Periodontal Complex Research Articles

Quercetin effects on adaptive immune response in experimental periodontitis of bacterial-immune genesis

In the article was studied the effects of flavonol quercetin on indices of adaptive immune response in experimental animals on the 14th day of the experimental bacterial-immune periodontitis development. Indices of immune protection were determined by the relative number of lymphocytes with CD3+, CD4+, CD8+, CD19+, CD16+ and immunoregulatory index (CD4+ / CD8+) in intact animals and on the 14th day of inflammatory process development in periodontal tissues as well as the therapeutic effects of flavonol quercetin. As a result of the study, characterized changes associated with the activity of both the cell-mediated and humoral-immune response were found, both in the development of experimental periodontitis, and apply of flavonol. In particular, there was an increase in the animal’s blood relative amount of CD8+, CD16+ cells on the 14th day, and content of CD3+, CD4+, CD19+ was decreased. In this case, the immunoregulatory index (CD4+ / CD8+) as an important index of immunological activity was decreased. The apply of flavonol quercetin in the period development of bacterial-immune periodontitis animals functional activity of the T-cell line of the immune system was increased, as evidenced percentage increase of B- and T-cells due to T-helper cells decrease as well as T-killers content during this period of inflammatory reaction in the periodontal complex, in comparison with animals, which were not treated.

Cells at the Edge: The Dentin-Bone Interface in Zebrafish Teeth.

Bone-producing osteoblasts and dentin-producing odontoblasts are closely related cell types, a result from their shared evolutionary history in the ancient dermal skeleton. In mammals, the two cell types can be distinguished based on histological characters and the cells’ position in the pulp cavity or in the tripartite periodontal complex. Different from mammals, teleost fish feature a broad diversity in tooth attachment modes, ranging from fibrous attachment to firm ankylosis to the underlying bone. The connection between dentin and jaw bone is often mediated by a collar of mineralized tissue, a part of the dental unit that has been termed “bone of attachment”. Its nature (bone, dentin, or an intermediate tissue type) is still debated. Likewise, there is a debate about the nature of the cells secreting this tissue: osteoblasts, odontoblasts, or yet another (intermediate) type of scleroblast. Here, we use expression of the P/Q rich secretory calcium-binding phosphoprotein 5 (scpp5) to characterize the cells lining the so-called bone of attachment in the zebrafish dentition. scpp5 is expressed in late cytodifferentiation stage odontoblasts but not in the cells depositing the “bone of attachment”. nor in bona fide osteoblasts lining the supporting pharyngeal jaw bone. Together with the presence of the osteoblast marker Zns-5, and the absence of covering epithelium, this links the cells depositing the “bone of attachment” to osteoblasts rather than to odontoblasts. The presence of dentinal tubule-like cell extensions and the near absence of osteocytes, nevertheless distinguishes the “bone of attachment” from true bone. These results suggest that the “bone of attachment” in zebrafish has characters intermediate between bone and dentin, and, as a tissue, is better termed “dentinous bone”. In other teleosts, the tissue may adopt different properties. The data furthermore support the view that these two tissues are part of a continuum of mineralized tissues. Expression of scpp5 can be a valuable tool to investigate how differentiation pathways diverge between osteoblasts and odontoblasts in teleost models and help resolving the evolutionary history of tooth attachment structures in actinopterygians.

A hierarchical bilayer architecture for complex tissue regeneration

Engineering a complete, physiologically functional, periodontal complex structure remains a great clinical challenge due to the highly hierarchical architecture of the periodontium and coordinated regulation of multiple growth factors required to induce stem cell multilineage differentiation. Using biomimetic self-assembly and microstamping techniques, we construct a hierarchical bilayer architecture consisting of intrafibrillarly mineralized collagen resembling bone and cementum, and unmineralized parallel-aligned fibrils mimicking periodontal ligament. The prepared biphasic scaffold possesses unique micro/nano structure, differential mechanical properties, and growth factor-rich microenvironment between the two phases, realizing a perfect simulation of natural periodontal hard/soft tissue interface. The interconnected porous hard compartment with a Young's modulus of 1409.00 ± 160.83 MPa could induce cross-arrangement and osteogenic differentiation of stem cells in vitro, whereas the micropatterned soft compartment with a Young's modulus of 42.62 ± 4.58 MPa containing abundant endogenous growth factors, could guide parallel arrangement and fibrogenic differentiation of stem cells in vitro. After implantation in critical-sized complete periodontal tissue defect, the biomimetic bilayer architecture potently reconstructs native periodontium with the insertion of periodontal ligament fibers into newly formed cementum and alveolar bone by recruiting host mesenchymal stem cells and activating the transforming growth factor beta 1/Smad3 signaling pathway. Taken together, integration of self-assembly and microstamping strategies could successfully fabricate a hierarchical bilayer architecture, which exhibits great potential for recruiting and regulating host stem cells to promote synergistic regeneration of hard/soft tissues.

State of collagenolysis in experimental periodontitis of bacterial-immune genesis and its correction with flavonol

The article presents an assessment of the dynamics of changes in the content of the marker of collagenolysis – free oxyproline in the homogeniate of soft tissues and bone in experimental bacterial-immune periodontitis and elucidation of the effect of flavonol quercetin on these indicators. The aim of this study was to determine the role of cytokinogenesis and the effect of flavonol on it in the pathogenesis, development and course of experimental periodontitis. During the experiment, a fragment of the mandible was taken from the animals, from which the soft tissues and bone were carefully separated. The state of collagen was determined by the content of free oxyproline in the soft and bone tissues. The concentration was determined according to the calibration graph and expressed in μmol/g. The results of studies of the indicators of the state of biopolymers of connective tissue structures of periodontium on the 7th, 14th and 30th day of experimental bacterial-immune periodontitis and after its correction with flavonol (from the 7th to the 14th day of the experiment) are presented. The data on the nature of changes in the content of collagen monomers in the process of formation of the inflammatory focus in the periodontal complex are given. During the acute phase of the inflammatory process in rats there was revealed a slight increase in blood free oxyproline in bone homogenate and homogenate of soft periodontal tissues, on the 14th day the dynamics continued to increase, at a later stage of the experiment, namely on the 30th day, increase in bone resorption continued as compared to the 7th and 14th day. During the correction of disorders resulted from the development of this pathological process there was a decrease in the level of free oxyproline in the bone homogenate and homogenate of soft tissues of mandibular periodontium, as compared to the same indicators of animals who did not receive quercetin on the 14th day. The use of flavonol quercetin, which, by affecting immune processes, limited the inflammatory response in periodontal tissues and stabilized collagenolysis processes in periodontal tissues was manifested by a decrease in free oxyproline in bone and soft tissue homogenates of experimental animals.

Treponema denticola-Induced RASA4 Upregulation Mediates Cytoskeletal Dysfunction and MMP-2 Activity in Periodontal Fibroblasts.

The periodontal complex consists of the periodontal ligament (PDL), alveolar bone, and cementum, which work together to turn mechanical load into biological responses that are responsible for maintaining a homeostatic environment. However oral microbes, under conditions of dysbiosis, may challenge the actin dynamic properties of the PDL in the context of periodontal disease. To study this process, we examined host-microbial interactions in the context of the periodontium via molecular and functional cell assays and showed that human PDL cell interactions with Treponema denticola induce actin depolymerization through a novel actin reorganization signaling mechanism. This actin reorganization mechanism and loss of cell adhesion is a pathological response characterized by an initial upregulation of RASA4 mRNA expression resulting in an increase in matrix metalloproteinase-2 activity. This mechanism is specific to the T. denticola effector protein, dentilisin, thereby uncovering a novel effect for Treponema denticola-mediated RASA4 transcriptional activation and actin depolymerization in primary human PDL cells.

Functional adaptation of interradicular alveolar bone to reduced chewing loads on dentoalveolar joints in rats

ObjectivesThe effects of reduced chewing loads on load bearing integrity of interradicular bone (IB) within dentoalveolar joints (DAJ) in rats were investigated. MethodsFour-week-old Sprague Dawley rats (N = 60) were divided into two groups; rats were either fed normal food, which is hard-pellet food (HF) (N = 30), or soft-powdered chow (SF) (N = 30). Biomechanical testing of intact DAJs and mapping of the resulting mechanical strains within IBs from 8- through 24-week-old rats fed HF or SF were performed. Tension- and compression-based mechanical strain profiles were mapped by correlating digital volumes of IBs at no load with the same IBs under load. Heterogeneity within IB was identified by mapping cement lines and TRAP-positive multinucleated cells using histology, and mechanical properties using nanoindentation technique. ResultsSignificantly decreased interradicular functional space, IB volume fraction, and elastic modulus of IB in the SF group compared with the HF group were observed, and these trends varied with an increase in age. The elastic modulus values illustrated significant heterogeneity within IB from HF or SF groups. Both compression- and tension-based strains were localized at the coronal portion of the IB and the variation in strain profiles complemented the observed material heterogeneity using histology and nanoindentation. SignificanceInterradicular space and IB material-related mechanoadaptations in a DAJ are optimized to meet soft food related chewing demands. Results provided insights into age-specific regulation of chewing loads as a plausible “therapeutic dose” to reverse adaptations within the periodontal complex as an attempt to regain functional competence of a dynamic DAJ.

Combined antimicrobial chemotherapy (fluoroquinolones and imidazoles) in the complex treatment of inflammatory diseases of the periodontal

In inflammatory periodontal diseases, the leading role in the emergence and development of the process is assigned to the microbial biofilm; therefore one of the requirements for antibiotics used in periodontology is the ability of the drug to easily penetrate into the microbial biofilm. The aim is to study the effect of a combination of drugs of the fluoroquinolone group — ciprofloxacin and the 5-nitroimidazole group — tinidazole on the clinical manifestations and microbial composition of biofilms in chronic generalized periodontitis. Materials and methods. 58 patients with exacerbation of moderate chronic periodontitis were examined. In the main group, a combined preparation of ciprofloxacin and tinidazole (Tsifran ST) was prescribed, in the comparison group — amoxicillin with clavulanic acid (Amoxiclav). The duration of the course of antimicrobial chemotherapy was 10—12 days. Results. In the course of treatment, normalization of the indices of hygiene indices, PMA and PBI in both groups was established. Representatives of the consortium P. gingivalis, T. forsythia, A. actinomycetemcomitans were identified by PCR diagnostics in 100% of patients in both groups. complex treatment of chronic generalized periodontitis with a combination of ciprofloxacin and tinidazole increases the efficiency of eradication of the periodontal pocket and tissues of the periodontal complex from periodontal pathogenic bacterial species. After the treatment, the eradication of periodontal pathogenic species in the main group (use of a combination of ciprofloxacin and tinidazole) was more complete than in the comparison group, and dysbiotic disorders were less pronounced than in the comparison group. Conclusion. The inclusion of a combination of ciprofloxacin and tinidazole in the algorithms for the complex treatment of chronic generalized periodontitis increases the efficiency of eradication of the periodontal pocket and tissues of the periodontal complex from periodontal pathogenic bacteria species.

Ablation of Pyrophosphate Regulators Promotes Periodontal Regeneration

Biomineralization is regulated by inorganic pyrophosphate (PPi), a potent physiological inhibitor of hydroxyapatite crystal growth. Progressive ankylosis protein (ANK) and ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) act to increase local extracellular levels of PPi, inhibiting mineralization. The periodontal complex includes 2 mineralized tissues, cementum and alveolar bone (AB), both essential for tooth attachment. Previous studies demonstrated that loss of function of ANK or ENPP1 (reducing PPi) resulted in increased cementum formation, suggesting PPi metabolism may be a target for periodontal regenerative therapies. To compare the effects of genetic ablation of Ank, Enpp1, and both factors concurrently on cementum and AB regeneration, mandibular fenestration defects were created in Ank knockout (Ank KO), Enpp1 mutant (Enpp1asj/asj), and double KO (dKO) mice. Genetic ablation of Ank, Enpp1, or both factors increased cementum regeneration compared to controls at postoperative days (PODs) 15 and 30 (Ank KO: 8-fold, 3-fold; Enpp1asj/asj: 7-fold, 3-fold; dKO: 11-fold, 4-fold, respectively) associated with increased fluorochrome labeling and expression of mineralized tissue markers, dentin matrix protein 1 (Dmp1/DMP1), osteopontin (Spp1/OPN), and bone sialoprotein (Ibsp/BSP). Furthermore, dKO mice featured increased cementum thickness compared to single KOs at POD15 and Ank KO at POD30. No differences were noted in AB volume between genotypes, but osteoblast/osteocyte markers were increased in all KOs, partially mineralized osteoid volume was increased in dKO versus controls at POD15 (3-fold), and mineral density was decreased in Enpp1asj/asj and dKOs at POD30 (6% and 9%, respectively). Increased numbers of osteoclasts were present in regenerated AB of all KOs versus controls. These preclinical studies suggest PPi modulation as a potential and novel approach for cementum regeneration, particularly targeting ENPP1 and/or ANK. Differences in cementum and AB regeneration in response to reduced PPi conditions highlight the need to consider tissue-specific responses in strategies targeting regeneration of the entire periodontal complex.

Role of Wnt5a in periodontal tissue development, maintenance, and periodontitis: Implications for periodontal regeneration (Review).

The periodontium is a highly dynamic microenvironment constantly adapting to changing external conditions. In the processes of periodontal tissue formation and remodeling, certain molecules may serve an essential role in maintaining periodontal homeostasis. Wnt family member 5a (Wnt5a), as a member of the Wnt family, has been identified to have extensive biological roles in development and disease, predominantly through the non-canonical Wnt signaling pathway or through interplay with the canonical Wnt signaling pathway. An increasing number of studies has also demonstrated that it serves crucial roles in periodontal tissues. Wnt5a participates in the development of periodontal tissues, maintains a non-mineralized state of periodontal ligament, and regulates bone homeostasis. In addition, Wnt5a is involved in the pathogenesis of periodontitis. Recently, it has been shown to serve a positive role in the regeneration of integrated periodontal complex. The present review article focuses on recent research studies of Wnt5a and its functions in development, maintenance, and pathological disorders of periodontal tissues, as well as its potential effect on periodontal regeneration.

FUNCTIONAL ACTIVITY CHANGES OF THE MONONUCLEAR PHAGOCYTE SYSTEM IN PATIENTS WITH RAPIDLY PROGRESSIVE GENERALIZED PERIDONTITIS WITH PERIODONTAL MICROORGANISMS SENSITIVE AND RESISTANT TO DRUGS

Purpose. To reveal peculiarities of the mononuclear phagocyte functional activity in patients with rapidly progressive generalized periodontitis depending upon colonization of periodontal tissue by causative agents, sensitive and resistant to drugs, on the basis of studying activated blood monocytes, phagocytic activity of mononuclear phagocytes and production of the main classes of immunoglobulins, cytokine profile state. Material and methods. The investigation was carried out on 74 patients with rapidly progressive generalized periodontitis I-II and II-III severity, aged 35 to 50 years. Complex of the laboratory studies included immunophenotypic changes in the subpopulation composition of the mononuclear blood cells (CD3 +, CD4 +, CD8 +, CD14 +, CD16 +, CD25 +, HLA-DR and CD95+), phagocytic activity of neutrophils, level of cytokine production and synthesis of sIgA, IgA, IgG and IgM in the oral fluid. Results. On the basis of the conducted complex clinical-laboratory data it has been established that a significant decrease of the functional activity of the mononuclear phagocyte system stipulates the formation of the severe secondary deficiency of the cellular and humoral immunity in patients who are carries of the resistant strains of periodontal pathogenic agents of the rapidly progressive generalized periodontitis and moderate - at colonization of the periodontal complex with causative agents sensitive to drugs. The pathogenetic dependence of the drug sensitivity upon the nature of the disorders of the systemic and local humoral immunity has been shown: at the marked immunodeficiency the development of the bacterial resistance to drugs is possible, and preservation of the drug sensitivity to the causative agents of the rapidly progressive generalized periodontitis is associated with moderate disorders of anti-infectious mechanisms of the immune response. Conclusion. The assessment of the functional activity of the mononuclear phagocyte system, based on the study of the state of immunophenotypic changes in the subpopulation composition of mononuclear blood cells, phagocytic activity of monocytes, the content of immunoglobulins and cytokines in the oral fluid, gives valuable information to clarify the mechanisms of the development of various sensitivity of the periodontal-pathogenic flora of the periodontal tissue to protocol antibacterial therapy in the patients with rapidly progressive generalized periodontitis.

Biological effect of the nanocrystalline calcium sulfate bone graft in the periodontal regeneration

BackgroundThe ultimate goal of tissue engineering is to reproduce functional alveolar∖Periodontal complex. This study aimed to asses micro- and nano-formulated crystalline calcium sulfate as possible treatment of intrabony defect utilizing an autologous Platelet rich fibrin scaffold. Subjectsand Methods: An experimental prospective split mouth design using eight healthy mongrel dog’s was conducted. After two months of extracting the first premolar, bilateral intrabony defects were created mesial to the mandibular second premolar. One side was grafted by nanocrystalline calcium sulfate, while, the opposite side was grafted with microcrystalline calcium sulfate graft. Dogs were randomly euthanized after one month (group I) and 3 months (group II). The primary outcomes were the histological changes of new bone formation in hematoxylin and eosin and Masson trichrome stains, while histomorphometric and radiographic analysis were the secondary outcome followed by statistical analysis (P value was set at .05). ResultsThere was a significant increase in the percentage of bone formation in relation to defect height in nanocrystalline compared to microcrystalline form after one month and three months in both histological (p-values of <0.0001) and radiographic results (p-values of <0.0001). ConclusionNanocrystalline calcium sulfate presented a significant enhanced periodontal regeneration compared to the microcrystalline form.

Динамика изменений митохондриального трансмембранного потенциала в моноцитах крови в условиях развития и течения экспериментального пародонтита и влияние на них корвитина

Inflammatory diseases of periodontal tissues remain one of the most complex and unresolved problems of modern dentistry. The most important internal stimulus for triggering apoptosis is DNA damage in response to various factors (including reactive oxygen species). Mitochondrial transmembrane potential (Δψm) is generated by the electrochemical gradient of protons on both sides of the membrane and is closely related to the functioning of mitochondria, its support is provided by the processes of electron transfer in the respiratory chain. The purpose of our study was to elucidate the pathogenetic role of changes in mitochondrial transmebranic potential in the dynamics of the inflammatory response in experimental bacterial-immune periodontitis and the effects of quercetin (Korvityn) on it. Material and methods. The study was performed on white clinically healthy rats. Experimental bacterial-immune periodontitis in experimental animals was induced by injection of a mixture of microorganisms diluted with egg protein into the tissues of the periodontal complex. Quercetin was administered by intramuscular injection for correction. Evaluation of changes in mitochondrial transmembrane potential of leukocytes was performed by flow cytofluorimetry. Results and discussion. In experimental bacterial-immune periodontitis, the percentage of cells with reduced mitochondrial transmembrane potential among blood monocytes significantly increased. In animals on the 7th day of the study, the number of cells with reduced mitochondrial transmembrane potential among blood monocytes increased significantly compared with the control group. For the next study period (14th day), the number of cells with reduced ∆ψm decreased compared to the 7th day of the experiment. Having analyzed the data of mitochondrial transmembrane potential of blood monocytes on the 30th day of the experiment, we noted that they decreased relative to those obtained on the 14th day of the study, indicating profound oxidative imbalance in cells and destabilization of the mitochondrial membrane. The use of quercetin led to a decrease in the values compared to the data of animals with our simulated pathology on the 14th day, the experiment without the introduction of flavonol, but they remained significantly higher than the control group of animals. Conclusion. Flavonol (Korvityn) quercetin reduced mitochondrial transmembrane potential in experimental bacterial-immune periodontitis, which was evidence by stabilization and attenuation of the inflammatory process

Tooth-Supporting Hard Tissue Regeneration Using Biopolymeric Material Fabrication Strategies.

The mineralized tissues (alveolar bone and cementum) are the major components of periodontal tissues and play a critical role to anchor periodontal ligament (PDL) to tooth-root surfaces. The integrated multiple tissues could generate biological or physiological responses to transmitted biomechanical forces by mastication or occlusion. However, due to periodontitis or traumatic injuries, affect destruction or progressive damage of periodontal hard tissues including PDL could be affected and consequently lead to tooth loss. Conventional tissue engineering approaches have been developed to regenerate or repair periodontium but, engineered periodontal tissue formation is still challenging because there are still limitations to control spatial compartmentalization for individual tissues and provide optimal 3D constructs for tooth-supporting tissue regeneration and maturation. Here, we present the recently developed strategies to induce osteogenesis and cementogenesis by the fabrication of 3D architectures or the chemical modifications of biopolymeric materials. These techniques in tooth-supporting hard tissue engineering are highly promising to promote the periodontal regeneration and advance the interfacial tissue formation for tissue integrations of PDL fibrous connective tissue bundles (alveolar bone-to-PDL or PDL-to-cementum) for functioning restorations of the periodontal complex.

Inflammasomes as contributors to periodontal disease.

A genome‐wide association study of ≈2.5 million markers identified unique biologically informed periodontal complex traits with distinct microbial communities and interleukin‐1β (IL‐1β) levels. Each trait was associated with different single nucleotide polymorphisms. These variants include genes associated with immune responses, microbial colonization, and the epithelial barrier function. The specific set of variants leads to individual biological paths that converge into an overlapping clinical phenotype of periodontal tissue destruction. This concept suggests that periodontal disease is a group of distinct conditions. We identified polymorphisms in inflammasome genes interferon gamma inducible protein 16 (IFI16) and absent in melanoma 2 (AIM2) that were associated with increased severity of periodontal disease. Inflammasomes respond to pathogen or tissue “danger” signals and assemble into multiprotein “machineries” that are essential for the cleavage of proinflammatory mediator IL‐1β into an active form. Thus, understanding how variants of IFI16 and AIM2 contribute to periodontal disease pathogenesis may lead to treatment options that address individual biological variations and precision therapies for oral health.

Regeneration of Tooth with Allogenous, Autoclaved Treated Dentin Matrix with Dental Pulpal Stem Cells: An In Vivo Study

IntroductionBiomaterials designed for tissue engineering should be nontoxic and nonimmunogenic and should achieve their intended functions. Treated dentin matrix (TDM), a bioactive extracellular matrix, is promising for tooth regeneration. However, the effect of sterilization on the surface properties of allogenous TDM in the animal model is unclear. MethodsThe biological characteristics and influences of dental pulp stem cells (DPSCs) with autoclaved TDM (a-TDM) were studied using scanning electron microscopy, immunofluorescence microscopy, immunohistochemistry, and reverse transcription polymerase chain reaction in vitro. In addition, a-TDM was implanted in a mouse model for 6 weeks and was a substrate with DPSCs for tooth reconstruction in a goat animal model in vivo. ResultsAllogenous a-TDM induced and supported DPSCs to develop new dentin pulp–like tissues, enamel dental pulp, and cementum periodontal complexes. Immunohistochemistry data showed that the markers dentin sialoprotein, βⅢ-tubulin, dentin matrix protein 1, amelogenin, VIII factors, type I collagen, cementum-derived attachment protein, and scleraxis transcription factor were positive stained in toothlike tissue. ConclusionsAllogenous a-TDM served as an effective scaffold enabling DPSCs to proliferate and differentiate into a broad array of resident cells including odontoblasts, fibroblasts, vascular cells, and neural endings. Allogenous a-TDM with DPSCs can provide an ideal biomaterial for optimizing the regeneration of tooth material.

RhBMP-2 Pre-Treated Human Periodontal Ligament Stem Cell Sheets Regenerate a Mineralized Layer Mimicking Dental Cementum.

The periodontal complex consisting of alveolar bone, cementum, and periodontal ligaments (PDL) supports human teeth through the systematic orchestration of mineralized tissues and fibrous tissues. Importantly, cementum, the outermost mineralized layer of dental roots, plays an essential role by bridging the inner ligaments from the dental root to the alveolar bone. When the periodontal complex is damaged, the regeneration of each component of the periodontal complex is necessary; however, it is still challenging to achieve complete functional regeneration. In this study, we tried to control the regeneration of cementum and PDL by using a human PDL stem cell (hPDLSC) sheet engineering technology with the pretreatment of recombinant human BMP-2 (rhBMP-2). Isolated hPDLSCs obtained from extracted human teeth were pretreated with rhBMP-2 for in vitro osteogenic differentiation and grafted on the micro/macro-porous biphasic calcium phosphate (MBCP) blocks, which represent dental roots. The MBCPs with hPDLSC sheets were implanted in the subcutaneous layer of immune-compromised mice, and rhBMP-2 pretreated hPDLSC sheets showed higher mineralization and collagen ligament deposition than the no-pretreatment group. Therefore, the rhBMP-2-hPDLSC sheet technique could be an effective strategy for the synchronized regeneration of two different tissues: mineralized tissue and fibrous tissues in periodontal complexes.

LRP&amp;lt;sub&amp;gt;5&amp;lt;/sub&amp;gt; Affects Homeostasis of the Periodontal Complex

Purpose: The signals responsible for homeostasis in the periodontal complex are unclear. The purpose of this study was to evaluate the role of Low-density lipoprotein receptor-related protein 5(LRP5) in this process by removing LRP5, and observing the effects of LRP5 depletion on cells of the periodontal structures. Material and Methods: The function of this LRP5 was evaluated by conditional elimination of the LRP5 gene using an Osteocalcin Cre driver. The OCN-Cre; mice were examined using micro-CT and histology, immunohistochemistry to evaluate the periodontal complex. Results: Elimination of LRP5 in the periodontal complex of OCN-Cre; mice results in a different expression of Fibromodulin in the periodontal ligament space. A decrease in osteoclastic activity was found in the periodontal ligament. Conclusion: Osteoclastic activities are decreased and expression of fibromodulin is decreased, which implies the involvement of LRP5 in homeostasis of the periodontal ligament.

The relationship of hemodynamic parameters of periodontal microvascular bed and lipid peroxidation products in adolescents with arterial hypertension

Of the study was to establish the relationship of hemodynamic parameters of periodontal tissues and lipid peroxidation products in adolescents with arterial hypertension (AH). The study included 132 adolescents (average age 14.51±1.91 years), from which 2 clinical groups (1 - the group with AH without periodontal disease (n=19, average age - 15±1.53 years) and 2 - the group with AH with periodontal diseases (n=57, average age - 14.7±1.89 years)) and 2 comparison groups (3 - the comparison group without AH and periodontal diseases (n=19, average age - 13.82±1.89 years) and 4 - comparison group without AH and with periodontal diseases (n=37, mean age - 14.57±2.01 years)) were formed. Hemodynamic analysis of the periodontal microcirculatory bed using the Doppler ultrasound method and the level of lipid peroxidation products using spectrophotometric and fluorometric methods was performed. In adolescents with hypertension without and with inflammatory periodontal diseases as a whole, unidirectional changes in the hemodynamics of the vascular bed of the periodontium were observed in the form of increased values of the maximum blood flow velocity in systole and an increase in the peripheral resistance index. At the same time, the group with hypertension and periodontal disease was distinguished by lower values of these indicators. In the system of lipid peroxidation, increased values of ketodienes and conjugated trienes occurred in patients with hypertension without periodontal disease and end products that actively reacting with thiobarbituric acid in patients with hypertension and periodontal disease. Correlation analysis showed the presence of intersystem relationships between the hemodynamic parameters of the vascular bed of periodontal adolescents with hypertension without periodontal disease. In the group of adolescents with arterial hypertension and periodontal disease, there was a decrease in the correlation coefficients between intersystem parameters by almost two times, as well as the appearance of pathological dependencies between toxic metabolites of the lipid peroxidation process - products that actively reacting with thiobarbituric acid and vascular blood flow indicators. It has been noted that in adolescent patients with hypertension and periodontal diseases on the background of lower vascular blood flow and accumulation of end toxic metabolites, pathological dependencies occur between them, which may contribute to more intense damage to the tissues of the periodontal complex in the presence of hypertension.

Efficiency of application of probiotics for correction of microbiocenosis and cytokine balance of the oral cavity of patients with chronic inflammatory diseases of periodontium

Цель исследования — оптимизировать комплексную схему лечения воспалительных заболеваний пародонта путем включения пробиотика и оценки микробиоценоза и цитокинового баланса во рту. Материалы и методы. Обследовано 120 пациентов, из них 50 больных с хроническим маргинальным гингивитом простым и 50 пациентов с хроническим генерализованным пародонтитом. Пациентам проведена клиническая, микробиологическая, микологическая и иммунологическая оценка состояния тканей пародонтального комплекса до и через 3, 6 и 12 месяцев после лечения. Из каждой группы 50% пациентов получали лечение по традиционной методике, а 50% — по усовершенствованной схеме с применением пробиотика «Бифидумбактерин форте». Результаты. Установлено, что у пациентов с хроническим маргинальным гингивитом простым и хроническим генерализованным пародонтитом средней степени тяжести определяется высокая степень обсемененности пародонтальных карманов дрожжеподобными грибами рода Candida и бактериальной условно-патогенной микрофлорой, что напрямую связано с повышением провоспалительных цитокинов (TNF-α, IL-8), уменьшением концентрации INF-γ и увеличением уровня противовоспалительного цитокина IL-4. Заключение. Динамическая оценка клинико-лабораторных показателей на фоне комплексной терапии с использованием пробиотика и традиционного метода лечения указывает на повышение эффективности лечебных мероприятий хронического маргинального гингивита простого на 40%, а хронического пародонтита на 37%.

Biomechanical pathways of dentoalveolar fibrous joints in health and disease.

Spatial and temporal adaptations within periodontal tissues and their interfaces result from functional loads. Functional loads can be physiologic and/or pathologic in nature. The prolonged effect of these loads can alter the overall biomechanics of a dentoalveolar fibrous joint (dentoalveolar joint) by changing the form of the tooth root and its socket. This "sculpting" of the tooth root and alveolar bony socket is a consequence of several mechano-biological changes that occur within the periodontal complex of a load-bearing dentoalveolar joint. These include changes in biochemical expressions, structure, elemental composition, and mechanical properties of alveolar bone, the underlying tissues of the roots of teeth, and their interfaces. These physicochemical changes in tissues continue to prompt mechano-responsive biochemical activities at the attachment sites of periodontal ligament (soft) with bone (hard), and ligament with cementum (hard), which are the entheses of a load-bearing dentoalveolar joint. Forces at soft-hard tissue attachment sites between disparate materials with different stiffness values theoretically generate strain singularities or discontinuities. These discontinuities under prolonged functional loading increase the probability for failure to occur specifically at the enthesial zones. However, in a normal dentoalveolar joint, gradual stiffness gradients exist from ligament to bone, and from ligament to cementum. The gradual transitions in stiffness from softer ligament (lower stiffness) to harder bone or cementum (higher stiffness) or vice versa optimize tissue and interfacial strains. Optimization of tissue and ligament-enthesial physical and chemical properties facilitates transmission of cyclic forces of varying magnitudes and frequencies that collectively maintain the overall biomechanics of a dentoalveolar joint. The objectives of this review are 3-fold: (i) to illustrate physicochemical adaptations at the periodontal ligament entheses of a human periodontal complex affected by subgingival calculus; (ii) to demonstrate how to "program" the hallmarks of periodontitis in small-scale vertebrates in vivo to generate spatiotemporal maps of physicochemical adaptations in a diseased dentoalveolar joint; and (iii) to correlate dentoalveolar joint biomechanics in healthy and diseased states to spatiotemporal maps of physicochemical adaptations within respective periodontal tissues. This interdisciplinary approach demonstrates that physicochemical adaptations within periodontal tissues using the mechanics of materials (tissue mechanics), materials science (tissue composition), and mechano-biology (matrix molecules) can help explain the mechano-adaptation of dentoalveolar joints in normal and diseased functional states. Multiscale biomechanics and mechano-biology approaches can provide insights into the functional competence of a diseased relative to a normal dentoalveolar joint. Insights gathered from interdisciplinary and multiscale biomechanics approaches include the following: (i) physiologic loads related to chewing maintain a balance between mineral-forming and-resorbing biochemical cellular events, resulting in gradual stiffness gradients at the periodontal ligament entheses, and, in turn, sustain the overall biomechanics of a normal "healthy" dentoalveolar joint; (ii) pathologic loads resulting from tissue degradation and physical changes to the periodontal complex promote an abrupt stiffness gradient at the periodontal ligament entheses. The shift from gradual to an abrupt stiffness gradient could prompt a shift in the biochemical cascades, exacerbate mechano-responsive biochemical expressions at periodontal ligament entheses farther away from the site of insult, and culminate in joint degradation; (iii) sustained pathologic function on periodontally diseased joints exacerbates degradation of periodontal ligament entheses providing insights into "rescue therapy", such as the use of an adequate "mechanocal dose" to regain joint function; and (iv) spatiotemporal maps of changes in biochemical expressions, and physicochemical properties of strain-dominated affected sites, including the periodontal ligament entheses, can guide anatomy-specific therapeutics for tissue regeneration and/or disease control with the purpose of regaining dentoalveolar joint function. Modulation of occlusal loads could minimize disease progression and potentially assist in regaining functional attachment of ligament to bone and/or ligament to cementum of the dentoalveolar joint. Elucidating mechanisms that drive the breakdown of the functionally active periodontal complex burdened with microbes will provide the required critical insights into regenerative medicine and/or biomimetic approaches that would facilitate rescue/regain of dentoalveolar joint function.