Journal of Dental Research最新文献

{"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":null,"pages":null},"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":null,"pages":null},"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":null,"pages":null},"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":null,"pages":null},"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}

{"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":null,"pages":null},"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}

{"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":null,"pages":null},"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}

{"title":"Apoptotic Vesicles: Therapeutic Mechanisms and Critical Issues","authors":"Q. Ou, W. Huang, B. Wang, L. Niu, Z. Li, X. Mao, S. Shi","doi":"10.1177/00220345241265676","DOIUrl":"https://doi.org/10.1177/00220345241265676","url":null,"abstract":"Apoptosis is the most prominent mode of programmed cell death and is necessary for the maintenance of tissue homeostasis. During cell apoptosis, a distinctive population of extracellular vesicles is generated, termed apoptotic vesicles (apoVs). ApoVs inherit a variety of biological molecules such as proteins, RNAs, nuclear components, lipids, and gasotransmitters from their parent cells. ApoVs have shown promising therapeutic potential for inflammation, tumors, immune disorders, and tissue regeneration. In addition, apoVs can be used as drug carriers, vaccine development, and disease diagnosis. Recently, apoVs have been used in clinical trials to treat a variety of diseases, such as temporomandibular joint osteoarthritis and the regeneration of functional alveolar bone. Here, we review the history of apoV research, current preclinical and clinical studies, and the potential issues of apoV application.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":null,"pages":null},"PeriodicalIF":7.6,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142233283","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":"Mechanics- and Behavior-Related Temporomandibular Joint Differences","authors":"J.C. Nickel, Y.M. Gonzalez, Y. Liu, H. Liu, L.M. Gallo, L.R. Iwasaki","doi":"10.1177/00220345241265670","DOIUrl":"https://doi.org/10.1177/00220345241265670","url":null,"abstract":"Fatigue of temporomandibular joint (TMJ) tissues reflects the effects of magnitude (energy density; ED) and frequency of loading (jaw muscle duty factor; DF). This observational study measured these variables and tested for differences in mechanobehavior scores (MBS = ED<jats:sup>2</jats:sup> × DF) and component variables in subjects with and without TMJ disc displacement (±D). In accordance with Institutional Review Board and STROBE guidelines, written informed consent was obtained, and examination and imaging protocols identified eligible adult subjects. Specifically, magnetic resonance imaging was used to assign subjects’ TMJs to ±D groups. Subjects were trained to record in-field jaw muscle activities, from which DFs (percentage of recording time) were determined. EDs (mJ/mm<jats:sup>3</jats:sup>) were estimated using modeled TMJ loads and in vivo dynamic stereometry. Multivariate analysis of variance, post hoc independent t tests, and K-means cluster analysis identified significant group differences ( P &lt; 0.05). Of 242 individuals screened, 65 females (TMJs: 78 +D, 52 −D) and 53 males (TMJs: 39 +D, 67 −D) participated. Subjects produced 312 daytime and 319 nighttime recordings of average duration 6.0 ± 0.2 h and 7.6 ± 0.1 h, respectively, and 219 (114 right, 105 left) intact dynamic stereometry recordings. Average EDs were 2-fold and significantly larger in +D than −D TMJs ( P &lt; 0.0001). DFs were on average 3-fold larger during the daytime versus nighttime for both masseter and temporalis muscles and 1.8- and 3.0-fold larger for the masseter versus temporalis muscle during the daytime and nighttime, respectively. Daytime masseter MBSs for +D TMJs in females were the largest overall at 621 ± 212 (mJ/mm<jats:sup>3</jats:sup>)<jats:sup>2</jats:sup>% and 2- to 43-fold larger versus −D TMJs in both sexes during daytime and nighttime. Cluster analysis ( P &lt; 0.0001) identified groups 2 and 3, which comprised 87% +D TMJs and had average MBSs 21-fold larger than group 1. The results show MBS as a potential biomarker to predict homeostasis versus progression or reversal of degenerative TMJ structural changes.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":null,"pages":null},"PeriodicalIF":7.6,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142233360","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":"Unveiling the Neurodegenerative Alterations through Oral Stem Cells","authors":"M. Tatullo, T. Cocco, A. Ferretta, R. Caroppo, B. Marrelli, G. Spagnuolo, F. Paduano","doi":"10.1177/00220345241265661","DOIUrl":"https://doi.org/10.1177/00220345241265661","url":null,"abstract":"Parkinson’s disease (PD) is a neurodegenerative condition characterized by the progressive and selective loss of dopaminergic (DAergic) neurons in the midbrain. The replacement of neuromelanin (NM)–containing DAergic neurons in the substantia nigra and the enhancement of NM concentration could offer a promising and safe approach to treating PD symptoms. The objective of this study was to investigate and compare the potential of human periapical-cysts mesenchymal stem cells (hPCy-MSCs) and dental pulp stem cells (DPSCs) to differentiate into DAergic NM-producing neurons and to generate functional 3-dimensional (3D) midbrain-like organoids in vitro. We assessed the changes in morphology and behavior of neuron-like cells (NLCs) as well as the expression of molecular markers characterizing the DAergic neurons. Furthermore, we observed electrically active and functionally mature DAergic neurons by means of electrophysiological assays, NM dosage assays, and the quantification of dopamine release by high-performance liquid chromatography. Our results demonstrate for the first time that both hPCy-MSCs and DPSCs are capable of differentiating into NLCs, further confirmed by the increase in lactate levels in the medium of cells exposed to neurogenic conditions. Importantly, we have induced such NLCs to further differentiate into functional DAergic NM-producing neurons. Finally, 3D midbrain-like organoids have been produced from oral stem cells: they appear as neurosphere-like structures diffusely expressing the neural marker β-III tubulin and containing NM-like granules. Our findings open up a novel and fascinating opportunity to rethink oral stem cells, and the derived 3D disease models, as a strategic and reliable tool for unveiling the neurodegenerative alterations.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":null,"pages":null},"PeriodicalIF":7.6,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142233447","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":"Computational Methods for Image Analysis in Craniofacial Development and Disease","authors":"E. James, A.J. Caetano, P.T. Sharpe","doi":"10.1177/00220345241265048","DOIUrl":"https://doi.org/10.1177/00220345241265048","url":null,"abstract":"Observation is at the center of all biological sciences. Advances in imaging technologies are therefore essential to derive novel biological insights to better understand the complex workings of living systems. Recent high-throughput sequencing and imaging techniques are allowing researchers to simultaneously address complex molecular variations spatially and temporarily in tissues and organs. The availability of increasingly large dataset sizes has allowed for the evolution of robust deep learning models, designed to interrogate biomedical imaging data. These models are emerging as transformative tools in diagnostic medicine. Combined, these advances allow for dynamic, quantitative, and predictive observations of entire organisms and tissues. Here, we address 3 main tasks of bioimage analysis, image restoration, segmentation, and tracking and discuss new computational tools allowing for 3-dimensional spatial genomics maps. Finally, we demonstrate how these advances have been applied in studies of craniofacial development and oral disease pathogenesis.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":null,"pages":null},"PeriodicalIF":7.6,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142233321","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}