Search Results (47)

Periodontitis is a multifactorial disease linked to host immune response and genetic predisposition. The TLR4 Asp299Gly single-nucleotide polymorphism (SNP, rs4986790) has been associated with altered responses to bacterial lipopolysaccharide (LPS) and may influence susceptibility to inflammatory diseases. Given the central role of TLR4 in innate immune recognition of periodontal pathogens, this study investigates the role of rs4986790 in modulating susceptibility to periodontal inflammatory destruction. A total of 1410 individuals from four populations were genotyped, with findings indicating a significant protective effect of the polymorphic allele. Functional assays demonstrated enhanced IL-8 secretion and increased sensitivity to CD14 inhibition in cells expressing the variant receptor. These results suggest that rs4986790 modifies the LPS response via TLR4, potentially offering protection against periodontal breakdown. Full article

Background/Objectives: Gingipains produced by P. gingivalis have been shown to be directly related to periodontal tissue degradation and are significant molecular targets in therapy of periodontitis. Blocking the activity of these enzymes should reduce survival of this pathogen and mitigate the effects of inflammation in periodontitis. Therefore, gingipains inhibitors and specific antibodies could be recommended in the treatment of periodontitis. Cysteine peptidase inhibitors can be obtained by chemical synthesis, or isolated from natural raw materials. This research has the following aims: 1. to analyze in vitro the inhibition of cysteine protease activity in the gingival crevicular fluid (GCF) and 2. to compare the toxicity of natural raw inhibitors (obtained from Fallopia japonica plant and egg white) with chlorhexidine (CHX) using an MTS viability test. Methods: Samples of GCF were collected from healthy (N = 17) individuals and (N = 65) periodontal patients. Cysteine peptidase activity was inhibited by adding a solution of cystatin from egg white (with 20% glycerol), or cystatin from knotweed, or low molecular weight inhibitors (MW < 3 kDa) from egg white and knotweed against Nα-Benzoyl-DL-arginine 4-nitroanilide hydrochloride. Results: There was a statistically significant difference between the inhibition means of cysteine protease activity for the five groups (p < 0.001). Means for the four groups of patients with periodontitis were not statistically significant different from each other (p = 0.320). The inhibition rates were higher in periodontitis patients. The toxicity of knotweed cystatin inhibitor was several times lower than the toxicity of E-64d, and of CHX. Conclusion: Cysteine protease inhibitors isolated from egg or plants were non-toxic, effectively inhibited the activity of cysteine proteases in GCF, and may be a promising alternative to more toxic standard antimicrobials (CHX) in preventing periodontal tissue breakdown. Full article

Aim: Despite a persistent presence in periodontitis, calculus remains a paradox. This narrative review reevaluates the role of calculus in periodontitis based on in situ, ex vivo, and in vitro studies published over the last two decades. Review: Results from multiple studies argue for the reconsideration of calculus as an independent risk factor in periodontitis. The results of a human study suggest that calculus contributes more to inflammation than simply serving as a substrate for biofilm accumulation. Ultrastructure studies have revealed residual calculus embedded in cementum following scaling and root planing (SRP). In vitro studies show that calculus particles can stimulate IL-1β secretion via the NLRP3 inflammasome in human and mouse phagocytes, and the crystalline structure is partially responsible for the activation. Other studies indicate that calculus particles may promote bone resorption via IL-1β induction in patients with periodontitis. Further, heat-treated calculus particles and hydroxyapatite crystals induce cell death in epithelial cell lines, suggesting that calculus plays a role in the breakdown of pocket epithelial integrity. Conclusions: Studies have shown that particles of microscopic calculus persist following traditional SRP. In vitro studies report that sterile and calcined calculus particles free of proteinaceous material are cytotoxic to cultured oral epithelial cells. Collectively, these studies suggest that residual microscopic calculus may be a potential risk factor for the failure of periodontal therapy. Full article

The sympathetic nervous system (SNS) is crucial for stress response regulation and immune modulation. Prolonged SNS activation, often induced by stress exposure, disrupts immune homeostasis and intensifies inflammatory processes, contributing to periodontal disease progression. This study investigates the relationship between SNS activity and periodontitis severity, utilizing salivary biomarkers chromogranin A (CgA) and alpha-amylase (sAA) alongside pro-inflammatory cytokines interleukin-1β (IL-1β) and interleukin-6 (IL-6). Saliva samples from 67 patients, categorized by periodontitis severity (Stages I/II and III/IV), were analyzed using enzyme-linked immunosorbent assay (ELISA). The results revealed significantly higher median levels of CgA (9.45 vs. 3.93 pmol/mL) and IL-1β (257.81 vs. 220.11 pg/mL) in patients with Stage III/IV periodontitis compared with those with Stage I/II, indicating heightened SNS activity and inflammatory response. Correlations between these biomarkers and clinical periodontal parameters, such as probing depth and clinical attachment loss, further support these findings. Despite elevated sAA levels in severe cases, statistical significance was not achieved. IL-6 levels also showed no significant variation across disease stages, although trends aligned with increased severity. This study highlights the interplay between SNA activation and periodontal inflammation, as evidenced by elevated salivary levels of CgA and IL-1β in patients with advanced periodontitis. By integrating neuroendocrine and inflammatory biomarkers into the diagnostic process, clinicians may be able to better identify patients at increased risk for periodontal breakdown and to consider adjunctive interventions such as stress management, thereby supporting more personalized approaches to periodontitis treatment. Full article

Background/Objectives: Oral health is a complex concept involving physical, psychological, emotional, and social components. A key factor in maintaining oral tissue integrity is redox balance, which is disrupted by oxidative stress (OS) through an imbalance between reactive oxygen species (ROS) and antioxidant defenses. This study examines the contribution of endogenous and exogenous sources to OS and explores the therapeutic potential of medicinal plants from the Asteraceae and Lamiaceae families in restoring redox homeostasis and improving oral health. Methods: A literature review was conducted, analyzing the role of OS in oral diseases and the antioxidant mechanisms of selected Asteraceae species. Special attention was given to their phytochemical contents—polyphenols, flavonoids, and essential oils—and their biological relevance to oral health. Results: OS plays a critical role in the onset and progression of oral conditions such as caries, periodontitis, gingivitis, aphthous ulcers, abscesses, precancerous lesions, and oral cancers. ROS and reactive nitrogen species (RNS) cause inflammation, tissue breakdown, and salivary gland dysfunction. Asteraceae plants like Matricaria chamomilla, Calendula officinalis, Cichorium intybus, Taraxacum officinale, Arctium lappa, Achillea millefolium, and Solidago virgaurea demonstrate notable antioxidant, anti-inflammatory, and antimicrobial properties that help counteract OS and support oral homeostasis. Conclusions: Asteraceae and Lamiaceae species show high therapeutic potential in addressing OS-related oral disorders. Their bioactive compounds aid in restoring redox balance and protecting oral tissues. These findings support the integration of phytotherapeutic agents into oral healthcare and call for further clinical validation of plant-based strategies for disease prevention and management. Full article

Background/Objectives: Most orthodontic forces are absorbed–dissipated before reaching the dental pulp and its neuro-vascular bundle (NVB); nonetheless, no data are available about this issue during the periodontal breakdown. The current study’s objective was to investigate how much orthodontic force reaches the dental pulp and NVB during the orthodontic movements in periodontal breakdown. Methods: Herein, an assessment was performed on the second lower premolar of nine patients (72 3D models) and included 1440 numerical simulations. A gradual horizontal periodontal breakdown (1–8 mm loss) was simulated. Five orthodontic movements (intrusion, extrusion, rotation, translation, and tipping) under 0.5 N/5 KPa and 4 N/40 KPa were assessed. The numerical methods used were Von Mises/VM (overall homogenous) and Tresca (shear non-homogenous), suitable for the ductile resemblance of dental tissues. Results: Both methods showed similar color-coded projections for the two forces. Quantitatively, Tresca was 1.14 times higher than VM and lower than the maximum physiological hydrostatic circulatory pressure. During the bone loss simulation, the NVB stress was 5.7–10.7 times higher than the pulpal stress. A gradual tissue stress increase was seen, strictly correlated with the bone loss level. For 1 mm bone loss, only 2–3% of the applied force manifested at the NVB level (0.27–0.5% for pulp), while for 8 mm loss, the received stress was 4–10% for the NVB (0.6–0.9% for pulp) when compared to the applied force. Only translation displayed pulpal stress. Conclusions: When assessing NVB stress, the tooth absorption–dissipation ability of dental tissues varied between 90 and 93% (8 mm loss) and 97% (1 mm bone loss) and 99% when assessing pulpal stress. Full article

Rheumatoid arthritis and periodontitis are comorbidities that share mutual pathways. IL-1β is a pro-inflammatory cytokine that plays a crucial role in both diseases. One of the treatment options for rheumatoid arthritis is the use of an IL-1 receptor antagonist (IL-1RA) such as anakinra. Anakinra tempers the disease by decreasing bone resorption and it could possibly stimulate bone formation. Here, we investigate the effect of anakinra in a periodontal disease setting on osteoclastogenesis by co-culturing periodontal ligament fibroblasts (PDLFs) and peripheral blood mononuclear cells (PBMCs) that contain monocytes, a source of osteoclast precursors, as well as by culturing PBMCs alone. The effect of anakinra on PDLF-mediated osteogenesis was studied under mineralization conditions. To mimic a chronic infection such as that prevalent in periodontitis, 10 ng/mL of IL-1β was added either alone or with 10 µg/mL of anakinra. Osteoclastogenesis experiments were performed using co-cultures of PDLF and PBMCs and PBMCs only. Osteoclastogenesis was determined through the formation of multinucleated cells in co-cultures of PDLF and PBMCs, as well as PBMCs alone, at day 21, and gene expression through qPCR at day 14. Osteogenesis was determined by measuring alkaline phosphatase activity (ALP) per cell at day 14. Anakinra is effective in downregulating IL-1β mediated leukocyte clustering and osteoclastogenesis in the co-cultures of both PDLF and PMBCs and PBMCs alone. Gene expression analysis shows that IL-1β increases the expression of the osteoclastogenic marker RANKL and its own expression. This higher expression of IL-1β at the RNA level is reduced by anakinra. Moreover, IL-1β downregulates OPG expression, which is upregulated by anakinra. No effects of anakinra on osteogenesis were seen. Clinically, these findings suggest that anakinra could have a beneficial systemic effect on periodontal breakdown in rheumatoid arthritis patients taking anakinra. Full article

This review explores the emerging relationship between obstructive sleep apnea (OSA) and periodontal disease (PD), emphasizing shared inflammatory pathways, overlapping risk factors, and potential systemic health implications. Both conditions are characterized by chronic inflammation and oxidative stress, which independently contribute to cardiovascular disease, diabetes, and other systemic disorders. Evidence suggests a bidirectional relationship, with OSA-related hypoxia exacerbating periodontal tissue breakdown and PD-induced inflammation potentially influencing OSA severity. However, the causative nature of the relationship between OSA and PD remains uncertain, largely due to inconsistencies in diagnostic criteria, methodological variability, and study heterogeneity. This review highlights the essential role of systematic reviews (SRs) in synthesizing current evidence, identifying research gaps, and guiding future studies. To maximize their impact, SRs should adhere to rigorous methodological quality standards, improve transparency in data reporting, and address the heterogeneity of included studies. Future research should focus on longitudinal and interventional designs, standardize diagnostic protocols, and investigate biomarkers, oral microbiome profiles, and inflammatory mediators to elucidate the mechanisms linking OSA and PD. Multidisciplinary collaboration between dental and sleep specialists is crucial to advancing evidence-based strategies that improve patient outcomes and address the broader health implications of these often coexisting conditions. Full article

Background/Objectives: This study assessed the biomechanical behavior of dental pulp and the neuro-vascular bundle/NVB as well as the ischemic risks during orthodontic movements in a gradual horizontal periodontal breakdown, using five methods and aiming to identify the most accurate one. Methods: Seventy-two models of second lower premolar (from nine patients) were subjected to 3 N of intrusion, extrusion, rotation, tipping, and translation. Five numerical methods, Tresca, Von Mises/VM, Maximum and Minimum Principal, and hydrostatic pressure were used in a total of 1800 numerical simulations. The results were color-coded projections of the stress areas that were then correlated with maximum physiological hydrostatic pressure/MHP and known clinical biomechanical behavior. Results: During periodontal breakdown, all five methods displayed, for all movements, quantitative stresses lower than MHP, suggesting that 3 N are not inducing any local tissular ischemic risks for the healthy intact tissues. All five methods displayed rotation as the most stressful movement during periodontal breakdown, while translation was the least. The NVB was more exposed to ischemic risks than dental pulp during the periodontal breakdown due to constant tissular deformations. Only VM and Tresca methods showed translation as more prone to expose dental pulp (both coronal and radicular) to ischemic risks (than the other movements) during the periodontal breakdown simulation. However, all five methods showed intrusion and extrusion as more prone to expose the NVB to higher ischemic risks than the other movements during the periodontal breakdown simulation. Conclusions: During periodontal breakdown, Tresca and Von Mises were more accurate, with Tresca being the most accurate of all. Full article

Autophagy is an intrinsic breakdown system that recycles organelles and macromolecules, which influences metabolic pathways, differentiation, and thereby cell survival. Oral health is an essential component of integrated well-being, and it is critical for developing therapeutic interventions to understand the molecular mechanisms underlying the maintenance of oral homeostasis. However, because of the complex dynamic relationship between autophagy and oral health, associated treatment modalities have not yet been well elucidated. Determining how autophagy affects oral health at the molecular level may enhance the understanding of prevention and treatment of targeted oral diseases. At the molecular level, hard and soft oral tissues develop because of complex interactions between epithelial and mesenchymal cells. Aging contributes to the progression of various oral disorders including periodontitis, oral cancer, and periapical lesions during aging. Autophagy levels decrease with age, thus indicating a possible association between autophagy and oral disorders with aging. In this review, we critically review various aspects of autophagy and their significance in the context of various oral diseases including oral cancer, periapical lesions, periodontal conditions, and candidiasis. A better understanding of autophagy and its underlying mechanisms can guide us to develop new preventative and therapeutic strategies for the management of oral diseases. Full article

Background/Objectives: There are few data about the ischemic risks induced by the large orthodontic forces during periodontal breakdown in dental pulp and neuro-vascular bundle (NVB) and none on the individual tissular stress distribution, despite their great importance for orthodontic treatment planning. Our aim was to assess, by a numerical analysis, the biomechanical behavior of dental pulp and the NVB during a simulated horizontal periodontal breakdown (1–8 mm), under 2–4 N of applied orthodontic forces and five movements (rotation, translation, tipping, intrusion, and extrusion). Additionally, the ischemic and degenerative-resorptive risks were assessed. Methods: The analysis involved 72 3D models of nine patients, totaling 720 simulations. The models were CBCT-based, having the second lower premolar and surrounding periodontium, and they suffered 1 mm of gradual horizontal periodontal breakdown (up to 8 mm loss). Results: Both forces displayed a similar qualitative stress distribution in all five movements, but with a quantitative increase (doubling of stress amounts for 4 N when compared with 2 N). The highest amounts of stress were displayed at 8 mm of periodontal loss, which is lower than the 16 KPa of the maximum hydrostatic pressure. The NVB stress was higher than the pulpal stress. Rotation was the most stressful, closely followed by tipping, intrusion, and extrusion. Conclusions: A total of 4 N of applied force seems to not induce any ischemic or degenerative-resorptive risks for healthy intact teeth, in up to 8 mm of periodontal breakdown. Intrusion and extrusion determined the highest visible tissular deformation in the NVB, with potential ischemic and resorptive-generative risks for previously traumatized/injured teeth (i.e., occlusal trauma). Rotation and translation (in particular) showed the highest coronal and radicular pulpal stress with potential ischemic and resorptive-generative risks for previously injured/traumatized dental pulp (i.e., direct-indirect pulp capping). It seems that 4 mm of periodontal breakdown could signal a clinical stress increase with potential ischemic and degenerative-resorptive risks for the previously traumatized/injured tissues. Full article

The periodontal disease pathobiont Aggregatibacter actinomycetemcomitans (A. actinomycetemcomitans) may exert a range of detrimental effects on periodontal diseases in general and, more specifically, with the initiation and progression of Localized Stage III Grade C periodontitis (molar–incisor pattern). In this review of the biogeography of this pathobiont, the full range of geographical scales for A. actinomycetemcomitans, from global origins and transmission to local geographical regions, to more locally exposed probands and families, to the individual host, down to the oral cavity, and finally, to spatial interactions with other commensals and pathobionts within the plaque biofilms at the micron/nanoscale, are reviewed. Using the newest technologies in genetics, imaging, in vitro cultures, and other research disciplines, investigators may be able to gain new insights to the role of this pathobiont in the unique initial destructive patterns of Localized Stage III Grade C periodontitis. These findings may incorporate the unique features of the microbiome that are influenced by variations in the geographic environment within the entire mouth. Additional insights into the geographic distribution of molar–incisor periodontal breakdown for Localized Stage III Grade C periodontitis may derive from the spatial interactions between A. actinomycetemcomitans and other pathobionts such as Porphyromonas gingivalis, Filifactor aclocis, and commensals such as Streptococcus gordonii. In addition, while the association of A. actinomycetemcomitans in systemic diseases is limited at the present time, future studies into possible periodontal disease–systemic disease links may also find A. actinomycetemcomitans and its geographical interactions with other microbiome members to provide important clues as to implications of pathobiological communications. Full article

This numerical analysis, by employing Tresca and Von Mises failure criteria, assessed the biomechanical behavior of a trabecular bone component subjected to 0.6, 1.2, and 2.4 N orthodontic forces under five movements (intrusion, extrusion, tipping, rotation, and translation) and during a gradual horizontal periodontal breakdown (0–8 mm). Additionally, they assessed the changes produced by bone loss, and the ischemic and resorptive risks. The analysis employed eighty-one models of nine patients in 405 simulations. Both failure criteria showed similar qualitative results, with Tresca being quantitatively higher by 1.09–1.21. No qualitative differences were seen between the three orthodontic loads. Quantitatively, a doubling (1.2 N) and quadrupling (2.4 N) were visible when compared to 0.6 N. Rotation and translation followed by tipping are the most stressful, especially for a reduced periodontium, prone to higher ischemic and resorptive risks. In an intact periodontium, 1.2 N can be safely applied but only in a reduced periodontium for extrusion and intrusion. More than 0.6 N is prone to increasing ischemic and resorptive risks for the other three movements. In an intact periodontium, stress spreads in the entire trabecular structure. In a reduced periodontium, stress concentrates (after a 4 mm loss—marker for the stress change distribution) and increases around the cervical third of the remaining alveolar socket. Full article

(1) Background: Herein, finite element analysis (FEA) of the periodontal ligament (PDL) was used to assess differences between Tresca (T-non-homogenous) and Von Mises (VM-homogenous) criterion, by simulating a 0–8 mm periodontal breakdown under five orthodontic movements (extrusion, intrusion, rotation, tipping, and translation) and three loads (0.6, 1.2, and 2.4 N). Additionally, we addressed the issues of proper boundary condition selection for more than 1 N loads and correlated the results with the maximum hydrostatic pressure (MHP) and available knowledge, evaluating ischemic and resorptive risks for more than 1 N orthodontic loads. (2) Methods: Eighty-one models of the second lower premolar (nine patients) with intact and 1–8 mm reduced periodontia were created. The assumed boundary conditions were isotropy, homogeneity, and linear elasticity. A total of 486 FEA simulations were performed in Abaqus. (3) Results: Both criteria displayed similar qualitative results, with T being quantitatively 15% higher and better suited. The assumed boundary conditions seem to be correct up to 2.4 N of the applied load. (4) Conclusions: Both criteria displayed constant deformations and displacements manifested in the same areas independently of the load’s amount, the only difference being their intensity (doubling—1.2 N; quadrupling—2.4 N). Moreover, 2.4 N seems safe for intact periodontium, while, after a 4 mm loss (seen as the reference point), a load of more than 1 N seems to have significant ischemic and resorptive risks. Full article

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). Full article