Periodontitis and periapical periodontitis have a high incidence rate and often result in the progressive absorption of alveolar bone. This is one of the main causes of tooth loosening and loss. Prolonged local inflammation leads to the proliferation of capillaries, fibroblasts, and inflammatory cells such as neutrophils and lymphocytes. This process results in the replacement of surrounding bone tissue with inflammatory granulation tissue. Traditionally, it has been advocated that inflammatory granulation tissue is pathological and should be completely removed from the extraction socket to avoid complications such as bleeding, infection, and poor bone healing after tooth extraction. Although the regenerative capacity of inflammatory granulation tissue is reduced, it can be enhanced by increasing the body’s immunity or by eliminating pathogenic stimuli (such as tooth extraction and root canal treatment). As a result, the fibrous components in the inflammatory granulation tissue gradually increase, while infiltrating inflammatory cells gradually decrease. Ultimately, this transformation leads to the formation of reparative granulation tissue, followed by ossification. Furthermore, the use of granulation tissue from the tooth extraction socket for immediate implantation to facilitate wound closure or soft tissue reconstruction has yielded favorable clinical outcomes, and histological studies simultaneously confirmed the presence of mesenchymal stem cells within the inflammatory granulation tissue. Therefore, it is necessary to reconsider the traditional belief that inflammatory granulation tissue must be completely removed. Given the potential of inflammatory granulation tissue to undergo osteogenic transformation under appropriate interventions, regulating the transformation of inflammatory granulation tissue into reparative granulation tissue with osteogenic potential represents a novel strategy for the regenerative treatment of dental alveolar inflammatory lesions. This approach holds broad clinical application prospects and is an important research direction for the future. Reactive oxygen species, NOD-like receptor protein 3, and matrix metalloproteinase K are key regulatory factors involved in the transformation of inflammatory granulation tissue into reparative granulation tissue. Furthermore, bone morphogenetic protein 2 and vascular endothelial growth factor are key regulatory factors involved in the osteogenic regeneration of reparative granulation tissue. However, the molecular mechanisms of these regulatory factors remain unclear; therefore, elucidating their molecular mechanisms will help identify suitable targets for promoting the regeneration of dental alveolar inflammatory lesions. Furthermore, this will contribute to the development of related biological treatment technologies and drugs, which may ultimately provide a more minimally invasive and effective treatment for inflammatory lesions of alveolar bone. However, it is important to note that research in this field is still in its early stages. There is still considerable progress to be made before clinical translation and application can be achieved.
Objective To investigate the effect of calcium ions on the expression of kallikrein-4 (KLK4) and cell growth of ameloblast, and to provide an experimental basis for calcium ion promoting normal mineralization of enamel. Methods ALC cells were treated with 0, 2.0, 2.5, 3.0, and 3.5 mmol/L CaCl2 for 24 and 48 h. KLK4 expression was analyzed by qRT-PCR and Western blot analysis. The viability of ALC cells was determined by using CCK-8. AnnexinV-FITC/PI dual staining combined with flow cytometry and Hoechst 33342 staining were used to detect the ALC cell cycle and cell apoptosis. The protein expression level of glucose-regulated protein 78 (GRP78) was measured by Western blot analysis. Results After 24 h of treatment with 2.5, 3.0, and 3.5 mmol/L CaCl2, the expression of KLK4 mRNA was increased (P<0.05), and after 24 h of treatment with 2.0, 2.5, 3.0, and 3.5 mmol/L CaCl2, the expression of KLK4 protein was increased (P<0.05). After 48 h of treatment with 3.0 mmol/L and 3.5 mmol/L CaCl2, the expression of KLK4 mRNA and protein was increased (P<0.05). Compared with the control group, the viability of ALC cells was increased after 24 and 48 h of treatment with 2.0, 2.5, and 3.0 mmol/L CaCl2 (P<0.05), and the highest cell viability was observed with 2.5 mmol/L CaCl2. Hoechst 33342 staining results showed that 3.0 mmol/L and 3.5 mmol/L CaCl2 may promote apoptosis in ALC cells. Flow cytometry showed that the proportion of G2/M phase cells and the apoptosis rate increased after 3.5 mmol /L CaCl2 treatment for 24 h (P<0.05), compared with the 0, 2.0, 2.5, and 3.0 mmol/L CaCl2 groups. After 24 h of treatment with 3.0 mmol/L and 3.5 mmol/L CaCl2, the expression of GRP78 protein was reduced (P<0.05), and after 48 h of treatment with 2.5 mmol/L CaCl2, the expression of GRP78 protein was reduced (P<0.05). Conclusion Calcium ions can promote the increase of KLK4 expression and cell viability in ALC cells, but a higher concentration of calcium ions can block the G2/M phase of ALC cells, thus inducing apoptosis of ALC cells and reducing the expression of apoptosation-related protein GRP78.
Objective To investigate the effect of the Piezo1 channel on tension-side angiogenesis and osteogenic remodeling during orthodontic tooth movement, so as to provide an experimental basis for accelerating orthodontic periodontal tissue remodeling. Methods This study was approved by the Animal Ethics Committee. Sixty healthy male Sprague-Dawley rats with bilateral maxillary incisors as the anchorage were selected, and nickel titanium tension springs were used to apply 0.5 N of force to the right maxillary first molar of the rats and construct an orthodontic tooth movement model. The rats were randomly divided into three groups (n = 20 per group). On Days 0 and 8 of force application, equal volumes of saline (control group), 100 μmol/L Piezo1 channel agonist (Yoda1 group), and 48 μmol/L Piezo1 channel inhibitor (GsMTx4 group) were injected into the buccal and palatal submucosa of the right maxillary first molar. Tooth movement distances were recorded on Days 1, 3, 7, and 14. Five rats from each group were sacrificed at each time point to obtain maxillary tissue samples. Hematoxylin and eosin (HE) staining was performed to observe the histophysiological changes in the tension-side periodontal tissues. Immunohistochemical staining was used to mark and count CD31-positive cells (microvascular quantification) and to detect the expression of osteocalcin (OCN) in the tension side. Results Measurements of tooth movement distance showed that the Yoda1 group exhibited significantly increased tooth movement distances on Days 3, 7, and 14 (0.238 ± 0.008 mm, 0.406 ± 0.011 mm, and 0.746 ± 0.013 mm, respectively) compared to the control group (P<0.05). In contrast, the GsMTx4 group showed significantly reduced tooth movement distances on Day 7 (0.282 ± 0.011 mm) and Day 14 (0.578 ± 0.008 mm) compared to the control group (P<0.05). HE staining results indicated that the periodontal ligament space on the tension side gradually widened with the duration of force application and then gradually returned to normal, with visible osteoblasts. Quantitative analysis of CD31-positive cells (microvascular quantification) showed that the Yoda1 group had significantly increased numbers of blood vessels on Day 3 (8.027 ± 0.225) and Day 7 (14.320 ± 0.471) compared to the control group (P<0.05), peaking on Day 7 and then gradually decreasing. The GsMTx4 group showed significantly fewer blood vessels in the periodontal ligament on the tension side on Day 3 (6.013 ± 0.177), Day 7 (9.187 ± 0.678), and Day 14 (12.613 ± 0.334) compared to the control group (P<0.05). Immunohistochemical results indicated that the Yoda1 group had significantly increased OCN expression on Days 1, 3, 7, and 14 compared to the control group (P<0.05), while the GsMTx4 group showed reduced OCN expression on Days 7 and 14 (P<0.05). Conclusion Activation of the Piezo1 channel promotes orthodontic tooth movement, tension-side angiogenesis, and osteogenic remodeling, while inhibition of the Piezo1 channel produces the opposite effect.
Objective To investigate the expression of trophoblast cell-surface antigen 2 (TROP2) in salivary adenoid cystic carcinoma (SACC) in order to analyze its relationship with TROP2 expression and clinicopathological features, as well as to clarify the correlation between TROP2 expression and the prognosis of patients with SACC. Methods With approval from the ethics committee, the expression of TROP2 in 85 SACC and paracancer tissue samples was detected by using the immunohistochemical method, and the relationship between TROP2 expression and clinicopathological characteristics was analyzed. The Kaplan-Meier method was used to analyze the relationship between TROP2 protein expression and 5-year disease-free survival (DFS) in 40 patients with SACC. Furthermore, the logistic regression model was used to analyze the prognostic factors of patients with SACC. Results The low or no expression rate of TROP2 in SACC tissues was significantly higher than that in paracancer tissues (P<0.001). Low or no expression of TROP2 was significantly positively correlated with tumor growth and clinical staging in patients with SACC (P<0.05). Kaplan-Meier survival analysis showed that the DFS of patients with SACC with low or no expression of TROP2 protein was significantly lower than those of patients with high expression of TROP2 protein (P<0.05), and the prognosis was poor. The logistic regression model showed that low or no expression of TROP2 protein (OR = 5.37; 95% CI: 1.03-28.08; P = 0.046) and Ⅲ-Ⅳ clinical staging (OR = 6.89; 95%CI: 1.37~34.77; P = 0.019) were risk factors affecting the prognosis of patients with SACC. Conclusion Low or no expression of TROP2 protein in SACC tissues leads to poor prognosis of patients and is positively correlated with tumor growth and clinical staging. In addition, low or no expression of TROP2 can be used as an independent prognostic risk factor for poor prognosis in patients with SACC, and TROP2 is a marker of poor prognosis in patients with SACC.
Objective To investigate the clinical characteristics and prognosis of crown fractures in immature permanent incisors due to trauma, and identify factors affecting their prognosisto provide a reference for clinical treatment. Methods This study was approved by the Medical Ethics Committee of West China Stomatology Hospital, Sichuan University. The study subjects were patients admitted to the pediatric stomatology department from December 2011 to December 2021, and a retrospective analysis was conducted on young permanent teeth with anterior crown fracture caused by injury and followed up for at least 1 year, which were diagnosed as enamel fractures, enamel-dentin fractures, and complicated crown fracture and treated by observation, pulpotomy etc. in the first appointment. The age, sex and time elapsed from trauma to baseline visit of the patients and the location, mobility, stage of root development, diagnosis and treatments were collected. The occurrence of pulp infection, pulp necrosis, and other events in the affected tooth is defined as clinical failure. Record whether clinical failure occurred and the timing of their occurrence of the traumatized tooth. Analyze factors related to the prognosis of various types of crown fractures in young permanent incisors and performsurvival analysis on the affected teeth. Results Among 358 cases of young permanent incisors, 50 cases were diagnosed with enamel fracture, 176 cases with enamel-dentin fracture, and 132 cases with complicated crown fracture. The clinical success rate of crown fractures was 73.7% (264/358) in young permanent incisors. The incidence rates of clinical failure cases, including pulp infection and necrosis, were 4% (2/50) for enamel fractures, 33.3% (58/176) for enamel-dentin fractures, and 25.8% (34/132) for complicated crown fractures respectively. The clinical failure rate of enamel-dentin fracture treated with indirect pulp capping and restoration was higher than restoration only and pulpotomy (χ2 = 10.077, P = 0.004). The clinical failure rate of complicated crown fractures treated with direct pulp capping was higher than pulpotomy (χ2 = 5.501, P = 0.038). The clinical failure rates between observation, smoothing edges and restoration of enamel fractures exhibit no significant differences (χ2 = 0.588, P = 0.999). Risk factors for clinical failure in this study population included patient age over 9 years old (HR = 2.11, 95%CI: 1.1-3.9, P = 0.017)、time elapsed from trauma to baseline visit greater than 3 days (HR = 2.3, 95%CI: 1-4.8, P = 0.028), traumatized teeth with mobility (HR = 1.95, 95%CI: 1.2-3, P = 0.004), enamel-dentin fractures treated with restoration (HR = 6.89, 95%CI: 1.6-29.6, P = 0.010), enamel-dentin fractures treated with indirect pulp capping and restoration (HR = 13.8, 95%CI: 3.2-58.3, P<0.001) and complicated crown fractures treated with direct pulp capping (HR = 46.07, 95%CI: 8-263.8, P<0.001). Conclusion Enamel fractures treated by observation, smoothing edges and restoration, and complicated crown fractures treated with pulpotomy generally had a good prognosis in young permanent incisors. Close follow-up was recommended for crown fractures in young permanent incisors with identified risk factors for poor prognosis.
Objective To explore the influence of apical dense bone islands on tooth movement during orthodontic treatment and its complications, and to provide a reference for orthodontic clinical treatment. Methods This study obtained approval from the hospital ethics committee. A retrospective analysis was conducted on 33 patients with apical dense bone islands who received full-mouth fixed orthodontic treatment in the Orthodontics Department of Huizhou Stomatological Hospital from 2018 to 2022. Cone-beam CT (CBCT) was used to determine the location, distribution, and wrapping severity of the apical dense bone islands before treatment. The number of loose teeth located in the apical dense bone islands and the degree of external apical root resorption in the apical area of teeth were analyzed before treatment, immediately after treatment, and 12 months after treatment. Results There were 33 orthodontic patients (aged 11 to 42 years, with an average age of 16.7 years and a median age of 15 years) included in this study, including 12 males (36.4%) and 21 females (63.6%). All apical dense bone islands involved a single tooth located in the mandible, mainly in the premolar-molar area. No gender differences were present in the location of the dense bone islands (P>0.05). The apical dense bone islands were mildly wrapped in 23 cases (69.7%), moderately wrapped in 10 cases (30.3%), and severely wrapped in no cases. No difficulty in tooth movement or incomplete closure of extraction space was found in the apical dense bone islands with different degrees of wrapping during orthodontic treatment. For teeth located in apical dense bone islands, 1 patient (3.0%) had loose teeth before treatment, 6 patients (18.2%) had loose teeth after treatment, and 2 patients (6.1%) had loose teeth 12 months after treatment. The number of patients with grade I loose teeth increased after treatment and 12 months after treatment. There was a statistically significant difference in the number of loose teeth before and after treatment (P<0.05), no statistically significant difference in the number of loose teeth before treatment and 12 months after treatment (P>0.05), and no statistically significant difference in the number of loose teeth after treatment and 12 months after treatment (P>0.05). After treatment, apical dense bone islands showed mild resorption in 26 cases (78.8%), moderate resorption in 7 cases (21.2%), and severe resorption in no cases. The apical dense bone islands showed mild resorption in 25 cases (75.8%), moderate resorption in 8 cases (24.2%), and severe resorption in no cases 12 months after treatment. For the severity of root resorption, there was a statistically significant difference between before and after treatment (P<0.05) as well as between before treatment and 12 months after treatment (P<0.05). However, no statistically significant difference was observed between after treatment and 12 months after treatment (P>0.05). Conclusion Apical dense bone islands were not found to affect tooth movement during orthodontic treatment. After orthodontic treatment, the number of loose teeth increased and mild-to-moderate tooth external apical root resorption occurred, which may be a potential risk of external apical root resorption. Thus, it is recommended to pay close attention during the orthodontic process.
Objective To study the effect of deep learning applied to the assisted diagnosis of radiolucent lesions and radiopaque lesions of the jaws in panoramic radiography and to reduce the missed diagnosis, with early screening to assist doctors to improve the diagnostic accuracy. Methods This study was approved by the Ethics Committee of the West China Stomatological Hospital of Sichuan University. The YOLO v8m-p2 neural network model was constructed with 443 panoramic images as a subject to read. The labeled images were divided into 354 training sets, 45 verification sets, and 44 test sets, which were used for model training, verification, and testing. Accuracy, recall, F-1 score, G score, and mAP50 were used to evaluate the detection performance of the model. Results 443 panoramic images covered the common benign lesions of the jaw, the number of radiolucent lesions of the jaw was 318, containing dentigerous cyst, odontogenic keratocyst, and ameloblastoma. The number of radiopaque lesions was 145, containing idiopathic osteosclerosis, odontoma, cementoma, and cemento-osseous dysplasia; the samples are well representative. The accuracy of the YOLO v8m-p2 neural network model in identifying jaw lesions was 0.887, and the recall, F-1 score, G score, and mAP50 were 0.860, 0.873, 0.873, and 0.863, respectively. The recall rates of dentigerous cyst, odontogenic keratocyst, and ameloblastoma were 0.833, 0.941, and 0.875, respectively. Conclusion YOLO v8m-p2 neural network model has good diagnostic performance in preliminary detection of radiolucent and radiopaque lesions of the jaws in panoramic radiography and multi-classification monitoring of radiolucent lesions of jaws, which can assist doctors to screen jaw diseases in panoramic radiography.
Alzheimer’s disease (AD), a common neurodegenerative disease, has been linked to periodontitis, especially Porphyromonas gingivalis (P. gingivalis) infection. This review summarizes the potential mechanisms and pathways through which P. gingivalis and its virulence factors are involved in AD pathogenesis, aiming to provide the scientific basis for the development of novel prevention and treatment strategies for AD. P. gingivalis can promote AD by exacerbating neuroinflammation, facilitating amyloid beta and Tau deposition, and disrupting the blood-brain barrier. Gingipains, secreted by P. gingivalis, serve as core effector molecules by increasing the blood-brain barrier permeability. The association between P. gingivalis and its effectors and AD pathology has been validated by metagenomic analysis and sample detection, indicating that P. gingivalis may be an environmental susceptibility factor or modifiable risk factor for AD. However, the precise mechanisms by which P. gingivalis influences AD, and its interactions with other potential AD-related factors, remain unclear. Moreover, further research needs to be conducted on the therapeutic potential of P. gingvalis intervention in improving AD.
Bone diseases, such as osteoporosis and osteoarthritis, have emerged as pressing public health concerns requiring immediate attention and resolution. Cellular therapy and tissue engineering techniques are among the most promising therapeutic approaches for such conditions. Human induced pluripotent stem cells (hiPSCs) possess remarkable capacity for indefinite self-renewal in vitro and the ability to differentiate into all somatic cell types originating from the three germ layers, thereby making them a promising source of osteoblasts. Consequently, it is crucial to establish a well-delineated system for osteogenic differentiation of hiPSCs in vitro, with the aim to generate osteoblast-like cells that conform to clinical application standards. Numerous research teams have achieved substantial advancements in both the direct osteogenic differentiation of hiPSCs and the indirect pathway via mesenchymal stem cells. In this article, we provide a comprehensive review of these two osteogenic differentiation pathways and their current applications, with the aim of serving as a valuable reference for bone regeneration technologies. Current research efforts have relied on embryoid body formation and monolayer induction methods utilizing biomaterials to develop a system that facilitates in vitro culture and osteogenic differentiation of hiPSCs. However, the existing research is primarily constrained by unclear system components and low efficiency. Therefore, the development of a stepwise and three-dimensional induction system based on stringent regulation by specific compounds is a primary research direction for the future.
Exosomes (EXOs) are important mediators of intercellular communication that contain a variety of substances, including miRNA, mRNA, DNA, and protein molecules, which can act on target cells and have broad medical prospects as “cell-free therapy”. The inclusion of EXOs varies with the type and state of the donor cell, thus EXOs from different cell types may exhibit different biological effects. Dental mesenchymal stem cell (DMSC)-derived EXOs (DMSC-EXOs) have gained increasing research attention in the fields of tissue regenerative medicine and immune regulation. Current research on EXOs is focused on the homeostasis between proinflammatory (M1)/anti-inflammatory (M2) macrophages and T-helper 17 (Th17)/regulatory T (Treg) cells during periodontal immune regulation. Studies have shown that DMSC-EXOs can promote the transformation of macrophages and T cells and that this function may be dependent on the surrounding microenvironment and the tissue origin of stem cells. For instance, miR-1246 in dental pulp stem cell-derived EXOs promotes M2 macrophage polarization by inhibiting nuclear factor kappa-B (NF-κB) p65. Meanwhile, EXOs derived from stem cells from apical papilla promote DNA demethylase Tet2-mediated demethylation of FoxP3, maintain stable FoxP3 expression, and promote Treg cell transformation, thus alleviating local inflammation in periodontitis. In addition, the immunomodulatory activities of DMSC-EXOs can be affected by inflammatory factors. For example, EXOs derived from lipopolysaccharide-preconditioned dental follicle stem cells can reduce the receptor activator of NF-κB ligand/osteoprotegerin ratio through the reactive oxygen species (ROS)/c-Jun N-terminal kinase signaling pathway and promote M2 macrophage polarization through the ROS/extracellular signal-regulated kinase signaling pathway. Additionally, EXOs derived from gingiva-derived mesenchymal stem cells pretreated with tumor necrosis factor-α and interferon-α proinflammatory cytokines can promote M2 macrophage polarization through high expression of CD73 and CD5L, while EXOs derived from inflammatory periodontal ligament stem cells can promote M1 macrophage polarization. This article reviews the research progress on the immunoregulation and effects of DMSC-EXOs on the homeostasis of M1/M2 macrophages and Th17/Treg cells during periodontal immune regulation and provides a reference for the treatment of periodontitis using DMSC-EXOs.
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