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.
{"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}
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.
{"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}
Pub Date : 2024-09-18DOI: 10.1177/00220345241266519
B P Bhattarai,A K Singh,R P Singh,R Chaulagain,T M Søland,B Hasséus,D Sapkota
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.
口腔白斑病（OL）的治疗具有挑战性，因为复发和恶性转化（MT）的风险很高，与非复发OL相比，复发OL的MT风险更高。本荟萃分析旨在研究 OL 复发与手术治疗技术及其临床病理因素之间的关系。我们在 EMBASE、PubMed、Scopus 和 Web of Science 中进行了电子检索，以检索报告手术后 OL 复发的研究。估算了手术切除后OL复发的总比例。根据手术技术、数据类型、上皮发育不良等级、解剖亚部位、病变的临床类型和大小、手术边缘和风险习惯进行了分组分析。通过元回归分析，确定年龄、性别、随访时间与 OL 复发之间的关系。还根据复发状况估算了MT的风险。为了确定与 OL 复发率最低相关的手术方式，还进行了网络荟萃分析。荟萃分析共纳入了 80 项研究，共计 7,614 个样本和各种手术方式（激光技术、传统手术刀手术、冷冻手术和光动力疗法）。经汇总观察，复发率为 22%。与其他手术方式相比，激光手术导致的OL复发率较低，激光切除和汽化相结合被认为是最佳治疗方法。后磨牙区和多个部位的OL、非均质OL、高龄、女性、手术切缘不足、回顾性数据和嚼槟榔的习惯与OL复发率较高有显著相关性。复发 OL 的 MT 风险是非复发 OL 的 7.39 倍。这些结果表明，激光切除和汽化治疗相结合可能会降低 OL 复发率。此外，老年患者、女性和非均质 OL 患者在接受任何手术治疗后都需要密切监测。
{"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}
Pub Date : 2024-09-17DOI: 10.1177/00220345241265664
S.S. Herren, E. Ioannidou, D. Drake, E. Bernstein, N. Mickel, C.H. Fox
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.
美国牙科、口腔和颅面研究协会（AADOCR）开发了一个名为 "美国牙科、口腔和颅面研究协会未来多元化劳动力包容性指导网络"（AADOCR MIND the Future）的全国性可持续指导和导师培训网络。该计划有助于培养牙科、口腔和颅面 (DOC) 研究领域的多元化早期职业研究人员。该网络的主要目的是建立一个由美国牙科和口腔颌面外科研究协会（AADOCR）集中管理的强大而持久的全国性指导计划。其总体目标是建立一个可持续的、全国认可的指导网络，以促进来自不同背景的早期 DOC 研究人员的职业发展。该计划与国家牙科和颅面研究所的战略计划相一致，旨在培养一批能够应对关键科学挑战的未来牙科和颅面研究所研究人员。AADOCR MIND the Future 指导导师和被指导者的个人职业发展，并通过传播导师和被指导者在该计划中的经验教训来提高指导质量。随着科学实践的发展，研究人员已经从孤立的个人项目转变为互动的多学科团队。在这一研究框架内，AADOCR MIND the Future 提供了全球性的基础设施和科学家/AADOCR 成员的多样性。虽然大多数机构的指导工作都是通过传统的单一指导者与被指导者配对的方式开展的，但 AADOCR MIND the Future 计划通过额外的小组指导（指导者与被指导者）和同伴指导（仅被指导者之间的互动）对这一模式进行了补充。被指导者要参加 12 个月的计划，致力于通过密集的实践工作、远程学习内容和参与指导下的赠款撰写体验来促进研究事业的发展。我们强烈鼓励被指导者在最初的 12 个月之后继续参与该计划。第 1 至第 3 年的校友（第 1 至第 3 组）将继续以有意义的方式参与该计划。
{"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}
Pub Date : 2024-09-14DOI: 10.1177/00220345241265676
Q. Ou, W. Huang, B. Wang, L. Niu, Z. Li, X. Mao, S. Shi
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.
{"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":"64 1","pages":""},"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}
Pub Date : 2024-09-14DOI: 10.1177/00220345241265670
J.C. Nickel, Y.M. Gonzalez, Y. Liu, H. Liu, L.M. Gallo, L.R. Iwasaki
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 = ED2 × 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/mm3) 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 < 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 < 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/mm3)2% and 2- to 43-fold larger versus −D TMJs in both sexes during daytime and nighttime. Cluster analysis ( P < 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.
{"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 < 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 < 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 < 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":"12 1","pages":""},"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}
Pub Date : 2024-09-14DOI: 10.1177/00220345241265661
M. Tatullo, T. Cocco, A. Ferretta, R. Caroppo, B. Marrelli, G. Spagnuolo, F. Paduano
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.
{"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":"6 1","pages":""},"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}
Pub Date : 2024-09-14DOI: 10.1177/00220345241265048
E. James, A.J. Caetano, P.T. Sharpe
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.
{"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":"32 1","pages":""},"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}
Pub Date : 2024-05-03DOI: 10.1177/00220345241246529
J. Tanum, H.E. Kim, S.M. Lee, A. Kim, J. Korostoff, G. Hwang
The oral cavity, a unique ecosystem harboring diverse microorganisms, maintains health through a balanced microflora. Disruption may lead to disease, emphasizing the protective role of gingival epithelial cells (GECs) in preventing harm from pathogenic oral microbes. Shifting GECs’ response from proinflammatory to antimicrobial could be a novel strategy for periodontitis. Photobiomodulation therapy (PBMT), a nonpharmacologic host modulatory approach, is considered an alternative to drugs. While the host cell response induced by a single type of pathogen-associated molecular patterns (PAMPs) was widely studied, this model does not address the cellular response to intact microbes that exhibit multiple PAMPs that might modulate the response. Inspired by this, we developed an in vitro model that simulates direct interactions between host cells and intact pathogens and evaluated the effect of PBMT on the response of human gingival keratinocytes (HGKs) to challenge viable oral microbes at both the cellular and molecular levels. Our data demonstrated that LED pretreatment on microbially challenged HGKs with specific continuous wavelengths (red: 615 nm; near-infrared: 880 nm) induced the production of various antimicrobial peptides, enhanced cell viability and proliferation, promoted reactive oxygen species scavenging, and down-modulated proinflammatory activity. The data also suggest a potential explanation regarding the superior efficacy of near-infrared light treatment compared with red light in enhancing antimicrobial activity and reducing cellular inflammation of HGKs. Taken together, the findings suggest that PBMT enhances the overall barrier function of gingival epithelium while minimizing inflammation-mediated breakdown of the underlying structures.
{"title":"Photobiomodulation of Gingival Cells Challenged with Viable Oral Microbes","authors":"J. Tanum, H.E. Kim, S.M. Lee, A. Kim, J. Korostoff, G. Hwang","doi":"10.1177/00220345241246529","DOIUrl":"https://doi.org/10.1177/00220345241246529","url":null,"abstract":"The oral cavity, a unique ecosystem harboring diverse microorganisms, maintains health through a balanced microflora. Disruption may lead to disease, emphasizing the protective role of gingival epithelial cells (GECs) in preventing harm from pathogenic oral microbes. Shifting GECs’ response from proinflammatory to antimicrobial could be a novel strategy for periodontitis. Photobiomodulation therapy (PBMT), a nonpharmacologic host modulatory approach, is considered an alternative to drugs. While the host cell response induced by a single type of pathogen-associated molecular patterns (PAMPs) was widely studied, this model does not address the cellular response to intact microbes that exhibit multiple PAMPs that might modulate the response. Inspired by this, we developed an in vitro model that simulates direct interactions between host cells and intact pathogens and evaluated the effect of PBMT on the response of human gingival keratinocytes (HGKs) to challenge viable oral microbes at both the cellular and molecular levels. Our data demonstrated that LED pretreatment on microbially challenged HGKs with specific continuous wavelengths (red: 615 nm; near-infrared: 880 nm) induced the production of various antimicrobial peptides, enhanced cell viability and proliferation, promoted reactive oxygen species scavenging, and down-modulated proinflammatory activity. The data also suggest a potential explanation regarding the superior efficacy of near-infrared light treatment compared with red light in enhancing antimicrobial activity and reducing cellular inflammation of HGKs. Taken together, the findings suggest that PBMT enhances the overall barrier function of gingival epithelium while minimizing inflammation-mediated breakdown of the underlying structures.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"68 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140821595","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}
Pub Date : 2024-04-30DOI: 10.1177/00220345241238154
X. Zhao, D. Leng, H. Wang, H. Jin, Y. Wu, Z. Qin, D. Wu, X. Wei
Oral squamous cell carcinoma (OSCC) is the most common type of oral cancer, characterized by invasiveness, local lymph node metastasis, and poor prognosis. Traditional treatment and medications have limitations, making the specific inhibition of OSCC growth, invasion, and metastasis a challenge. The tumor microenvironment exhibits mildly acidity and high concentrations of H2O2, and its exploitation for cancer treatment has been widely researched across various cancers, but research in the oral cancer field is relatively limited. In this study, by loading ultra-small Prussian blue nanoparticles (USPBNPs) into mesoporous calcium–silicate nanoparticles (MCSNs), we developed an acid-responsive iron-based nanocomposite, USPBNPs@MCSNs (UPM), for the OSCC treatment. UPM demonstrated excellent dual enzyme activities, generating toxic ·OH in a mildly acidic environment, effectively killing OSCC cells and producing O2 in a neutral environment to alleviate tissue hypoxia. The results showed that UPM could effectively inhibit the proliferation, migration, and invasion of OSCC cells, as well as the growth of mice solid tumors, without obvious systemic toxicity. The mechanisms may involve UPM inducing ferroptosis of OSCC cells by downregulating the xCT/GPX4/glutathione (GSH) axis, characterized by intracellular iron accumulation, reactive oxygen species accumulation, GSH depletion, lipid peroxidation, and abnormal changes in mitochondrial morphology. Therefore, this study provides empirical support for ferroptosis as an emerging therapeutic target for OSCC and offers a valuable insight for future OSCC treatment.
{"title":"An Acid-Responsive Iron-Based Nanocomposite for OSCC Treatment","authors":"X. Zhao, D. Leng, H. Wang, H. Jin, Y. Wu, Z. Qin, D. Wu, X. Wei","doi":"10.1177/00220345241238154","DOIUrl":"https://doi.org/10.1177/00220345241238154","url":null,"abstract":"Oral squamous cell carcinoma (OSCC) is the most common type of oral cancer, characterized by invasiveness, local lymph node metastasis, and poor prognosis. Traditional treatment and medications have limitations, making the specific inhibition of OSCC growth, invasion, and metastasis a challenge. The tumor microenvironment exhibits mildly acidity and high concentrations of H<jats:sub>2</jats:sub>O<jats:sub>2</jats:sub>, and its exploitation for cancer treatment has been widely researched across various cancers, but research in the oral cancer field is relatively limited. In this study, by loading ultra-small Prussian blue nanoparticles (USPBNPs) into mesoporous calcium–silicate nanoparticles (MCSNs), we developed an acid-responsive iron-based nanocomposite, USPBNPs@MCSNs (UPM), for the OSCC treatment. UPM demonstrated excellent dual enzyme activities, generating toxic ·OH in a mildly acidic environment, effectively killing OSCC cells and producing O<jats:sub>2</jats:sub> in a neutral environment to alleviate tissue hypoxia. The results showed that UPM could effectively inhibit the proliferation, migration, and invasion of OSCC cells, as well as the growth of mice solid tumors, without obvious systemic toxicity. The mechanisms may involve UPM inducing ferroptosis of OSCC cells by downregulating the xCT/GPX4/glutathione (GSH) axis, characterized by intracellular iron accumulation, reactive oxygen species accumulation, GSH depletion, lipid peroxidation, and abnormal changes in mitochondrial morphology. Therefore, this study provides empirical support for ferroptosis as an emerging therapeutic target for OSCC and offers a valuable insight for future OSCC treatment.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"25 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2024-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140818000","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}
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