
Vol 28 (6) ◽  
pp. 679-687 ◽  
Author(s):  
Fabrício Gibertoni ◽  
Meire Ellen Ligia Sommer ◽  
Marcelo Augusto Marretto Esquisatto ◽  
Maria Esméria Corezola do Amaral ◽  
Camila Andrea de Oliveira ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Immune Response ◽  
Bone Loss ◽  
Periodontal Disease ◽  
Immunohistochemical Analysis ◽  
Inflammatory Cells ◽  
Gingival Tissue ◽  
Cervical Region ◽  
Nitric Oxide Concentration ◽  
Gene Transcripts

Abstract The aim of this study was to evaluate markers of bone loss and immune response present in evolution of periodontal disease. One hundred and two Wistar rats were divided into three animals groups: PD0, without ligation and PD15 days and PD60 days, submitted to ligation placement with a sterile 3-0 silk cord in the cervical region of the upper first molar on both sides. Samples were obtained from the gingival tissue for histomorphometric analysis, immunohistochemical analysis of RANK, RANKL, OPG, characterization of the inflammatory infiltrate, quantification of nitric oxide, MCP-1, RANTES, IP10 chemokines, and expression of the TGF-b1, VEG, and bFGF. The number of inflammatory cells in gingival tissue was higher in PD60 samples. The collagen content and the area occupied by birefringent collagen fibers were lower for PD60. Differential leukocyte counting showed that there was a significantly higher polymorphonuclear influx in group PD15, while PD60 showed a greater number of lymphocytes. PD60 showed higher RANTES, IP-10, MCP-1 gene transcripts, as well as a higher nitric oxide concentration. Clinical evaluation revealed that the PD60 group presented an increase in furcal area. In conclusion, in this animal model the increase of RANK/RANKL and HGF markers is related to a specific immune response, and probably contributed to the evolution of periodontal disease. Investigating the effect of these biomarkers can help in targeted therapy for bone resorption, since blocking these can inhibit bone loss.

scholarly journals Morphometric analysis of collagen and inflammatory cells in periodontal disease

2015 ◽  
Vol 72 (3) ◽  
pp. 219-224 ◽  
Author(s):  
Ranko Golijanin ◽  
Bojan Kujundzic ◽  
Zoran Milosavljevic ◽  
Dragan Milovanovic ◽  
Zlatibor Andjelkovic ◽  
...  
Keyword(s):  
Periodontal Disease ◽  
Morphometric Analysis ◽  
Plasma Cells ◽  
Relative Proportion ◽  
Inflammatory Cells ◽  
Test System ◽  
Clinical Staging ◽  
Gingival Tissue ◽  
Tissue Destruction ◽  
Immunochemical Method

Background/Aim. Periodontal disease affects gingival tissue and supporting apparatus of the teeth leading to its decay. The aim of this study was to highlight and precisely determine histological changes in the gum tissue. Methods. Gingival biopsy samples from 53 healthy and parodontopathy-affected patients were used. Clinical staging of the disease was performed. Tissue specimens were fixed and routinely processed. Sections, 5 ?m thin, were stained with hematoxylin and eosin, histochemical Van-Gieson for the collagen content, Spicer method for mast-cells and immunochemical method with anti-CD68 and anti-CD38 for the labelling of the macrophages and plasma-cells. Morphometric analysis was performed by a M42 test system. Results. While the disease advanced, collagen and fibroblast volume density decreased almost twice in the severe cases compared to the control ones, but a significant variation was observed within the investigated groups. The mast-cell number increased nearly two times, while the macrophage content was up to three times higher in severe parodontopathy than in healthy gingival tissue. However, the relative proportion of these cells stayed around 6% in all cases. Plasma-cells had the most prominent increase in the number (over 8 times) compared to the control, but again, a variation within investigated groups was very high. Conclusion. Gingival tissue destruction caused by inflammatory process leads to significant changes in collagen density and population of resident connective tissue cells. Although inflammatory cells dominated with the disease advancing, a high variation within the same investigated groups suggests fluctuation of the pathological process. <br><br><font color="red"><b> This article has been corrected. Link to the correction <u><a href="http://dx.doi.org/10.2298/VSP1704391E">10.2298/VSP1704391E</a><u></b></font>

scholarly journals Metformin Hydrochloride-Loaded PLGA Nanoparticle in Periodontal Disease Experimental Model Using Diabetic Rats

2018 ◽  
Vol 19 (11) ◽  
pp. 3488 ◽  
Author(s):  
Aline Pereira ◽  
Gerly Brito ◽  
Maria Lima ◽  
Arnóbio Silva Júnior ◽  
Emanuell Silva ◽  
...  
Keyword(s):  
Bone Loss ◽  
Cathepsin K ◽  
Immunohistochemical Analysis ◽  
Entrapment Efficiency ◽  
Inflammatory Cells ◽  
Plga Nanoparticles ◽  
Diabetic Rats ◽  
Metformin Hydrochloride ◽  
Tnf Α ◽  
Mean Diameter

Evidence shows that metformin is an antidiabetic drug, which can exert favorable anti-inflammatory effects and decreased bone loss. The development of nanoparticles for metformin might be useful for increased therapeutic efficacy. The aim of this study was to evaluate the effect of metformin hydrochloride-loaded Poly (d,l-Lactide-co-glycolide) (PLGA)/(MET-loaded PLGA) on a ligature-induced periodontitis model in diabetic rats. MET-loaded PLGA were characterized by mean diameter, particle size, polydispensity index, and entrapment efficiency. Maxillae were scanned using Microcomputed Tomography (µCT) and histopathological and immunohistochemical analysis. IL-1β and TNF-α levels were analyzed by ELISA immunoassay. Quantitative RT-PCR was used (AMPK, NF-κB p65, HMGB1, and TAK-1). The mean diameter of MET-loaded PLGA nanoparticles was in a range of 457.1 ± 48.9 nm (p < 0.05) with a polydispersity index of 0.285 (p < 0.05), Z potential of 8.16 ± 1.1 mV (p < 0.01), and entrapment efficiency (EE) of 66.7 ± 3.73. Treatment with MET-loaded PLGA 10 mg/kg showed low inflammatory cells, weak staining by RANKL, cathepsin K, OPG, and osteocalcin, and levels of IL-1β and TNF-α (p < 0.05), increased AMPK expression gene (p < 0.05) and decreased NF-κB p65, HMGB1, and TAK-1 (p < 0.05). It is concluded that MET-loaded PLGA decreased inflammation and bone loss in periodontitis in diabetic rats.

scholarly journals Lipopolysaccharide triggers different transcriptional signatures in taurine and indicine cattle macrophages: Reactive oxygen species and potential outcomes to the development of immune response to infections

PLoS ONE ◽  
2020 ◽  
Vol 15 (11) ◽  
pp. e0241861
Author(s):  
Raquel Morais de Paiva Daibert ◽  
Carlos Alberto Oliveira de Biagi Junior ◽  
Felipe de Oliveira Vieira ◽  
Marcos Vinicius Gualberto Barbosa da Silva ◽  
Eugenio Damaceno Hottz ◽  
...  
Keyword(s):  
Gene Expression ◽  
Nitric Oxide ◽  
Immune Response ◽  
Inflammatory Responses ◽  
Macrophage Polarization ◽  
Experimental Models ◽  
Buffy Coat ◽  
Nf Kappa B ◽  
Amyloid A ◽  
Nitric Oxide Concentration

Macrophages are classified upon activation as classical activated M1 and M2 anti-inflammatory regulatory populations. This macrophage polarization is well characterized in humans and mice, but M1/M2 profile in cattle has been far less explored. Bos primigenius taurus (taurine) and Bos primigenius indicus (indicine) cattle display contrasting levels of resistance to infection and parasitic diseases such as C57BL/6J and Balb/c murine experimental models of parasite infection outcomes based on genetic background. Thus, we investigated the differential gene expression profile of unstimulated and LPS stimulated monocyte-derived macrophages (MDMs) from Holstein (taurine) and Gir (indicine) breeds using RNA sequencing methodology. For unstimulated MDMs, the contrast between Holstein and Gir breeds identified 163 Differentially Expressed Genes (DEGs) highlighting the higher expression of C-C chemokine receptor type five (CCR5) and BOLA-DQ genes in Gir animals. LPS-stimulated MDMs from Gir and Holstein animals displayed 1,257 DEGs enriched for cell adhesion and inflammatory responses. Gir MDMs cells displayed a higher expression of M1 related genes like Nitric Oxide Synthase 2 (NOS2), Toll like receptor 4 (TLR4), Nuclear factor NF-kappa-B 2 (NFKB2) in addition to higher levels of transcripts for proinflammatory cytokines, chemokines, complement factors and the acute phase protein Serum Amyloid A (SAA). We also showed that gene expression of inflammatory M1 population markers, complement and SAA genes was higher in Gir in buffy coat peripheral cells in addition to nitric oxide concentration in MDMs supernatant and animal serum. Co-expression analyses revealed that Holstein and Gir animals showed different transcriptional signatures in the MDMs response to LPS that impact on cell cycle regulation, leukocyte migration and extracellular matrix organization biological processes. Overall, the results suggest that Gir animals show a natural propensity to generate a more pronounced M1 inflammatory response than Holstein, which might account for a faster immune response favouring resistance to many infection diseases.

scholarly journals Quantification of mast cells in different stages of periodontal disease

2016 ◽  
Vol 73 (5) ◽  
pp. 458-462 ◽  
Author(s):  
Dragan Marjanovic ◽  
Zlatibor Andjelkovic ◽  
Zlata Brkic ◽  
Goran Videnovic ◽  
Meliha Sehalic ◽  
...  
Keyword(s):  
Mast Cells ◽  
Periodontal Disease ◽  
Mononuclear Cells ◽  
Inflammatory Cells ◽  
Biologically Active ◽  
Gingival Tissue ◽  
Blue Staining ◽  
Toluidine Blue Staining ◽  
Inflammatory Processes ◽  
Severe Periodontal Disease

Background/Aim. Mast cells are mononuclear cells originating from bone marrow. They produce various biologically active substances, which allow them to actively participate in immune and inflammatory processes associated with periodontal disease. The study focused on distribution and density of mast cells in healthy gingiva as well as in different stages of periodontal disease. Methods. The material used for this purpose was gingival biopsies taken from 96 patients classified into 4 groups: healthy gingiva, gingivitis, initial and severe periodontal disease. Toluidine blue staining according to Spicer was utilized for identifying mast cells. Results. Basing on our study, the density of mast cells in the gingival tissue increases with the progression of the infection, which means they are more numerous in gingivitis compared to healthy gingiva, as well as in periodontal disease compared to gingivitis. Conclusion. Increase in the number of mast cells in the infected gingiva can be correlated with an increased influx of inflammatory cells from blood circulation into the gingival stroma, as well as with the collagen lysis, since these cells produce substances with collagenolytic potential. Based on the distribution of mast cells, it could be concluded that in the evolution of periodontal disease there are significant dynamic alterations in migration and localization of these cells.

scholarly journals Toll-Like Receptor Signaling and Immune Regulatory Lymphocytes in Periodontal Disease

2020 ◽  
Vol 21 (9) ◽  
pp. 3329 ◽  
Author(s):  
Yingzhi Gu ◽  
Xiaozhe Han
Keyword(s):  
Immune Response ◽  
B Cells ◽  
Bone Loss ◽  
Periodontal Disease ◽  
B Lymphocytes ◽  
Inflammatory Responses ◽  
Tlr Signaling ◽  
Periodontal Inflammation ◽  
Regulatory Lymphocytes

Periodontitis is known to be initiated by periodontal microbiota derived from biofilm formation. The microbial dysbiotic changes in the biofilm trigger the host immune and inflammatory responses that can be both beneficial for the protection of the host from infection, and detrimental to the host, causing tissue destruction. During this process, recognition of Pathogen-Associated Molecular Patterns (PAMPs) by the host Pattern Recognition Receptors (PRRs) such as Toll-like receptors (TLRs) play an essential role in the host–microbe interaction and the subsequent innate as well as adaptive responses. If persistent, the adverse interaction triggered by the host immune response to the microorganisms associated with periodontal biofilms is a direct cause of periodontal inflammation and bone loss. A large number of T and B lymphocytes are infiltrated in the diseased gingival tissues, which can secrete inflammatory mediators and activate the osteolytic pathways, promoting periodontal inflammation and bone resorption. On the other hand, there is evidence showing that immune regulatory T and B cells are present in the diseased tissue and can be induced for the enhancement of their anti-inflammatory effects. Changes and distribution of the T/B lymphocytes phenotype seem to be a key determinant of the periodontal disease outcome, as the functional activities of these cells not only shape up the overall immune response pattern, but may directly regulate the osteoimmunological balance. Therefore, interventional strategies targeting TLR signaling and immune regulatory T/B cells may be a promising approach to rebalance the immune response and alleviate bone loss in periodontal disease. In this review, we will examine the etiological role of TLR signaling and immune cell osteoclastogenic activity in the pathogenesis of periodontitis. More importantly, the protective effects of immune regulatory lymphocytes, particularly the activation and functional role of IL-10 expressing regulatory B cells, will be discussed.

scholarly journals Effects of Selective Versus Non-Selective COX-2 Inhibition on Experimental Periodontitis

2019 ◽  
Vol 30 (2) ◽  
pp. 133-138 ◽  
Author(s):  
Marcella Goetz Moro ◽  
Marilia Dantas dos Santos Oliveira ◽  
Leticia Rodrigues de Oliveira ◽  
Simone Aparecida Teixeira ◽  
Marcelo Nicolas Muscará ◽  
...  
Keyword(s):  
Bone Loss ◽  
Periodontal Disease ◽  
Periodontal Ligament ◽  
Alveolar Bone ◽  
Alveolar Bone Loss ◽  
Cervical Region ◽  
Radiographic Examination ◽  
Tissue Samples ◽  
Disease Induction ◽  
Cox 2

Abstract In the present study we compared the effects of the selective COX-2 inhibitor etoricoxib with those of the classical non-selective NSAID diclofenac on the inflammatory process and alveolar bone loss in an experimental model of periodontitis in rats. Ninety male Holtzman rats (250 g) were randomly sorted into four experimental groups: Sham+CMC and Ligature+CMC (control) groups which received 0.5% carboxymethylcellulose sodium (CMC) solution; Ligature+Diclofenac and Ligature+Etoricoxib groups which received Potassium Diclofenac and Etoricoxib, respectively, suspended in 0.5% CMC (10 mg/kg/day). At 7, 14 and 21 days after placing ligatures in the cervical region of both the lower right and left first molars, the animals were euthanized. At the end of each period, the mandibles were collected for radiographic examination of alveolar bone loss. In addition, alveolar bone and periodontal ligament tissue samples were collected for COX-2 expression analysis and gingival tissues were collected for measurement of PGE2 contents. Animals with ligature-induced periodontal disease showed significant increased COX-2 gene expression at days 7, 14 and 21 (p<0.05) on alveolar bone and periodontal ligament. However, both treatments resulted in significantly reduced alveolar bone loss when compared to the untreated Ligature group (p<0.05), with no statistical difference between Etoricoxib and Diclofenac Potassium groups. This study shows that both drugs were able to reduce alveolar bone loss after periodontal disease induction.

scholarly journals Hydroxyapatite composited PEEK with 3D porous surface enhances osteoblast differentiation through mediating NO by macrophage

2021 ◽  
Author(s):  
Xingdan Liu ◽  
Liping Ouyang ◽  
Lan Chen ◽  
Yuqin Qiao ◽  
Xiaohan Ma ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Immune Response ◽  
Bone Repair ◽  
Three Dimensional ◽  
Porous Surface ◽  
Mouse Bone Marrow ◽  
Inos Protein Expression ◽  
Oxide Concentration ◽  
Marrow Mesenchymal Stem Cells ◽  
Nitric Oxide Concentration

Abstract The adverse immune response mediated by macrophages is one of the main factors that are prone to lead poor osseointegration of polyetheretherketone (PEEK) implants in clinic. Hence, endowing PEEK with immunomodulatory ability to avoid the adverse immune response becomes a promise strategy to promote bone repair. In this work, sulfonation and hydrothermal treatment were used to fabricate a three-dimensional porous surface on PEEK and hydroxyapatite composited PEEK. The hydroxyapatite composited PEEK with three-dimensional porous surface inhibited macrophages polarizing to M1 phenotype and down-regulated iNOS protein expression, which led to a nitric oxide concentration reduction in culture medium of mouse bone marrow mesenchymal stem cells (mBMSCs) under co-culture condition. The decrease of nitric oxide concentration could help to increase bone formation related OSX and ALP genes expressions and decrease bone resorption related MMP-9 and MMP-13 genes expressions via cAMP-PKA-RUNX2 pathway in mBMSCs. In summary, the hydroxyapatite composited PEEK with three-dimensional porous surface has the potential to promote osteogenesis of PEEK through immunomodulation, which provides a promising strategy to improve the bone repair ability of PEEK.

scholarly journals Bisleuconothine A protects periodontal tissue via the regulation of RANKL expression and infiltration of inflammatory cells

2020 ◽  
Vol 19 (3) ◽  
pp. 497-503
Author(s):  
Fang Wang ◽  
Ping Sun ◽  
Qiang Sun
Keyword(s):  
Bone Loss ◽  
Alveolar Bone ◽  
Inflammatory Cells ◽  
Alveolar Bone Loss ◽  
Gingival Tissue ◽  
Enzyme Linked Immunosorbent Assay ◽  
Periodontal Tissue ◽  
Rankl Expression ◽  
Periodontal Tissues ◽  
Tnf Α

Purpose: To investigate the protective effect of bisleuconothine A on periodontal tissue in rats and the mechanism involved. Methods: Adult male Sprague Dawley rats (n = 32) weighing 180 - 200 g (mean weight, 190 ± 10 g) were randomly assigned to four groups of eight rats each: control group, periodontitis group, bisleuconothine A (50 mg/kg) group and bisleuconothine A (100 mg/kg) group. Rats in the treatment groups received bisleuconothine intraperitoneally for two weeks. Periodontitis was induced in the rats using standard procedures. Serum and tissue samples were used for biochemical analysis. Alveolar bone loss was measured in rat maxillae, while the activity of bone alkaline phosphatase (BALP) was determined in serum. Tumor necrosis factor α (TNF-α) interleukin-1β and interleukin-6 (IL-1β and IL-6) were determined in gingival tissue using enzyme-linked immunosorbent assay (ELISA) kit. Gene and protein expressions of receptor activator of nuclear factor kappa-Β ligand (RANKL), osteoprotegerin (OPG), and matrix metallopeptidase-9 (MMP-9) were measured in gingival tissue using real-time quantitative polymerase chain reaction (qRT-PCR) and Western blotting, respectively. Results: Bisleuconothine A treatment significantly and dose-dependently reduced alveolar bone loss, as well as serum levels of TNF-α, IL-1β and IL-6, but increased BALP activity in periodontitis rats (p < 0.05). It also significantly and dose-dependently reduced mRNA expressions of RANKL and MMP-9, but significantly increased OPG mRNA expression (p < 0.05). Similarly, treatment with bisleuconothine A significantly and dose-dependently down-regulated RANKL, p-NF-kB, p-IkBα and iNOS proteins in gingival tissue of periodontitis rats (p < 0.05). The results of histopathological examination indicated that bisleuconothine A treatment significantly reversed histological changes in periodontal tissues of periodontitis rats. It also significantly reduced the degree of polymorphonuclear (PMN) cell infiltration in periodontal tissue. Conclusion: The results obtained show that bisleuconothine A protects periodontal tissue via the regulation of RANKL expression and infiltration of inflammatory cells. Keywords: Bisleuconothine A, Expression, Inflammation, Periodontitis, RANKL

scholarly journals Protein citrullination as a source of cancer neoantigens

2021 ◽  
Vol 9 (6) ◽  
pp. e002549
Author(s):  
Hiroyuki Katayama ◽  
Makoto Kobayashi ◽  
Ehsan Irajizad ◽  
Alejandro Sevillarno ◽  
Nikul Patel ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Immune Response ◽  
Protein Expression ◽  
Cell Lines ◽  
Cancer Cell ◽  
Family Members ◽  
Immunohistochemical Analysis ◽  
Cancer Cell Lines ◽  
Mhc Ii

BackgroundCitrulline post-translational modification of proteins is mediated by protein arginine deiminase (PADI) family members and has been associated with autoimmune diseases. The role of PADI-citrullinome in immune response in cancer has not been evaluated. We hypothesized that PADI-mediated citrullinome is a source of neoantigens in cancer that induces immune response.MethodsProtein expression of PADI family members was evaluated in 196 cancer cell lines by means of indepth proteomic profiling. Gene expression was assessed using messenger RNA data sets from The Cancer Genome Atlas. Immunohistochemical analysis of PADI2 and peptidyl-citrulline was performed using breast cancer tissue sections. Citrullinated 12–34-mer peptides in the putative Major Histocompatibility Complex-II (MHC-II) binding range were profiled in breast cancer cell lines to investigate the relationship between protein citrullination and antigen presentation. We further evaluated immunoglobulin-bound citrullinome by mass spectrometry using 156 patients with breast cancer and 113 cancer-free controls.ResultsProteomic and gene expression analyses revealed PADI2 to be highly expressed in several cancer types including breast cancer. Immunohistochemical analysis of 422 breast tumor tissues revealed increased expression of PADI2 in ER− tumors (p<0.0001); PADI2 protein expression was positively correlated (p<0.0001) with peptidyl-citrulline staining. PADI2 expression exhibited strong positive correlations with a B cell immune signature and with MHC-II-bound citrullinated peptides. Increased circulating citrullinated antigen–antibody complexes occurred among newly diagnosed breast cancer cases relative to controls (p=0.0012).ConclusionsAn immune response associated with citrullinome is a rich source of neoantigens in breast cancer with a potential for diagnostic and therapeutic applications.

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