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Keywords = pulpal response

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22 pages, 2194 KB  
Review
Objectively Diagnosing Pulpitis: Opportunities and Methodological Challenges in the Development of Point-of-Care Assays
by Darren Walsh, Ross Quigley, Anthonia Ekperuoh and Henry F. Duncan
Int. J. Mol. Sci. 2026, 27(1), 355; https://doi.org/10.3390/ijms27010355 - 29 Dec 2025
Viewed by 429
Abstract
Pulpitis is the inflammatory response of the dental pulp to microbial challenge and can range from mild to severe in nature, with severe pulpitis traditionally resulting in pulp removal and root canal treatment (RCT). In the pursuit of more conservative treatments, recent clinical [...] Read more.
Pulpitis is the inflammatory response of the dental pulp to microbial challenge and can range from mild to severe in nature, with severe pulpitis traditionally resulting in pulp removal and root canal treatment (RCT). In the pursuit of more conservative treatments, recent clinical practice guidelines have recommended strategies that preserve the vitality of the dental pulp, rather than RCT, when possible. This has increased the focus on improving the accuracy of pulp diagnosis, which will direct treatment and improve management outcomes. Unfortunately, current point-of-care (PoC) tools are subjective, lack discrimination and rely on the stimulation of pulpal neurons, limiting dentists’ ability to objectively identify the level of inflammation. Molecular biomarker assessment has the potential to dynamically analyse pulpitis and correlate this with inflammatory thresholds and treatment outcomes. Numerous chemokines, cytokines, proteases and growth factors exhibit altered expression during pulpitis and can be collected intraoperatively as part of routine dental treatment. Although current data indicate several markers that could be used as next-generation diagnostic chairside tools for pulpitis, there are currently no commercial kits. Considering the interest in vital pulp treatment, there is an urgent need to engage researchers, industry, dentists and other stakeholders in the development of PoC diagnostic assays for pulpitis. Full article
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
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39 pages, 2194 KB  
Review
Tooth Pulp Afferents and Transient Receptor Potential (TRP) Ion Channels as Key Regulators of Pulp Homeostasis, Inflammation, and Pain
by Man-Kyo Chung, Swarnalakshmi Raman and Arpad Szallasi
Int. J. Mol. Sci. 2026, 27(1), 182; https://doi.org/10.3390/ijms27010182 - 23 Dec 2025
Viewed by 326
Abstract
Dental pain often arises from the compromised integrity of the tooth pulp due to dental injury or caries. The dentin–pulp complex has long been considered to be central to the unique biology of dental pain. Most trigeminal ganglion afferents projecting into tooth pulp [...] Read more.
Dental pain often arises from the compromised integrity of the tooth pulp due to dental injury or caries. The dentin–pulp complex has long been considered to be central to the unique biology of dental pain. Most trigeminal ganglion afferents projecting into tooth pulp are myelinated neurons, which lose their myelination at the site of peripheral dentin innervation. The pulpal afferents likely combine multiple internal and external stimuli to mediate nociception and maintain pulp homeostasis. Transient receptor potential (TRP) ion channels in neurons and odontoblasts, along with mechanosensitive ion channels such as Piezo, form a key molecular hub for pulpal nociception by sensing thermal, chemical, and hydrodynamic stimuli. Among these, TRP vanilloid 1 (TRPV1) mediates nociception and the release of calcitonin-gene-related peptides (CGRPs), while TRP canonical 5 (TRPC5) mediates cold pain. TRP melastatin 8 (TRPM8) mediates the transduction of hyperosmotic stimuli. Pulpitis elevates endogenous TRPV1 and TRPA1 agonists, while inflammatory mediators sensitize TRP channels, amplifying pain. CGRP recruits immune cells and promotes bacterial clearance and reparative dentinogenesis, yet the roles of TRP channels in these processes remain unclear. Future studies should use advanced multi-omics and in vivo or organotypic models in animal and human teeth to define TRP channel contributions to pain, immune responses, and regeneration. Understanding neuronal and non-neuronal TRP channel interactions and their integration with other ion channels may enable novel analgesic and regenerative strategies in dentistry. Full article
(This article belongs to the Special Issue TRP Channels for Pain, Itch and Inflammation Relief: 2nd Edition)
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26 pages, 1377 KB  
Review
The Role of Inflammasomes in Chronic Oral Inflammatory Disease and Oral Cancer: A Narrative Review
by Banan Al-Natour, Issam Rasheed and Ikhlas A. El Elkarim
Dent. J. 2025, 13(12), 609; https://doi.org/10.3390/dj13120609 - 18 Dec 2025
Viewed by 517
Abstract
Background: Chronic inflammation is a hallmark of many oral and systemic diseases and has long been recognised as a risk factor for cancer development. Central to inflammatory responses are inflammasomes—multiprotein complexes that, upon activation, trigger caspase-1–mediated release of the pro-inflammatory cytokines interleukin-1β (IL-1β) [...] Read more.
Background: Chronic inflammation is a hallmark of many oral and systemic diseases and has long been recognised as a risk factor for cancer development. Central to inflammatory responses are inflammasomes—multiprotein complexes that, upon activation, trigger caspase-1–mediated release of the pro-inflammatory cytokines interleukin-1β (IL-1β) and interleukin-18 (IL-18). Their emerging contribution to chronic oral inflammatory conditions has generated interest in understanding whether persistent inflammasome activity may also influence pathways involved in oral carcinogenesis. This review summarises current evidence on the role of inflammasomes in oral inflammatory diseases and explores their potential involvement in the transition from chronic inflammation to malignant transformation. Methods: A narrative review of the literature was conducted by searching major scientific databases for studies investigating inflammasome activation in oral tissues, inflammatory oral diseases, and mechanisms linking chronic inflammation to oral cancer. Eligible articles included experimental studies, animal models, observational clinical research, and review papers that provided mechanistic or associative insights. Due to heterogeneity in study designs, a qualitative synthesis was performed. Results: Available evidence indicates that inflammasomes, particularly NLRP3 and AIM2, contribute to the pathophysiology of pulpitis, periodontitis, and several systemic conditions that affect oral health. Preclinical and observational findings also suggest potential involvement of inflammasome-related pathways in early tumorigenic processes, although these associations require further clarification. Preliminary biomarker-based studies demonstrate that inflammasome components measurable in saliva, pulpal blood, or gingival crevicular fluid may offer minimally invasive indicators of inflammatory burden and oral health status. Conclusions: Inflammasomes appear to play a meaningful role in oral inflammatory diseases, and growing evidence links their persistent activation to mechanisms relevant to oral carcinogenesis. However, current findings are largely associative and derived primarily from experimental and early clinical research. Additional work is needed to define precisely how inflammasomes contribute to the progression from chronic oral inflammation toward malignant change and to evaluate whether targeting inflammasome pathways offers viable therapeutic or diagnostic potential. Full article
(This article belongs to the Special Issue Feature Review Papers in Dentistry: 2nd Edition)
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10 pages, 2036 KB  
Article
An Updated Digital Approach to Regional Anesthesia: A Pilot Study on Computer-Guided Maxillary Nerve Block via the Greater Palatine Canal
by Ioannis Fotopoulos, Anastasia Fardi, Vasileios Zisis, Athanasios Poulopoulos, Nikolaos Dabarakis and Theodoros Lillis
Dent. J. 2025, 13(11), 521; https://doi.org/10.3390/dj13110521 - 6 Nov 2025
Viewed by 971
Abstract
Objectives: Maxillary nerve block via the greater palatine canal (GPC) offers the potential for profound regional anesthesia of the maxilla but remains underutilized due to anatomical variability and technical complexity. The aim of this study was to explore the clinical feasibility, accuracy, and [...] Read more.
Objectives: Maxillary nerve block via the greater palatine canal (GPC) offers the potential for profound regional anesthesia of the maxilla but remains underutilized due to anatomical variability and technical complexity. The aim of this study was to explore the clinical feasibility, accuracy, and anesthetic effectiveness of a computer-guided approach by using CBCT-based surgical guides to access the pterygopalatine fossa via the GPC. Methods: Thirty-one patients underwent the procedure with patient-specific guides designed from cone-beam computerized tomography (CBCT) and intraoral scans. A 27G needle was directed through the guide to deliver 1.8 mL of 2% lidocaine with epinephrine 1:80.000. Pulpal anesthesia was assessed via electric pulp testing (EPT), and soft tissue anesthesia via pressure algometry at predefined oral and facial sites. Success was defined as absence of EPT response at maximum output and pressure pain threshold ≥ 700 g. To assess variations in anesthetic efficacy among multiple related groups, Cochran’s Q test and McNemar’s test were employed. Results: Successful needle placement was achieved in 30 out of 31 patients (96.7%) using the computer-guided approach, with a mean of 1.45 insertion attempts per case. Complete palatal soft tissue anesthesia was achieved in all subjects across the tested sites (100%). Pulpal anesthesia was most effective in posterior teeth, with success rates of 96.7% for first molars and 93.3% for first premolars, while the central incisor showed a reduced success rate of 50%. Transient visual disturbances occurred in three patients (10%), with no other adverse effects reported. Conclusions: These findings support the use of computer-guided GPC block as a method for achieving maxillary nerve anesthesia. Although anesthetic spread to anterior and buccal regions was limited, the technique demonstrated consistent effectiveness in the posterior maxilla, highlighting its potential utility in complex dental and surgical interventions requiring deep and long-lasting regional anesthesia. Full article
(This article belongs to the Special Issue New Trends in Digital Dentistry)
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20 pages, 10152 KB  
Article
In Vivo Comparison of Resin-Modified and Pure Calcium-Silicate Cements for Direct Pulp Capping
by Fatma Fenesha, Aonjittra Phanrungsuwan, Brian L. Foster, Anibal Diogenes and Sarah B. Peters
Appl. Sci. 2025, 15(19), 10639; https://doi.org/10.3390/app151910639 - 1 Oct 2025
Viewed by 1996
Abstract
Introduction: Direct pulp capping (DPC) aims to preserve the vitality of the dental pulp by placing a protective biocompatible material over the exposed pulp tissue to facilitate healing. There are several calcium-silicate materials that have been designed to promote mineralization and the regulation [...] Read more.
Introduction: Direct pulp capping (DPC) aims to preserve the vitality of the dental pulp by placing a protective biocompatible material over the exposed pulp tissue to facilitate healing. There are several calcium-silicate materials that have been designed to promote mineralization and the regulation of inflammation. These have strong potential for the repair and regeneration of dental pulp. Among them, Biodentine (BD) and EndoSequence RRM Putty (ES) have been found to promote in vitro and in vivo mineralization while minimizing some of the limitations of the first-generation calcium-silicate-based materials. Theracal-LC (TLC), a light-cured, resin-modified calcium-silicate material, is a newer product with potential to improve the clinical outcomes of DPC, but existing studies have reported conflicting findings regarding its biocompatibility and ability to support pulpal healing in direct contact with the pulp. A comprehensive assessment of the biocompatibility and pulpal protection provided by these three capping materials has not yet been performed. Aim: We aimed to quantify the inflammatory response, dentin bridge formation, and material adaptation following DPC using three calcium-silicate materials: ES, BD, and TLC. Materials and Methods: DPC was performed on the maxillary first molar of C57BL/6 female mice. Maxilla were collected and processed at 1 and 21 days post-DPC. The early inflammatory response was measured 24 h post-procedure using confocal imaging of anti-Lys6G6C, which indicates the extent of neutrophil and monocyte infiltration. Reparative mineralized bridge formation was assessed at 21 days post-procedure using high-resolution micro-computed tomography (micro-CT) and histology. Lastly, the homogeneity of the capping materials was evaluated by quantifying voids in calcium-silicate restorations using micro-CT. Results: DPC using TLC induced less infiltration of Lys6G6C+ cells at 24 h than BD or ES. BD promoted higher volumes of tertiary dentin than TLC, but TLC and ES showed no significant differences in volume. No differences were observed in material adaptation and void spaces among the three capping materials. Conclusions: All three materials under investigation supported pulp healing and maintained marginal integrity. However, TLC induced a lower inflammatory response on day 1 and induced similar levels of tertiary dentin to ES. These observations challenge the common perception that resin-based capping materials are not suitable for direct pulp capping. Our findings underscore the need to balance biological responses with physical properties when selecting pulp capping materials to improve long-term clinical success. Full article
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14 pages, 7820 KB  
Article
Role of Dystrophic Calcification in Reparative Dentinogenesis After Rat Molar Pulpotomy
by Naoki Edanami, Kunihiko Yoshiba, Razi Saifullah Ibn Belal, Nagako Yoshiba, Shoji Takenaka, Naoto Ohkura, Shintaro Takahara, Takako Ida, Rosa Baldeon, Susan Kasimoto, Pemika Thongtade and Yuichiro Noiri
Int. J. Mol. Sci. 2025, 26(15), 7130; https://doi.org/10.3390/ijms26157130 - 24 Jul 2025
Cited by 2 | Viewed by 1095
Abstract
Vital pulp therapy with calcium hydroxide or mineral trioxide aggregate (MTA) rapidly induces dystrophic calcification and promotes the accumulation of two members of small integrin-binding ligand N-linked glycoproteins: osteopontin (OPN) and dentin matrix protein-1 (DMP1). However, the precise relationship between these initial events [...] Read more.
Vital pulp therapy with calcium hydroxide or mineral trioxide aggregate (MTA) rapidly induces dystrophic calcification and promotes the accumulation of two members of small integrin-binding ligand N-linked glycoproteins: osteopontin (OPN) and dentin matrix protein-1 (DMP1). However, the precise relationship between these initial events and their roles in reparative dentinogenesis remain unclear. This study aimed to clarify the relationship between dystrophic calcification, OPN and DMP1 accumulation, and reparative dentin formation. Pulpotomy was performed on rat molars using MTA or zirconium oxide (ZrO2). ZrO2 was used as a control to assess pulp healing in the absence of dystrophic calcification. Pulpal responses were evaluated from 3 h to 7 days postoperatively via elemental mapping, micro-Raman spectroscopy, and histological staining. In the MTA-treated group, a calcium-rich dystrophic calcification zone containing calcite and hydroxyapatite was observed at 3 h after treatment; OPN and DMP1 accumulated under the dystrophic calcification zone by day 3; reparative dentin formed below the region of OPN and DMP1 accumulation by day 7. In contrast, these reactions did not occur in the ZrO2-treated group. These results suggest that dystrophic calcification serves as a key trigger for OPN and DMP1 accumulation and plays a pivotal role in reparative dentinogenesis. Full article
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16 pages, 1128 KB  
Systematic Review
The Influence of Diabetes on Orthodontic Treatment: A Systematic Review of the Clinical Considerations and Challenges in Response
by Paula García-Rios, Francisco Javier Rodríguez-Lozano, Julia Guerrero-Gironés, Miguel R. Pecci-Lloret, Ricardo E. Oñate-Sánchez and Nuria Pérez-Guzmán
J. Clin. Med. 2025, 14(14), 4879; https://doi.org/10.3390/jcm14144879 - 9 Jul 2025
Cited by 1 | Viewed by 1553
Abstract
Background/Objectives: Diabetes mellitus is defined as a group of metabolic diseases characterized by chronically elevated blood glucose levels. This condition influences the course of orthodontic treatment, as it affects various clinical aspects of the patient that must be taken into consideration prior to [...] Read more.
Background/Objectives: Diabetes mellitus is defined as a group of metabolic diseases characterized by chronically elevated blood glucose levels. This condition influences the course of orthodontic treatment, as it affects various clinical aspects of the patient that must be taken into consideration prior to initiation. Therefore, achieving adequate control and management of diabetic patients undergoing orthodontic therapy is essential. This article presents a qualitative synthesis of studies addressing how diabetes affects orthodontic treatments, emphasizing the importance of understanding the necessary considerations prior to initiating treatment and how to manage potential complications. Methods: This systematic review was conducted in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. A database search was performed on 5 May 2025, in PubMed, Scopus, Scielo, and The Cochrane Library, using terms related to “diabetes mellitus” and “orthodontic treatments”. Studies meeting the search criteria were included, particularly those that were published in the past ten years and reported on the influence of diabetes on orthodontic treatment. The quality of the case–control studies was assessed using the Newcastle–Ottawa Scale (NOS); for cross-sectional studies, the Joanna Briggs Institute (JBI) critical appraisal checklist was used; and for experimental studies, the SYRCLE’s Risk of Bias Tool was applied. Results: Fourteen studies ultimately met the inclusion criteria. The evidence showed that diabetes increases gingival bleeding due to elevated levels of advanced glycation end-products (AGEs) and pro-inflammatory cytokines; reduces the efficiency of tooth movement; increases root resorption and affects bone remodeling; and compromises both periodontal and pulpal responses, thereby hindering tissue regeneration. It was also observed that the use of insulin or antidiabetic agents such as metformin may partially mitigate these adverse effects. Conclusions: This systematic review reveals a clear relationship between diabetes and various clinical aspects that influence the progression of orthodontic treatments. Nonetheless, further studies are needed to better understand the impact of this systemic condition on dental treatment outcomes. Full article
(This article belongs to the Special Issue Orthodontics: State of the Art and Prospects)
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11 pages, 1939 KB  
Case Report
Delayed Management of Concurrent Coronal Extrusions and Root Fractures in Two Traumatized Maxillary Immature Permanent Central Incisors: A Case Study
by Thi Thuy Tien Vo and Thi Ngoc Anh Do
J. Clin. Med. 2025, 14(10), 3605; https://doi.org/10.3390/jcm14103605 - 21 May 2025
Cited by 2 | Viewed by 1848
Abstract
Background: The combination of two or more different types of traumatic dental injuries occurring concurrently to the same tooth presents a significant clinical challenge. By focusing on a rare combination of injuries, this case study explores the issues of delayed management of root [...] Read more.
Background: The combination of two or more different types of traumatic dental injuries occurring concurrently to the same tooth presents a significant clinical challenge. By focusing on a rare combination of injuries, this case study explores the issues of delayed management of root fractures accompanied by coronal extrusions in immature maxillary permanent central incisors, underscoring the necessity for tailored approaches when guidelines for intervention were unmet. Methods: The case involves an eight-year-old boy who delayed seeking care for approximately a year after suffering trauma to his upper front teeth in a fall accident at school. The clinical examination revealed partial displacement of two maxillary central incisors in an incisal direction, resulting in increased mobility. Radiographs further showed horizontal root fractures in the apical third of both extruded incisors. Encouragingly, the injured teeth exhibited a normal response to electric pulp testing without signs or symptoms of pulpal pathology, suggesting pulp vitality and eliminating the need for root canal treatment. The extruded coronal fragments were repositioned orthodontically using a utility arch. Results: At the 14-month follow-up, the affected incisors were clinically asymptomatic, functionally satisfactory, and esthetically pleasing. Conclusions: Conservative orthodontic management of extrusive luxation concomitant with root fracture in immature permanent teeth may prove effective in select cases, particularly when long-term follow-up and proper oral care are maintained. Full article
(This article belongs to the Section Clinical Pediatrics)
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12 pages, 4430 KB  
Article
Pulpal Responses to Leukocyte- and Platelet-Rich Plasma Treatment in Mouse Models for Immediate and Intentionally Delayed Tooth Replantation
by Angela Quispe-Salcedo, Kiyoko Suzuki-Barrera, Mauricio Zapata-Sifuentes, Taisuke Watanabe, Tomoyuki Kawase and Hayato Ohshima
Appl. Sci. 2024, 14(23), 11358; https://doi.org/10.3390/app142311358 - 5 Dec 2024
Viewed by 1459
Abstract
This study aimed to evaluate the effect of leukocyte and platelet-rich plasma (L-PRP) on the pulpal healing process following immediate and intentionally delayed tooth replantation in mice. After the maxillary first molars of 3-week-old mice were extracted, the teeth were immersed for 1 [...] Read more.
This study aimed to evaluate the effect of leukocyte and platelet-rich plasma (L-PRP) on the pulpal healing process following immediate and intentionally delayed tooth replantation in mice. After the maxillary first molars of 3-week-old mice were extracted, the teeth were immersed for 1 min [immediate reimplantation (IR)] or 30 min [intentionally delayed reimplantation (IDR)] in phosphate-buffered saline (PBS) solution. The alveolar socket was filled with or without 1.5 μL of L-PRP [experimental or control groups (EG or CG)] followed by tooth replantation. Samples were collected from day 1 to week 4 after the operation, processed for histology, and evaluated by immunohistochemistry for Nestin and Ki-67 expression. Quantitative analysis revealed positive Nestin staining during pulpal healing in the EG at week 1 following IR and week 2 following IDR. Hard tissue deposition was significantly increased in the EG after IR at week 2. Cell proliferation was higher in the EG compared with that in the CG at week 1 and significantly decreased in the coronal pulp of the EG after the IDR at week 2. Our data suggest that treatment with L-PRP may have a positive effect on pulpal healing, even in teeth replanted after an extended extra-oral period. Full article
(This article belongs to the Special Issue Advances in Dental Materials and Their Applications)
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19 pages, 11128 KB  
Article
Role of DDR1 in Regulating MMPs in External Root Resorption
by Yuhan Wang, Bing Han, Hongyan Tian, Kaining Liu and Xiaoyan Wang
Int. J. Mol. Sci. 2024, 25(22), 12111; https://doi.org/10.3390/ijms252212111 - 11 Nov 2024
Cited by 1 | Viewed by 1774
Abstract
Human periodontal ligament cells (hPDLCs) express matrix metalloproteinases (MMPs), a group of enzymes responsible for the destruction of most extracellular matrix proteins in dental tissues, especially MMP-1, MMP-2, and MMP-13. Exploring the regulatory mechanism of MMPs is crucial for understanding external root resorption [...] Read more.
Human periodontal ligament cells (hPDLCs) express matrix metalloproteinases (MMPs), a group of enzymes responsible for the destruction of most extracellular matrix proteins in dental tissues, especially MMP-1, MMP-2, and MMP-13. Exploring the regulatory mechanism of MMPs is crucial for understanding external root resorption (ERR), one of the most severe complications, along with substantial loss of dental tissue, induced by trauma, pulpal infection, tooth bleaching, and orthodontic treatment, etc. Discoidin domain receptor 1 (DDR1), a cell surface receptor binding to collagen, has the potential to regulate the expression of MMP-1, MMP-2, and MMP-13, but the mechanism remains unclear. Thus, the present study aimed to investigate the connection and underlying mechanism between MMP-1, MMP-2, MMP-13, and DDR1 in hPDLCs. Our post-replantation ERR model revealed that Mmp-1, Mmp-2, Mmp-13, and Ddr1 all increased in the sites of ERR. hPDLCs with DDR1 knockdown exhibited a substantial reduction in MMP-1, MMP-2, and MMP-13 expression. To further confirm the underlying mechanism, we conducted further in vitro experiments, including RNA sequencing, RNA interference, RT-qPCR, Western blotting, and ELISA. Based on our results, MMP-1 was positively regulated by the Smad2/3 and MEK-ERK1/2 pathways and negatively regulated by the PI3K-Akt pathway through CCN2. MMP-2 and MMP-13 were positively regulated by the Smad2/3 pathway. MMP-13 was positively regulated by the MEK-ERK1/2 and PI3K/Akt signaling pathways. Collectively, DDR1 is a potent regulator of MMP-1, MMP-2, and MMP-13 expression through the Smad2/3, MEK-ERK1/2, and PI3K/Akt signaling pathways. Clarifying the significance and underlying mechanism by which DDR1 is involved in ERR might bring the chances to hinder the pathogenic process of ERR, hence reducing its incidence rate. Full article
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
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16 pages, 3486 KB  
Article
Effects of Synthetic Toll-Like Receptor 9 Ligand Molecules on Pulpal Immunomodulatory Response and Repair after Injuries
by Angela Quispe-Salcedo, Tomohiko Yamazaki and Hayato Ohshima
Biomolecules 2024, 14(8), 931; https://doi.org/10.3390/biom14080931 - 1 Aug 2024
Cited by 3 | Viewed by 2031
Abstract
Synthetic oligodeoxynucleotides (ODNs) containing unmethylated cytosine–phosphate–guanine (CpG) motifs (CpG-ODNs) are ligand molecules for Toll-like receptor 9 (TLR9), which is expressed by odontoblasts in vitro and dental pulp cells. This study determined the effects of CpG-ODNs on pulpal immunomodulatory response and repair following injury. [...] Read more.
Synthetic oligodeoxynucleotides (ODNs) containing unmethylated cytosine–phosphate–guanine (CpG) motifs (CpG-ODNs) are ligand molecules for Toll-like receptor 9 (TLR9), which is expressed by odontoblasts in vitro and dental pulp cells. This study determined the effects of CpG-ODNs on pulpal immunomodulatory response and repair following injury. Briefly, the upper right first molars of three-week-old mice were extracted, immersed in Type A (D35) or B (K3) CpG-ODN solutions (0.1 or 0.8 mM) for 30 min, and then replanted. Pulpal healing and immunomodulatory activity were assessed by hematoxylin–eosin and AZAN staining, as well as immunohistochemistry. One week following the operation, inflammatory reactions occurred in all of the experimental groups; however, re-revascularization and newly formed hard tissue deposition were observed in the pulp chamber of all groups at week 2. A positive trend in the expression of immune cell markers was observed toward the CpG-ODN groups at 0.1 mM. Our data suggest that synthetic CpG-ODN solutions at low concentrations may evoke a long-lasting macrophage–TLR9-mediated pro-inflammatory, rather than anti-inflammatory, response in the dental pulp to modulate the repair process and hard tissue formation. Further studies are needed to determine the effects of current immunomodulatory agents in vitro and in vivo and develop treatment strategies for dental tissue regeneration. Full article
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16 pages, 16192 KB  
Article
Impaired Tertiary Dentin Secretion after Shallow Injury in Tgfbr2-Deficient Dental Pulp Cells Is Rescued by Extended CGRP Signaling
by Monica Stanwick, Fatma Fenesha, Ahmed Hamid, Khushroop Kang, Dane Kanniard, Irene Kim, Nicholas Mandarano, Fernanda L. Schumacher and Sarah B. Peters
Int. J. Mol. Sci. 2024, 25(13), 6847; https://doi.org/10.3390/ijms25136847 - 21 Jun 2024
Cited by 2 | Viewed by 2455
Abstract
The transforming growth factor β (TGFβ) superfamily is a master regulator of development, adult homeostasis, and wound repair. Dysregulated TGFβ signaling can lead to cancer, fibrosis, and musculoskeletal malformations. We previously demonstrated that TGFβ receptor 2 (Tgfbr2) signaling regulates odontoblast differentiation, [...] Read more.
The transforming growth factor β (TGFβ) superfamily is a master regulator of development, adult homeostasis, and wound repair. Dysregulated TGFβ signaling can lead to cancer, fibrosis, and musculoskeletal malformations. We previously demonstrated that TGFβ receptor 2 (Tgfbr2) signaling regulates odontoblast differentiation, dentin mineralization, root elongation, and sensory innervation during tooth development. Sensory innervation also modulates the homeostasis and repair response in adult teeth. We hypothesized that Tgfbr2 regulates the neuro-pulpal responses to dentin injury. To test this, we performed a shallow dentin injury with a timed deletion of Tgfbr2 in the dental pulp mesenchyme of mice and analyzed the levels of tertiary dentin and calcitonin gene-related peptide (CGRP) axon sprouting. Microcomputed tomography imaging and histology indicated lower dentin volume in Tgfbr2cko M1s compared to WT M1s 21 days post-injury, but the volume was comparable by day 56. Immunofluorescent imaging of peptidergic afferents demonstrated that the duration of axon sprouting was longer in injured Tgfbr2cko compared to WT M1s. Thus, CGRP+ sensory afferents may provide Tgfbr2-deficient odontoblasts with compensatory signals for healing. Harnessing these neuro-pulpal signals has the potential to guide the development of treatments for enhanced dental healing and to help patients with TGFβ-related diseases. Full article
(This article belongs to the Special Issue Molecular Advances in Dental Pulp Tissue Engineering, 2nd Edition)
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15 pages, 18831 KB  
Article
Effect of Simulated Dental Pulpal Pressure Using Fetal Bovine Serum for the Bonding Performance of Contemporary Adhesive to Dentin
by Yitong Li, Masahiko Maeno, Carolina Cecilia Cifuentes-Jimenez, Mei Komoto, Yunqing Liu, Yoichiro Nara, Hidehiko Sano, Pedro Alvarez-Lloret, Monica Yamauti and Atsushi Tomokiyo
Polymers 2024, 16(9), 1219; https://doi.org/10.3390/polym16091219 - 26 Apr 2024
Viewed by 1742
Abstract
This study evaluated the effect of simulated pulpal pressure (SPP) conditions and storage time on contemporary adhesive systems’ microtensile bond strength (µTBS) to dentin. Extracted human molars were prepared and randomly divided into four groups according to the adhesives: Clearfil Megabond 2 (CSE), [...] Read more.
This study evaluated the effect of simulated pulpal pressure (SPP) conditions and storage time on contemporary adhesive systems’ microtensile bond strength (µTBS) to dentin. Extracted human molars were prepared and randomly divided into four groups according to the adhesives: Clearfil Megabond 2 (CSE), Beautibond Xtreme Universal (BXU), G2-Bond (G2B), and Scotchbond Universal Plus (SBP). Each adhesive group was further divided following the SPP conditions: control with no simulation (SPP-CTR), SPP with distilled water (SPP-DTW), and SPP with fetal bovine serum (SPP-FBS). Resin composite build-ups were prepared, and teeth were stored in water (37 °C) for 24 h (24 h) and 3 months (3 m). Then, teeth were sectioned to obtain resin–dentin bonded beams and tested to determine the µTBS. Data were analyzed using three-way ANOVA, Tukey post hoc tests (=0.05), and Weibull failure analysis. Failure mode was observed using scanning electron microscopy. The µTBS response was affected by adhesive systems, simulated pulpal pressure conditions, and storage time. SPP-CTR groups presented a higher overall bond strength than SPP-DTW and SPP-FBS, which were not significantly different from each other. Only for SBP, the SPP-FBS group showed higher µTBS than the SPP-DTW group. The Weibull analysis showed that the bonding reliability and durability under SPP-DTW and SPP-FBS were inferior to SPP-CTR, and the 24 h bonding quality of adhesives to dentin was superior to that of 3 m. SPP drastically reduced the µTBS of all adhesives to dentin regardless of solution (distilled water or fetal bovine serum). Storage after 3 m also decreased µTBS despite the SPP condition. Full article
(This article belongs to the Special Issue Polymers Strategies in Dental Therapy)
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17 pages, 881 KB  
Article
Evaluating Knowledge, Self-Reported Confidence Levels, and Prescription Patterns among Dental Practitioners Regarding Analgesics in Dentistry: A Cross-Sectional Study
by Marija Badrov and Antonija Tadin
Medicina 2024, 60(3), 467; https://doi.org/10.3390/medicina60030467 - 12 Mar 2024
Cited by 2 | Viewed by 2675
Abstract
Background and Objectives: Dental pain is a common problem that often leads to unscheduled dental visits and requires a comprehensive understanding of analgesics, including their indications and contraindications. The aim of this study was to investigate dentists’ knowledge, self-reported confidence levels, and [...] Read more.
Background and Objectives: Dental pain is a common problem that often leads to unscheduled dental visits and requires a comprehensive understanding of analgesics, including their indications and contraindications. The aim of this study was to investigate dentists’ knowledge, self-reported confidence levels, and prescribing patterns of analgesics in dentistry. Materials and Methods: A nationwide cross-sectional online survey was conducted, resulting in 379 responses. Of these, 68.6% were general dentists, and 31.4% were specialists. The collected data included sociodemographic information, levels of knowledge, and prescription patterns. The survey questionnaire explored self-perceived practices, patient information during prescription, and guiding factors. Descriptive statistics and a generalized linear model for regression were used for data analysis. Results: Higher levels of knowledge were observed in specific contexts such as secondary/tertiary healthcare (p = 0.022), specialization in endodontics (p = 0.003), and a higher number of working hours with patients (p = 0.038). Conversely, increased self-confidence was observed among endodontists (p = 0.008), oral surgeons (p = 0.011), and dentists with more than 6 h of patient interaction (p ≤ 0.001). Orthodontists and prosthodontists demonstrated lower knowledge levels, while specialists in family dentistry exhibited lower self-confidence. Self-confidence and knowledge displayed a significant positive correlation (r = 0.039, p < 0.001). The most frequently prescribed medication was ibuprofen (97.9%), primarily for surgical (83.9%) and endodontic procedures (60.9%), with the main indications being pulpal (85.8%), periradicular (57.3%), and postoperative pain (40.1%). Conclusions: This study reveals significant knowledge and confidence gaps among dentists, including limited awareness of the efficacy of nonsteroidal anti-inflammatory drugs for odontogenic pain, a lack of time for effective counseling, and perceived deficits in pharmacology education. To address these issues, targeted educational interventions are recommended to improve analgesic prescribing practice, close knowledge gaps, and increase dentists’ confidence in more effective pain management. Full article
(This article belongs to the Section Dentistry and Oral Health)
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Article
The Reparative Function of MMP13 in Tertiary Reactionary Dentinogenesis after Tooth Injury
by Henry F. Duncan, Yoshifumi Kobayashi, Yukako Yamauchi and Emi Shimizu
Int. J. Mol. Sci. 2024, 25(2), 875; https://doi.org/10.3390/ijms25020875 - 10 Jan 2024
Cited by 1 | Viewed by 2441
Abstract
MMP13 gene expression increases up to 2000-fold in mineralizing dental pulp cells (DPCs), with research previously demonstrating that global MMP13 deletion resulted in critical alterations in the dentine phenotype, affecting dentine–tubule regularity, the odontoblast palisade, and significantly reducing the dentine volume. Global MMP13-KO [...] Read more.
MMP13 gene expression increases up to 2000-fold in mineralizing dental pulp cells (DPCs), with research previously demonstrating that global MMP13 deletion resulted in critical alterations in the dentine phenotype, affecting dentine–tubule regularity, the odontoblast palisade, and significantly reducing the dentine volume. Global MMP13-KO and wild-type mice of a range of ages had their molar teeth injured to stimulate reactionary tertiary dentinogenesis. The response was measured qualitatively and quantitatively using histology, immunohistochemistry, micro-CT, and qRT-PCR in order to assess changes in the nature and volume of dentine deposited as well as mechanistic links. MMP13 loss affected the reactionary tertiary dentine quality and volume after cuspal injury and reduced Nestin expression in a non-exposure injury model, as well as mechanistic links between MMP13 and the Wnt-responsive gene Axin2. Acute pulpal injury and pulp exposure to oral fluids in mice teeth showed upregulation of the MMP13 in vivo, with an increase in the gene expression of Mmp8, Mmp9, and Mmp13 evident. These results indicate that MMP13 is involved in tertiary reactionary dentine formation after tooth injury in vivo, potentially acting as a key molecule in the dental pulp during dentine–pulp repair processes. Full article
(This article belongs to the Special Issue The MMPs and Its Associated Proteins and Substrates on the Cell)
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