RESUMEN
Signal regulatory protein alpha (SIRPα) is mainly expressed by cells of myeloid origin. This membrane glycoprotein is shown to be involved in regulation of different inflammatory conditions, such as colitis and arthritis. However, SIRPα has not been investigated in relationship to periodontitis, an inflammatory condition affecting the tooth supporting tissues. We aim to investigate if resident cells in the periodontium express SIRPα and whether a possible expression is affected by inflammatory conditions. Primary human keratinocytes, fibroblasts, periodontal ligament cells, and osteoblasts were cultured with or without the pro-inflammatory cytokines tumor necrosis factor alpha (TNF-α) or interleukin-1-beta (IL-1ß). All different periodontal cell types showed a basal mRNA expression of SIRPα. Pro-inflammatory cytokines induced a 2-3-fold significant increase in SIRPα expression in both cultured human gingival fibroblasts and osteoblasts but neither in keratinocytes nor in periodontal ligament cells. Tissue sections from human gingival tissue biopsies were histochemically stained for SIRPα. Epithelial keratinocytes and gingival fibroblasts stained positive in sections from periodontally healthy as well as in sections from periodontitis. In periodontitis sections, infiltrating leukocytes stained positive for SIRPα. We highlight our finding that oral keratinocytes, gingival fibroblasts, and periodontal ligament cells do express SIRPα, as this has not been presented before. The fact that inflammatory stimulation of gingival fibroblasts increased the expression of SIRPα, while an increased expression by gingival fibroblasts in periodontitis tissue in situ could not be detected, is indeed contradictory.
Asunto(s)
Receptores Inmunológicos , Humanos , Receptores Inmunológicos/metabolismo , Células Cultivadas , Periodoncio/metabolismo , Periodoncio/patología , Ligamento Periodontal/citología , Ligamento Periodontal/metabolismo , Antígenos de Diferenciación/metabolismo , Queratinocitos/metabolismo , Periodontitis/metabolismo , Fibroblastos/metabolismoRESUMEN
Mechanical forces affect periodontal health through multiple mechanisms. Normally, mechanical forces can boost soft and hard tissue metabolism. However, excessive forces may damage the periodontium or result in irreversible inflammation, whereas absence of occlusion forces also leads to tissue atrophy and bone resorption. We systemically searched the PubMed and Web of Science databases and found certain mechanisms of mechanical forces on immune defence, extracellular matrix (ECM) metabolism, specific proteins, bone metabolism, characteristic periodontal ligament stem cells (PDLSCs) and non-coding RNAs (ncRNAs) as these factors contribute to periodontal homeostasis. The immune defence functions change under forces; genes, signalling pathways and proteinases are altered under forces to regulate ECM metabolism; several specific proteins are separately discussed due to their important functions in mechanotransduction and tissue metabolism. Functions of osteocytes, osteoblasts, and osteoclasts are activated to maintain bone homeostasis. Additionally, ncRNAs have the potential to influence gene expression and thereby, modify tissue metabolism. This review summarizes all these mechanisms of mechanical forces on periodontal homeostasis. Identifying the underlying causes, this review provides a new perspective of the mechanisms of force on periodontal health and guides for some new research directions of periodontal homeostasis.
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Homeostasis , Mecanotransducción Celular , Ligamento Periodontal , Periodoncio , Humanos , Periodoncio/metabolismo , Animales , Ligamento Periodontal/metabolismo , Matriz Extracelular/metabolismo , Estrés Mecánico , Enfermedades Periodontales/metabolismo , Enfermedades Periodontales/inmunología , ARN no Traducido/genética , ARN no Traducido/metabolismo , Células Madre/metabolismoRESUMEN
Sex steroid hormones (SSH) are extremely versatile molecules with a myriad of physiological functions. Next to their well-known role in sexual development and reproduction, SSH play active roles in practically every tissue in the human body, including the oral cavity. It has long been demonstrated that periodontal tissues express SSH receptors and therefore are responsive to the presence of SSH. Interestingly, SSH not only interact with the periodontal tissues but also with other tissues in the oral cavity such as dental enamel, pulp, cementum, oral mucosa, and salivary glands. Questions concerning the possible physiological functions of these receptors and their role in maintenance of oral health, remain unanswered. The purpose of this scoping review was to gather and summarize all the available evidence on the role of SSH in physiological processes in the oral cavity in humans. Two comprehensive literature searches were performed. References were screened and selected based on title, abstract and full text according to our inclusion criteria. Both searches yielded 18,992 results of which 73 were included. Results were divided into four categories: (1) Periodontium; (2) Dental structure; (3) Mucosa; and (4) Salivary glands. The interaction of these tissues with progestagens, androgens and estrogens are summarized. Sex steroid hormones are an overlooked yet fundamental factor in oral homeostasis. They play important roles in the development and function of the periodontium, dental structure, mucosa and salivary glands. Dentists and healthcare providers should consider these hormonal factors when assessing and treating oral health conditions.
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Hormonas Esteroides Gonadales , Homeostasis , Humanos , Hormonas Esteroides Gonadales/metabolismo , Homeostasis/fisiología , Boca/metabolismo , Periodoncio/metabolismo , Salud BucalRESUMEN
As the biological mechanisms of orthodontic tooth movement have been explored further, scholars have gradually focused on the remodelling mechanism of the extracellular matrix (ECM) in the periodontal ligament (PDL). The ECM of the PDL consists of various types of collagens and other glycoproteins. The specific process and mechanism of ECM remodelling during orthodontic tooth movement remains unclear. Collagen I and III, which constitute major components of the PDL, are upregulated under orthodontic force. The changes in the contents of ECM proteins also depend on the expression of ECM-related enzymes, which organise new collagen fibre networks to adapt to changes in tooth position. The matrix metalloproteinase family is the main enzyme that participates in collagen hydrolysis and renewal and changes its expression under orthodontic force. Moreover, ECM adhesion molecules, such as integrins, are also regulated by orthodontic force and participate in the dynamic reaction of cell adhesion and separation with the ECM. This article reviews the changes in ECM components, related enzymes and adhesion molecules in the PDL under orthodontic force to lay the foundation for the exploration of the regulatory mechanism of ECM remodelling during orthodontic tooth movement.
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Matriz Extracelular , Ligamento Periodontal , Técnicas de Movimiento Dental , Matriz Extracelular/metabolismo , Humanos , Técnicas de Movimiento Dental/métodos , Ligamento Periodontal/citología , Periodoncio/metabolismo , Metaloproteinasas de la Matriz/metabolismo , Integrinas/metabolismo , Colágeno/metabolismoRESUMEN
Periodontitis affects billions of people worldwide. To address relationships of periodontal niche cell types and microbes in periodontitis, we generated an integrated single-cell RNA sequencing (scRNAseq) atlas of human periodontium (34-sample, 105918-cell), including sulcular and junctional keratinocytes (SK/JKs). SK/JKs displayed altered differentiation states and were enriched for effector cytokines in periodontitis. Single-cell metagenomics revealed 37 bacterial species with cell-specific tropism. Fluorescence in situ hybridization detected intracellular 16 S and mRNA signals of multiple species and correlated with SK/JK proinflammatory phenotypes in situ. Cell-cell communication analysis predicted keratinocyte-specific innate and adaptive immune interactions. Highly multiplexed immunofluorescence (33-antibody) revealed peri-epithelial immune foci, with innate cells often spatially constrained around JKs. Spatial phenotyping revealed immunosuppressed JK-microniches and SK-localized tertiary lymphoid structures in periodontitis. Here, we demonstrate impacts on and predicted interactomics of SK and JK cells in health and periodontitis, which requires further investigation to support precision periodontal interventions in states of chronic inflammation.
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Comunicación Celular , Queratinocitos , Periodontitis , Análisis de la Célula Individual , Humanos , Queratinocitos/metabolismo , Queratinocitos/inmunología , Periodontitis/microbiología , Periodontitis/metabolismo , Periodontitis/inmunología , Periodontitis/patología , Citocinas/metabolismo , Periodoncio/microbiología , Periodoncio/metabolismo , Periodoncio/patología , Inmunidad Innata , Hibridación Fluorescente in Situ , Masculino , Metagenómica/métodos , Bacterias/metabolismo , Bacterias/genética , Femenino , Adulto , Inmunidad AdaptativaRESUMEN
OBJECTIVE: Increasing the effectiveness of treatment of chronic generalized periodontitis using PDT based on clinical and functional substantiation of the effects of a photosensitizer. MATERIALS AND METHODS: A clinical and functional study and treatment of moderate chronic generalized periodontitis was carried out in 62 people (26 men and 36 women) aged from 35 to 55 years without a somatic model with an orthognathic occlusion diagnosed according to ICD-10 - K05.3. Of these, 2 groups were divided depending on the type of treatment: Group 1 (main) - patients with moderate chronic generalized periodontitis - 32 people. (17 men and 15 women, average age of the group - 43.2±2.2 years); Group 2 (control) - patients with moderate chronic generalized periodontitis - 30 people. (14 men and 16 women, average age of the group - 44.0±3.3 years). Complex treatment consisted of sanitation of the mouth, removal of dental plaque and curettage of periodontal pockets in group 1, followed by PDT with Revixan gel using a special wired aligner REVIXAN DENTAL LED (16 r). The clinical condition of the periodontium was assessed using the Greene Vermillion Hygienic Index (OHI-S), the Mühlleman Bleeding Index (SBI) modified by Cowell, and the periodontal index PI. To study the state of microcirculation in the gum tissue, the laser Doppler flowmetry (LDF) method was used using the LAKK-M device (NPP «Lazma¼, Russia). The state of microcirculation was assessed by the microcirculation index (M), which characterizes the level of tissue blood flow; parameter - «σ¼, which determines the fluctuation of the erythrocyte flow. According to Wavelet analysis of LDF-grams, the shunt index (SH) of blood flow was determined. In the «LDF + spectrometry¼ mode, oxygenation in periodontal tissues was studied using optical tissue oximetry (OTO), based on the results of which the perfusion saturation index (Sm) and the specific oxygen consumption index (U, %) were determined. RESULTS: According to LDF data, after PDT (group 1), normalization of clinical indices and the level of microcirculation in periodontal tissues was established, which was accompanied by an increase in the level of blood flow (M) and its activity (σ), which persisted after 3 and 6 months. after PDT. The perfusion saturation index (Sm) and specific oxygen consumption (U) increased more significantly after PDT, which persisted after 3 and 6 months. In the control group, the dynamics of indicators was less pronounced. CONCLUSION: The use of PDT with Revixan gel normalizes the clinical condition of the periodontium, indicators of microhemodynamics and oxygen metabolism.
Asunto(s)
Periodontitis Crónica , Microcirculación , Fotoquimioterapia , Humanos , Femenino , Masculino , Adulto , Microcirculación/efectos de los fármacos , Persona de Mediana Edad , Periodontitis Crónica/tratamiento farmacológico , Periodontitis Crónica/terapia , Fotoquimioterapia/métodos , Fármacos Fotosensibilizantes/uso terapéutico , Periodoncio/irrigación sanguínea , Periodoncio/efectos de los fármacos , Periodoncio/metabolismo , Oxígeno/metabolismoRESUMEN
Chronic periodontitis (CP), an inflammatory disease of periodontal tissues driven by a dysbiotic subgingival bacterial biofilm, is also associated with several systemic diseases, including rheumatoid arthritis (RA). Porphyromonas gingivalis, one of the bacterial species implicated in CP as a keystone pathogen produces peptidyl arginine deiminase (PPAD) that citrullinates C-terminal arginine residues in proteins and peptides. Autoimmunity to citrullinated epitopes is crucial in RA, hence PPAD activity is considered a possible mechanistic link between CP and RA. Here we determined the PPAD enzymatic activity produced by clinical isolates of P. gingivalis, sequenced the ppad gene, and correlated the results with clinical determinants of CP in patients from whom the bacteria were isolated. The analysis revealed variations in PPAD activity and genetic diversity of the ppad gene in clinical P. gingivalis isolates. Interestingly, the severity of CP was correlated with a higher level of PPAD activity that was associated with the presence of a triple mutation (G231N, E232T, N235D) in PPAD in comparison to W83 and ATCC 33277 type strains. The relation between mutations and enhanced activity was verified by directed mutagenesis which showed that all three amino acid residue substitutions must be introduced into PPAD expressed by the type strains to obtain the super-active enzyme. Cumulatively, these results may lead to the development of novel prognostic tools to assess the progress of CP in the context of associated RA by analyzing the ppad genotype in CP patients infected with P. gingivalis.
Asunto(s)
Periodontitis Crónica , Porphyromonas gingivalis , Humanos , Desiminasas de la Arginina Proteica/genética , Desiminasas de la Arginina Proteica/metabolismo , Péptidos , Periodoncio/metabolismo , Periodontitis Crónica/genéticaRESUMEN
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.
Asunto(s)
Pérdida de Hueso Alveolar , Factor Neurotrófico Derivado del Encéfalo , Cementogénesis , Animales , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Factor Neurotrófico Derivado del Encéfalo/uso terapéutico , Perros , Cementogénesis/efectos de los fármacos , Antígeno Nuclear de Célula en Proliferación/metabolismo , Osteopontina , Ligamento Periodontal/patología , Ligamento Periodontal/efectos de los fármacos , Masculino , Regeneración Tisular Guiada Periodontal/métodos , Regeneración Ósea/efectos de los fármacos , Cemento Dental/patología , Cemento Dental/efectos de los fármacos , Periodoncio/patología , Periodoncio/metabolismo , Mandíbula , Proliferación Celular/efectos de los fármacosRESUMEN
The extracellular matrix (ECM) is a complex non-cellular three-dimensional macromolecular network present within all tissues and organs, forming the foundation on which cells sit, and composed of proteins (such as collagen), glycosaminoglycans, proteoglycans, minerals, and water. The ECM provides a fundamental framework for the cellular constituents of tissue and biochemical support to surrounding cells. The ECM is a highly dynamic structure that is constantly being remodeled. Matrix metalloproteinases (MMPs) are among the most important proteolytic enzymes of the ECM and are capable of degrading all ECM molecules. MMPs play a relevant role in physiological as well as pathological processes; MMPs participate in embryogenesis, morphogenesis, wound healing, and tissue remodeling, and therefore, their impaired activity may result in several problems. MMP activity is also associated with chronic inflammation, tissue breakdown, fibrosis, and cancer invasion and metastasis. The periodontium is a unique anatomical site, composed of a variety of connective tissues, created by the ECM. During periodontitis, a chronic inflammation affecting the periodontium, increased presence and activity of MMPs is observed, resulting in irreversible losses of periodontal tissues. MMP expression and activity may be controlled in various ways, one of which is the inhibition of their activity by an endogenous group of tissue inhibitors of metalloproteinases (TIMPs), as well as reversion-inducing cysteine-rich protein with Kazal motifs (RECK).
Asunto(s)
Metaloproteinasas de la Matriz , Periodontitis , Humanos , Metaloproteinasas de la Matriz/metabolismo , Periodontitis/metabolismo , Periodoncio/metabolismo , Matriz Extracelular/metabolismo , Colágeno/metabolismo , Inflamación/metabolismo , Inhibidores Tisulares de Metaloproteinasas/metabolismo , Proteínas Ligadas a GPI/metabolismoRESUMEN
Calcitonin gene-related peptide (CGRP), a neuropeptide composed of 37 amino acids secreted from the sensory nerve endings, reportedly possesses various physiological effects, such as vasodilation and neurotransmission. Recently, there have been increasing reports of the involvement of CGRP in bone metabolism; however, its specific role in the pathogenesis of periodontitis, particularly in the repair and healing processes, remains to be elucidated. Therefore, this study aimed to investigate dynamic expression patterns of CGRP during the destruction and regeneration processes of periodontal tissues in a mouse model of experimental periodontitis. We also explored the effects of CGRP on periodontal ligament cells, which can differentiate to hard tissue-forming cells (cementoblasts or osteoblasts). Our findings demonstrated that CGRP stimulation promotes the differentiation of periodontal ligament cells into hard tissue-forming cells. Experimental results using a ligature-induced periodontitis mouse model also suggested fluctuations in CGRP expression during periodontal tissue healing, underscoring the vital role of CGRP signaling in alveolar bone recovery. The study results highlight the important role of nerves in the periodontal ligament not only in sensory reception in the periphery, as previously known, but also in periodontal tissue homeostasis and tissue repair processes.
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Tejido Nervioso , Periodontitis , Ratones , Animales , Péptido Relacionado con Gen de Calcitonina/genética , Péptido Relacionado con Gen de Calcitonina/metabolismo , Periodoncio/metabolismo , Ligamento Periodontal/metabolismo , Periodontitis/genética , Periodontitis/metabolismo , Tejido Nervioso/metabolismoRESUMEN
OBJECTIVES: To determine the abilities of salivary E-cadherin to differentiate between periodontal health and periodontitis and to discriminate grades of periodontitis. BACKGROUND: E-cadherin is the main protein responsible for maintaining the integrity of epithelial-barrier function. Disintegration of this protein is one of the events associated with the destructive forms of periodontal disease leading to increase concentration of E-cadherin in the oral biofluids. MATERIALS AND METHODS: A total of 63 patients with periodontitis (case) and 35 periodontally healthy subjects (control) were included. For each patient, periodontal parameters including bleeding on probing (BOP), probing pocket depth (PPD), and clinical attachment level (CAL) were recorded. Concentration of salivary E-cadherin was determined by ELISA. Receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to determine the diagnostic potentials of E-cadherin. RESULTS: Level of salivary E-cadherin was significantly higher in periodontitis cases than controls. The ROC analysis showed that salivary E-cadherin exhibits excellent sensitivity and specificity (AUC 1.000) to differentiate periodontal health from periodontitis with a cutoff concentration equal to 1.325 ng/mL. The AUCs of E-cadherin to differentiate grade A from grade B and C periodontitis were 0.731 (cutoff point = 1.754 ng/mL) and 0.746 (cutoff point = 1.722 ng/mL), respectively. However, the AUC of salivary E-cadherin to differentiate grade B from grade C periodontitis was lower (0.541). Additionally, BOP and PPD were significantly and positively correlated with the concentration of salivary E-cadherin. CONCLUSION: Salivary E-cadherin exhibited excellent sensitivity and specificity to differentiate periodontitis from a healthy periodontium. The level of accuracy of E-cadherin was also sufficient to recognize grade A periodontitis from grade B and C periodontitis.
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Enfermedades Periodontales , Periodontitis , Humanos , Periodontitis/diagnóstico , Periodontitis/metabolismo , Enfermedades Periodontales/metabolismo , Periodoncio/metabolismo , Biomarcadores/metabolismo , Cadherinas/metabolismo , Saliva/químicaRESUMEN
Periodontitis is a prevalent disease and one of the leading causes of tooth loss. Biofilms are initiating factor of periodontitis, which can destroy periodontal tissue by producing virulence factors. The overactivated host immune response is the primary cause of periodontitis. The clinical examination of periodontal tissues and the patient's medical history are the mainstays of periodontitis diagnosis. However, there is a lack of molecular biomarkers that can be used to identify and predict periodontitis activity precisely. Non-surgical and surgical treatments are currently available for periodontitis, although both have drawbacks. In clinical practice, achieving the ideal therapeutic effect remains a challenge. Studies have revealed that bacteria produce extracellular vesicles (EVs) to export virulence proteins to host cells. Meanwhile, periodontal tissue cells and immune cells produce EVs that have pro- or anti-inflammatory effects. Accordingly, EVs play a critical role in the pathogenesis of periodontitis. Recent studies have also presented that the content and composition of EVs in saliva and gingival crevicular fluid (GCF) can serve as possible periodontitis diagnostic indicators. In addition, studies have indicated that stem cell EVs may encourage periodontal regeneration. In this article, we mainly review the role of EVs in the pathogenesis of periodontitis and discuss their diagnostic and therapeutic potential.
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Vesículas Extracelulares , Periodontitis , Humanos , Periodontitis/diagnóstico , Periodontitis/etiología , Periodontitis/terapia , Líquido del Surco Gingival/química , Líquido del Surco Gingival/metabolismo , Biomarcadores/análisis , Periodoncio/metabolismo , Vesículas Extracelulares/metabolismoRESUMEN
Objectives: Periodontium regeneration remains a significant challenge in clinics and research, and it is essential to understand the stage-specific biological process in situ. However, differing findings have been reported, and the mechanism has yet to be elucidated. The periodontium of adult mice molars is considered to be stable remodeling tissue. At the same time, the continuously growing incisors and the developing dental follicle (DF) of postnatal mice highly represent fast remodeling tissue. In this study, we attempted to explore different clues of temporal and spatial comparisons to provide improved references for periodontal regeneration. Methods: Periodontal tissues from the developing periodontium (DeP) of postnatal mice, and continuously growing periodontium (CgP) and stable remodeling periodontium (ReP) of adult mice were isolated and compared using RNA sequencing. Based on the Dep and CgP separately compared with the ReP, differentially expressed genes and signaling pathways were analyzed using GO, KEGG databases, and Ingenuity Pathway Analysis (IPA). The results and validation were obtained by immunofluorescence staining and RT-PCR assays. Data were expressed as means ± standard deviation (SD) and analyzed by GraphPad Prism 8 software package, and one-way ANOVA was used to test multiple groups. Results: Principal component analysis showed that the three groups of periodontal tissue were successfully isolated and had distinct expression profiles. A total of 792 and 612 DEGs were identified in the DeP and CgP groups compared with the ReP. Upregulated DEGs in the DeP were closely related to developmental processes, while the CgP showed significantly enhanced cellular energy metabolism. The DeP and CgP showed a common downregulation of the immune response, with activation, migration, and recruitment of immune cells. IPA and further validation jointly suggested that the MyD88/p38 MAPK pathway played an essential regulatory role in periodontium remodeling. Conclusion: Tissue development, energy metabolism, and immune response were critical regulatory processes during periodontal remodeling. Developmental and adult stages of periodontal remodeling showed different expression patterns. These results contribute to a deeper understanding of periodontal development and remodeling and may provide references for periodontal regeneration.
Asunto(s)
Ligamento Periodontal , Periodoncio , Ratones , Animales , Periodoncio/metabolismo , Ligamento Periodontal/metabolismo , TranscriptomaRESUMEN
OBJECTIVES: The regulatory mechanisms of GCN5 (General control non-repressed protein5) in the osteogenic differentiation of mesenchymal stem cells (MSCs) in periodontitis are still unclear. The purpose of this review focuses on the regulating roles of GCN5 in bone metabolism and periodontitis, discusses the potential molecular mechanism and provides targets and new ideas for the treatment of periodontitis. MATERIAL AND METHODS: The integrative review methodology was used. Data sources include PubMed, Cochrane Library, and additional sources. RESULTS: MSCs play an important role in the osteogenesis balance of periodontal tissue. Periodontal ligament stem cells (PDLSCs) from periodontitis patients exhibited defective osteogenic differentiation capacities. Histone acetylation is important in regulating the differentiation of different types of MSCs cells and is closely related to the reduced osteogenic differentiation of PDLSCs. GCN5, one of the first histone acetyltransferase linked to gene transcriptional activation, participates in many biological processes of mesenchymal stem cells. Downregulation of GCN5 expression and lack of GCN5 caused decreased osteogenic differentiation of PDLSCs. Intercellular information exchange may be an important way for MSCs to exert their regulatory and therapeutic functions. CONCLUSIONS: GCN5 affects the function of cell metabolism-related genes by regulating the acetylation status of histones or non-histones, thereby regulating some important progress of MSCs such as PDLSCs' osteogenic differentiation and BMCS osteogenic differentiation.
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Células Madre Mesenquimatosas , Periodontitis , Humanos , Osteogénesis/fisiología , Periodontitis/metabolismo , Periodoncio/metabolismo , Diferenciación Celular/fisiologíaRESUMEN
The principles of periodontal therapy are based on the control of microbial pathogens and host factors that contribute to biofilm dysbiosis, with the aim of modulating the progression of periodontitis and periodontal tissue destruction. It is currently known how differently each individual responds to periodontal treatment, depending on both the bacterial subtypes that make up the dysbiotic biofilm and interindividual variations in the host inflammatory response. This has allowed the current variety of approaches for the management of periodontitis to be updated by defining the goals of target strategies, which consist of reducing the periodontopathogenic microbial flora and/or modulating the host-mediated response. Therefore, this review aims to update the current variety of approaches for the management of periodontitis based on recent target therapies. Recently, encouraging results have been obtained from several studies exploring the effects of some targeted therapies in the medium- and long-term. Among the most promising target therapies analyzed and explored in this review include: cell-based periodontal regeneration, mediators against bone resorption, emdogain (EMD), platelet-rich plasma, and growth factors. The reviewed evidence supports the hypothesis that the therapeutic combination of epigenetic modifications of periodontal tissues, interacting with the dysbiotic biofilm, is a key step in significantly reducing the development and progression of disease in periodontal patients and improving the therapeutic response of periodontal patients. However, although studies indicate promising results, these need to be further expanded and studied to truly realize the benefits that targeted therapies could bring in the treatment of periodontitis.
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Microbiota , Periodontitis , Humanos , Periodontitis/microbiología , Metagenoma , Metagenómica , Periodoncio/metabolismo , Disbiosis/terapiaRESUMEN
OBJECTIVES: This review article aims to describe some of the roles of Matrix metalloproteinases (MMPs) in enamel, dentine, dental caries, hybrid layer degradation, pulp and periodontal tissues, throwing light on their current inhibitors. The article addresses the potential of MMPs to serve as biomarkers with diagnostic and therapeutic value. DESIGN: The sections of this review discuss MMPs' involvement in developmental, remodeling, degradational and turnover aspects of dental and periodontal tissues as well as their signals in the pathogenesis, progress of different lesions and wound healing of these tissues. The literature was searched for original research articles, review articles and theses. The literature search was conducted in PubMed and MEDLINE for articles published in the last 20 years. RESULTS: 119 published papers, two textbooks and two doctoral theses were selected for preparing the current review. CONCLUSIONS: MMPs are significant proteases, of evident contribution in dental and periapical tissue development, health and disease processes, with promising potential for use as diagnostic and prognostic disease biomarkers. Continuing understanding of their role in pathogenesis and progress of different dental, periapical and periodontal lesions, as well as in dentine-pulp wound healing could be a keystone to future diagnostic and therapeutic regimens.
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Caries Dental , Biomarcadores , Humanos , Metaloproteinasas de la Matriz/metabolismo , Periodoncio/metabolismoRESUMEN
Advanced glycation end-products (AGEs) are heterogeneous compounds formed when excess sugars condense with the amino groups of nucleic acids and proteins. Increased AGEs are associated with insulin resistance and poor glycemic control. Recently, inflamed periodontal tissues and certain oral bacteria were observed to increase the local and systemic AGE levels in both normoglycemic and hyperglycemic individuals. Although hyperglycemia induced AGE and its effect on the periodontal tissues is known, periodontitis as an endogenous source of AGE formation is not well explored. Hence, this systematic review is aimed to explore, for the first time, whether inflamed periodontal tissues and periodontal pathogens have the capacity to modulate AGE levels in individuals with or without T2DM and how this affects the glycemic load. Six electronic databases were searched using the following keywords: (Periodontitis OR Periodontal disease OR Periodontal Inflammation) AND (Diabetes mellitus OR Hyperglycemia OR Insulin resistance) AND Advanced glycation end products. The results yielded 1140 articles, of which 13 articles were included for the review. The results showed that the mean AGE levels in gingival crevicular fluid was higher in individuals with diabetes mellitus and periodontitis (521.9 pg/mL) compared to healthy individuals with periodontitis (234.84 pg/mL). The serum AGE levels in normoglycemic subjects having periodontitis was higher compared to those without periodontitis (15.91 ng/mL vs. 6.60 ng/mL). Tannerella forsythia, a common gram-negative anaerobe periodontal pathogen in the oral biofilm, was observed to produce methylglyoxal (precursor of AGE) in the gingival tissues. Increased AGE deposition and activate of AGE receptors was noted in the presence of periodontitis in both normoglycemic and hyperglycemic individuals. Hence, it can be concluded that periodontitis can modulate the local and systemic levels of AGE levels even in absence of hyperglycemia. This explains the bidirectional relationship between periodontitis and development of prediabetes, incident diabetes, poor glycemic control, and insulin resistance.
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Diabetes Mellitus , Hiperglucemia , Resistencia a la Insulina , Periodontitis , Humanos , Hiperglucemia/complicaciones , Periodontitis/complicaciones , Periodoncio/metabolismoRESUMEN
OBJECTIVE: Periodontitis is a chronic inflammatory disease caused by microbial dental plaque which leads to the destruction and loss of supporting tissues of the tooth. Microbial plaque alone, however, is not enough to cause the disease. The body's response plays an important role, in which an imbalance between the pro-inflammatory and anti-inflammatory effects of cytokines leads to an inflammatory reaction. PATIENTS AND METHODS: We detected changes in mRNA expression and protein levels of MIP-1α, and metalloproteinases (MMP-2, MMP-9) contributing to cascades in the initiation and progression of inflammatory bone resorption and destruction of periodontal soft tissues in patients with aggressive (AP) or chronic (CP) forms of periodontitis in comparison with healthy individuals (control). RESULTS: MIP-1α mRNA levels were highest in AP (280 ± 23% higher than the control) also in comparison with CP. The difference in protein level was less pronounced. MMP-2 mRNA expression values were similar (300 ± 12% higher in comparison with control), but protein levels were lower, also when compared to CP. Only in CP MMP-9 mRNA levels were significantly higher than the control (30 ± 8%), while protein levels were again higher in AP. Both AP and CP showed a positive correlation between the level of MIP-1a and MMP-2 (0.879, and 0.954 respectively). However, a strong positive correlation was only found between the levels of MMP-2 and MMP-9 in CP (0.812). CONCLUSIONS: MIP-1α, MMP-2 and MMP-9 mRNA expression, along with the concentration of proteins in saliva in patients with periodontal disease, is higher than in healthy individuals and correlates with the severity of the disease.
Asunto(s)
Líquido del Surco Gingival , Periodontitis , Líquido del Surco Gingival/metabolismo , Humanos , Índice Periodontal , Periodontitis/metabolismo , Periodoncio/metabolismo , Saliva/metabolismoRESUMEN
Periodontitis is a chronic inflammatory immune disease associated with a dysbiotic state, influenced by keystone bacterial species responsible for disrupting the periodontal tissue homeostasis. Furthermore, the severity of periodontitis is determined by the interaction between the immune cell response in front of periodontitis-associated species, which leads to the destruction of supporting periodontal tissues and tooth loss in a susceptible host. The persistent bacterial challenge induces modifications in the permeability and ulceration of the sulcular epithelium, which facilitates the systemic translocation of periodontitis-associated bacteria into distant tissues and organs. This stimulates the secretion of pro-inflammatory molecules and a chronic activation of immune cells, contributing to a systemic pro-inflammatory status that has been linked with a higher risk of several systemic diseases, such as type 2 diabetes mellitus (T2DM) and gestational diabetes mellitus (GDM). Although periodontitis and GDM share the common feature of systemic inflammation, the molecular mechanistic link of this association has not been completely clarified. This review aims to examine the potential biological mechanisms involved in the association between periodontitis and GDM, highlighting the contribution of both diseases to systemic inflammation and the role of new molecular participants, such as extracellular vesicles and non-coding RNAs, which could act as novel molecular intercellular linkers between periodontal and placental tissues.
Asunto(s)
Diabetes Gestacional , Periodontitis , Periodoncio , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/microbiología , Diabetes Gestacional/metabolismo , Diabetes Gestacional/microbiología , Femenino , Humanos , Periodontitis/etiología , Periodontitis/metabolismo , Periodontitis/microbiología , Periodoncio/metabolismo , Periodoncio/microbiología , EmbarazoRESUMEN
Increase of sympathetic activity has been known to exacerbate osteoporosis through promotion of bone resorption. However, it is largely unknown about involvement of sympathetic activity in exacerbation of periodontitis. In this study, we investigated whether α2-adrenergic receptor (α2-AR) agonist guanabenz which decreases sympathetic activity, attenuates alveolar bone resorption in rats having high sympathetic activity with periodontitis. Volumes of residual alveolar bone and attachment levels in periodontium were examined using micro-computed tomography and hematoxylin-eosin staining, respectively. Furthermore, osteoclast numbers per bone surface and osteoclast surface per bone surface were measured using tartrate-resistant acid phosphatase staining. To examine the suppressive effects of guanabenz on pro-inflammatory cytokines, expression levels of tyrosine hydroxylase (TH), TNF-α, IL1-ß, and IL-6 in periodontium were measured using immunohistostaining. Administration of guanabenz attenuated loss of alveolar bone and attachment levels in rats having high sympathetic activity. Furthermore, its administration suppressed osteoclast numbers in rats having high sympathetic activity. TH, TNF-α, IL-1ß, and IL-6 positive cells in periodontium in rats treated with guanabenz for 12 weeks, were lower than those in control rats having high sympathetic activity. This study demonstrated administration of α2-AR agonist guanabenz attenuates alveolar bone resorption through decrease of sympathetic activity in rats.