Journal of dental research最新文献

Due to the multiple factors contributing to dentin demineralization and hypersensitivity among individuals, the effectiveness of the available treatments in the long term remains unclear. A recent study reported a simple strategy to potentially mimic natural remineralization with increased crystallization on the enamel caries using fluoride iontophoresis. Such an effect is also ideal for accomplishing dentin biomineralization and structural strength. This study aimed to investigate structural and compositional characteristics and permeability changes after fluoride iontophoresis with different polarities, cathodal iontophoresis (CIP), anodal iontophoresis (AIP), and the control without iontophoresis for the treatment of etched dentin under simulated pulpal pressure. The 24 premolars were divided into 3 groups: CIP, AIP, and topical application of 5% sodium fluoride (NaF) for 40 s. Relative to before treatment, iontophoresis with both polarities significantly decreased the permeability with a visible increase in occluding tubules containing crystal formation and growth throughout the dentin structure and depth. The CIP not only restored the etched dentin surface into a sound condition but also reinforced the dentin across the structure and depth by the synergistic effects of remineralization, increasing crystal formation and transformation toward the more crystalline structure of fluorohydroxyapatite. Following topical treatment, X-ray diffraction analysis and Raman spectra revealed a significant reduction in the crystal size and crystallinity associated with the raised B-type carbonate substitution into the hydroxyapatite compared with that in the sound dentin. The result was the first to reveal the ideal strategy to rapidly restore the etched dentin surface into a sound condition, including reinforcing the dentin across the structure and depth by the synergistic effects of decreasing permeability, increasing crystal formation, and transformation toward the more crystalline structure of fluorohydroxyapatite using the 5% NaF applied with the DC cathode iontophoresis. The technique is noninvasive and simple and deserves further development for clinical application.

Computer-aided design (CAD)/computer-aided manufacturing (CAM) milling and handpiece grinding are critical procedures in the fabrication and adjustment of ceramic dental restorations. However, due to the formation of microfractures, these procedures are detrimental to the strength of ceramics. This study analyzes the damage associated with current brittle-regime grinding and presents a potential remedy in the application of a safer yet still efficient grinding regime known as "ductile-regime grinding." Disc-shaped specimens of a lithium disilicate glass-ceramic material (IPS e.max CAD) were obtained by cutting and crystallizing the lithium metasilicate CAD/CAM blanks (the so-called blue blocks) following the manufacturer's instructions. The discs were then polished to a 1 µm diamond suspension finish. Single-particle micro-scratch tests (n = 10) with a conical diamond indenter were conducted to reproduce basic modes of deformation and fracture. Key parameters such as coefficient of friction and penetration depth were recorded as a function of scratch load. Further, biaxial flexure strength tests (n = 6) were performed after applying various scratch loads to analyze their effects on ceramic strength. Scanning electron microscopy (SEM) and focused ion beam (FIB) were used to characterize surface and subsurface damage. Statistical analysis was performed using one-way analysis of variance and Tukey tests. While the SEM surface analysis of scratch tracks revealed the occurrence of both ductile and brittle removal modes, it failed to accurately determine the threshold load for the brittle-ductile transition. The threshold load for brittle-ductile transition was determined to be 70 mN based on FIB subsurface damage analyses in conjunction with strength degradation studies. Below 70 mN, the specimens exhibited neither strength degradation nor the formation of subsurface cracks. Determination of the brittle-ductile thresholds is significant because it sets a foundation for future research on the feasibility of implementing ductile-regime milling/grinding protocols for fabricating damage-free ceramic dental restorations.

Inflammation and loss of articular cartilage are considered the major cause of temporomandibular joint osteoarthritis (TMJOA), a painful condition of the temporomandibular joint (TMJ). To determine the cause of TMJ osteoarthritis in these patients, synovial fluid of TMJOA patients was compared prior to and after hyaluronic lavage, revealing substantially elevated levels of interleukin (IL) 1β, reactive oxidative stress (ROS), and an overload of Fe³⁺ and Fe²⁺ prior to lavage, indicative of ferroptosis as a mode of chondrocyte cell death. To ask whether prolonged inflammatory conditions resulted in ferroptosis-like transformation in vitro, we subjected TMJ chondrocytes to IL-1β treatment, resulting in a shift in messenger RNA sequencing gene ontologies related to iron homeostasis and oxidative stress-related cell death. Exposure to rat unilateral anterior crossbite conditions resulted in reduced COL2A1 expression, fewer chondrocytes, glutathione peroxidase 4 (GPX4) downregulation, and 4-hydroxynonenal (4-HNE) upregulation, an effect that was reversed after intra-articular injections of the ferroptosis inhibitor ferrostatin 1 (Fer-1). Our study demonstrated that ferroptosis conditions affected mitochondrial structure and function, while the inhibitor Fer-1 restored mitochondrial structure and the inhibition of hypoxia-inducible factor 1α (HIF-1α) or the transferrin receptor 1 (TFRC) rescued IL-1β-induced loss of mitochondrial membrane potential. Inhibition of HIF-1α downregulated IL-1β-induced TFRC expression, while inhibition of TFRC did not downregulate IL-1β-induced HIF-1α expression in chondrocytes. Moreover, inhibition of HIF-1α or TFRC downregulated the IL-1β-induced MMP13 expression in chondrocytes, while inhibition of HIF-1α or TFRC rescued IL-1β-inhibited COL2A1 expression in chondrocytes. Furthermore, upregulation of TFRC promoted Fe²⁺ entry into chondrocytes, inducing the Fenton reaction and lipid peroxidation, which in turn caused ferroptosis, a disruption in chondrocyte functions, and an exacerbation of condylar cartilage degeneration. Together, these findings illustrate the far-reaching effects of chondrocyte ferroptosis in TMJOA as a mechanism causing chondrocyte death through iron overload, oxidative stress, and articular cartilage degeneration and a potential major cause of TMJOA.

We aimed to evaluate the impact of 2 visual diagnostic strategies for assessing secondary caries and managing permanent posterior restorations on long-term survival. We conducted a diagnostic cluster-randomized clinical trial with 2 parallel groups using different diagnostic strategies: (C+AS) based on caries assessment, marginal adaptation, and marginal staining aspects of the FDI (World Dental Federation) criteria and (C) based on caries assessment using the Caries Associated with Restorations or Sealants (CARS) criteria described by the International Caries Detection and Assessment System (ICDAS). The treatment for the restoration was conducted based on the decision made following the allocated diagnostic strategy. The restorations were then clinically reevaluated for up to 71 mo. The primary outcome was restoration failure (including tooth-level failure: pain, endodontic treatment, and extraction). Cox regression analyses with shared frailty were conducted in the intention-to-treat population, and hazard ratios (HRs) and 95% confidence intervals (95% CIs) were derived. We included 727 restorations from 185 participants and reassessed 502 (69.1%) restorations during follow-up. The evaluations occurred between 6 and 71 mo. At baseline, C led to almost 4 times fewer interventions compared with the C+AS strategy. A total of 371 restorations were assessed in the C group, from which 31 (8.4%) were repaired or replaced. In contrast, the C+AS group had 356 restorations assessed, from which 113 (31.7%) were repaired or replaced. During follow-up, 34 (9.2%) failures were detected in the restorations allocated to the C group and 30 (8.4%) allocated to the C+AS group in the intention-to-treat population, with no significant difference between the groups (HR = 0.83; 95% CI = 0.51 to 1.38; P = 0.435, C+AS as reference). In conclusion, a diagnostic strategy focusing on marginal defects results in more initial interventions but does not improve longevity over the caries-focused strategy, suggesting the need for more conservative approaches.

Scleroderma (systemic sclerosis, SSc) is an autoimmune fibrosing connective tissue disease of unknown etiology. SSc patients show increased levels of autoantibodies, profibrotic cytokines, and extracellular matrix remodeling enzymes that collectively cause activated (myo)fibroblasts, the effector cell type of fibrosis. Despite these impacts, no disease-modifying therapy exists; individual symptoms are treated on a patient-to-patient basis. SSc research has been principally focused on symptoms observed in the lung and skin. However, SSc patients display significant oral complications that arise due to fibrosis of the not only skin, causing microstomia, but also the gastrointestinal tract, causing acid reflux, and the oral cavity itself, causing xerostomia and gingival recession. Due to these complications, SSc patients have impaired quality of life, including periodontitis, tooth loss, reduced tongue mobility, and malnutrition. Indeed, due to their characteristic oral presentation, SSc patients are often initially diagnosed by dentists. Despite their clinical importance, the oral complications of SSc are severely understudied; high-quality publications on this topic are scant. However, SSc patients with periodontal complications possess increased levels of matrix metalloproteinase-9 and chemokines, such as interleukin-6 and chemokine (C-X-C motif) ligand-4. Although many unsuccessful clinical trials, mainly exploring the antifibrotic effects of anti-inflammatory agents, have been conducted in SSc, none have used oral symptoms, which may be more amenable to anti-inflammatory drugs, as clinical end points. This review summarizes the current state of knowledge regarding oral complications in SSc with the goal of inspiring future research in this extremely important and underinvestigated area.

Head and neck cancer (HNC) is the sixth most diagnosed cancer, and treatment typically consists of surgical removal of the tumor followed by ionizing radiation (IR). While excellent at controlling tumor growth, IR often damages salivary glands due to their proximity to common tumor sites. Radiation damage to salivary glands results in loss of secretory function, causing severe and chronic reductions in salivary flow. This leads to the patient-reported sensation of dry mouth, termed xerostomia, which significantly reduces quality of life for HNC patients and survivors. The mechanisms underlying salivary gland damage remain elusive, and therefore, treatment options are scarce. Available therapies provide temporary symptom relief, but there is no standard of care for permanent restoration of function. There is a significant gap in understanding the chronic mechanistic responses to radiation as well as treatments that can be given in the months to years following cessation of treatment. HNC cases are steadily rising; particularly, the number of young patients diagnosed with nonfatal human papillomavirus + HNC continues to increase. The growing number of HNC diagnoses and improved prognoses results in more people living with xerostomia, which highlights the mounting need for restorative treatments. Mechanisms underlying chronic damage include decreases in acinar differentiation markers, increases in acinar cell proliferation, immune and inflammatory dysregulation, and metabolic changes including increases in amino acids and reductions in glycolysis and oxidative phosphorylation, fibrosis, and dysregulated neuronal responses. Currently, promising treatment options include adenoviral gene transfers and stem cell therapy. Thus, this review describes in depth known mechanisms contributing to chronic damage and discusses therapeutic advances in treating chronically damaged glands. Understanding the chronic response to radiation offers potential in development of new therapeutics to reverse salivary gland damage and improve the quality of life of HNC survivors.

After nasal bone fractures, fractures of the mandible are the most frequently encountered injuries of the facial skeleton. Accurate identification of fracture locations is critical for effectively managing these injuries. To address this need, JawFracNet, an innovative artificial intelligence method, has been developed to enable automated detection of mandibular fractures in cone-beam computed tomography (CBCT) scans. JawFracNet employs a 3-stage neural network model that processes 3-dimensional patches from a CBCT scan. Stage 1 predicts a segmentation mask of the mandible in a patch, which is subsequently used in stage 2 to predict a segmentation of the fractures and in stage 3 to classify whether the patch contains any fracture. The final output of JawFracNet is the fracture segmentation of the entire scan, obtained by aggregating and unifying voxel-level and patch-level predictions. A total of 164 CBCT scans without mandibular fractures and 171 CBCT scans with mandibular fractures were included in this study. Evaluation of JawFracNet demonstrated a precision of 0.978 and a sensitivity of 0.956 in detecting mandibular fractures. The current study proposes the first benchmark for mandibular fracture detection in CBCT scans. Straightforward replication is promoted by publicly sharing the code and providing access to JawFracNet on grand-challenge.org.

Multiple genetic and environmental etiologies contribute to the pathogenesis of cleft palate, which is the most common of the inherited disorders of the craniofacial complex. Insights into the molecular mechanisms regulating osteogenic differentiation and patterning in the palate during embryogenesis are limited and needed for the development of innovative diagnostics and cures. This study used the Pax9^-/- mouse model with a consistent phenotype of cleft secondary palate to investigate the role of Pax9 in the process of palatal osteogenesis. Although prior research has identified the upregulation of Wnt pathway modulators Dkk1 and Dkk2 in Pax9^-/- palate mesenchyme, limitations of spatial resolution and technology restricted a more robust analysis. Here, data from single-nucleus transcriptomics and chromatin accessibility assays validated by in situ highly multiplex targeted single-cell spatial profiling technology suggest a distinct relationship between Pax9+ and osteogenic populations. Loss of Pax9 results in spatially restricted osteogenic domains bounded by Dkk2, which normally interfaces with Pax9 in the mesenchyme. Moreover, the loss of Pax9 leads to a disruption in the normal osteodifferentiaion of palatal osteogenic mesenchymal cells. These results suggest that Pax9-dependent Wnt signaling modulators influence osteogenic programming during palate formation, potentially contributing to the observed cleft palate phenotype.