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14 pages, 3029 KiB  
Article
In Vitro Bioactivity and Cytotoxicity Assessment of Two Root Canal Sealers
by Yicheng Ye, Sepanta Hosseinpour, Juan Wen and Ove A. Peters
Materials 2025, 18(15), 3717; https://doi.org/10.3390/ma18153717 (registering DOI) - 7 Aug 2025
Abstract
The development of bioactive materials in endodontics has advanced tissue regeneration by enhancing the biological responses of periradicular tissues. Recently, calcium silicate-based sealers have gained attention for their superior biological properties, including biocompatibility, osteoconductivity, and cementogenic potential. This study aimed to evaluate the [...] Read more.
The development of bioactive materials in endodontics has advanced tissue regeneration by enhancing the biological responses of periradicular tissues. Recently, calcium silicate-based sealers have gained attention for their superior biological properties, including biocompatibility, osteoconductivity, and cementogenic potential. This study aimed to evaluate the cytotoxicity, biocompatibility, and bioactivity of EndoSequence BC Sealer (ES BC) and AH Plus Bioceramic Sealer (AHP BC) using human periodontal ligament stromal cells (hPDLSCs). Biocompatibility was assessed using MTT, Live/Dead, and wound healing assays. ES BC and AHP BC demonstrated significantly higher cell viability and proliferation compared to AH Plus used as a control. Gene expression analysis via real-time quantitative PCR demonstrated that ES BC, especially in set form, significantly upregulated osteogenic markers—alkaline phosphatase (2.49 ± 0.10, p < 0.01), runt-related transcription factor 2 (2.33 ± 0.13), and collagen type I alpha 1 chain (2.85 ± 0.40, p < 0.001)—more than cementogenic markers (cementum protein 1, cementum attachment protein, and cementum protein 23). This differential response may reflect the fibroblast-dominant nature of hPDLSCs, which contain limited cementoblast-like cells. This study supports the superior biocompatibility and regenerative capacity of ES BC and AHP BC compared to AH Plus. While in vitro models provide foundational insights, advanced ex vivo approaches are crucial for translating findings to clinical practice. Full article
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16 pages, 1826 KiB  
Article
Epigenetic Signatures of Dental Stem Cells: Insights into DNA Methylation and Noncoding RNAs
by Rosanna Guarnieri, Agnese Giovannetti, Giulia Marigliani, Michele Pieroni, Tommaso Mazza, Ersilia Barbato and Viviana Caputo
Appl. Sci. 2025, 15(15), 8749; https://doi.org/10.3390/app15158749 (registering DOI) - 7 Aug 2025
Abstract
Tooth development (odontogenesis) is regulated by interactions between epithelial and mesenchymal tissues through signaling pathways such as Bone Morphogenetic Protein (BMP), Wingless-related integration site (Wnt), Sonic Hedgehog (SHH), and Fibroblast Growth Factor (FGF). Mesenchymal stem cells (MSCs) derived from dental tissues—including dental pulp [...] Read more.
Tooth development (odontogenesis) is regulated by interactions between epithelial and mesenchymal tissues through signaling pathways such as Bone Morphogenetic Protein (BMP), Wingless-related integration site (Wnt), Sonic Hedgehog (SHH), and Fibroblast Growth Factor (FGF). Mesenchymal stem cells (MSCs) derived from dental tissues—including dental pulp stem cells (DPSCs), periodontal ligament stem cells (PDLSCs), and dental follicle progenitor cells (DFPCs)—show promise for regenerative dentistry due to their multilineage differentiation potential. Epigenetic regulation, particularly DNA methylation, is hypothesized to underpin their distinct regenerative capacities. This study reanalyzed publicly available DNA methylation data generated with Illumina Infinium HumanMethylation450 BeadChip arrays (450K arrays) from DPSCs, PDLSCs, and DFPCs. High-confidence CpG sites were selected based on detection p-values, probe variance, and genomic annotation. Principal Component Analysis (PCA) and hierarchical clustering identified distinct methylation profiles. Functional enrichment analyses highlighted biological processes and pathways associated with specific methylation clusters. Noncoding RNA analysis was integrated to construct regulatory networks linking DNA methylation patterns with key developmental genes. Distinct epigenetic signatures were identified for DPSCs, PDLSCs, and DFPCs, characterized by differential methylation across specific genomic contexts. Functional enrichment revealed pathways involved in odontogenesis, osteogenesis, and neurodevelopment. Network analysis identified central regulatory nodes—including genes, such as PAX6, FOXC2, NR2F2, SALL1, BMP7, and JAG1—highlighting their roles in tooth development. Several noncoding RNAs were also identified, sharing promoter methylation patterns with developmental genes and being implicated in regulatory networks associated with stem cell differentiation and tissue-specific function. Altogether, DNA methylation profiling revealed that distinct epigenetic landscapes underlie the developmental identity and differentiation potential of dental-derived mesenchymal stem cells. This integrative analysis highlights the relevance of noncoding RNAs and regulatory networks, suggesting novel biomarkers and potential therapeutic targets in regenerative dentistry and orthodontics. Full article
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13 pages, 401 KiB  
Article
The Correlation Between Cracked Teeth and National Insurance Coverage of Dental Implants in South Korea: A Retrospective Cohort Analysis
by Se Hoon Kahm, YoungHa Shim and SungEun Yang
J. Clin. Med. 2025, 14(15), 5507; https://doi.org/10.3390/jcm14155507 - 5 Aug 2025
Abstract
Background/Objectives: The expansion of National Health Insurance (NHI) coverage for dental implants in South Korea has substantially increased implant placements among older adults. While implants offer functional and esthetic benefits, their lack of periodontal ligaments alters occlusal force distribution, potentially increasing biomechanical [...] Read more.
Background/Objectives: The expansion of National Health Insurance (NHI) coverage for dental implants in South Korea has substantially increased implant placements among older adults. While implants offer functional and esthetic benefits, their lack of periodontal ligaments alters occlusal force distribution, potentially increasing biomechanical stress on adjacent or opposing teeth. This study aimed to investigate the association between the increased number of dental implants and the incidence of cracked teeth following the introduction of implant insurance. Methods: A retrospective analysis was conducted using the Clinical Data Warehouse of Seoul St. Mary’s Dental Hospital. Patients who underwent molar crown restorations between 2014 and 2022 were included. The incidence and clinical features of cracked teeth were compared before (2014–2015) and after (2016–2022) the introduction of implant insurance. Statistical analyses assessed differences in symptom presentation, pulp status, and treatment outcomes. Results: Among 5044 molars restored with crowns, 1692 were diagnosed with cracks. The incidence of cracked teeth significantly increased after NHI coverage for implants (25.5% vs. 32.6%, p < 0.001). Cases after insurance implementation showed fewer signs and symptoms at initial presentation (67.4% vs. 50.0%, p < 0.001), reduced irreversible pulpitis (37.2% vs. 25.8%, p < 0.001), and increased preservation of pulp vitality (46.9% vs. 57.8%, p < 0.001). These shifts may reflect changes in occlusal adjustment practices and earlier clinical intervention. Conclusions: The findings suggest a temporal link between increased implant placement and the rising incidence of cracked teeth. Implant-induced occlusal changes may contribute to this trend. Careful occlusal evaluation and follow-up are essential after implant placement, and further prospective studies are warranted to confirm causality and refine prevention strategies. Full article
(This article belongs to the Special Issue Research Progress in Osseointegrated Oral Implants)
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14 pages, 6123 KiB  
Article
Effects of Near-Infrared Diode Laser Irradiation on Pain Relief and Neuropeptide Markers During Experimental Tooth Movement in the Periodontal Ligament Tissues of Rats: A Pilot Study
by Kanako Okazaki, Ayaka Nakatani, Ryo Kunimatsu, Isamu Kado, Shuzo Sakata, Hirotaka Kiridoshi and Kotaro Tanimoto
Int. J. Mol. Sci. 2025, 26(15), 7404; https://doi.org/10.3390/ijms26157404 - 31 Jul 2025
Viewed by 169
Abstract
Pain following orthodontic treatment is the chief complaint of patients undergoing this form of treatment. Although the use of diode lasers has been suggested for pain reduction, the mechanism of laser-induced analgesic effects remains unclear. Neuropeptides, such as substance P (SP) and calcitonin [...] Read more.
Pain following orthodontic treatment is the chief complaint of patients undergoing this form of treatment. Although the use of diode lasers has been suggested for pain reduction, the mechanism of laser-induced analgesic effects remains unclear. Neuropeptides, such as substance P (SP) and calcitonin gene-related peptide (CGRP), contribute to the transmission and maintenance of inflammatory pain. Heat shock protein (HSP) 70 plays a protective role against various stresses, including orthodontic forces. This study aimed to examine the effects of diode laser irradiation on neuropeptides and HSP 70 expression in periodontal tissues induced by experimental tooth movement (ETM). For inducing ETM for 24 h, 50 g of orthodontic force was applied using a nickel–titanium closed-coil spring to the upper left first molar and the incisors of 20 male Sprague Dawley rats (7 weeks old). The right side without ETM treatment was considered the untreated control group. In 10 rats, diode laser irradiation was performed on the buccal and palatal sides of the first molar for 90 s with a total energy of 100.8 J/cm2. A near-infrared (NIR) laser with a 808 nm wavelength, 7 W peak power, 560 W average power, and 20 ms pulse width was used for the experiment. We measured the number of facial groomings and vacuous chewing movements (VCMs) in the ETM and ETM + laser groups. Immunohistochemical staining of the periodontal tissue with SP, CGRP, and HSP 70 was performed. The number of facial grooming and VCM periods significantly decreased in the ETM + laser group compared to the ETM group. Moreover, the ETM + laser group demonstrated significant suppression of SP, CGRP, and HSP 70 expression. These results suggest that the diode laser demonstrated analgesic effects on ETM-induced pain by inhibiting SP and CGRP expression, and decreased HSP 70 expression shows alleviation of cell damage. Thus, although further validation is warranted for human applications, an NIR diode laser can be used for reducing pain and neuropeptide markers during orthodontic tooth movement. Full article
(This article belongs to the Special Issue Advances in Photobiomodulation Therapy)
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16 pages, 1855 KiB  
Article
Emodin-Loaded Thermoresponsive Hydrogel as a Potential Drug Delivery System for Periodontal Disease in a Rat Model of Ligature-Induced Periodontitis
by Gyu-Yeon Shim, Seong-Hee Moon, Seong-Jin Shin, Hyun-Jin Kim, Seunghan Oh and Ji-Myung Bae
Polymers 2025, 17(15), 2108; https://doi.org/10.3390/polym17152108 - 31 Jul 2025
Viewed by 208
Abstract
Periodontitis, a chronic inflammatory disease, causes alveolar bone loss. Current treatments show limitations in achieving dual antimicrobial and anti-inflammatory effects. We evaluated an emodin-loaded thermoresponsive hydrogel as a local drug delivery system for periodontitis treatment. Emodin itself demonstrated antibacterial activity against Porphyromonas gingivalis [...] Read more.
Periodontitis, a chronic inflammatory disease, causes alveolar bone loss. Current treatments show limitations in achieving dual antimicrobial and anti-inflammatory effects. We evaluated an emodin-loaded thermoresponsive hydrogel as a local drug delivery system for periodontitis treatment. Emodin itself demonstrated antibacterial activity against Porphyromonas gingivalis, with minimal inhibitory and minimal bactericidal concentrations of 50 μM. It also suppressed mRNA expression of proinflammatory cytokines [tumor necrosis factor alpha, interleukin (IL)-1β, and IL-6] in lipopolysaccharide-stimulated RAW 264.7 cells. The hydrogel, formulated with poloxamers and carboxymethylcellulose, remained in a liquid state at room temperature and formed a gel at 34 °C, providing sustained drug release for 96 h and demonstrating biocompatibility with human periodontal ligament stem cells while exhibiting antibacterial activity against P. gingivalis. In a rat model of periodontitis, the hydrogel significantly reduced alveolar bone loss and inflammatory responses, as confirmed by micro-computed tomography and reverse transcription quantitative polymerase chain reaction of gingival tissue. The dual antimicrobial and anti-inflammatory properties of emodin, combined with its thermoresponsive delivery system, provide advantages over conventional treatments by maintaining therapeutic concentrations in the periodontal pocket while minimizing systemic exposure. This shows the potential of emodin-loaded thermoresponsive hydrogels as effective local delivery systems for periodontitis treatment. Full article
(This article belongs to the Section Smart and Functional Polymers)
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20 pages, 1220 KiB  
Systematic Review
The Evolving Role of Stem Cells in Oral Health and Regeneration: A Systematic Review
by Gianna Dipalma, Grazia Marinelli, Arianna Fiore, Liviana Balestriere, Claudio Carone, Silvio Buongiorno, Francesco Inchingolo, Giuseppe Minervini, Andrea Palermo, Angelo Michele Inchingolo and Alessio Danilo Inchingolo
Surgeries 2025, 6(3), 65; https://doi.org/10.3390/surgeries6030065 - 30 Jul 2025
Viewed by 337
Abstract
Background: Mesenchymal stem cells (MSCs), multipotent and immune-regulatory cells derived from tissues such as bone marrow, dental pulp, and periodontal ligament, emerged as promising agents in regenerative dentistry. Their clinical applications include endodontic tissue regeneration, periodontal healing, and alveolar bone repair, addressing [...] Read more.
Background: Mesenchymal stem cells (MSCs), multipotent and immune-regulatory cells derived from tissues such as bone marrow, dental pulp, and periodontal ligament, emerged as promising agents in regenerative dentistry. Their clinical applications include endodontic tissue regeneration, periodontal healing, and alveolar bone repair, addressing critical challenges in dental tissue restoration. Methods: A systematic review was conducted following PRISMA guidelines and registered in PROSPERO. We searched PubMed, Scopus, and Web of Science databases for open-access, English-language clinical trials and observational studies published from 2015 to 2025. Studies focusing on the application of MSCs in dental tissue regeneration were included based on predefined eligibility criteria. Results: Out of 2400 initial records, 13 studies met the inclusion criteria after screening and eligibility assessment. Most studies investigated MSCs derived from dental pulp and periodontal ligament for regenerating periodontal tissues and alveolar bone defects. The majority reported improved clinical outcomes; however, variations in MSC sources, delivery methods, sample sizes, and follow-up periods introduced methodological heterogeneity. Conclusions: MSCs show significant potential in enhancing bone and periodontal regeneration in dental practice. Nonetheless, the current evidence is limited by small sample sizes, short follow-up, and inconsistent methodologies. Future large-scale, standardized clinical trials are required to validate MSC-based regenerative therapies and optimize treatment protocols. Full article
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16 pages, 587 KiB  
Systematic Review
Autogenous Transplantation of Teeth Across Clinical Indications: A Systematic Review and Meta-Analysis
by Martin Baxmann, Karin Christine Huth, Krisztina Kárpáti and Zoltán Baráth
J. Clin. Med. 2025, 14(14), 5126; https://doi.org/10.3390/jcm14145126 - 18 Jul 2025
Viewed by 321
Abstract
Autogenous tooth transplantation offers a biologically favorable approach to tooth replacement, preserving the periodontal ligament, promoting alveolar development, and maintaining proprioception. Background/Objectives: Its broader clinical applicability is limited by variability in techniques and outcome definitions. This systematic review and meta-analysis evaluated the [...] Read more.
Autogenous tooth transplantation offers a biologically favorable approach to tooth replacement, preserving the periodontal ligament, promoting alveolar development, and maintaining proprioception. Background/Objectives: Its broader clinical applicability is limited by variability in techniques and outcome definitions. This systematic review and meta-analysis evaluated the clinical success of autogenous tooth transplantation across donor tooth types, developmental stages, surgical techniques, and fixation methods. Methods: Following PRISMA 2020 guidelines and a PROSPERO-registered protocol (CRD42024625550), five databases and the gray literature were searched through July 2025. Eligible studies reported clinical outcomes for autogenous tooth transplantation. Risk of bias was assessed using the Newcastle–Ottawa Scale. A random-effects meta-analysis of logit-transformed proportions was conducted, with subgroup and sensitivity analyses by tooth type, root development stage, surgical technique, and fixation method. Results: Twenty studies involving 1366 transplanted teeth were included. The pooled success rate was 94.0% (95% CI: 22.5–99.9%) across follow-up periods ranging from one month to twenty-nine years. However, interpretation is limited by distinct heterogeneity (I2 = 99.8%) and the wide confidence interval. Subgroup analyses by tooth type, root maturity, surgical technique, and fixation method are, therefore, emphasized to support clinical interpretation. Conclusions: Autogenous tooth transplantation achieves consistently high success across clinical contexts when biologic handling is respected. These findings support its broader use in dental and orthodontic practice and underscore the need for standardized outcome reporting and prospective research. Interpretation is limited by heterogeneity and variation in reporting standards. Full article
(This article belongs to the Special Issue Current Advances in Endodontics and Dental Traumatology)
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14 pages, 858 KiB  
Article
Twelve-Month Follow-Up After the Treatment of Periodontal Conditions Using Scaling and Root Planning Alone vs. Laser-Assisted New Attachment Procedure
by Edwin Sever Bechir, Farah Bechir, Mircea Suciu, Anamaria Bechir and Andrada Camelia Nicolau
Diagnostics 2025, 15(14), 1799; https://doi.org/10.3390/diagnostics15141799 - 16 Jul 2025
Viewed by 442
Abstract
Background/Objectives: Periodontitis is a chronic inflammation of the periodontium that induces damage in the periodontal ligaments and the surrounding alveolar bone. This study aimed to comparatively evaluate the clinical outcomes of two therapies used in the management of periodontal conditions, represented by [...] Read more.
Background/Objectives: Periodontitis is a chronic inflammation of the periodontium that induces damage in the periodontal ligaments and the surrounding alveolar bone. This study aimed to comparatively evaluate the clinical outcomes of two therapies used in the management of periodontal conditions, represented by scaling and root planing (SRP) alone and laser-assisted new attachment procedure (LANAP). Methods: Two quadrants of the oral cavity from each selected patient were randomly allocated to one of the treatment groups, SRP or LANAP. The periodontal status was documented in a periodontal chart at baseline, six weeks, and one year after treatment. SRP was performed in the first group of patients. The LANAP protocol was carried out on the patients belonging to the second group. Results: The outcomes of the study highlighted that LANAP leads to a reduction in periodontal disease signs (pocket depth, bleeding on probing, and gingival recession), contributing to the formation of new attachment tissues. LANAP shows more stability in maintaining the improvements achieved during six weeks, while SRP shows a slight deterioration in several parameters, particularly attachment loss, between six weeks and one year. The collected data at six-week and one-year follow-ups show improvements in periodontal health, thus improving oral health. Conclusions: Both minimally invasive periodontal procedures were effective, with LANAP demonstrating greater efficiency in patients with chronic periodontal disease, a greater reduction in pocket depth, and improved clinical outcomes compared to SRP alone. Full article
(This article belongs to the Section Clinical Diagnosis and Prognosis)
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16 pages, 4472 KiB  
Article
Effect of Low-Level Laser Therapy on Periodontal Host Cells and a Seven-Species Periodontitis Model Biofilm
by Selma Dervisbegovic, Susanne Bloch, Vera Maierhofer, Christian Behm, Xiaohui Rausch-Fan, Andreas Moritz, Christina Schäffer and Oleh Andrukhov
Int. J. Mol. Sci. 2025, 26(14), 6803; https://doi.org/10.3390/ijms26146803 - 16 Jul 2025
Viewed by 328
Abstract
Low-level laser therapy (LLLT) is gaining attention as an effective adjunct to non-surgical periodontal treatment. This study evaluates the potential of LLLT to reduce bacterial load in a clinically relevant in vitro subgingival biofilm model and its impact on the inflammatory response. A [...] Read more.
Low-level laser therapy (LLLT) is gaining attention as an effective adjunct to non-surgical periodontal treatment. This study evaluates the potential of LLLT to reduce bacterial load in a clinically relevant in vitro subgingival biofilm model and its impact on the inflammatory response. A subgingival biofilm model consisting of seven bacterial species was established. Primary human gingival fibroblasts (GFs) and periodontal ligament cells (PDLs) were cultured. Both biofilms and host cells were treated with the DenLase Diode Laser (980 nm) under various clinically relevant settings. The composition and structure of the seven-species biofilms were evaluated using quantitative PCR and fluorescence microscopy, respectively. The inflammatory response in host cells was analyzed by measuring the gene and protein expression levels of various inflammatory mediators. Laser treatment at power outputs ranging from 0.3 to 2 W had no significant effect on biofilm composition or architecture. LLLT, particularly at higher power settings, reduced the viability in both GFs and PDLs up to 70%. Gene expression levels of inflammatory mediators were only minimally influenced by laser treatment. However, LLLT significantly decreased the secretion of all examined cytokines. These findings suggest that LLLT with a 980 nm diode laser, under clinically relevant conditions, exerts anti-inflammatory rather than antimicrobial effects. Full article
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14 pages, 2241 KiB  
Article
Cross-Sectional Study of Occlusal Loading and Periodontal Status of Teeth with Deflective Occlusal Contacts
by Ximena Anca Nicolae, Elena Preoteasa, Catalina Murariu Magureanu and Cristina Teodora Preoteasa
Bioengineering 2025, 12(7), 766; https://doi.org/10.3390/bioengineering12070766 - 16 Jul 2025
Viewed by 426
Abstract
Aim: To evaluate whether maximum occlusal loading and periodontal status are different between teeth presenting deflective occlusal contacts and those without such contacts, specifically adjacent and homologous teeth. Method: A cross-sectional study was conducted using OccluSense to detect deflective contacts and quantify occlusal [...] Read more.
Aim: To evaluate whether maximum occlusal loading and periodontal status are different between teeth presenting deflective occlusal contacts and those without such contacts, specifically adjacent and homologous teeth. Method: A cross-sectional study was conducted using OccluSense to detect deflective contacts and quantify occlusal load per tooth. For group comparisons, the Kruskal–Wallis, Friedman, Cochran’s Q, and chi-squared tests were used. Results: A total of 493 teeth with deflective contacts were compared to 473 adjacent (first control group) and 457 homologous teeth (second control group). Teeth with deflective contacts showed significantly higher occlusal loading (mean value: 208) than adjacent (72) and homologous teeth (97) (p < 0.05). They also exhibited more advanced periodontal damage, including deeper probing depths, greater gingival recession, alveolar bone loss, and a wider periodontal ligament space. Deflective contacts in centric relation were more strongly linked to periodontal deterioration than those in protrusive or lateral mandibular movements, despite similar occlusal forces. Conclusions: Within this study’s limitations, deflective occlusal contacts are associated with increased occlusal forces and more severe periodontal damage, suggesting a biomechanical factor in periodontal disease progression. Full article
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28 pages, 1081 KiB  
Review
The Role of Cytokines in Orthodontic Tooth Movement
by Hideki Kitaura, Fumitoshi Ohori, Aseel Marahleh, Jinghan Ma, Angyi Lin, Ziqiu Fan, Kohei Narita, Kou Murakami and Hiroyasu Kanetaka
Int. J. Mol. Sci. 2025, 26(14), 6688; https://doi.org/10.3390/ijms26146688 - 11 Jul 2025
Cited by 1 | Viewed by 473
Abstract
A challenge in orthodontic treatment is the long time taken to move teeth, which extends the long treatment period. Accordingly, various treatment protocols and orthodontic materials have been developed to shorten the orthodontic treatment period. However, controlling biological reactions is considered necessary to [...] Read more.
A challenge in orthodontic treatment is the long time taken to move teeth, which extends the long treatment period. Accordingly, various treatment protocols and orthodontic materials have been developed to shorten the orthodontic treatment period. However, controlling biological reactions is considered necessary to further shorten this treatment period. Orthodontic force results in compression of the periodontal ligament in the direction of tooth movement, resulting in various reactions in the periodontal ligament that induce osteoclast development, alveolar bone absorption, and teeth movement. The aforementioned reactions include immune reactions. Cytokines are substances responsible for intercellular communication and are involved in various physiological actions, including immune and inflammatory reactions. They cause various cellular responses, including cell proliferation, differentiation, cell death, and functional expression. Various cytokines are involved in biological reactions during orthodontic tooth movement (OTM). It is important to understand the role of cytokines during OTM in order to elucidate their biological response. This review discusses the role of cytokines during OTM. Full article
(This article belongs to the Special Issue Regulatory Network of Bone Metabolism)
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14 pages, 520 KiB  
Review
Activation of the Nrf2 Signaling Pathway as a Therapeutic Strategy Against Periodontal Disease: A Narrative Review
by Sarmistha Saha, Nadezhda Sachivkina, Ekaterina Lenchenko, Olga Pilshchikova and Alexandr Muraev
Dent. J. 2025, 13(7), 314; https://doi.org/10.3390/dj13070314 - 11 Jul 2025
Viewed by 296
Abstract
Periodontitis (PD), is a chronic inflammatory disease of the periodontal system, which includes gingiva, periodontal ligament, alveolar bone, and tooth cement. It is becoming increasingly prevalent globally, and its implications for oral health are profound. The Nrf2 signaling pathway is crucial in managing [...] Read more.
Periodontitis (PD), is a chronic inflammatory disease of the periodontal system, which includes gingiva, periodontal ligament, alveolar bone, and tooth cement. It is becoming increasingly prevalent globally, and its implications for oral health are profound. The Nrf2 signaling pathway is crucial in managing the relationship between inflammation and oxidative stress, making it vital for understanding this disease. Nrf2 interacts with key redox-sensitive inflammatory pathways, playing a vital role in the development of periodontitis. Acknowledging these dynamics underscores the importance of proactively addressing the complex aspects of periodontal disease. This review emphasizes its intricate interactions with redox-sensitive transcription factors vital for sustaining the self-perpetuating inflammatory processes underlying the disease. Additionally, it explores promising therapeutic strategies aimed at Nrf2 activation and encourages more effective management of PD. Full article
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22 pages, 5259 KiB  
Article
Ameliorating Effect of Glehnia littoralis Extract on Periodontitis Through Regulation of 11β-Hydroxysteroid Dehydrogenase Type 1 in an Experimental Periodontitis Model
by Eun-Nam Kim, Nguyen Minh Trang, Chae Lee Park, Sang-Yoon Kim, MinKyun Na and Gil-Saeng Jeong
Molecules 2025, 30(14), 2903; https://doi.org/10.3390/molecules30142903 - 9 Jul 2025
Viewed by 244
Abstract
Glehnia littoralis Fr. Schmidt ex Miq. has been cultivated in China for a long time and used as a medicinal plant called “Beishashen” in traditional Chinese medicine and has been traditionally known to have antibacterial and anti-inflammatory effects, but its direct role in [...] Read more.
Glehnia littoralis Fr. Schmidt ex Miq. has been cultivated in China for a long time and used as a medicinal plant called “Beishashen” in traditional Chinese medicine and has been traditionally known to have antibacterial and anti-inflammatory effects, but its direct role in periodontitis has not been known. Currently used periodontal treatments require long-term administration, which causes many side effects. Therefore, in this study, we evaluated the effects of G. littoralis extract (GLE) on periodontitis in an experimental periodontitis-induced in vitro and vivo model and understood its potential molecular mechanism. The effect of GLE on periodontitis in vitro was investigated using human periodontal ligament (HPDL) cells mediated by PG-LPS. Additionally, a ligature-induced periodontitis model and a PG-LPS-induced periodontal inflammation model were used to investigate the effect of GLE in vivo. In vitro study results showed that GLE down-regulated the increased inflammatory cytokines and mediators in HPDL cells stimulated with PG-LPS, and simultaneously down-regulated the levels of 11β-HSD1 and glucocorticoid receptor (GR), thereby alleviating periodontal inflammation. At the same time, it restored the lost osteoblast differentiation potential of HPDL cells. In addition, in an in vivo model representatively used for periodontitis research, the periodontal inflammation-alleviating effect and the effect of restoring or protecting damaged periodontal tissue were confirmed. GLE can be considered as a new periodontitis treatment agent through regulating 11β-HSD1. Full article
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11 pages, 1776 KiB  
Article
Preclinical Performance of Customized Polycaprolactone-Based Hybrid Bone Grafts
by Ildefonso Serrano-Belmonte, Javier Montero, Ángel Román-Maciá, Virginia Pérez-Fernández, Luis M. Rodríguez-Lorenzo, Nieves Cubo-Mateo, Angélica Lara-Nuñez and Ascensión Martínez-Cánovas
Appl. Sci. 2025, 15(13), 7540; https://doi.org/10.3390/app15137540 - 4 Jul 2025
Viewed by 328
Abstract
(1) Introduction: Polycaprolactone (PCL) materials have been developed with components that promote bone growth. The main objective of this work was to evaluate the biocompatibility and cytotoxic effects that different combinations of PCL with nanohydroxyapatite and strontium could produce on periodontal ligament stem [...] Read more.
(1) Introduction: Polycaprolactone (PCL) materials have been developed with components that promote bone growth. The main objective of this work was to evaluate the biocompatibility and cytotoxic effects that different combinations of PCL with nanohydroxyapatite and strontium could produce on periodontal ligament stem cells (PDLSC). (2) Materials and Methods: PDLSCs were seeded in six 96-well plates. Three plates were used for the MTT test, and three were used for the Hoechst 33342 test. In each of the plates, three samples of different concentrations of PCL were introduced (PCL 100%, PCL 95% combined with nanohydroxyapatite functionalized with strontium, and PCL 90% with nanohydroxyapatite). Apoptosis was analyzed using Hoechst and cell viability combined with MTT at 24, 48, and 72 h. (3) Results: No statistically significant differences (p < 0.05) were found between the different concentrations of PCL or regarding the duration for which the cells were subjected to elution. (4) Conclusions: Pure PCL and both PCL combined with nanohydroxyapatite/strontium and nanohydroxyapatite are biocompatible materials, and there are no significant differences between them after apoptosis and in cell viability assays. Full article
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24 pages, 7732 KiB  
Review
The Morphogenesis, Pathogenesis, and Molecular Regulation of Human Tooth Development—A Histological Review
by Dorin Novacescu, Cristina Stefania Dumitru, Flavia Zara, Marius Raica, Cristian Silviu Suciu, Alina Cristina Barb, Marina Rakitovan, Antonia Armega Anghelescu, Alexandu Cristian Cindrea, Szekely Diana and Pusa Nela Gaje
Int. J. Mol. Sci. 2025, 26(13), 6209; https://doi.org/10.3390/ijms26136209 - 27 Jun 2025
Viewed by 574
Abstract
Odontogenesis, the development of teeth, is a complex, multistage process that unfolds from early embryogenesis through tooth eruption and maturation. It serves as a classical model of organogenesis due to the intricate reciprocal interactions between cranial neural crest-derived mesenchyme and oral epithelium. This [...] Read more.
Odontogenesis, the development of teeth, is a complex, multistage process that unfolds from early embryogenesis through tooth eruption and maturation. It serves as a classical model of organogenesis due to the intricate reciprocal interactions between cranial neural crest-derived mesenchyme and oral epithelium. This narrative review synthesizes current scientific knowledge on human tooth development, tracing the journey from the embryological origins in the first branchial arch to the formation of a fully functional tooth and its supporting structures. Key morphogenetic stages—bud, cap, bell, apposition, and root formation—are described in detail, highlighting the cellular events and histological features characterizing each stage. We discuss the molecular and cellular regulatory networks that orchestrate odontogenesis, including the conserved signaling pathways (Wnt, BMP, FGF, SHH, EDA) and transcription factors (e.g., PAX9, MSX1/2, PITX2) that drive tissue patterning and cell differentiation. The coordinated development of supporting periodontal tissues (cementum, periodontal ligament, alveolar bone, gingiva) is also examined as an integral part of tooth organogenesis. Finally, developmental anomalies (such as variations in tooth number, size, and form) and the fate of residual embryonic epithelial cells are reviewed to underscore the clinical significance of developmental processes. Understanding the normal course of odontogenesis provides crucial insight into congenital dental disorders and lays a foundation for advances in regenerative dental medicine. Full article
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