Journal of dental research最新文献

{"title":"Targeting Aurora A to Overcome Cisplatin Resistance in Head and Neck Cancer.","authors":"X Li, Z Wang, G G Oakley, L Wang, E A Lanzel, M R Buchakjian, A Peng","doi":"10.1177/00220345241309624","DOIUrl":"https://doi.org/10.1177/00220345241309624","url":null,"abstract":"<p><p>Cisplatin-based chemotherapy is a cornerstone treatment for advanced recurrent head and neck squamous cell carcinoma (HNSCC). However, the effectiveness of the treatment is often hindered by intrinsic and acquired resistance and associated toxicity, highlighting a pressing unmet clinical need. Here, our compound screening identified Aurora kinase inhibitors, particularly those targeting Aurora A kinase, as potential agents to sensitize resistant HNSCC cells to cisplatin. While Aurora kinases are well-established regulators of mitosis, their precise role in cisplatin resistance is largely unknown, given that cisplatin confers toxicity primarily in cells undergoing DNA replication. We confirmed that depletion of Aurora A or its activators enhanced cisplatin response in resistant HNSCC cells. Analyses of a comprehensive database and locally treated HNSCC patient samples revealed compelling associations between Aurora A overexpression/activation and cisplatin resistance, tumor recurrence, and poor patient survival. Pharmacologic inhibition of Aurora A effectively synergized with cisplatin treatment in cellular assays and a syngeneic mouse tumor model of HNSCC. Mechanistically, Aurora A inhibition enhanced apoptosis induction after cisplatin treatment, particularly in S-phase cells; induced replication stress; and suppressed the repair of cisplatin-induced DNA crosslinking. Taken together, our findings shed light on important functions of Aurora A kinase beyond mitotic regulation. The multifaceted roles of Aurora A suggest its potential as a prime anticancer drug target. Given the ongoing investigations into numerous Aurora inhibitors for cancer therapy, exploring their clinical applications in HNSCC, especially in combination with platinum drugs, may hold significant promise.</p>","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":" ","pages":"220345241309624"},"PeriodicalIF":0.0,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143525604","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":"Injectable Hydrogel as Intracanal Medication for Root Canal Disinfection.","authors":"M Cao, D Wu, H Tu, B Mou, J Kang, J Liao, J Yang","doi":"10.1177/00220345241309865","DOIUrl":"https://doi.org/10.1177/00220345241309865","url":null,"abstract":"<p><p>Due to the complex anatomical structures of the root canal, thorough intracanal disinfection has always been challenging in endodontic treatment. Existing intracanal medicaments exhibit limitations such as low permeability and suboptimal antibacterial performance. Thus, an intracanal medicament that combines excellent operating performance with potent antibacterial properties is required. Therefore, we designed an injectable hydrogel loaded with modified triple antibiotic drugs (mTAD) through a Schiff base reaction of carboxymethyl chitosan (CMCS) and polyethylene glycol aldehyde (OHC-PEG-CHO), mTAD/CMCS/OHC-PEG-CHO (mTCP). We subsequently evaluated the characteristics of mTCP. Moreover, the antibacterial capacity of the hydrogels was assessed in vitro. The effects of mTCP on the cell biocompatibility and odonto-/osteogenic differentiation of stem cells from the apical papilla (SCAPs) were also examined. Furthermore, we established a periapical inflammation model in the young permanent teeth of a Beagle dog and explored the effects of mTCP on root canal disinfection and root development. Our findings revealed that mTCP exhibited excellent operability, fluidity, and ease of removal from the root canal. mTCP presented outstanding antibacterial efficacy both in vitro and in vivo, attributed to its exceptional permeability and sustained release of mTAD. The odonto-/osteogenic differentiation of SCAPs was augmented by adding mTCP. Moreover, mTCP facilitated root elongation, dentinal wall thickening, and apical closure in the Beagle dog model. mTCP exhibited a pronounced effect on promoting periapical tissue healing and root development. In conclusion, mTCP hydrogel has promising potential for root canal disinfection in endodontic therapy.</p>","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":" ","pages":"220345241309865"},"PeriodicalIF":0.0,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143485039","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":"Letter to the Editor: \"A Deep Learning System to Predict Epithelial Dysplasia in Oral Leukoplakia\".","authors":"J M Aguirre-Urizar, I Lafuente-Ibañez de Mendoza","doi":"10.1177/00220345251317097","DOIUrl":"https://doi.org/10.1177/00220345251317097","url":null,"abstract":"","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":" ","pages":"220345251317097"},"PeriodicalIF":0.0,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143451296","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":"Corrigendum to Molecular Profiling of Odontoclasts during Physiological Tooth Replacement.","authors":"","doi":"10.1177/00220345251322122","DOIUrl":"10.1177/00220345251322122","url":null,"abstract":"","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":" ","pages":"220345251322122"},"PeriodicalIF":0.0,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143412081","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":"Pericytes Are Odontoblast Progenitor Cells Depending on ER Stress.","authors":"T Ouchi, M Ando, R Kurashima, M Kimura, N Saito, A Iwasaki, H Sekiya, K Nakajima, T Hasegawa, T Mizoguchi, Y Shibukawa","doi":"10.1177/00220345241307944","DOIUrl":"10.1177/00220345241307944","url":null,"abstract":"<p><p>Odontoblasts are terminally differentiated cells that exhibit mechanosensitivity and mineralization capacity. Mechanosensitive ion channels such as Piezo1 are present in odontoblasts and are associated with their physiological functions via Ca²⁺ signaling. Both Ca²⁺ signals via Ca²⁺ influx from mechanosensitive ion channels and Ca²⁺ release from Ca²⁺ stores function as secondary messenger systems for various biological phenomena. The endoplasmic reticulum (ER) serves as an intracellular Ca²⁺ store that mobilizes intracellular Ca²⁺. Changes in Ca²⁺ concentration inside the ER are among the factors that cause ER stress. Perivascular cells are located around odontoblasts in the dental pulp. Although such formation indicates that perivascular cells interact with odontoblasts, their detailed profiles under developmental and pathological conditions remain unclear. In this study, we revealed that pericyte marker, neural/glial antigen 2 (NG2)-positive cells, in cell-rich zones (CZs) can differentiate into Piezo1-positive odontoblasts following genetic odontoblast depletion in mice, and modeled as odontoblast death after severe dentin injury and as reparative dentin formation. NG2-positive pericytes differentiated into odontoblasts faster than glial cells. To determine how NG2-positive cells differentiate into Piezo1-positive odontoblasts, we focused on the ER-stress sensor protein, activating transcription factor 6a (ATF6a). After genetic odontoblast depletion, NG2-positive cells regenerated in the odontoblast layer and were capable of acting as functional odontoblasts. In the presence of extracellular Ca²⁺, the application of a sarco/ER Ca²⁺-ATPase (SERCA) inhibitor, thapsigargin, known as an ER-stress inducer, increased the intracellular Ca²⁺ concentration in the odontoblast lineage cells (OLCs). The increase was significantly inhibited by the application of a pharmacologic Piezo1 inhibitor, indicating that ER stress by SERCA inhibition augmented Piezo1-induced responses in odontoblast progenitor cells. However, the physiological activation of G_q-coupled receptors by adenosine diphosphate did not induce Piezo1 activation. Gene silencing of <i>ATF6a</i> and/or <i>NG2</i> impaired the mineralization of OLCs. Overall, ATF6a orchestrates the differentiation of NG2-positive pericytes into functional odontoblasts that act as sensory receptor cells and dentin-forming cells.</p>","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":" ","pages":"220345241307944"},"PeriodicalIF":0.0,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143191564","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":"<i>Streptococcus mutans</i> and Caries: A Systematic Review and Meta-Analysis.","authors":"D Mazurel, B W Brandt, M Boomsma, W Crielaard, M Lagerweij, R A M Exterkate, D M Deng","doi":"10.1177/00220345241303880","DOIUrl":"https://doi.org/10.1177/00220345241303880","url":null,"abstract":"<p><p>It has been questioned whether <i>Streptococcus mutans</i> can still be considered the major etiological agent for caries. The main argument is that most evidence has been based on single-species identification. The composition of the oral microbiome was not analyzed. This systemic review aims to assess the prevalence and abundance of <i>S. mutans</i> in caries-active (CA) and caries-free (CF) subjects based on clinical studies in which the microbiome was investigated. Three databases (PubMed, Cochrane, Embase) were searched until May 22, 2023, for eligible publications that included CA and CF subjects and reported the detection of both <i>S. mutans</i> and the oral microbial community, using DNA-based methods. The clinical and microbial outcomes were summarized and further analyzed using a random-effects model. Of 22 eligible studies, 3 were excluded due to the high risk of bias. In the remaining 19 studies, 16 reported the prevalence of <i>S. mutans</i>, 11 reported its relative abundance, and 8 reported both parameters. The prevalence of <i>S. mutans</i> in CA was either similar to (<i>n</i> = 4) or higher than (<i>n</i> = 12) the CF group. The reported relative abundance in CA was higher than CF in all 11 studies, although the values varied from 0.001% to 5%. Meta-analysis confirmed the significance of these findings. The summary of microbial community data did not reveal other caries-associated bacterial genera/species than <i>S. mutans</i>. In conclusion, the collected evidence based on microbiome studies suggests a strong association between the prevalence and abundance of <i>S. mutans</i> and caries experience. While the cariogenic role of <i>S. mutans</i> in the oral ecosystem should be recognized, its actual function warrants further exploration.</p>","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":" ","pages":"220345241303880"},"PeriodicalIF":0.0,"publicationDate":"2025-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143082741","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":"Guidelines for Reporting Oral Epidemiologic Studies to Inform Burden Estimation (GROESBE).","authors":"E Bernabé, C C Salomon-Ibarra, W Marcenes","doi":"10.1177/00220345241293410","DOIUrl":"10.1177/00220345241293410","url":null,"abstract":"<p><p>High-quality prevalence and incidence studies of oral conditions are essential for estimation of disease burden and comparison of estimates among countries and over time, as well as for priority setting, resource allocation, and planning public health action. Existing systematic reviews of the epidemiology of untreated dental caries, severe periodontitis, and edentulism, carried out for the Global Burden of Disease study, showed inadequate and incomplete reporting of the measurement of oral conditions as well as a lack of consistency and comparability with other health conditions. These issues are more accentuated in studies from low- and middle-income countries. Studies must meet the highest standards so that these efforts do not waste resources. This report extends the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines to improve and standardize the reporting of descriptive oral epidemiologic studies of common oral conditions. The aim of the Guidelines for Reporting Oral Epidemiologic Studies to Inform Burden Estimation (GROESBE) is to promote transparency, clarity, and comparability of scientific reporting, specifically for prevalence and incidence studies of untreated caries, severe periodontitis, and edentulism. The GROESBE guidelines and checklist were developed following a structured and formal consultation process with a geographically diverse group of 23 individuals involved in the conduct and analysis of oral epidemiologic studies. GROESBE focuses on elements that are not included in STROBE, adding 14 specific recommendations to existing guidelines. They will facilitate reliable comparison of emerging prevalence and incidence data on untreated caries, severe periodontitis, and edentulism across settings worldwide and the synthesis of robust evidence to inform estimation of disease burden in future iterations of the Global Burden of Disease study.</p>","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":" ","pages":"140-146"},"PeriodicalIF":0.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11752649/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142788160","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":"DNA and RNA Methylation in Periodontal and Peri-implant Diseases.","authors":"L Larsson, P M Giraldo-Osorno, C Garaicoa-Pazmino, W V Giannobile, F Asa'ad","doi":"10.1177/00220345241291533","DOIUrl":"10.1177/00220345241291533","url":null,"abstract":"<p><p>Periodontal and peri-implant diseases are primarily biofilm-induced pathologies in susceptible hosts affecting the periodontium and dental implants. Differences in disease susceptibility, severity, and patterns of progression have been attributed to immune regulatory mechanisms such as epigenetics. DNA methylation is an essential epigenetic mechanism governing gene expression that plays pivotal roles in genomic imprinting, chromosomal stability, apoptosis, and aging. Clinical studies have explored DNA methylation inhibitors for cancer treatment and predictive methylation profiles for disease progression. In periodontal health, DNA methylation has emerged as critical, evidenced by clinical studies unraveling its complex interplay with inflammatory genes and its regulatory role in periodontitis contributing to disease severity. Human studies have shown that methylation enzymes associated with gene reactivation (e.g., ten-eleven translocation-2) are elevated in periodontitis compared with gingivitis. Dysregulation of these genes can lead to the production of inflammatory cytokines and an altered initial response to bacteria via the toll-like receptor signaling pathway in periodontal diseases. In addition, in peri-implant diseases, this dysregulation can result in altered DNA methylation levels and enzymatic activity influenced by the properties of the titanium surface. Beyond traditional perspectives, recent evidence highlights the involvement of RNA methylation (e.g., N6-methyladenosine [m6A], N6,2'-0-dimethyladenosine [m6Am]) in periodontitis and peri-implantitis lesions, playing vital roles in the innate immune response, production of inflammatory cytokines, and activation of dendritic cells. Both DNA and RNA methylation can influence the gene expression, virulence, and bacterial behavior of well-known periodontal pathogens such as <i>Porphyromonas gingivalis</i>. Alterations in bacterial methylation patterns result in changes in the metabolism, drug resistance, and gene expression related to survival in the host, thereby promoting tissue degradation and chronic inflammatory responses. In summary, the present state-of-the-art review navigates the evolving landscape of DNA and RNA methylation in periodontal and peri-implant diseases, integrating recent developments and mechanisms to reshape the understanding of epigenetic dynamics in oral health.</p>","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":" ","pages":"131-139"},"PeriodicalIF":0.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11752639/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142775777","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":"REV-ERBα Inhibits Osteoclastogenesis and Protects against Alveolar Bone Loss.","authors":"C Zhang, L Tan, J Li, Z Shen, J Yao, Y Huang, L Wu, C Yu, L Gao, C Zhao","doi":"10.1177/00220345241290444","DOIUrl":"10.1177/00220345241290444","url":null,"abstract":"<p><p>Circadian rhythm disruption is thought to be associated with periodontitis, and molecular clock genes play critical roles in regulating bone homeostasis. However, the specific contribution of molecular clock genes to alveolar bone resorption caused by periodontitis is poorly understood. In this study, we introduced a novel Periodontitis Circadian Rhythm Score (PeriCRS) model that was established through machine learning using periodontal transcriptomic data from periodontitis clinical cohorts in the Gene Expression Omnibus (GEO) database. This approach revealed the potential regulatory role of circadian rhythm disruption in periodontitis and identified key molecular clock genes associated with alveolar bone destruction. Moreover, we established an experimental periodontitis model with circadian rhythm disturbance via periodontal ligation in mice exposed to a 6-h advanced LD12:12 cycle every 2 d. Our bioinformatics analysis revealed that <i>NR1D1</i>, which encodes REV-ERBα, is a pivotal factor in the impact of circadian rhythm disruption on periodontitis in periodontal tissues. Next, we confirmed the abnormal expression of the molecular clock gene Rev-erbα in inflammatory periodontal tissue in mice and confirmed that circadian rhythm disruption altered REV-ERBα expression. Furthermore, the activation of REV-ERBα with the agonist SR9009 notably decreased RANKL-induced osteoclast differentiation and suppressed the expression of osteoclast-related factors. Subsequent in vivo experiments demonstrated that SR9009 mitigated alveolar bone loss caused by periodontitis. Mechanistically, we found that the IL-22-STAT3 pathway inhibited REV-ERBα expression and modulated RANKL-induced osteoclast differentiation in vitro. Our results elucidate the role of REV-ERBα in osteoclastogenesis and suggest a potential new therapeutic avenue for addressing alveolar bone resorption associated with periodontitis.</p>","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":" ","pages":"193-203"},"PeriodicalIF":0.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142775913","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":"Canada's First National Oral Health Research Strategy (2024-2030).","authors":"L D Rock, G Akade, H Al-Waeli, S Allin, K Altabtbaei, N Ameli, C Bassim, C Bedos, P Benbow, A Y Bhagirath, D Chvartszaid, V D'Souza, K Da Silva, A Elseoudi, A Fadl, B Ganss, P Ghanouni, S Ghavami, N Gomaa, S G Gong, D Graf, G D Guttmann, A Jessani, P Kengne Talla, L Kenwell, M Khurram, A Leask, S Madathil, S McKinstry, H Mulhall, B Nicolau, O O Olatosi, C Powder, F Propser, C Quiñonez, S Abbasgholizadah Rahimi, D P Richards, M Rouabhia, R J Schroth, P Sharma, H Szabo-Rogers, A Velly, L A C Vieira, D T Wu, K Zhou, P J Allison","doi":"10.1177/00220345241299360","DOIUrl":"10.1177/00220345241299360","url":null,"abstract":"<p><p>Recent years have seen significant positive changes and developments in oral health-related policy and data on oral health and oral health care in Canada. Simultaneously, on the international stage, the momentum for oral health and related research continues to build. These changes have led to an initiative to create Canada's first National Oral Health Research Strategy (NOHRS), which was recently published by the Canadian Institutes of Health Research-Institute of Musculoskeletal Health and Arthritis (Allison and Rock 2024). In this communication, we describe the process that was used to undertake this work. We present the resulting guiding principles, the research priority areas, and the framework that emerged, which included 6 strategic priorities grouped into 3 themes: (A) Leading Issues: (1) access to care, (2) inequities, identities, and oral health; (B) Emerging Methods: (3) artificial intelligence, (4) omics; and (C) Overarching Approaches: (5) environmental sustainability, (6) knowledge mobilization and implementation science. In addition, NOHRS includes a series of proposed goals and a timeline over the coming years. The point is to encourage a broad range of individuals and groups of people to engage with this high-level strategy and create plans to implement it. This strategy directly answers the call by the World Health Organization for countries to establish a national oral health research strategy (World Health Organization 2024). We have engaged in an extensive, broad consultative process, resulting in a Canadian NOHRS that is tailored to the needs of our community. Its aim is to galvanize our community into action to address the priorities we have identified. By engaging in this process, we build upon multiple oral health-related initiatives in Canada and on the international stage. We hope to inspire and facilitate similar, much-needed work elsewhere.</p>","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":" ","pages":"113-118"},"PeriodicalIF":0.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11752638/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142857346","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}