Periodontal tissue regeneration with cementogenesis after application of brain-derived neurotrophic factor in 3-wall inflamed intra-bony defect.

OBJECTIVE: The purpose of this study is to investigate regenerative process by immunohistochemical analysis and evaluate periodontal tissue regeneration following a topical application of BDNF to inflamed 3-wall intra-bony defects. BACKGROUND: Brain-derived neurotrophic factor (BDNF) plays a role in the survival and differentiation of central and peripheral neurons. BDNF can regulate the functions of non-neural cells, osteoblasts, periodontal ligament cells, endothelial cells, as well as neural cells. Our previous study showed that a topical application of BDNF enhances periodontal tissue regeneration in experimental periodontal defects of dog and that BDNF stimulates the expression of bone (cementum)-related proteins and proliferation of human periodontal ligament cells. METHODS: Six weeks after extraction of mandibular first and third premolars, 3-wall intra-bony defects were created in mandibular second and fourth premolars of beagle dogs. Impression material was placed in all of the artificial defects to induce inflammation. Two weeks after the first operation, BDNF (25 and 50 µg/mL) immersed into atelocollagen sponge was applied to the defects. As a control, only atelocollagen sponge immersed in saline was applied. Two and four weeks after the BDNF application, morphometric analysis was performed. Localizations of osteopontin (OPN) and proliferating cell nuclear antigen (PCNA)-positive cells were evaluated by immunohistochemical analysis. RESULTS: Two weeks after application of BDNF, periodontal tissue was partially regenerated. Immunohistochemical analyses revealed that cells on the denuded root surface were positive with OPN and PCNA. PCNA-positive cells were also detected in the soft connective tissue of regenerating periodontal tissue. Four weeks after application of BDNF, the periodontal defects were regenerated with cementum, periodontal ligament, and alveolar bone. Along the root surface, abundant OPN-positive cells were observed. Morphometric analyses revealed that percentage of new cementum length and percentage of new bone area of experimental groups were higher than control group and dose-dependently increased. CONCLUSION: These findings suggest that BDNF could induce cementum regeneration in early regenerative phase by stimulating proliferation of periodontal ligament cells and differentiation into periodontal tissue cells, resulting in enhancement of periodontal tissue regeneration in inflamed 3-wall intra-bony defects.

The impacts of oral and gut microbiota on alveolar bone loss in periodontitis.

Periodontitis, a chronic infectious disease, primarily arises from infections and the invasion of periodontal pathogens. This condition is typified by alveolar bone loss resulting from host immune responses and inflammatory reactions. Periodontal pathogens trigger aberrant inflammatory reactions within periodontal tissues, thereby exacerbating the progression of periodontitis. Simultaneously, these pathogens and metabolites stimulate osteoclast differentiation, which leads to alveolar bone resorption. Moreover, a range of systemic diseases, including diabetes, postmenopausal osteoporosis, obesity and inflammatory bowel disease, can contribute to the development and progression of periodontitis. Many studies have underscored the pivotal role of gut microbiota in bone health through the gut-alveolar bone axis. The circulation may facilitate the transfer of gut pathogens or metabolites to distant alveolar bone, which in turn regulates bone homeostasis. Additionally, gut pathogens can elicit gut immune responses and direct immune cells to remote organs, potentially exacerbating periodontitis. This review summarizes the influence of oral microbiota on the development of periodontitis as well as the association between gut microbiota and periodontitis. By uncovering potential mechanisms of the gut-bone axis, this analysis provides novel insights for the targeted treatment of pathogenic bacteria in periodontitis.

Regulation of the Host Immune Microenvironment in Periodontitis and Periodontal Bone Remodeling.

The periodontal immune microenvironment is a delicate regulatory system that involves a variety of host immune cells including neutrophils, macrophages, T cells, dendritic cells and mesenchymal stem cells. The dysfunction or overactivation of any kind of local cells, and eventually the imbalance of the entire molecular regulatory network, leads to periodontal inflammation and tissue destruction. In this review, the basic characteristics of various host cells in the periodontal immune microenvironment and the regulatory network mechanism of host cells involved in the pathogenesis of periodontitis and periodontal bone remodeling are summarized, with emphasis on the immune regulatory network that regulates the periodontal microenvironment and maintains a dynamic balance. Future strategies for the clinical treatment of periodontitis and periodontal tissue regeneration need to develop new targeted synergistic drugs and/or novel technologies to clarify the regulatory mechanism of the local microenvironment. This review aims to provide clues and a theoretical basis for future research in this field.

Transcriptional Signatures and Network-Based Approaches Identified Master Regulators Transcription Factors Involved in Experimental Periodontitis Pathogenesis.

Periodontitis is a chronic inflammatory disease characterized by the progressive and irreversible destruction of the periodontium. Its aetiopathogenesis lies in the constant challenge of the dysbiotic biofilm, which triggers a deregulated immune response responsible for the disease phenotype. Although the molecular mechanisms underlying periodontitis have been extensively studied, the regulatory mechanisms at the transcriptional level remain unclear. To generate transcriptomic data, we performed RNA shotgun sequencing of the oral mucosa of periodontitis-affected mice. Since genes are not expressed in isolation during pathological processes, we disclose here the complete repertoire of differentially expressed genes (DEG) and co-expressed modules to build Gene Regulatory Networks (GRNs) and identify the Master Transcriptional Regulators of periodontitis. The transcriptional changes revealed 366 protein-coding genes and 42 non-coding genes differentially expressed and enriched in the immune response. Furthermore, we found 13 co-expression modules with different representation degrees and gene expression levels. Our GRN comprises genes from 12 gene clusters, 166 nodes, of which 33 encode Transcription Factors, and 201 connections. Finally, using these strategies, 26 master regulators of periodontitis were identified. In conclusion, combining the transcriptomic analyses with the regulatory network construction represents a powerful and efficient strategy for identifying potential periodontitis-therapeutic targets.

CHANGES IN THE ULTRASTRUCTURAL ELEMENTS OF PERIODONTAL NEUROTROPHY UNDER CONDITIONS OF ACUTE SIMPLE COAGULATION DYSTROPHY IN THE EXPERIMENT.

OBJECTIVE: Aim: To determine the role of damage to the ultrastructural elements of the periodontal nervous system in the pathogenesis of dystrophic periodontal disease. PATIENTS AND METHODS: Materials and Methods: The basis of the experimental part of the study was the preparation of ultrathin sections from blocks of gum tissue of white rats, which were prepared using the UMTP-3M device. The study and analysis of biopsy samples was carried out with the help of an electron microscope UEMV-100K. RESULTS: Results: With the help of transmission electron microscopy, it was found that from the first minutes after the injection of hemolysate of isogenic erythrocytes into the rats, aggregates of erythrocytes, clumps of blood plasma, clusters of fibrin monomer masses, bundles of fibrin fibers, platelet and homogeneous were present in the connective tissue of the gums, and in particular in the lumens of hemocapillaries microthrombi, which confirms damage to the ultrastructures of the periodontium, which lead to the development of a pathological process, which is described when simple coagulation dystrophy is reproduced. CONCLUSION: Conclusions: Coagulative damage to the ultrastructural elements of the periodontal nervous system is one of the important factors in the pathogenesis of dystrophic periodontal damage. Under these conditions, trophic disturbances occur, similar to those that occur when the integrity of the nerve is disturbed - neurotrophic mechanism of dystrophy.

Neutrophil N1 and N2 Subsets and Their Possible Association with Periodontitis: A Scoping Review.

Periodontitis is a chronic non-communicable disease caused by dysbiotic changes that affect the subgingival microbiota. During periodontitis, neutrophils play a central role in the initial recognition of bacteria, and their number increases with the appearance of the first signs of periodontal inflammation. Recent evidence has led to the proposition that neutrophils can also functionally polarize, determining selective activity patterns related to different diseases. Two well-defined neutrophil phenotypes have been described, the pro-inflammatory N1 subset and the suppressor N2 subset. To date, it has not been established whether these different neutrophil subtypes play a role in the pathogenesis of periodontitis. Thus, this scoping review aimed to determine whether there was evidence to suggest that the neutrophils present in periodontal tissues can be associated with certain phenotypes. The research question, population, concept, and context sought to identify original articles, in humans, that detected the presence of neutrophils in the periodontal tissues of people affected by periodontitis. Based on the search strategy, we found 3658 studies. After removing the papers with abstracts not related to the outcome measures and eligibility criteria, 16 articles were included for qualitative analysis. Several studies identified the presence of different neutrophil subsets, specifically, the naive, pro- and para-inflammatory, hyper-reactive and hyper-active, and high- and low-responder phenotypes. The existing evidence demonstrates the presence of pro-inflammatory, hyper-reactive and high-responder neutrophils in periodontal tissues affected with periodontitis. There is no evidence demonstrating the presence of the N1 or N2 phenotypes in periodontal tissues during periodontitis. However, the existence of pro-inflammatory phenotypes, which increase NETosis and degranulation, and increase the production of pro-inflammatory cytokines, could be suggestive of the N1 phenotypes.

Hyperhomocysteinemia: an instigating factor for periodontal disease.

Hyperhomocysteinemia (HHcy) affects bone remodeling, since a destructive process in cortical alveolar bone has been linked to it; however, the mechanism remains at large. HHcy increases proinflammatory cytokines viz. TNF-α, IL-1b, IL-6, and IL-8 that leads to a cascade that negatively impacts methionine metabolism and homocysteine cycling. Further, chronic inflammation decreases vitamins B12, B6, and folic acid that are required for methionine homocysteine homeostasis. This study aims to investigate a HHcy mouse model (cystathionine ß-synthase deficient, CBS+/-) for studying the potential pathophysiological changes, if any, in the periodontium (gingiva, periodontal ligament, cement, and alveolar bone). We compared the periodontium side-by-side in the CBS+/- model with that of the wild-type (C57BL/6J) mice. Histology and histomorphometry of the mandibular bone along with gene expression analyses were carried out. Also, proangiogenic proteins and metalloproteinases were studied. To our knowledge, this research shows, for the first time, a direct connection between periodontal disease during CBS deficiency, thereby suggesting the existence of disease drivers during the hyperhomocysteinemic condition. Our findings offer opportunities to develop diagnostics/therapeutics for people who suffer from chronic metabolic disorders like HHcy.

Inflammation in the Human Periodontium Induces Downregulation of the α1- and ß1-Subunits of the sGC in Cementoclasts.

Nitric oxide (NO) binds to soluble guanylyl cyclase (sGC), activates it in a reduced oxidized heme iron state, and generates cyclic Guanosine Monophosphate (cGMP), which results in vasodilatation and inhibition of osteoclast activity. In inflammation, sGC is oxidized and becomes insensitive to NO. NO- and heme-independent activation of sGC requires protein expression of the α1- and ß1-subunits. Inflammation of the periodontium induces the resorption of cementum by cementoclasts and the resorption of the alveolar bone by osteoclasts, which can lead to tooth loss. As the presence of sGC in cementoclasts is unknown, we investigated the α1- and ß1-subunits of sGC in cementoclasts of healthy and inflamed human periodontium using double immunostaining for CD68 and cathepsin K and compared the findings with those of osteoclasts from the same sections. In comparison to cementoclasts in the healthy periodontium, cementoclasts under inflammatory conditions showed a decreased staining intensity for both α1- and ß1-subunits of sGC, indicating reduced protein expression of these subunits. Therefore, pharmacological activation of sGC in inflamed periodontal tissues in an NO- and heme-independent manner could be considered as a new treatment strategy to inhibit cementum resorption.

Oral Microbiome in Relation to Periodontitis Severity and Systemic Inflammation.

Systemic inflammation induced by periodontitis is suggested to be the link between periodontitis and cardiovascular disease. The aim of this work was to explore the oral microbiome in periodontitis in relation to disease severity and systemic inflammation. The saliva and subgingival microbiome from periodontal pocket samples of patients with severe (n = 12) and mild periodontitis (n = 13) were analyzed using metagenomic shotgun sequencing. The taxa and pathways abundances were quantified. The diversity was assessed and the abundances to phenotype associations were performed using ANCOM and linear regression. A panel of inflammatory markers was measured in blood and was associated with taxa abundance. The microbial diversity and species richness did not differ between severe and mild periodontitis in either saliva or periodontal pockets. However, there were significant differences in the microbial composition between severe and mild periodontitis in the subgingival microbiome (i.e., pocket samples) and, in a lower grade, in saliva, and this is positively associated with systemic inflammatory markers. The "red complex" and "cluster B" abundances in periodontal pockets were strongly associated with inflammatory markers interleukin-6 and the white blood cell count. Our data suggest that systemic inflammation in severe periodontitis may be driven by the oral microbiome and may support the indirect (inflammatory) mechanism for the association between periodontitis and cardiovascular disease.

Epigenetic modifier trichostatin A enhanced osteogenic differentiation of mesenchymal stem cells by inhibiting NF-κB (p65) DNA binding and promoted periodontal repair in rats.

We wished to evaluate whether epigenetic modifiers have a beneficial effect on treating experimental periodontitis and mechanisms for regulating the cell fate of mesenchymal stem cells (MSCs) in inflammatory microenvironments. We isolated MSCs from healthy and inflamed gingival tissues to investigate whether trichostatin A (TSA) could improve osteogenic differentiation and resolve inflammation in vitro. The tissue regenerative potentials were evaluated when treated with a temperature-dependent, chitosan-scaffold-encapsulated TSA, in a rat model of periodontitis. After induction with the conditioned medium, TSA treatment increased the osteogenic differentiation potential of inflamed MSCs and healthy MSCs. In addition, interleukin-6 and interleukin-8 levels in supernatants were significantly decreased after TSA treatment. Moreover, TSA promoted osteogenic differentiation by inhibiting nuclear factor-κB (p65) DNA binding in MSCs. In rats with experimental periodontitis, 7 weeks after local injections of chitosan-scaffold-encapsulated TSA, histology and microcomputed tomography showed a significant increase in alveolar bone volume and less inflammatory infiltration compared with vehicle-treated rats. The concentrations of interferon-γ and interleukin-6 were significantly decreased in the gingival crevicular fluid after TSA treatment. This study demonstrated that TSA had anti-inflammatory properties and could promote periodontal tissue repair, which indicated that epigenetic modifiers hold promise as a potential therapeutic option for periodontal tissue repair.

The tissue renin-angiotensin system (tRAS) and the impact of its inhibition on inflammation and bone loss in the periodontal tissue.

Recently, the existence of the tissue renin-angiotensin system (tRAS) has been described for multiple tissues in humans, suggesting its fundamental role in the progression of inflammation and fibrosis. Evidence arises that tRAS might have an impact on the progression of periodontitis and bone loss. However, neither the role of tRAS nor its impact as a therapeutic target have been systematically evaluated for periodontal tissue. The present study sought to characterise tRAS in the periodontal tissue and the effect of its inhibition on periodontal inflammation and bone loss. This systematic review was performed according to the preferred reporting items for systematic reviews and meta analyses (PRISMA) statement. Literature was searched using Web of Science core collection (Web of Science), Medline (Ovid), Cochrane central register of controlled trials (Ovid), Cochrane database of systematic reviews (Ovid), Google Scholar databases and the references of the retrieved studies in March 2020. Information on study design, sample size, population, procedure, type of intervention, observation time, as well as information on sources of bias, was extracted and evaluated. From 455 identified articles, 17 were included in the qualitative synthesis and 11 were included in the quantitative synthesis. Outcomes of studies indicated that the inhibition of tRAS components led to a reduction of periodontal bone loss and inflammation, dependent on the inhibitor used. The findings suggested an important role of tRAS in the periodontal tissue and indicate a potential therapeutic approach for periodontal diseases.

Periodontal Disease and Senescent Cells: New Players for an Old Oral Health Problem?

The recent identification of senescent cells in periodontal tissues has the potential to provide new insights into the underlying mechanisms of periodontal disease etiology. DNA damage-driven senescence is perhaps one of the most underappreciated delayed consequences of persistent Gram-negative bacterial infection and inflammation. Although the host immune response rapidly protects against bacterial invasion, oxidative stress generated during inflammation can indirectly deteriorate periodontal tissues through the damage to vital cell macromolecules, including DNA. What happens to those healthy cells that reside in this harmful environment? Emerging evidence indicates that cells that survive irreparable genomic damage undergo cellular senescence, a crucial intermediate mechanism connecting DNA damage and the immune response. In this review, we hypothesize that sustained Gram-negative bacterial challenge, chronic inflammation itself, and the constant renewal of damaged tissues create a permissive environment for the abnormal accumulation of senescent cells. Based on emerging data we propose a model in which the dysfunctional presence of senescent cells may aggravate the initial immune reaction against pathogens. Further understanding of the role of senescent cells in periodontal disease pathogenesis may have clinical implications by providing more sophisticated therapeutic strategies to combat tissue destruction.

Clinical and radiographic evaluation of the Periodontium with biologic width invasion.

BACKGROUND: The biologic width is defined as the coronal dimension to the alveolar bone that is occupied by healthy gingival tissue. The objective of the present study was to correlate radiographic findings of biologic width invasion with the periodontium status. METHODS: It were included 14 patients with restored teeth with biological width invasion, on the proximal sites, observed clinically and radiographically. 122 proximal sites were evaluated, 61 in the test group (biological width invasion) and 61 in the control group (adequate biological width). Smokers and patients presenting periodontal disease or restorations with contact in eccentric movements, horizontal over-contour or secondary caries were excluded from the sample. The invasion of the biologic width was diagnosed when the distance from the gingival margin of restoration to the bony crest was less than 3 mm. Intrabony defect and bone crest level, as well as, their vertical and horizontal components were radiographically evaluated when present. Plaque index, bleeding on probing, probing depth, gingival recession height, keratinized gingival height and thickness, and clinical attachment level were clinically evaluated. Data were subjected to Spearman's Correlation and Wilcoxon's test. RESULT: The most prevalent tooth with biological width invasion was the first molar. There was a statistically significant correlation between the bone crest (p < 0.001), vertical (p < 0.001) and horizontal (p = 0.001) components. In the test group, there was a statistically significant correlation between bleeding on probing (p < 0.001; r = 0.618) and width of gingival recession (p = 0.030; r = - 0.602) with the intraosseous component; and between keratinized gingival height and bone level (p = 0.037; r = - 0.267). In the control group, there was a correlation between plaque index (p = 0.027; r = - 0.283) with bone level and correlation between keratinized gingival thickness and bone level (p = 0.034; r = - 0.273) and intrabony component (p = 0.042; r = 0.226). CONCLUSION: A statistically significant relationship was found between bleeding on probing and gingival recession in patients who presented intrabony defects due to the invasion of biological width, which may be also related to the thickness of the keratinized gingiva.

Inflammasome and cytokine expression profiling in experimental periodontitis in the integrin ß6 null mouse.

Epithelial αvß6 integrin participates in immune surveillance in many organs, including the gastrointestinal track. Expression of αvß6 integrin is reduced in the junctional epithelium of the gingiva in periodontal diseases, and mutations in the ITGB6 gene are associated with these diseases in humans and mice. The aim of this study was to unravel potential differences in the inflammatory responses in the periodontal tissues of FVB wild-type (WT) and ß6 integrin-null (Itgb6-/-) mice, using a ligature-induced periodontitis model and assessing inflammation, bone loss and expression profiles of 34 genes associated with periodontal disease. Using micro-CT and histology, we demonstrated more advanced inflammation and bone loss in the control and ligatured Itgb6-/- mice compared to the WT animals. Neutrophil and macrophage marker genes were significantly upregulated by ligation in both WT and Itgb6-/- mice while the expression of T-cell and B-cell markers was downregulated, suggesting acute-type of inflammation. Expression of inflammasome NLRP3-related genes Nlpr3 and Il1b was also significantly increased in both groups. However, the expression of Il18 was significantly lower in non-ligatured Itgb6-/- mice than in the WT mice and was further downregulated in both groups by the ligatures. IL-18 mediates many effects of the AIM2 inflammasome, including regulation of the microbiome. Interestingly, expression of Aim2 was significantly lower in both control and ligatured Itgb6-/- mice than in WT animals. Overall, ligature-induced periodontitis was associated with increased expression of pro-inflammatory cytokines, chemokines and osteoclastogenic regulatory molecules. Another significant difference between the Itgb6-/- and WT mice was that mRNA expression of the anti-inflammatory cytokine IL-10 was increased in ligatured WT mice but reduced in the Itgb6-/- mice. In conclusion, αvß6 integrin in junctional epithelium of the gingiva appears to positively regulate the expression of the AIM2 inflammasome and anti-inflammatory IL-10, thus providing protection against periodontal inflammation.

Changes in characteristics of periodontal ligament stem cells in spheroid culture.

OBJECTIVES: The periodontal ligament (PDL) has important roles in maintaining homeostasis, wound healing, and regeneration of periodontal tissues by supplying stem/progenitor cells. Periodontal ligament stem cells (PDLSCs) have mesenchymal stem cell (MSC)-like characteristics and can be isolated from periodontal tissues. The aim of this study was to examine the effect of three-dimensional spheroid culture on the characteristics of PDLSCs. MATERIAL AND METHODS: Periodontal ligament stem cells were isolated and cultured from healthy teeth, and PDLSC spheroids were formed by pellet culture in polypropylene tubes. The proliferation of PDLSCs in spheroids and conventional two-dimensional (2D) cultures were examined by immunostaining for Ki67. Cell death and cell size were analyzed using flow cytometry. Gene expression changes were investigated by quantitative real time PCR. RESULTS: Periodontal ligament stem cells spontaneously formed spheroid masses in pellet culture. The size of PDLSC spheroids was inversely proportional to the culture period. Fewer Ki67-positive cells were detected in PDLSC spheroids compared to those in 2D culture. Flow cytometry revealed an increase in dead cells and a decrease in cell size in PDLSC spheroids. The expression levels of genes related to anti-inflammation (TSG6, COX2, MnSOD) and angiogenesis (VEGF, bFGF, HGF) were drastically increased by spheroid culture compared to 2D culture. TSG6 gene expression was inhibited in PDLSC spheroids in the presence of the apoptosis signal inhibitor, Z-VAD-FMK. Additionally, PDLSC spheroid transplantation into rat periodontal defects did not induce the regeneration of periodontal tissues. CONCLUSIONS: We found that spheroid culture of PDLSCs affected several characteristics of PDLSCs, including the expression of genes related to anti-inflammation and angiogenesis; apoptosis signaling may be involved in these changes. Our results revealed the characteristics of PDLSCs in spheroid culture and have provided new information to the field of stem cell research.

The periodontal stem/progenitor cell inflammatory-regenerative cross talk: A new perspective.

Adult multipotent stem/progenitor cells, with remarkable regenerative potential, have been isolated from various components of the human periodontium. These multipotent stem/progenitor cells include the periodontal ligament stem/progenitor cells (PDLSCs), stem cells from the apical papilla (SCAP), the gingival mesenchymal stem/progenitor cells (G-MSCs), and the alveolar bone proper stem/progenitor cells (AB-MSCs). Whereas inflammation is regarded as the reason for tissue damage, it also remains a fundamental step of any early healing process. In performing their periodontal tissue regenerative/reparative activity, periodontal stem/progenitor cells interact with their surrounding inflammatory micro-environmental, through their expressed receptors, which could influence their fate and the outcome of any periodontal stem/progenitor cell-mediated reparative/regenerative activity. The present review discusses the current understanding about the interaction of periodontal stem/progenitor cells with their surrounding inflammatory micro-environment, elaborates on the inflammatory factors influencing their stemness, proliferation, migration/homing, differentiation, and immunomodulatory attributes, the possible underlying intracellular mechanisms, as well as their proposed relationship to the canonical and noncanonical Wnt pathways.

Molecular evaluation of tissue proteins in vivo during controlled orthodontic movement.

Orthodontic tooth movement determines a biological response of all the tissues surrounding the teeth to which force is applied. The aim of this study is to evaluate which ideal orthodontic force, at the biological level, arouses an acute inflammatory response on periodontal tissues, and the duration of the force in order to establish an ideal experimental model of dental movement. The periodontal ligament and the alveolar bone change abruptly due to the biochemical adaptive response, resulting in a re-organization of the intracellular and the extracellular matrix. There is a modification of the local vascularization which stimulates a cascade production, synthesis and the release of arachidonic acid, metabolites, proteins, such as cytokines, and growth factors. Every dentist can control and should know the above-mentioned mechanism. Moreover, the production of proteins by modulating the direction and the intensity of the force can be changed but, above all, the duration.

An overview on periodontal changes and dental movements.

Only in recent times has been enhanced the importance of gingival crevicular fluid in periodontal health and in particular in maintaining the integrity of periodontium during application of orthodontic forces. The aim of this short review is to evaluate the importance of substances as valid biomarkers of periodontal health during orthodontic movements. A search on PubMed and Cochrane database was performed considering the literature from 2003 to 2014, using the following key words: gingival crevicular fluid, biomarkers of periodontal tissue, orthodontic movements. After abstracts screening, the full-texts of selected papers were analyzed and the papers found from the reference lists were also considered. The search focused on clinical applications documented in studies in the English language: levels of evidence included in the literature analysis were I, II and III. Literature analysis showed 28 papers that fulfilled the inclusion criteria. The conclusion is that GCF is a powerful vehicle for clinical diagnostics, since it contains different biochemical and cellular arrays in relation to different clinical situations indicative of the state of periodontal health during orthodontic treatment.

Comparative Analysis of the Morphology of Dentition in Normotensive and Hypertensive Rats Exposed to Chronic Stress.

The peculiarities of the histological structure and morphometrical parameters of the dentition in ISIAH rats (inherited stress-induced arterial hypertension) before stress and after modeling of everyday life stress regimen (chronic stress) were compared with those in WAG rats. The area of blood vessels of the periodontium, the thickness of the endothelium in the periodontal and pulp vessels, and the number of fibroblasts were increased, while the level of odontoblasts was reduced in ISIAH rats both before and after exposure to chronic stress, which can reflect more pronounced reaction to stress in hypertensive animals.

Changes in the Periodontium and Pulp in ISIAH Rats Caused by Stress Exposures in Different Modes.

It was shown that the intensity of morphological changes in the dental system tissues (periodontium and pulp) of ISIAH rats depends on the mode of stress exposure. Acute stress was associated with a significant increase in the area of periodontal and pulp vessels, a decrease in the area of connective tissue of these components, and an increase in the thickness of the vascular endothelium. Chronic stress in these animals induced an increase in the thickness of the endothelial layer of the periodontal and pulp vessels, fibromatosis (increase in the number of fibroblasts), and a sharp decrease in the level of odontoblasts.