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Journal of the Mechanical Behavior of... Oct 2023The periodontium is a biological structure that supports the tooth in the jaw and behave as a developmental, biological, and functional unit. Teeth may be considered to...
The periodontium is a biological structure that supports the tooth in the jaw and behave as a developmental, biological, and functional unit. Teeth may be considered to be 'suspended' in their tooth sockets which provides teeth the ability to move in response to an applied load. In terms of the protection the suspension effect of the periodontal ligament may offer dental restorations, movement in an axial direction is of interest. No device or system to measure this movement is readily available, thus a novel approach had to be developed to address the questions of this research. The device developed allowed images to be taken of the participants teeth before, during and after a participant bit down on the tooth and used to measure the displacement of the tooth in image processing software. Average maximum tooth displacement from all participants of 73.8 μm (sd = 22.5 μm) were recorded. Longer application time of bite force was associated with greater cumulative tooth displacement, for a given level of force, and female participants experienced approximately 2 μm more displacement per Newton than males. The device and methods utilised in this study has shown good potential as a measurement protocol for measurement of vertical tooth movements in vivo. The response to load the teeth in this study has shown, highlighted the visco-elastic properties of the periodontal ligament and the amount of movement recorded supports the protection that controlled tooth movement offers teeth.
Topics: Male; Humans; Female; Periodontal Ligament; Bite Force; Image Processing, Computer-Assisted; Movement; Software
PubMed: 37604099
DOI: 10.1016/j.jmbbm.2023.106059 -
International Journal of Molecular... Nov 2022The tooth-periodontium complex and its nerves have active reciprocal regulation during development and homeostasis. These effects are predominantly mediated by a range... (Review)
Review
The tooth-periodontium complex and its nerves have active reciprocal regulation during development and homeostasis. These effects are predominantly mediated by a range of molecules secreted from either the nervous system or the tooth-periodontium complex. Different strategies mimicking tooth development or physiological reparation have been applied to tooth regeneration studies, where the application of these nerve- or tooth-derived molecules has been proven effective. However, to date, basic studies in this field leave many vacancies to be filled. This literature review summarizes the recent advances in the basic studies on neural responses and regulation during tooth-periodontium development and homeostasis and points out some research gaps to instruct future studies. Deepening our understanding of the underlying mechanisms of tooth development and diseases will provide more clues for tooth regeneration.
Topics: Odontogenesis; Periodontal Ligament; Tooth; Periodontium; Homeostasis
PubMed: 36430624
DOI: 10.3390/ijms232214150 -
International Journal of Oral Science Feb 2023Fusobacterium nucleatum (F. nucleatum) is an early pathogenic colonizer in periodontitis, but the host response to infection with this pathogen remains unclear. In this...
Fusobacterium nucleatum (F. nucleatum) is an early pathogenic colonizer in periodontitis, but the host response to infection with this pathogen remains unclear. In this study, we built an F. nucleatum infectious model with human periodontal ligament stem cells (PDLSCs) and showed that F. nucleatum could inhibit proliferation, and facilitate apoptosis, ferroptosis, and inflammatory cytokine production in a dose-dependent manner. The F. nucleatum adhesin FadA acted as a proinflammatory virulence factor and increased the expression of interleukin(IL)-1β, IL-6 and IL-8. Further study showed that FadA could bind with PEBP1 to activate the Raf1-MAPK and IKK-NF-κB signaling pathways. Time-course RNA-sequencing analyses showed the cascade of gene activation process in PDLSCs with increasing durations of F. nucleatum infection. NFκB1 and NFκB2 upregulated after 3 h of F. nucleatum-infection, and the inflammatory-related genes in the NF-κB signaling pathway were serially elevated with time. Using computational drug repositioning analysis, we predicted and validated that two potential drugs (piperlongumine and fisetin) could attenuate the negative effects of F. nucleatum-infection. Collectively, this study unveils the potential pathogenic mechanisms of F. nucleatum and the host inflammatory response at the early stage of F. nucleatum infection.
Topics: Humans; Fusobacterium nucleatum; NF-kappa B; Periodontal Ligament; Signal Transduction; Fusobacterium Infections; Stem Cells
PubMed: 36754953
DOI: 10.1038/s41368-022-00213-0 -
Stem Cell Research & Therapy Dec 2022Periodontitis often causes irrevocable destruction of tooth-supporting tissues and eventually leads to tooth loss. Currently, stem cell-based tissue engineering has... (Review)
Review
BACKGROUND
Periodontitis often causes irrevocable destruction of tooth-supporting tissues and eventually leads to tooth loss. Currently, stem cell-based tissue engineering has achieved a favorable result in regenerating periodontal tissues. Moreover, cell-free therapies that aim to facilitate the recruitment of resident repair cell populations to injured sites by promoting cell mobilization and homing have become alternative options to cell therapy.
MAIN TEXT
Cell aggregates (e.g., cell sheets) retain a large amount of extracellular matrix which can improve cell viability and survival rates after implantation in vivo. Electrostatic spinning and 3D bioprinting through fabricating specific alignments and interactions scaffold structures have made promising outcomes in the construction of a microenvironment conducive to periodontal regeneration. Cell-free therapies with adding biological agents (growth factors, exosomes and conditioned media) to promote endogenous regeneration have somewhat addressed the limitations of cell therapy.
CONCLUSION
Hence, this article reviews the progress of stem cell-based tissue engineering and advanced strategies for endogenous regeneration based on stem cell derivatives in periodontal regeneration.
Topics: Humans; Periodontium; Periodontitis; Tissue Engineering; Stem Cells; Cell- and Tissue-Based Therapy; Periodontal Ligament
PubMed: 36575471
DOI: 10.1186/s13287-022-03225-z -
Genesis (New York, N.Y. : 2000) Sep 2022The periodontium supports and attaches teeth via mineralized and nonmineralized tissues. It consists of two, unique mineralized tissues, cementum and alveolar bone. In... (Review)
Review
The periodontium supports and attaches teeth via mineralized and nonmineralized tissues. It consists of two, unique mineralized tissues, cementum and alveolar bone. In between these tissues, lies an unmineralized, fibrous periodontal ligament (PDL), which distributes occlusal forces, nourishes and invests teeth, and harbors progenitor cells for dentoalveolar repair. Many unanswered questions remain regarding periodontal biology. This review will focus on recent research providing insights into one enduring mystery: the precise regulation of the hard-soft tissue borders in the periodontium which define the interfaces of the cementum-PDL-alveolar bone structure. We will focus on advances in understanding the molecular mechanisms that maintain the unmineralized PDL "between a rock and a hard place" by regulating the mineralization of cementum and alveolar bone.
Topics: Bone and Bones; Periodontal Ligament; Periodontium; Stem Cells; Tooth
PubMed: 35460154
DOI: 10.1002/dvg.23474 -
Genesis (New York, N.Y. : 2000) Sep 2022The periodontium is comprised of multiple units of mineralized and nonmineralized tissues including the cementum on the root surface, the alveolar bone, periodontal... (Review)
Review
The periodontium is comprised of multiple units of mineralized and nonmineralized tissues including the cementum on the root surface, the alveolar bone, periodontal ligament (PDL), and the gingiva. PDL contains a variety of cell populations including mesenchymal stem/progenitor cells (MSCs) termed PDLSCs, which contribute to periodontal regeneration. Recent studies utilizing mouse genetic models shed light on the identities of these mesenchymal progenitors in their native environment, particularly regarding how they contribute to homeostasis and repair of the periodontium. The current concept is that mesenchymal progenitors in the PDL are localized to the perivascular niche. Single-cell RNA sequencing (scRNA-seq) analyses reveal heterogeneity and cell-type specific markers of cells in the periodontium, as well as their developmental relationship with precursor cells in the dental follicle. The characteristics of PDLSCs and their diversity in vivo are now beginning to be unraveled thanks to insights from mouse genetic models and scRNA-seq analyses, which aid to uncover the fundamental properties of stem cells in the human PDL. The new knowledge will be highly important for developing more effective stem cell-based regenerative therapies to repair periodontal tissues in the future.
Topics: Animals; Cells, Cultured; Humans; Mesenchymal Stem Cells; Mice; Periodontal Ligament; Periodontium; Stem Cells
PubMed: 35916433
DOI: 10.1002/dvg.23495 -
Cellular & Molecular Biology Letters Jul 2023The preference for glucose oxidative mode has crucial impacts on various physiological activities, including determining stem cell fate. External mechanical factors can...
BACKGROUND
The preference for glucose oxidative mode has crucial impacts on various physiological activities, including determining stem cell fate. External mechanical factors can play a decisive role in regulating critical metabolic enzymes and pathways of stem cells. Periodontal ligament stem cells (PDLSCs) are momentous effector cells that transform mechanical force into biological signals during the reconstruction of alveolar bone. However, mechanical stimuli-induced alteration of oxidative characteristics in PDLSCs and the underlying mechanisms have not been fully elucidated.
METHODS
Herein, we examined the expression of LDH and COX4 by qRT-PCR, western blot, immunohistochemistry and immunofluorescence. We detected metabolites of lactic acid and reactive oxygen species for functional tests. We used tetramethylrhodamine methyl ester (TMRM) staining and a transmission electron microscope to clarify the mitochondrial status. After using western blot and immunofluorescence to clarify the change of DRP1, we further examined MFF, PINK1, and PARKIN by western blot. We used cyclosporin A (CsA) to confirm the regulation of mitophagy and ceased the stretching as a rescue experiment.
RESULTS
Herein, we ascertained that mechanical force could increase the level of LDH and decrease the expression of COX4 in PDLSCs. Simultaneously, the yield of reactive oxygen species (ROS) in PDLSC reduced after stretching, while lactate acid augmented significantly. Furthermore, mitochondrial function in PDLSCs was negatively affected by impaired mitochondrial membrane potential (MMP) under mechanical force, and the augment of mitochondrial fission further induced PRKN-dependent mitophagy, which was confirmed by the rescue experiments via blocking mitophagy. As a reversible physiological stimulation, the anaerobic preference of PDLSCs altered by mechanical force could restore after the cessation of force stimulation.
CONCLUSIONS
Altogether, our study demonstrates that PDLSCs under mechanical force preferred anaerobic oxidation induced by the affected mitochondrial dynamics, especially mitophagy. Our findings support an association between mechanical stimulation and the oxidative profile of stem cells, which may shed light on the mechanical guidance of stem cell maintenance and commitment, and lay a molecular foundation for periodontal tissue regeneration.
Topics: Periodontal Ligament; Anaerobiosis; Mitophagy; Reactive Oxygen Species; Oxidation-Reduction
PubMed: 37480044
DOI: 10.1186/s11658-023-00453-w -
International Journal of Oral Science Jan 2024Pyroptosis, an inflammatory caspase-dependent programmed cell death, plays a vital role in maintaining tissue homeostasis and activating inflammatory responses....
Pyroptosis, an inflammatory caspase-dependent programmed cell death, plays a vital role in maintaining tissue homeostasis and activating inflammatory responses. Orthodontic tooth movement (OTM) is an aseptic force-induced inflammatory bone remodeling process mediated by the activation of periodontal ligament (PDL) progenitor cells. However, whether and how force induces PDL progenitor cell pyroptosis, thereby influencing OTM and alveolar bone remodeling remains unknown. In this study, we found that mechanical force induced the expression of pyroptosis-related markers in rat OTM and alveolar bone remodeling process. Blocking or enhancing pyroptosis level could suppress or promote OTM and alveolar bone remodeling respectively. Using Caspase-1 mice, we further demonstrated that the functional role of the force-induced pyroptosis in PDL progenitor cells depended on Caspase-1. Moreover, mechanical force could also induce pyroptosis in human ex-vivo force-treated PDL progenitor cells and in compressive force-loaded PDL progenitor cells in vitro, which influenced osteoclastogenesis. Mechanistically, transient receptor potential subfamily V member 4 signaling was involved in force-induced Caspase-1-dependent pyroptosis in PDL progenitor cells. Overall, this study suggested a novel mechanism contributing to the modulation of osteoclastogenesis and alveolar bone remodeling under mechanical stimuli, indicating a promising approach to accelerate OTM by targeting Caspase-1.
Topics: Animals; Humans; Mice; Rats; Bone Remodeling; Caspase 1; Periodontal Ligament; Pyroptosis; Tooth Movement Techniques
PubMed: 38221531
DOI: 10.1038/s41368-023-00268-7 -
Frontiers in Endocrinology 2023Periodontium regeneration remains a significant challenge in clinics and research, and it is essential to understand the stage-specific biological process in situ....
OBJECTIVES
Periodontium regeneration remains a significant challenge in clinics and research, and it is essential to understand the stage-specific biological process in situ. However, differing findings have been reported, and the mechanism has yet to be elucidated. The periodontium of adult mice molars is considered to be stable remodeling tissue. At the same time, the continuously growing incisors and the developing dental follicle (DF) of postnatal mice highly represent fast remodeling tissue. In this study, we attempted to explore different clues of temporal and spatial comparisons to provide improved references for periodontal regeneration.
METHODS
Periodontal tissues from the developing periodontium (DeP) of postnatal mice, and continuously growing periodontium (CgP) and stable remodeling periodontium (ReP) of adult mice were isolated and compared using RNA sequencing. Based on the Dep and CgP separately compared with the ReP, differentially expressed genes and signaling pathways were analyzed using GO, KEGG databases, and Ingenuity Pathway Analysis (IPA). The results and validation were obtained by immunofluorescence staining and RT-PCR assays. Data were expressed as means ± standard deviation (SD) and analyzed by GraphPad Prism 8 software package, and one-way ANOVA was used to test multiple groups.
RESULTS
Principal component analysis showed that the three groups of periodontal tissue were successfully isolated and had distinct expression profiles. A total of 792 and 612 DEGs were identified in the DeP and CgP groups compared with the ReP. Upregulated DEGs in the DeP were closely related to developmental processes, while the CgP showed significantly enhanced cellular energy metabolism. The DeP and CgP showed a common downregulation of the immune response, with activation, migration, and recruitment of immune cells. IPA and further validation jointly suggested that the MyD88/p38 MAPK pathway played an essential regulatory role in periodontium remodeling.
CONCLUSION
Tissue development, energy metabolism, and immune response were critical regulatory processes during periodontal remodeling. Developmental and adult stages of periodontal remodeling showed different expression patterns. These results contribute to a deeper understanding of periodontal development and remodeling and may provide references for periodontal regeneration.
Topics: Mice; Animals; Periodontium; Periodontal Ligament; Transcriptome
PubMed: 37008900
DOI: 10.3389/fendo.2023.1154931 -
International Journal of Molecular... Feb 2022Leptin is a non-glycosylated 16 kDa protein synthesized mainly in adipose cells. The main function of leptin is to regulate energy homeostasis and weight control in a... (Review)
Review
Leptin is a non-glycosylated 16 kDa protein synthesized mainly in adipose cells. The main function of leptin is to regulate energy homeostasis and weight control in a central manner. There is increasing evidence that leptin also has systemic effects, acting as a link between innate and acquired immune responses. The expression of leptin and its receptor in human dental pulp and periradicular tissues have already been described, as well as several stimulatory effects of leptin protein expression in dental and periodontal tissues. The aim of this paper was to review and to compile the reported scientific literature on the role and effects of leptin in the dental pulp and periapical tissues. Twelve articles accomplished the inclusion criteria, and a comprehensive narrative review was carried out. Review of the available scientific literature concluded that leptin has the following effects on pulpal and periapical physiology: 1) Stimulates odontogenic differentiation of dental pulp stem cells (DPSCs), 2) Increases the expression of dentin sialophosphoprotein (DSPP) and dentin matrix protein-1 (DMP-1), odontoblastic proteins involved in odontoblastic differentiation and dentin mineralization, 3) Stimulates vascular endothelial growth factor (VEGF) expression in human dental pulp tissue and primary cultured cells of human dental pulp (hDPCs), 4) Stimulates angiogenesis in rat dental pulp cells, and 5) Induces the expression of interleucinas 6 and 8 in human periodontal ligament cells (hPDLCs). There is evidence which suggests that leptin is implicated in the dentin mineralization process and in pulpal and periapical inflammatory and reparative responses.
Topics: Animals; Cell Differentiation; Dental Pulp; Humans; Leptin; Odontogenesis; Periodontal Ligament
PubMed: 35216099
DOI: 10.3390/ijms23041984