-
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 -
Cellular Reprogramming Apr 2023Exosomes are one kind of small-cell extracellular membranous vesicles that can regulate intercellular communication and give rise to mediating the biological behaviors... (Review)
Review
Exosomes are one kind of small-cell extracellular membranous vesicles that can regulate intercellular communication and give rise to mediating the biological behaviors of cells, involving in tissue formation, repair, the modulation of inflammation, and nerve regeneration. The abundant kinds of cells can secret exosomes, among them, mesenchymal stem cells (MSCs) are very perfect cells for mass production of exosomes. Dental tissue-derived mesenchymal stem cells (DT-MSCs), including dental pulp stem cells, stem cells from exfoliated deciduous teeth, stem cells from apical papilla, stem cells from human periodontal ligament (PDLSCs), gingiva-derived mesenchymal stem cells, dental follicle stem cells, tooth germ stem cells, and alveolar bone-derived mesenchymal stem cells, are now known as a potent tool in the area of cell regeneration and therapy, more importantly, DT-MSCs can also release numerous types of exosomes, participating in the biological functions of cells. Hence, we briefly depict the characteristics of exosomes, give a detailed description of the biological functions and clinical application in some respects of exosomes from DT-MSCs through systematically reviewing the latest evidence, and provide a rationale for their use as tools for potential application in tissue engineering.
Topics: Humans; Exosomes; Mesenchymal Stem Cells; Periodontal Ligament; Gingiva; Stem Cells; Cell Differentiation
PubMed: 37053510
DOI: 10.1089/cell.2022.0147 -
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 -
Oral Diseases Apr 2024Periodontitis is the major cause of tooth loss in adults and is mainly characterized by alveolar bone destruction. Elucidating the mesenchymal stem cell (MSC)/progenitor... (Review)
Review
Periodontitis is the major cause of tooth loss in adults and is mainly characterized by alveolar bone destruction. Elucidating the mesenchymal stem cell (MSC)/progenitor populations of alveolar bone formation will provide valuable insights into regenerative approaches to clinical practice, such as endogenous regeneration and stem-cell-based tissue engineering therapies. Classically, MSCs residing in the bone marrow, periosteum, periodontal ligament (PDL), and even the gingiva are considered to be osteogenic progenitors. Furthermore, the contributions of MSCs expressing specific markers, including Gli1, Axin2, PTHrP, LepR, and α-SMA, to alveolar bone formation have been studied using cell lineage tracing and gene knockout models. In this review, we describe the MSCs/progenitors of alveolar bone and the biological properties of different subpopulations of MSCs involved in alveolar bone development, remodeling, injury repair, and regeneration.
Topics: Humans; Mesenchymal Stem Cells; Periodontium; Osteogenesis; Periodontitis; Periodontal Ligament; Animals
PubMed: 36648363
DOI: 10.1111/odi.14507 -
Journal of Periodontology May 2023The resolution of inflammation is an active process mediated by specialized lipid mediators called lipoxins and resolvins. Periodontal ligament fibroblasts (PDLFs) play...
BACKGROUND
The resolution of inflammation is an active process mediated by specialized lipid mediators called lipoxins and resolvins. Periodontal ligament fibroblasts (PDLFs) play a significant role in periodontal regeneration. The purpose of the current study was to determine the impact of resolvin D1 (RvD1) on human PDLF cell wound healing and proliferation, receptor expression (G-protein-coupled receptor 32 [GPR32] and formyl peptide receptor 2 [ALX/FPR2]), and cytokine expression and release.
METHODS
PDLFs were stimulated with interleukin-1β (IL-1β) (500 pg/ml) with and without RvD1 (100 nM). RvD1 receptor expression was determined by quantitative real-time polymerase chain reaction (qPCR), immunofluorescence microscopy, and fluorescence-activated cell sorting. Wound closure was measured by a scratch assay, and proliferation was determined by bromodeoxyuridine incorporation. Interleukin-6 (IL-6), interleukin-8 (IL-8), monocyte chemoattractant protein-1, cyclooxygenase-2, matrix metalloproteinases-1, -2, and -3 (MMP-1, -2, and -3), tissue inhibitors of metalloproteinases-1 and -2 (TIMP-1 and -2), prostaglandin E2, and osteoprotegerin (OPG) gene expression and production were measured using qPCR and Western blotting, multiplex immunoassay, and enzyme-linked immunosorbent assay.
RESULTS
PDLF expressed GPR32 and ALX/FPR2. RvD1 reversed IL-1β-induced inhibition of wound healing and proliferation of PDLF. IL-1β also induced the production of proinflammatory cytokines and MMPs. This effect was reversed by RvD1. RvD1 reversed IL-1β-induced inhibition of TIMP-1, TIMP-2, and OPG.
CONCLUSION
The data suggested that RvD1 has a pro-wound healing, proliferative, and anti-inflammatory impact on the PDLF that favors periodontal regeneration.
Topics: Humans; Tissue Inhibitor of Metalloproteinase-1; Periodontal Ligament; Inflammation; Docosahexaenoic Acids; Fibroblasts; Cytokines
PubMed: 36416879
DOI: 10.1002/JPER.22-0462 -
Journal of Veterinary Dentistry Mar 2022Periodontal disease is one of the most common diagnoses in small animal veterinary medicine. This infectious disease of the periodontium is characterized by the... (Review)
Review
Periodontal disease is one of the most common diagnoses in small animal veterinary medicine. This infectious disease of the periodontium is characterized by the inflammation and destruction of the supporting structures of teeth, including periodontal ligament, cementum, and alveolar bone. Traditional periodontal repair techniques make use of open flap debridement, application of graft materials, and membranes to prevent epithelial downgrowth and formation of a long junctional epithelium, which inhibits regeneration and true healing. These techniques have variable efficacy and are made more challenging in veterinary patients due to the cost of treatment for clients, need for anesthesia for surgery and reevaluation, and difficulty in performing necessary diligent home care to maintain oral health. Tissue engineering focuses on methods to regenerate the periodontal apparatus and not simply to repair the tissue, with the possibility of restoring normal physiological functions and health to a previously diseased site. This paper examines tissue engineering applications in periodontal disease by discussing experimental studies that focus on dogs and other animal species where it could potentially be applied in veterinary medicine. The main areas of focus of tissue engineering are discussed, including scaffolds, signaling molecules, stem cells, and gene therapy. To date, although outcomes can still be unpredictable, tissue engineering has been proven to successfully regenerate lost periodontal tissues and this new possibility for treating veterinary patients is discussed.
Topics: Animals; Dental Cementum; Dog Diseases; Dogs; Guided Tissue Regeneration, Periodontal; Humans; Periodontal Diseases; Periodontal Ligament; Periodontium; Tissue Engineering
PubMed: 34935526
DOI: 10.1177/08987564211065137 -
Journal of Periodontal Research Jun 2020The periodontium is a highly hierarchically organized organ composed of gingiva, alveolar bone, periodontal ligament and cementum. Periodontitis leads to the destruction... (Review)
Review
The periodontium is a highly hierarchically organized organ composed of gingiva, alveolar bone, periodontal ligament and cementum. Periodontitis leads to the destruction of hard and soft tissues ultimately leading to a loss of the teeth supporting apparatus. Current treatments are capable of limiting the disease progression; however, true regeneration, characterized by perpendicularly oriented periodontal ligament fibre attachment to cementum on the root surface remains challenging. Tissue engineering approaches have been developed to enhance regeneration via micro-engineered topographical features, purposely designed to guide the insertion of the regenerated ligament to the root surface. This review reports on the recent advancements in scaffold manufacturing methodologies for generating fibre guiding properties and provides a critical insight in the current limitations of these techniques for the formation of functional periodontal attachment.
Topics: Dental Cementum; Humans; Periodontal Ligament; Periodontium; Regeneration; Tissue Engineering; Tissue Scaffolds
PubMed: 32134120
DOI: 10.1111/jre.12729 -
The Chinese Journal of Dental Research Sep 2021Tooth eruption is closely linked to the normal development of dentition and proper establishment of occlusion. Disturbances in tooth eruption may affect oral... (Review)
Review
Tooth eruption is closely linked to the normal development of dentition and proper establishment of occlusion. Disturbances in tooth eruption may affect oral physiological functions, facial contour and aesthetics; it is therefore important to understand the eruption process. This process is a complex biological event involving dynamic changes at the tissue and cellular levels. It is guided by anatomical structures as well as biological and molecular factors that result in the movement of the tooth to its final functional position in the oral cavity. Evidence increasingly suggests that stem cells contribute to tooth development and eruption. Multiple stem cell populations have been discovered in teeth and in their supporting tissues, such as dental follicle precursor cells, orofacial bone-/bone marrow-derived mesenchymal stem cells, periodontal ligament stem cells, stem cells from the apical papilla and dental pulp stem cells. These stem cells exhibit distinct differentiation capacities and are closely linked to alveolar bone remodelling, periodontium development and root formation during the eruption process. The present review summarises the current knowledge of the characteristics and functions of orofacial stem cells in tooth eruption, with a particular focus on recent discoveries concerning their lineage allocation and regulatory mechanisms.
Topics: Cell Differentiation; Periodontal Ligament; Stem Cells; Tooth; Tooth Eruption
PubMed: 34491008
DOI: 10.3290/j.cjdr.b1965049 -
Genesis (New York, N.Y. : 2000) Sep 2022Periodontium possesses stem cell populations for its self-maintenance and regeneration, and has been proved to be an optimal stem cell source for tissue engineering. In... (Review)
Review
Periodontium possesses stem cell populations for its self-maintenance and regeneration, and has been proved to be an optimal stem cell source for tissue engineering. In vitro studies have shown that stem cells can be isolated from periodontal ligament, alveolar bone marrow and gingiva. In recent years, more studies have focused on identification of periodontal stem cells in vivo. Multiple genetic markers, including Gli1, Prx1, Axin2, αSMA, and LepR, were identified with the lineage tracing approaches. Characteristics, functions, and regulatory mechanisms of specific populations expressing one of these markers have been investigated. In vivo studies also revealed that periodontal stem cells can be regulafrted by different niche and mechanisms including intercellular interactions, ECM and multiple secreted factors. In this review, we summarized the current knowledge of in vitro characteristics and in vivo markers of periodontal stem cells, and discussed the specific regulating niche.
Topics: Genetic Markers; Guided Tissue Regeneration, Periodontal; Periodontal Ligament; Stem Cells; Zinc Finger Protein GLI1
PubMed: 35894656
DOI: 10.1002/dvg.23494