Journal of dental research最新文献

{"title":"Association between Periodontal Diseases and the Risk of Site-Specific Gastrointestinal Cancers: A Systematic Review and Meta-Analysis.","authors":"Q Wang, W-J Gu, F-L Ning, M Sun, Z-M G Zhao, M U Abe, Z-N Li, C-D Zhang","doi":"10.1177/00220345241263768","DOIUrl":"10.1177/00220345241263768","url":null,"abstract":"<p><p>The association between periodontal diseases and the risk of gastrointestinal cancers, especially site-specific gastrointestinal cancers, remains unclear. Here, we comprehensively searched PubMed, EMBASE, Web of Science, and Google Scholar from inception to April 2024 to identify relevant studies. The pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated with a random-effects model. Subgroup analyses and sensitivity analyses were conducted to confirm the robustness of the main findings in different populations. This study was reported according to PRISMA 2020 guidelines. In total, we identified 19 studies, including 16.6 million participants. Individuals with periodontal diseases had an increased risk of overall gastrointestinal cancers compared with those without periodontal diseases (HR 1.31, 95% CI 1.16-1.49). Periodontal diseases significantly increased the risk of esophageal cancer by 39% (HR 1.39, 95% CI 1.15-1.68), gastric cancer by 13% (HR 1.13, 95% CI 1.01-1.26), colorectal cancer by 21% (HR 1.21, 95% CI 1.05-1.39), pancreatic cancer by 35% (HR 1.35, 95% CI 1.00-1.82), and liver cancer by 9% (HR 1.09, 95% CI 1.04-1.13). The risk of gastrointestinal cancers was significantly increased by periodontitis (HR 1.45, 95% CI 1.14-1.85), gingivitis (HR 1.03, 95% CI 1.01-1.04), and periodontitis/gingivitis (HR 1.27, 95% CI 1.07-1.51). Furthermore, severe periodontal diseases showed a significantly increased risk of gastrointestinal cancer (HR 1.79, 95% CI 1.07-2.99). Results of sensitivity analyses for site-specific gastrointestinal cancers were robust with the main findings. In summary, periodontal diseases, especially severe periodontitis, increase the risk of overall and site-specific gastrointestinal cancers. Interventions to prevent and manage periodontal diseases may reduce the risk of developing gastrointestinal cancers.</p>","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142057672","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Complete Loss of Natural Teeth and Loneliness: A Fixed-Effect Analysis.","authors":"Y Matsuyama","doi":"10.1177/00220345241263265","DOIUrl":"10.1177/00220345241263265","url":null,"abstract":"<p><p>Psychosocial properties of oral health have been reported. The present study aimed to investigate the causal effect of complete loss of natural teeth on loneliness by using fixed-effects analysis to control for confounding factors, including unmeasured time-invariant factors. Data from older adults participating in at least 2 consecutive waves of the English Longitudinal Study of Ageing in waves 3 (2006/2007), 5 (2010/2011), and 7 (2014/2015) were analyzed (<i>N</i> = 18,682 observations from 7,298 individuals). The association between complete loss of natural teeth and loneliness score (ranging from 3 to 9) was examined using fixed-effect linear regression analysis adjusting for time-varying confounders, including sociodemographic and health characteristics. The prevalence of complete tooth loss was 12.7%, 12.8%, and 10.6% in waves 3, 5, and 7, respectively. Individuals who transitioned to complete tooth loss during any 2 consecutive waves had an increase in loneliness score by 0.27 (95% confidence interval [CI] 0.03, 0.52), which was greater than those who maintained natural teeth (-0.03; 95% CI -0.05, -0.01). Fixed-effects analysis adjusting for time-varying confounders revealed a significant association between complete loss of natural teeth and an increase in loneliness score by 0.31 (95% CI 0.17, 0.46). Complete loss of natural teeth among older adults in England was associated with loneliness, even after accounting for measured time-varying and (un)measured time-invariant confounders. Retaining natural teeth may reduce the risk of loneliness.</p>","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141891320","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Salivary Microbiome Relates to Neoadjuvant Immunotherapy Response in OSCC.","authors":"X X Wang, Y T Liu, J G Ren, H M Liu, Q Fu, Y Yang, Q Y Fu, G Chen","doi":"10.1177/00220345241262759","DOIUrl":"10.1177/00220345241262759","url":null,"abstract":"<p><p>Most patients diagnosed with oral squamous cell carcinoma (OSCC) present with locally advanced stages, which are typically associated with poor outcomes. Although immunotherapy offers potential improvements in patient survival, its efficacy is hampered by low response rates. The microbiome is widely involved in tumor immunity and may play a role in immunotherapy. This study aimed to investigate the potential association between the oral (salivary) microbiome and immunotherapy response in patients with OSCC. Salivary metagenome sequencing was performed on 47 patients with OSCC undergoing neoadjuvant immunotherapy (NAIT) in a clinical trial (NCT04649476). Patients were divided into responders and nonresponders based on their pathological responses. The results showed that the species richness of the salivary microbiome was lower in the nonresponders before NAIT than in the responders. Differential analysis revealed that nonresponders exhibited a lower relative abundance of 34 bacterial species and a higher relative abundance of 4 bacterial species. Notably, low levels of <i>Eubacterium infirmum</i>, <i>Actinobaculum</i>, and <i>Selenomas</i> (EAS) in the saliva may be associated with the nonresponse of patients with OSCC to NAIT. A nomogram based on EAS was developed and validated to determine the efficacy of NAIT. The area under the curve for the training cohort was 0.81 (95% confidence interval, 0.66 to 0.81). Quantitative polymerase chain reaction confirmed that low levels of salivary EAS effectively identified nonresponders to NAIT. Furthermore, the low abundance of salivary EAS was closely correlated with a low density of intratumoral CD4⁺, CD14⁺, CD68⁺, and FOXP3⁺ cells. Metabolic functional annotation revealed numerous biosynthetic processes associated with EAS that were more active in responders. In summary, this study provides valuable data resources for the salivary microbiome and reveals that nonresponders have different salivary microbiome profiles than responders do before NAIT. Low salivary EAS levels can serve as potential biomarkers for distinguishing nonresponders from responders.</p>","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141891323","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Two-Sample Mendelian Randomization Study of Neuroticism and Sleep Bruxism.","authors":"T Strausz, S Strausz, S E Jones, T Palotie, F Lobbezoo, J Ahlberg, H M Ollila","doi":"10.1177/00220345241264749","DOIUrl":"10.1177/00220345241264749","url":null,"abstract":"<p><p>Sleep bruxism (SB) affects a considerable part of the population and is associated with neuroticism, stress, and anxiety in various studies. However, the causal mechanisms between neuroticism and SB have not been examined. Understanding the reasons for SB is important as understanding bruxism may allow improved comprehensive management of the disorders and comorbidities related to it. Previous studies on the association of risk factors to SB have provided important symptomatic insight but were mainly questionnaire based or limited in sample size and could not adequately assess causal relationships. The aim of this study was to elaborate the possible causal relationship of neuroticism as a risk factor for SB through a Mendelian randomization (MR) approach by combining questionnaires, registry data, and genetic information in large scale. We performed a two-sample MR study using instrumental genetic variants of neuroticism, including neuroticism subcategories, in the UK Biobank (<i>n</i> = 380,506) and outcome data of probable SB using FinnGen (<i>n</i> [cases/controls] = 12,297/364,980). We discovered a causal effect from neuroticism to SB (odds ratio [OR] = 1.38 [1.10-1.74], <i>P</i> = 0.0057). A phenotype sensitive to stress and adversity had the strongest effect (OR = 1.59 [1.17-2.15], <i>P</i> = 0.0028). Sensitivity analyses across MR methods supported a causal relationship, and we did not observe pleiotropy between neuroticism and SB (MR-Egger intercept, <i>P</i> = 0.87). Our findings are in line with earlier observational studies that connect stress and SB. Furthermore, our results provide evidence that neurotic traits increase the risk of probable SB.</p>","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11409563/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142057671","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolic and Aging Influence on Anticancer Immunity in Oral Cancer.","authors":"T P M D Santos, W L Hicks, W J Magner, A Al Afif, K L Kirkwood","doi":"10.1177/00220345241264728","DOIUrl":"10.1177/00220345241264728","url":null,"abstract":"<p><p>The average age and obesity prevalence are increasing globally. Both aging and metabolic disease burden increase the risk of oral squamous cell carcinoma (OSCC) through profound effects on the immunological and metabolic characteristics within the OSCC tumor microenvironment. While the mechanisms that link aging and obesity to OSCC remain unclear, there is evidence that the antitumor responses are diminished in both conditions. Remarkably, however, immune checkpoint blockade, a form of cancer immunotherapy, remains intact despite the enhanced immunosuppressive tumor microenvironment in the context of either aging or obesity. Herein, we review the current knowledge of how aging and systemic metabolic changes affect antitumor immunity with an emphasis on the role of tumor-associated macrophages that greatly contribute to tumor immunosuppression. Key aspects discussed include the mechanisms of angiogenesis, cytokine release, phagocytosis attenuation, and immune cell recruitment during obesity and aging that create an immune-suppressive tumor microenvironment by recruitment and repolarization of tumor-associated macrophages. Through a deeper appreciation of these mechanisms, the development of novel therapeutic approaches to control OSCC will provide more refined management of the tumor microenvironment in the context of aging and obesity.</p>","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142057675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Autophagy Regulates Age-Related Jawbone Loss via LepR⁺ Stromal Cells.","authors":"B Sun, Y Xu, H Wang, F Wang, Q Li, Y Chen, Z Wang","doi":"10.1177/00220345241264810","DOIUrl":"10.1177/00220345241264810","url":null,"abstract":"<p><p>Bone aging and decreased autophagic activity are related but poorly explored in the jawbone. This study aimed to characterize the aging jawbones and jawbone-derived stromal cells (JBSCs) and determine the role of autophagy in jawbone mass decline. We observed that the jawbones of older individuals and mice exhibited similar age-related bone loss. Furthermore, leptin receptor (LepR)-lineage cells served as the primary source for in vitro cultured and expanded JBSCs, referred to as LepR-Cre⁺/JBSCs. RNA-sequencing data from the jawbones and LepR-Cre⁺/JBSCs showed the upregulated expression of the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway during aging. Through single-cell transcriptomics, we identified a decrease in the proportion of osteogenic lineage cells and the activation of the PI3K/AKT pathway in LepR-lineage cells in aging bone tissues. Reduced basal autophagic activity, diminished autophagic flux, and decreased osteogenesis occurred in the jawbones and LepR-Cre⁺/JBSCs from older mice (O-mice; O-JBSCs). Pharmacologic and constitutive autophagy activation alleviated the impaired osteogenesis in O-JBSCs. In addition, the suppression of mTOR-induced autophagy improved the aging phenotype of O-JBSCs. The activation of autophagy in LepR-Cre+/JBSCs using chemical autophagic activators reduced the alveolar bone resorption in O-mice. Therefore, our study demonstrated that ATG molecules and pathways are crucial in jawbone aging, providing novel approaches to understanding age-related jawbone loss.</p>","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142057673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Engineered 3D Periodontal Ligament Model with Magnetic Tensile Loading.","authors":"P Mulimani, N A Mazzawi, A J Goldstein, A M Obenaus, S M Baggett, D Truong, T E Popowics, N J Sniadecki","doi":"10.1177/00220345241264792","DOIUrl":"10.1177/00220345241264792","url":null,"abstract":"<p><p>In vitro models are invaluable tools for deconstructing the biological complexity of the periodontal ligament (PDL). Model systems that closely reproduce the 3-dimensional (3D) configuration of cell-cell and cell-matrix interactions in native tissue can deliver physiologically relevant insights. However, 3D models of the PDL that incorporate mechanical loading are currently lacking. Hence, we developed a model where periodontal tissue constructs (PTCs) are made by casting PDL cells in a collagen gel suspended between a pair of slender, silicone posts for magnetic tensile loading. Specifically, one of the posts was rigid and the other was flexible with a magnet embedded in its tip so that PTCs could be subjected to tensile loading with an external magnet. Additionally, the deflection of the flexible post could be used to measure the contractile force of PDL cells in the PTCs. Prior to tensile loading, second harmonics generation analysis of collagen fibers in PTCs revealed that incorporation of PDL cells resulted in collagen remodeling. Biomechanical testing of PTCs by tensile loading revealed an elastic response at 4 h, permanent deformation by 1 d, and creep elongation by 1 wk. Subsequently, contractile forces of PDL cells were substantially lower for PTCs under tensile loading. Immunofluorescence analysis revealed that tensile loading caused PDL cells to increase in number, express higher levels of F-actin and α-smooth muscle actin, and become aligned to the tensile axis. Second harmonics generation analysis indicated that collagen fibers in PTCs progressively remodeled over time with tensile loading. Gene expression analysis also confirmed tension-mediated upregulation of the F-actin/Rho pathway and osteogenic genes. Our model is novel in demonstrating the mechanobiological behavior that results in cell-mediated remodeling of the PDL tissue in a 3D context. Hence, it can be a valuable tool to develop therapeutics for periodontitis, periodontal regeneration, and orthodontics.</p>","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11465412/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142057674","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The PerioGene North Study Uncovers Serum Proteins Related to Periodontitis.","authors":"M Wänman, S Betnér, A Esberg, C K Holm, C Isehed, A Holmlund, P Palmqvist, A Lövgren, S Lindquist, L Hänström, U H Lerner, E Kindstedt, P Lundberg","doi":"10.1177/00220345241263320","DOIUrl":"10.1177/00220345241263320","url":null,"abstract":"<p><p>The sequalae of periodontitis include irreversible degradation of tooth-supporting structures and circulatory spread of inflammatory mediators. However, the serum protein profile in periodontitis is not well described, which is partly attributable to the limited number of studies based on large and well-characterized periodontitis cohorts. This study aims to identify novel, circulating inflammation-related proteins associated with periodontitis within the PerioGene North case-control study, which includes 478 cases with severe periodontitis and 509 periodontally healthy controls. The serum concentrations of high-sensitivity C-reactive protein (hs-CRP) and a panel of 45 inflammation-related proteins were analyzed using targeted proteomics. A distinguishable serum protein profile was evident in periodontitis cases. The protein pattern could separate cases from controls with a sensitivity of 0.81 and specificity of 0.81 (area under the curve = 0.87). Adjusted levels for hs-CRP and 24 of the 45 proteins were different between cases and controls. High levels of hs-CRP and matrix metalloproteinase-12, and low levels of epidermal growth factor (EGF) and oxidized low-density lipoprotein receptor 1 (OLR-1) were detected among the cases. Furthermore, the levels of C-C motif chemokine-19, granulocyte colony-stimulating factor-3 (CSF-3), interleukin-7 (IL-7), and hs-CRP were significantly higher in cases with a high degree of gingival inflammation. The levels of CSF-3 and tumor necrosis factor ligand superfamily member-10 TNFSF-10 were higher in cases with many deep periodontal pockets. The PerioGene North study includes detailed clinical periodontal data and uncovers a distinct serum protein profile in periodontitis. The findings of lower EGF and OLR-1 among the cases are highlighted, as this has not been presented before. The role of EGF and OLR-1 in periodontitis pathogenesis and as possible future biomarkers should be further explored.</p>","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11402264/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141891377","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Visualization of Pulpal Structures by SWIR in Endodontic Access Preparation.","authors":"L Benz, K Heck, D Hevisov, D Kugelmann, P-C Tseng, Z Sreij, F Litzenburger, J Waschke, F Schwendicke, A Kienle, R Hickel, K-H Kunzelmann, E Walter","doi":"10.1177/00220345241262949","DOIUrl":"https://doi.org/10.1177/00220345241262949","url":null,"abstract":"<p><p>Endodontic access preparation is one of the initial steps in root canal treatments and can be hindered by the obliteration of pulp canals and formation of tertiary dentin. Until now, methods for direct intraoperative visualization of the 3-dimensional anatomy of teeth have been missing. Here, we evaluate the use of shortwave infrared radiation (SWIR) for navigation during stepwise access preparation. Nine teeth (3 anteriors, 3 premolars, and 3 molars) were explanted <i>en bloc</i> with intact periodontium including alveolar bone and mucosa from the upper or lower jaw of human body donors. Analysis was performed at baseline as well as at preparation depths of 5 mm, 7 mm, and 9 mm, respectively. For reflection, SWIR was used at a wavelength of 1,550 nm from the occlusal direction, whereas for transillumination, SWIR was passed through each sample at the marginal gingiva from the buccal as well as oral side at a wavelength of 1,300 nm. Pulpal structures could be identified as darker areas approximately 2 mm before reaching the pulp chamber using SWIR transillumination, although they were indistinguishable under normal circumstances. Furcation areas in molars appeared with higher intensity than areas with canals. The location of pulpal structures was confirmed by superimposition of segmented micro-computed tomography (µCT) images. By radiomic analysis, significant differences between pulpal and parapulpal areas could be detected in image features. With hierarchical cluster analysis, both segments could be confirmed and associated with specific clusters. The local thickness of µCTs was calculated and correlated with SWIR transillumination images, by which a linear dependency of thickness and intensity could be demonstrated. Lastly, by <i>in silico</i> simulations of light propagation, dentin tubules were shown to be a crucial factor for understanding the visibility of the pulp. In conclusion, SWIR transillumination may allow direct clinical live navigation during endodontic access preparation.</p>","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141891378","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Periodontal Ligament Cell Apoptosis Activates Lepr+ Osteoprogenitors in Orthodontics.","authors":"H Liu, Y Zhang, Y Zhang, Y Huang, Y Yang, Y Zhao, S Chen, J Deng, W Li, B Han","doi":"10.1177/00220345241262706","DOIUrl":"10.1177/00220345241262706","url":null,"abstract":"<p><p>Alveolar bone (AB) remodeling, including formation and absorption, is the foundation of orthodontic tooth movement (OTM). However, the sources and mechanisms underlying new bone formation remain unclear. Therefore, we aimed to understand the potential mechanism of bone formation during OTM, focusing on the leptin receptor+ (Lepr+) osteogenitors and periodontal ligament cells (PDLCs). We demonstrated that Lepr+ cells activated by force-induced PDLC apoptosis served as distinct osteoprogenitors during orthodontic bone regeneration. We investigated bone formation both in vivo and in vitro. Single-cell RNA sequencing analysis and lineage tracing demonstrated that Lepr represents a subcluster of stem cells that are activated and differentiate into osteoblasts during OTM. Targeted ablation of Lepr+ cells in a mouse model disrupted orthodontic force-guided bone regeneration. Furthermore, apoptosis and sequential fluorescent labeling assays revealed that the apoptosis of PDLCs preceded new bone deposition. We found that PDL stem cell-derived apoptotic vesicles activated Lepr+ cells in vitro. Following apoptosis inhibition, orthodontic force-activated osteoprogenitors and osteogenesis were significantly downregulated. Notably, we found that bone formation occurred on the compression side during OTM; this has been first reported here. To conclude, we found a potential mechanism of bone formation during OTM that may provide new insights into AB regeneration.</p>","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141895081","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}