K. Yama, S. Morishima, K. Tsutsumi, R. Jo, Y. Aita, T. Inokuchi, T. Okuda, D. Watai, K. Ohara, M. Maruyama, T. Chikazawa, T. Iwamoto, Y. Kakizawa, T. Oniki
{"title":"Oral Microbiota Development in the First 60 Months: A Longitudinal Study","authors":"K. Yama, S. Morishima, K. Tsutsumi, R. Jo, Y. Aita, T. Inokuchi, T. Okuda, D. Watai, K. Ohara, M. Maruyama, T. Chikazawa, T. Iwamoto, Y. Kakizawa, T. Oniki","doi":"10.1177/00220345241272011","DOIUrl":"https://doi.org/10.1177/00220345241272011","url":null,"abstract":"Childhood is considered crucial in the establishment of future oral microbiota. However, the precise period of oral microbiota development remains unclear. This study aimed to identify the progression of oral microbiota formation in children. We longitudinally investigated the salivary microbiota of 54 children across 13 time points from 1 wk to 60 mo (5 y) old and their parents at 2 time points as a representative sample of the adult microbiota. Using next-generation sequencing, we obtained 10,000 gene sequences of the 16s rRNA V1-V2 region for each sample. The detection rate in children of 110 operational taxonomic units commonly detected in more than 85% of mothers and fathers, defined as the main constituent bacteria, was 25% at 1 wk old, increased to 80% between 6 and 18 mo old, and reached approximately 90% by 36 mo old. Early main constituent bacteria detected at 1 wk old were limited to Streptococcus, Rothia, and Gemella. At 6 to 18 mo old, the detection rates of various main constituent bacteria, including Neisseria, Haemophilus, and Fusobacterium, increased. UniFrac distance analysis showed that the oral microbiota of children approached that of adults at 6 to 18 mo old. In the weighted UniFrac distance index, unlike the unweighted index, there were no significant changes in children between 36 and 60 mo old from adults, and microbiota formation at 60 mo old was sufficiently advanced to be included within the range of adult individual differences. Our findings suggest that the initial 36 mo, particularly the period from 6 to 18 mo old, consists of a time window for oral microbiota maturation. In addition, the development of microbiota during this period may be critical for future oral disease prevention.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"11 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2024-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142430440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Y.Y. Zhang, J. Xiang, Y.Y. He, X. Liu, H.Y. Ye, L. Xu, H.L. Bai, H. Zhang, H.M. Zhang, W.Z. Liu, Q.M. Zhai, P. Ji, R.D. Cannon
{"title":"Fumarate Restrains Alveolar Bone Restoration via Regulating H3K9 Methylation","authors":"Y.Y. Zhang, J. Xiang, Y.Y. He, X. Liu, H.Y. Ye, L. Xu, H.L. Bai, H. Zhang, H.M. Zhang, W.Z. Liu, Q.M. Zhai, P. Ji, R.D. Cannon","doi":"10.1177/00220345241279555","DOIUrl":"https://doi.org/10.1177/00220345241279555","url":null,"abstract":"Nonresolving inflammation causes irreversible damage to periodontal ligament stem cells (PDLSCs) and impedes alveolar bone restoration. The impaired tissue regeneration ability of stem cells is associated with abnormal mitochondrial metabolism. However, the impact of specific metabolic alterations on the differentiation process of PDLSCs remains to be understood. In this study, we found that inflammation altered the metabolic flux of the tricarboxylic acid cycle and induced the accumulation of fumarate through metabolic testing and metabolic flux analysis. Transcriptome sequencing revealed the potential of fumarate in modulating epigenetics. Specifically, histone methylation typically suppresses the expression of genes related to osteogenesis. Fumarate was found to impede the osteogenic differentiation of PDLSCs that exhibited high levels of H3K9me3. Various techniques, including assay for transposase-accessible chromatin with high-throughput sequencing, chromatin immunoprecipitation sequencing, and RNA sequencing, were used to identify the target genes regulated by H3K9me3. Mechanistically, accumulated fumarate inhibited lysine-specific demethylase 4B (KDM4B) activity and increased H3K9 methylation, thus silencing asporin gene transcription. Preventing fumarate from binding to the histone demethylase KDM4B with α-ketoglutarate effectively restored the impaired osteogenic capacity of PDLSCs and improved alveolar bone recovery. Collectively, our research has revealed the significant impact of accumulated fumarate on the regulation of osteogenesis in stem cells, suggesting that inhibiting fumarate production could be a viable therapeutic approach for treating periodontal diseases.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"67 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2024-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142430424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
S.L. Reckelkamm, Z. Alayash, B. Holtfreter, M. Nolde, S.-E. Baumeister
{"title":"Response to the Letter to the Editor, “Sjögren’s Disease Is Not a Clinical Risk Factor for Periodontitis”","authors":"S.L. Reckelkamm, Z. Alayash, B. Holtfreter, M. Nolde, S.-E. Baumeister","doi":"10.1177/00220345241276783","DOIUrl":"https://doi.org/10.1177/00220345241276783","url":null,"abstract":"","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"58 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142363065","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
C Behm,O Miłek,K Schwarz,A Kovar,S Derdak,X Rausch-Fan,A Moritz,O Andrukhov
{"title":"Heterogeneity in Dental Tissue-Derived MSCs Revealed by Single-Cell RNA-seq.","authors":"C Behm,O Miłek,K Schwarz,A Kovar,S Derdak,X Rausch-Fan,A Moritz,O Andrukhov","doi":"10.1177/00220345241271997","DOIUrl":"https://doi.org/10.1177/00220345241271997","url":null,"abstract":"Mesenchymal stromal cells (MSCs) are multipotent, progenitor cells that reside in tissues across the human body, including the periodontal ligament (PDL) and gingiva. They are a promising therapeutic tool for various degenerative and inflammatory diseases. However, different heterogeneity levels caused by tissue-to-tissue and donor-to-donor variability, and even intercellular differences within a given MSCs population, restrict their therapeutic potential. There are considerable efforts to decipher these heterogeneity levels using different \"omics\" approaches, including single-cell transcriptomics. Previous studies applied this approach to compare MSCs isolated from various tissues of different individuals, but distinguishing between donor-to-donor and tissue-to-tissue variability is still challenging. In this study, MSCs were isolated from the PDL and gingiva of 5 periodontally healthy individuals and cultured in vitro. A total of 3,844 transcriptomes were generated using single-cell mRNA sequencing. Clustering across the 2 different tissues per donor identified PDL- and gingiva-specific and tissue-spanning MSCs subpopulations with unique upregulated gene sets. Gene/pathway enrichment and protein-protein interaction (PPI) network analysis revealed differences restricted to several cellular processes between tissue-specific subpopulations, indicating a limited tissue-of-origin variability in MSCs. Gene expression, pathway enrichment, and PPI network analysis across all donors' PDL- or gingiva-specific subpopulations showed significant but limited donor-to-donor differences. In conclusion, this study demonstrates tissue- and donor-specific variabilities in the transcriptome level of PDL- and gingiva-derived MSCs, which seem restricted to specific cellular processes. Identifying tissue-specific and tissue-spanning subpopulations highlights the intercellular differences in dental tissue-derived MSCs. It could be reasonable to control MSCs at a single-cell level to ensure their properties before transplantation.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"11 1","pages":"220345241271997"},"PeriodicalIF":7.6,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142328862","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Toward Better Reporting in Oral Health Research","authors":"N.S. Jakubovics, F. Schwendicke","doi":"10.1177/00220345241275459","DOIUrl":"https://doi.org/10.1177/00220345241275459","url":null,"abstract":"","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"21 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2024-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142275870","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Multiscale Imaging to Monitor Functional SHED-Supported Engineered Vessels.","authors":"E Chatzopoulou,N Bousaidi,T Guilbert,G Rucher,J Rose,S Germain,F Rouzet,C Chaussain,L Muller,C Gorin","doi":"10.1177/00220345241271122","DOIUrl":"https://doi.org/10.1177/00220345241271122","url":null,"abstract":"Regeneration of orofacial tissues is hampered by the lack of adequate vascular supply. Implantation of in vitro engineered, prevascularized constructs has emerged as a strategy to allow the rapid vascularization of the entire graft. Given the angiogenic properties of dental pulp stem cells, we hereby established a preclinical model of prevascularized constructs loaded with stem cells from human exfoliating deciduous teeth (SHED) in a 3-dimensional-printed material and provided a functional analysis of their in vivo angiogenesis, vascular perfusion, and permeability. Three different cell-loaded collagen hydrogels (SHED-human umbilical vein endothelial cell [HUVEC], HUVEC with SHED-conditioned medium, and SHED alone) were cast in polylactic acid (PLA) grids and ectopically implanted in athymic mice. At day 10, in vivo positron emission tomography (PETscan) revealed a significantly increased uptake of radiotracer targeting activated endothelial cells in the SHED-HUVEC group compared to the other groups. At day 30, ex vivo micro-computed tomography imaging confirmed that SHED-HUVEC constructs had a significantly increased vascular volume compared to the other ones. Injection of species-specific lectins analyzed by 2-photon microscopy demonstrated blood perfusion of the engineered human vessels in both prevascularized groups. However, in vivo quantification showed increased vessel density in the SHED-HUVEC group. In addition, coinjection of fluorescent lectin and dextran revealed that prevascularization with SHED prevented vascular leakage, demonstrating the active role of SHED in the maturation of human-engineered microvascular networks. This preclinical study introduces a novel PLA prevascularized and implantable construct, along with an array of imaging techniques, to validate the ability of SHED to promote functional human-engineered vessels, further highlighting the interest of SHED for orofacial tissue engineering. Furthermore, this study validates the use of PETscan for the early detection of in vivo angiogenesis, which may be applied in the clinic to monitor the performance of prevascularized grafts.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"10 1","pages":"220345241271122"},"PeriodicalIF":7.6,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142245297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"m6Am Methyltransferase PCIF1 Regulates Periodontal Inflammation.","authors":"W Song,L Liu,H Liang,H Cheng,W He,Q Yin,Z Zhang,W Lin,H Li,Q Li,W Liu,D Zhang,D Chen,Q Yuan","doi":"10.1177/00220345241271078","DOIUrl":"https://doi.org/10.1177/00220345241271078","url":null,"abstract":"N6,2'-O-dimethyladenosine (m6Am), a common mRNA modification in eukaryotic capped mRNAs, plays a pivotal role in cellular functions and disease progression. However, its involvement in host inflammation remains elusive. Here, we demonstrate that loss of m6Am methyltransferase phosphorylated CTD interacting factor 1 (PCIF1) attenuates periodontal inflammation in whole-body and myeloid lineage-specific knockout mouse models. Pcif1 deletion inhibits macrophage phagocytosis and migration through m6Am-Csf1r signaling. In addition, colony-stimulating factor-1 receptor (CSF1R) is identified as a potential target for the treatment of periodontitis. We thus reveal a previously unrecognized role for PCIF1-mediated m6Am modification in governing macrophage responses and periodontal inflammation.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"7 1","pages":"220345241271078"},"PeriodicalIF":7.6,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142245333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
B P Bhattarai,A K Singh,R P Singh,R Chaulagain,T M Søland,B Hasséus,D Sapkota
{"title":"Recurrence in Oral Leukoplakia: A Systematic Review and Meta-analysis.","authors":"B P Bhattarai,A K Singh,R P Singh,R Chaulagain,T M Søland,B Hasséus,D Sapkota","doi":"10.1177/00220345241266519","DOIUrl":"https://doi.org/10.1177/00220345241266519","url":null,"abstract":"The management of oral leukoplakia (OL) is challenging because of a high risk for recurrence and malignant transformation (MT), and recurrent OL is associated with a higher risk of MT than nonrecurrent OL. The present meta-analysis aimed to examine the association between OL recurrence and surgical techniques used for their management as well as their clinicopathological factors. Electronic searches were conducted in EMBASE, PubMed, Scopus, and Web of Science to retrieve studies reporting OL recurrence after surgery. The pooled proportion of OL recurrence after surgical excision was estimated. Subgroup analyses were conducted based on the surgical technique, data type, grades of epithelial dysplasia, anatomical subsites, clinical type and size of the lesion, surgical margin, and risk habits. Meta-regression analyses were conducted to identify the association between age, sex, and follow-up duration and OL recurrence. The risk of MT based on the recurrence status was also estimated. A network meta-analysis was performed to determine the surgical modality associated with the least OL recurrence. Eighty studies with a total of 7,614 samples and various surgical modalities (laser-based techniques, conventional scalpel surgery, cryosurgery, and photodynamic therapy) were included in the meta-analysis. A pooled proportion of recurrence of 22% was observed. Laser-based surgeries resulted in fewer OL recurrences than other surgical modalities, and the combination of laser excision and vaporization was identified to be the best treatment approach. OL in the retromolar area and multiple sites, nonhomogeneous OL, advanced age, female sex, inadequate surgical margin, retrospective data, and betel quid chewing habit were significantly associated with higher OL recurrence. Recurrent OL showed a 7.39 times higher risk of MT than nonrecurrent OL. These results suggest that the combination of laser excision and vaporization might reduce OL recurrence. Furthermore, OL in older patients, females, and nonhomogeneous OL need close monitoring after any surgical therapy.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"331 1","pages":"220345241266519"},"PeriodicalIF":7.6,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142245335","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
S.S. Herren, E. Ioannidou, D. Drake, E. Bernstein, N. Mickel, C.H. Fox
{"title":"A Mentoring Network for Diversity in Dental, Oral, and Craniofacial Research","authors":"S.S. Herren, E. Ioannidou, D. Drake, E. Bernstein, N. Mickel, C.H. Fox","doi":"10.1177/00220345241265664","DOIUrl":"https://doi.org/10.1177/00220345241265664","url":null,"abstract":"The American Association for Dental, Oral, and Craniofacial Research (AADOCR) has developed a national and sustainable mentoring and mentor training network titled AADOCR Mentoring an Inclusive Network for a Diverse Workforce of the Future (AADOCR MIND the Future). This program is instrumental in fostering a diverse group of early-career investigators in dental, oral, and craniofacial (DOC) research. The network’s principal purpose has been to establish a robust and enduring national mentoring program centrally managed by AADOCR. The overarching goal is to develop a sustainable, nationally recognized mentoring network that enhances the career development of early-career DOC researchers from diverse backgrounds. The program aligns with the National Institute of Dental and Craniofacial Research Strategic Plan and aims to cultivate a robust pipeline of future DOC researchers who can address critical scientific challenges. AADOCR MIND the Future guides mentors and mentees in individual career development as well as improving the quality of mentoring at the home institution through dissemination of lessons learned by mentors and mentees in the program. As science practices have evolved, investigators have moved from isolated individual projects to interactive multidisciplinary teams. Within this research framework, AADOCR MIND the Future offers the global infrastructure and the variety of scientists/AADOCR members. While most institutional mentoring efforts have been developed using conventional single mentor-mentee pairs, the AADOCR MIND the Future program supplements this model with additional group mentoring (mentors-mentees) and peer mentoring (interactions between just the mentees). Mentees commit to 12 mo of programming devoted to enhancing research career development through intensive hands-on work, distance-learning components, and engagement in a mentored grant-writing experience. Mentees are strongly encouraged to remain engaged with the program beyond the initial 12-mo period. Years 1 to 3 alumni (cohorts 1 to 3) mentees continue to participate in a meaningful way, and after the completion of the program, it is envisioned these alumni will become mentors for another generation.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"329 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142236371","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}