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Search Results (9)

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Keywords = healthy and reduced periodontium

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27 pages, 1010 KiB  
Review
The Multifaceted Role of IL-35 in Periodontal Disease and Beyond: From Genetic Polymorphisms to Biomarker Potential
by Zdravka Pashova-Tasseva, Antoaneta Mlachkova, Kamen Kotsilkov and Hristina Maynalovska
Genes 2025, 16(8), 891; https://doi.org/10.3390/genes16080891 - 28 Jul 2025
Viewed by 363
Abstract
Periodontitis is a prevalent chronic inflammatory disease with complex etiopathogenesis involving microbial dysbiosis, host immune response, environmental factors, and genetic susceptibility. Among the cytokines implicated in periodontal immunoregulation, interleukin-35 (IL-35) has emerged as a novel anti-inflammatory mediator with potential diagnostic and therapeutic relevance. [...] Read more.
Periodontitis is a prevalent chronic inflammatory disease with complex etiopathogenesis involving microbial dysbiosis, host immune response, environmental factors, and genetic susceptibility. Among the cytokines implicated in periodontal immunoregulation, interleukin-35 (IL-35) has emerged as a novel anti-inflammatory mediator with potential diagnostic and therapeutic relevance. This narrative review evaluates the role of IL-35 in periodontal disease by exploring its local and systemic expression, response to non-surgical periodontal therapy (NSPT), and association with clinical disease severity. Additionally, current evidence regarding IL-35 gene polymorphisms and their potential contribution to individual susceptibility and disease progression, as well as their relevance in related systemic conditions, is assessed. A comprehensive review and synthesis of recent clinical and experimental studies were conducted, focusing on IL-35 levels in saliva, serum, and gingival crevicular fluid (GCF) among patients with healthy periodontium, gingivitis, and various stages of periodontitis, both before and after NSPT. Emphasis was placed on longitudinal studies evaluating IL-35 dynamics in correlation with periodontal parameters, as well as genetic association studies investigating IL-12A and EBI3 gene polymorphisms. IL-35 levels were generally found to be higher in healthy individuals and reduced in periodontitis patients, indicating a possible protective role in maintaining periodontal homeostasis. Following NSPT, IL-35 levels significantly increased, corresponding with clinical improvement and reduced inflammatory burden. Genetic studies revealed variable associations between IL-35 polymorphisms and susceptibility to periodontitis and related systemic conditions, although further research is needed for validation. IL-35 appears to function as a modulator of immune resolution in periodontal disease, with potential utility as a non-invasive biomarker for disease activity and therapeutic response. Its upregulation during periodontal healing supports its role in promoting tissue stabilization. The integration of cytokine profiling and genetic screening may enhance personalized risk assessment and targeted interventions in periodontal care. Full article
(This article belongs to the Section Human Genomics and Genetic Diseases)
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12 pages, 1114 KiB  
Article
Cystatin SN (CST1) as a Novel Salivary Biomarker of Periodontitis
by Federica Romano, Francesco Franco, Matteo Corana, Giuliana Abbadessa, Federica Di Scipio, Barbara Pergolizzi, Chiara Castrignano, Mario Aimetti and Giovanni N. Berta
Int. J. Mol. Sci. 2023, 24(18), 13834; https://doi.org/10.3390/ijms241813834 - 8 Sep 2023
Cited by 4 | Viewed by 1864
Abstract
Identification of biomarkers could help in assessing periodontal health status and monitoring treatment outcomes. Therefore, the aim of this cross-sectional study was to identify potential innovative salivary biomarkers for the diagnosis of periodontitis using an untargeted proteomic approach. Forty-five healthy non-smoker participants diagnosed [...] Read more.
Identification of biomarkers could help in assessing periodontal health status and monitoring treatment outcomes. Therefore, the aim of this cross-sectional study was to identify potential innovative salivary biomarkers for the diagnosis of periodontitis using an untargeted proteomic approach. Forty-five healthy non-smoker participants diagnosed as having periodontally healthy conditions (H), severe periodontitis (P), and healthy but reduced periodontium after active periodontal treatment (T) were consecutively enrolled (15 per each group) in the study. A higher number of spots were identified in the proteome of unstimulated whole saliva collected from H and T subjects compared with P group, mainly within the range of 8–40 kDa. Protein spots of interest were analysed by MALDI-TOF-MS, allowing the identification of cystatin SN (CST1) isoform, as confirmed by Western blot. CST1 was markedly expressed in the H group, while it was absent in most P samples (p < 0.001). Interestingly, a distinct CST1 expression was observed in saliva from T patients. CST1 was negatively correlated with the percentage of pathological sites (p < 0.001) and was effective in discriminating active periodontitis from healthy periodontal status (whether H or T). Therefore, salivary CST1 may be a promising non-invasive biomarker for periodontal disease diagnosis and monitoring. Full article
(This article belongs to the Special Issue Oral Soft Tissue Repair and Oral Diseases)
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17 pages, 1154 KiB  
Article
Evidence Linking PPARG Genetic Variants with Periodontitis and Type 2 Diabetes Mellitus in a Brazilian Population
by Thamiris Cirelli, Ingra G. Nicchio, Diego G. Bussaneli, Bárbara R. Silva, Rafael Nepomuceno, Silvana R. P. Orrico, Joni A. Cirelli, Letícia H. Theodoro, Silvana P. Barros and Raquel M. Scarel-Caminaga
Int. J. Mol. Sci. 2023, 24(7), 6760; https://doi.org/10.3390/ijms24076760 - 5 Apr 2023
Cited by 7 | Viewed by 2959
Abstract
The peroxisome proliferator-activated receptor gamma (PPARG) gene encodes a transcription factor involved in the regulation of complex metabolic and inflammatory diseases. We investigated whether single nucleotide polymorphisms (SNPs) and haplotypes of the PPARG gene could contribute with susceptibility to develop periodontitis [...] Read more.
The peroxisome proliferator-activated receptor gamma (PPARG) gene encodes a transcription factor involved in the regulation of complex metabolic and inflammatory diseases. We investigated whether single nucleotide polymorphisms (SNPs) and haplotypes of the PPARG gene could contribute with susceptibility to develop periodontitis alone or together with type 2 diabetes mellitus (T2DM). Moreover, we evaluated the gene–phenotype association by assessing the subjects’ biochemical and periodontal parameters, and the expression of PPARG and other immune response–related genes. We examined 345 subjects with a healthy periodontium and without T2DM, 349 subjects with moderate or severe periodontitis but without T2DM, and 202 subjects with moderate or severe periodontitis and T2DM. PPARG SNPs rs12495364, rs1801282, rs1373640, and rs1151999 were investigated. Multiple logistic regressions adjusted for age, sex, and smoking status showed that individuals carrying rs1151999-GG had a 64% lower chance of developing periodontitis together with T2DM. The CCGT haplotype increased the risk of developing periodontitis together with T2DM. The rs1151999-GG and rs12495364-TC were associated with reduced risk of obesity, periodontitis, elevated triglycerides, and elevated glycated hemoglobin, but there was no association with gene expression. Polymorphisms of the PPARG gene were associated with developing periodontitis together with T2DM, and with obesity, lipid, glycemic, and periodontal characteristics. Full article
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17 pages, 4100 KiB  
Article
Cryptic Oral Microbiota: What Is Its Role as Obstructive Sleep Apnea-Related Periodontal Pathogens?
by Mayra A. Téllez Corral, Eddy Herrera Daza, Hayde K. Cuervo Jimenez, María del Mar Bravo Becerra, Jean Carlos Villamil, Patricia Hidalgo Martinez, Nelly S. Roa Molina, Liliana Otero, María E. Cortés and Claudia M. Parra Giraldo
Int. J. Environ. Res. Public Health 2023, 20(3), 1740; https://doi.org/10.3390/ijerph20031740 - 18 Jan 2023
Cited by 4 | Viewed by 3830
Abstract
Periodontitis has been commonly linked to periodontopathogens categorized in Socransky’s microbial complexes; however, there is a lack of knowledge regarding “other microorganisms” or “cryptic microorganisms”, which are rarely thought of as significant oral pathogens and have been neither previously categorized nor connected to [...] Read more.
Periodontitis has been commonly linked to periodontopathogens categorized in Socransky’s microbial complexes; however, there is a lack of knowledge regarding “other microorganisms” or “cryptic microorganisms”, which are rarely thought of as significant oral pathogens and have been neither previously categorized nor connected to illnesses in the oral cavity. This study hypothesized that these cryptic microorganisms could contribute to the modulation of oral microbiota present in health or disease (periodontitis and/or obstructive sleep apnea (OSA) patients). For this purpose, the presence and correlation among these cultivable cryptic oral microorganisms were identified, and their possible role in both conditions was determined. Data from oral samples of individuals with or without periodontitis and with or without OSA were obtained from a previous study. Demographic data, clinical oral characteristics, and genera and species of cultivable cryptic oral microorganisms identified by MALDI-TOF were recorded. The data from 75 participants were analyzed to determine the relative frequencies of cultivable cryptic microorganisms’ genera and species, and microbial clusters and correlations tests were performed. According to periodontal condition, dental-biofilm-induced gingivitis in reduced periodontium and stage III periodontitis were found to have the highest diversity of cryptic microorganism species. Based on the experimental condition, these findings showed that there are genera related to disease conditions and others related to healthy conditions, with species that could be related to different chronic diseases being highlighted as periodontitis and OSA comorbidities. The cryptic microorganisms within the oral microbiota of patients with periodontitis and OSA are present as potential pathogens, promoting the development of dysbiotic microbiota and the occurrence of chronic diseases, which have been previously proposed to be common risk factors for periodontitis and OSA. Understanding the function of possible pathogens in the oral microbiota will require more research. Full article
(This article belongs to the Section Oral Health)
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12 pages, 1098 KiB  
Article
WNT-5a and SOST Levels in Gingival Crevicular Fluid Depend on the Inflammatory and Osteoclastogenic Activities of Periodontal Tissues
by Georgios S. Chatzopoulos, Massimo Costalonga, Kim C. Mansky and Larry F. Wolff
Medicina 2021, 57(8), 788; https://doi.org/10.3390/medicina57080788 - 31 Jul 2021
Cited by 6 | Viewed by 2529
Abstract
Background and Objectives: Wnt signaling leads to stimulation of osteoblasts and it reduces osteoclastogenesis and bone resorption via the regulation of the osteprotegrin and receptor activator of nuclear factor kappa-Β ligan (RANKL). Wnt signaling pathways are regulated by their physiological antagonists such as [...] Read more.
Background and Objectives: Wnt signaling leads to stimulation of osteoblasts and it reduces osteoclastogenesis and bone resorption via the regulation of the osteprotegrin and receptor activator of nuclear factor kappa-Β ligan (RANKL). Wnt signaling pathways are regulated by their physiological antagonists such as sclerostin (SOST) as well as WNT-5a. The aim of this study was to determine the total amount of Sclerostin and WNT-5a in the gingival crevicular fluid (GCF) in sites with a continuum from a healthy to diseased periodontium. Materials and Methods: In this cross-sectional study, a total of 20 patients with generalized periodontitis, 10 subjects with gingivitis as well as 14 individuals with a healthy periodontium were recruited upon clinical and radiographic periodontal examination. In patients diagnosed with periodontitis, GCF samples were collected from periodontitis, gingivitis and healthy sites, while gingivitis patients provided samples from gingivitis and healthy sites. In healthy patients, only healthy sites were sampled. Protein total amount of SOST and WNT-5a were quantified by sandwich enzyme-linked immunosorbent assay (ELISA). Results: A total of 108 GCF samples were collected from a total of 44 individuals. When all periodontitis (n = 51), gingivitis (n = 12) and healthy (n = 45) sites were analyzed regardless of the patient diagnosis, periodontitis sites demonstrated significantly elevated WNT-5a total amounts (p = 0.03) when compared to gingivitis sites. Gingivitis sites demonstrated a trend of more total SOST (p = 0.09) when compared to periodontitis and healthy sites. Within each patient diagnostic category, sites showed similar SOST and WNT-5a total amounts (p > 0.05). Conclusions: WNT-5a levels in GCF depend on the stage of periodontitis sites. SOST trended higher in the GCF of gingivitis sites but similar in chronic periodontitis and healthy sites. WNT-5a and SOST play a crucial role in periodontal tissue remodeling and depend on the inflammatory and osteoclastogenic activities. Full article
(This article belongs to the Section Dentistry and Oral Health)
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16 pages, 2476 KiB  
Article
Monocyte Differentiation into Destructive Macrophages on In Vitro Administration of Gingival Crevicular Fluid from Periodontitis Patients
by Hammam Ibrahim Fageeh, Hytham N. Fageeh and Shankargouda Patil
J. Pers. Med. 2021, 11(6), 555; https://doi.org/10.3390/jpm11060555 - 15 Jun 2021
Cited by 10 | Viewed by 3313
Abstract
Background: Periodontitis is an inflammatory condition of the tooth-supporting structures initiated and perpetuated by pathogenic bacteria present in the dental plaque biofilm. In periodontitis, immune cells infiltrate the periodontium to prevent bacterial insult. Macrophages derived from monocytes play an important role in antigen [...] Read more.
Background: Periodontitis is an inflammatory condition of the tooth-supporting structures initiated and perpetuated by pathogenic bacteria present in the dental plaque biofilm. In periodontitis, immune cells infiltrate the periodontium to prevent bacterial insult. Macrophages derived from monocytes play an important role in antigen presentation to lymphocytes. However, they are also implicated in causing periodontal destruction and bystander damage to the host tissues. Objectives: The objective of the present study was to quantify the cytokine profile of gingival crevicular fluid (GCF) samples obtained from patients with periodontitis. The study further aimed to assess if GCF of periodontitis patients could convert CD14+ monocytes into macrophages of destructive phenotype in an in vitro setting. The secondary objectives of the study were to assess if macrophages that resulted from GCF treatment of monocytes could affect the synthetic properties, stemness, expression of extracellular matrix proteins, adhesion molecules expressed by gingival stem cells, gingival mesenchymal stromal cells, and osteoblasts. Methods: GCF, blood, and gingival tissue samples were obtained from periodontitis subjects and healthy individuals based on specific protocols. Cytokine profiles of the GCF samples were analyzed. CD14+ monocytes were isolated from whole blood, cultured, and treated with the GCF of periodontitis patients to observe if they differentiated into macrophages. Further, the macrophages were assessed for a phenotype by surface marker analysis and cytokine assays. These macrophages were co-cultured with gingival stem cells, epithelial, stromal cells, and osteoblasts to assess the effects of the macrophages on the synthetic activity of the cells. Results: The GCF samples of periodontitis patients had significantly higher levels of IFN gamma, M-CSF, and GM-CSF. Administration of the GCF samples to CD14+ monocytes resulted in their conversion to macrophages that tested positive for CD80, CD86, and CD206. These macrophages produced increased levels of IL-1β, TNF-α, and IL-6. Co-culture of the macrophages with gingival stem cells, epithelial cells, and stromal cells resulted in increased cytotoxicity and apoptotic rates to the gingival cells. A reduced expression of markers related to stemness, extracellular matrix, and adhesion namely OCT4, NANOG, KRT5, POSTN, COL3A1, CDH1, and CDH3 were seen. The macrophages profoundly affected the production of mineralized nodules by osteoblasts and significantly reduced the expression of COL1A1, OSX, and OCN genes. Conclusion: In periodontitis patients, blood-derived monocytes transform into macrophages of a destructive phenotype due to the characteristic cytokine environment of their GCF. Further, the macrophages affect the genotype and phenotype of the resident cells of the periodontium, aggravate periodontal destruction, as well as jeopardize periodontal healing and resolution of inflammation. Full article
(This article belongs to the Special Issue Precision Medicine for Immunology and Immunogenetics)
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14 pages, 1442 KiB  
Review
Photodynamic Therapy in Orthodontics: A Literature Review
by Marcin Olek, Agnieszka Machorowska-Pieniążek, Wojciech Stós, Janusz Kalukin, Dorota Bartusik-Aebisher, David Aebisher, Grzegorz Cieślar and Aleksandra Kawczyk-Krupka
Pharmaceutics 2021, 13(5), 720; https://doi.org/10.3390/pharmaceutics13050720 - 14 May 2021
Cited by 17 | Viewed by 4515
Abstract
Treatment of malocclusions using fixed orthodontic appliances makes it difficult for patients to perform hygiene procedures. Insufficient removal of bacterial biofilm can cause enamel demineralization, manifesting by visible white spot lesions or periodontal diseases, such as gingivitis periodontitis or gingival hyperplasia. The classic [...] Read more.
Treatment of malocclusions using fixed orthodontic appliances makes it difficult for patients to perform hygiene procedures. Insufficient removal of bacterial biofilm can cause enamel demineralization, manifesting by visible white spot lesions or periodontal diseases, such as gingivitis periodontitis or gingival hyperplasia. The classic methods of preventing the above problems include, in addition to proper hygiene, ultrasonic scaling, periodontal debridement, and oral rinses based on chlorhexidine. New alternative methods of reducing plaque around brackets are being developed. There is a growing interest among researchers in the possibility of using photodynamic therapy in orthodontics. A literature search for articles corresponding to the topic of this review was performed using the PubMed and Scopus databases and the following keywords: ‘photodynamic therapy’, ‘orthodontics’, and ‘photosensitizer(s)’. Based on the literature review, two main directions of research can be distinguished: clinical research on the use of photodynamic therapy in the prevention of white spot lesions and periodontal diseases, and ex vivo research using a modified orthodontic adhesive by adding photosensitizers to them. Methylene blue is the most frequently used photosensitizer in clinical trials. The effectiveness of antimicrobial photodynamic therapy is mainly compared to the ultrasonic scaler as a single therapy or as an adjunct to the ultrasonic scaler. In their conclusions, the researchers most often emphasize the effectiveness of antimicrobial photodynamic therapy in reducing microbial levels in patients treated with fixed appliances and the possibility of using it as an alternative to routine procedures aimed at maintaining a healthy periodontium. The authors suggest further research on the use of photodynamic therapy to prove the validity of this method in orthodontics. It should also not be forgotten that proper hygiene is the basis for maintaining oral cavity health, and its neglect is a contraindication to orthodontic treatment. Full article
(This article belongs to the Special Issue Light and Oxygen for the Cellular Drug Delivery and Tracking)
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17 pages, 4558 KiB  
Article
Finite Element Analysis of Mandibular Anterior Teeth with Healthy, but Reduced Periodontium
by Ioana-Andreea Sioustis, Mihai Axinte, Marius Prelipceanu, Alexandra Martu, Diana-Cristala Kappenberg-Nitescu, Silvia Teslaru, Ionut Luchian, Sorina Mihaela Solomon, Nicanor Cimpoesu and Silvia Martu
Appl. Sci. 2021, 11(9), 3824; https://doi.org/10.3390/app11093824 - 23 Apr 2021
Cited by 11 | Viewed by 3157
Abstract
Finite element analysis studies have been of interest in the field of orthodontics and this is due to the ability to study the stress in the bone, periodontal ligament (PDL), teeth and the displacement in the bone by using this method. Our study [...] Read more.
Finite element analysis studies have been of interest in the field of orthodontics and this is due to the ability to study the stress in the bone, periodontal ligament (PDL), teeth and the displacement in the bone by using this method. Our study aimed to present a method that determines the effect of applying orthodontic forces in bodily direction on a healthy and reduced periodontium and to demonstrate the utility of finite element analysis. Using the cone-beam computed tomography (CBCT) of a patient with a healthy and reduced periodontium, we modeled the geometric construction of the contour of the elements necessary for the study. Afterwards, we applied a force of 1 N and a force of 0.8 N in order to achieve bodily movement and to analyze the stress in the bone, in the periodontal ligament and the absolute displacement. The analysis of the applied forces showed that a minimal ligament thickness is correlated with the highest value of the maximum stress in the PDL and a decreased displacement. This confirms the results obtained in previous clinical practice, confirming the validity of the simulation. During orthodontic tooth movement, the morphology of the teeth and of the periodontium should be taken into account. The effect of orthodontic forces on a particular anatomy could be studied using FEA, a method that provides real data. This is necessary for proper treatment planning and its particularization depends on the patient’s particular situation. Full article
(This article belongs to the Special Issue Active Materials for Medical Applications)
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13 pages, 6949 KiB  
Article
Inflammation in the Human Periodontium Induces Downregulation of the α1- and β1-Subunits of the sGC in Cementoclasts
by Yüksel Korkmaz, Behrus Puladi, Kerstin Galler, Peer W. Kämmerer, Agnes Schröder, Lina Gölz, Tim Sparwasser, Wilhelm Bloch, Andreas Friebe and James Deschner
Int. J. Mol. Sci. 2021, 22(2), 539; https://doi.org/10.3390/ijms22020539 - 7 Jan 2021
Cited by 5 | Viewed by 3557
Abstract
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. [...] Read more.
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 β1-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 β1-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 β1-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. Full article
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