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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 -
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 -
Journal of Prosthodontic Research Oct 2014Periodontal ligament (PDL) plays critical roles in the development and maintenance of periodontium such as tooth eruption and dissipation of masticatory force. The... (Review)
Review
Periodontal ligament (PDL) plays critical roles in the development and maintenance of periodontium such as tooth eruption and dissipation of masticatory force. The mechanical properties of PDL are mainly derived from fibrillar type I collagen, the most abundant extracellular component. The biosynthesis of type I collagen is a long, complex process including a number of intra- and extracellular post-translational modifications. The final modification step is the formation of covalent intra- and intermolecular cross-links that provide collagen fibrils with stability and connectivity. It is now clear that collagen post-translational modifications are regulated by groups of specific enzymes and associated molecules in a tissue-specific manner; and these modifications appear to change in response to mechanical force. This review focuses on the effect of mechanical loading on collagen biosynthesis and fibrillogenesis in PDL with emphasis on the post-translational modifications of collagens, which is an important molecular aspect to understand in the field of prosthetic dentistry.
Topics: Animals; Collagen Type I; Epigenesis, Genetic; Gene Expression Regulation, Developmental; Humans; Molecular Chaperones; Peptidylprolyl Isomerase; Periodontal Ligament; Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase; Prolyl Hydroxylases; Prosthodontics; Protein Processing, Post-Translational
PubMed: 25311991
DOI: 10.1016/j.jpor.2014.08.003 -
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 -
Journal of Dental Research Mar 2018The load-bearing dentoalveolar fibrous joint is composed of biomechanically active periodontal ligament (PDL), bone, cementum, and the synergistic entheses of PDL-bone... (Review)
Review
The load-bearing dentoalveolar fibrous joint is composed of biomechanically active periodontal ligament (PDL), bone, cementum, and the synergistic entheses of PDL-bone and PDL-cementum. Physiologic and pathologic loads on the dentoalveolar fibrous joint prompt natural shifts in strain gradients within mineralized and fibrous tissues and trigger a cascade of biochemical events within the widened and narrowed sites of the periodontal complex. This review highlights data from in situ biomechanical simulations that provide tooth movements relative to the alveolar socket. The methods and subsequent results provide a reasonable approximation of strain-regulated biochemical events resulting in mesial mineral formation and distal resorption events within microanatomical regions at the ligament-tethered/enthesial ends. These biochemical events, including expressions of biglycan, decorin, chondroitin sulfated neuroglial 2, osteopontin, and bone sialoprotein and localization of various hypertrophic progenitors, are observed at the alkaline phosphatase-positive widened site, resulting in mineral formation and osteoid/cementoid layers. On the narrowed side, tartrate-resistant acid phosphatase regions can lead to a sequence of clastic activities resulting in resorption pits in bone and cementum. These strain-regulated biochemical and subsequently biomineralization events in the load-bearing periodontal complex are critical for maintenance of the periodontal space and overall macroscale joint biomechanics.
Topics: Adaptation, Physiological; Animals; Biomechanical Phenomena; Bone and Bones; Dental Cementum; Dental Stress Analysis; Humans; Mastication; Mouth Diseases; Periodontal Ligament; Tooth Crown
PubMed: 29364757
DOI: 10.1177/0022034517744556 -
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 -
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 -
Frontiers of Oral Biology 2016The periodontal ligament (PDL) and alveolar bone are two critical tissues for understanding orthodontic tooth movement. The current literature is replete with... (Review)
Review
The periodontal ligament (PDL) and alveolar bone are two critical tissues for understanding orthodontic tooth movement. The current literature is replete with descriptive studies of multiple cell types and their matrices in the PDL and alveolar bone, but is deficient with how stem/progenitor cells differentiate into PDL and alveolar bone cells. Can one type of orthodontic force with a specific magnitude and frequency activate osteoblasts, whereas another force type activates osteoclasts? This chapter will discuss the biology of not only mature cells and their matrices in the periodontal ligament and alveolar bone, but also stem/progenitor cells that differentiate into fibroblasts, osteoblasts and osteoclasts. Key advances in tooth movement rely on further understanding of osteoblast and fibroblast differentiation from mesenchymal stem/progenitor cells, and osteoclastogenesis from the hematopoietic/monocyte lineage.
Topics: Adaptation, Physiological; Alveolar Process; Cell Differentiation; Cell Lineage; Fibroblasts; Humans; Mesenchymal Stem Cells; Osteoblasts; Osteoclasts; Periodontal Ligament; Tooth Movement Techniques
PubMed: 26599112
DOI: 10.1159/000351894