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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 -
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 -
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 -
Postepy Higieny I Medycyny... Dec 2013The mechanism of orthodontic teeth movement is not entirely explained. The principal reaction on tissues at the cellular and molecular level is initiated by the force... (Review)
Review
The mechanism of orthodontic teeth movement is not entirely explained. The principal reaction on tissues at the cellular and molecular level is initiated by the force applied to the tooth crown and transferred in turn upon the periodontal ligament (PDL). It seems, therefore, that the PDL and particularly its properties play a key role in bone remodelling. One of the more commonly used methods, which is capable of analysis of a wide range of orthodontic movements or distribution of stress and strain within teeth and periodontium, is the finite element method (FEM). Aiming to achieve the FEM model as close as possible to in vivo conditions, it is necessary to account for accurate material properties. The aim of the present study is to compare particular studies and descriptions of material characteristics of the PDL. The analysis of available articles shows how imperfect modern descriptions of PDL material properties available today are, which in the precise method could allow the analysis of the occurrences within the in vivo processes in a non-destructive manner. The complicated anatomy and physiology of PDL, which incur significant parameter changes with age and disease susceptibility, make the accurate description of this material so difficult. The available study results show that those characteristics should be precise and complicated, which undoubtedly impedes the calculation processes but generates reliable results.
Topics: Bone Remodeling; Computer Simulation; Finite Element Analysis; Humans; Models, Biological; Periodontal Ligament; Stress, Mechanical; Tooth Migration; Tooth Mobility
PubMed: 24379266
DOI: 10.5604/17322693.1079820 -
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 -
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 -
Annals of Biomedical Engineering Jan 2017Periodontitis is defined as a chronic inflammatory condition, characterized by destruction of the periodontium, composed of hard (i.e. alveolar bone and cementum) and... (Review)
Review
Periodontitis is defined as a chronic inflammatory condition, characterized by destruction of the periodontium, composed of hard (i.e. alveolar bone and cementum) and soft tissues (i.e. gingiva and periodontal ligament) surrounding and supporting the teeth. In severe cases, reduced periodontal support can lead to tooth loss, which requires tissue augmentation or procedures that initiate a repair, yet ideally a regenerative response. However, mimicking the three-dimensional complexity and functional integration of the different tissue components via scaffold- and/or matrix-based guided tissue engineering represents a great challenge. Additive biomanufacturing, a manufacturing method in which objects are designed and fabricated in a layer-by-layer manner, has allowed a paradigm shift in the current manufacturing of medical devices and implants. This shift from design-to-manufacture to manufacture-to-design, seen from a translational research point of view, provides the biomedical engineering and periodontology communities a technology with the potential to achieve tissue regeneration instead of repair. In this review, the focus is put on additively biomanufactured scaffolds for periodontal applications. Besides a general overview of the concept of additive biomanufacturing within this field, different developed scaffold designs are described. To conclude, future directions regarding advanced biomaterials and additive biomanufacturing technologies for applications in regenerative periodontology are highlighted.
Topics: Animals; Biocompatible Materials; Gingiva; Humans; Implants, Experimental; Periodontal Ligament; Periodontitis; Regeneration; Tissue Scaffolds
PubMed: 27473707
DOI: 10.1007/s10439-016-1687-2 -
Biomedicine & Pharmacotherapy =... Jan 2021Periodontitis is the most common chronic inflammatory disease, and a leading cause of tooth loss. Characterized by resorption of alveolar process and destruction of... (Review)
Review
Periodontitis is the most common chronic inflammatory disease, and a leading cause of tooth loss. Characterized by resorption of alveolar process and destruction of periodontal ligaments, periodontitis can impact not only periodontal tissues but also systemic diseases, such as diabetes, cardiovascular diseases, and respiratory infections. Currently, it is a hotspot to manage destruction and gain regeneration of periodontal tissues. Increasing evidence indicates that the Wnt signaling plays an important role in homeostasis of periodontal tissues, functions of periodontal derived cells, and progression of periodontitis. Its molecule expressions were abnormal in periodontitis. As such, modulators targeting the Wnt signaling may be an adjuvant therapy for periodontitis treatment. This review elucidates the role of Wnt signaling and its molecules, with a view to develop a potential application of drugs targeting the Wnt signaling for periodontitis treatment.
Topics: Animals; Anti-Inflammatory Agents; Humans; Molecular Targeted Therapy; Periodontal Ligament; Periodontitis; Periodontium; Stem Cells; Wnt Signaling Pathway
PubMed: 33227711
DOI: 10.1016/j.biopha.2020.110935 -
Journal of Dental Research Nov 2022Successful periodontal repair and regeneration requires the coordinated responses from soft and hard tissues as well as the soft tissue-to-bone interfaces. Inspired by...
Successful periodontal repair and regeneration requires the coordinated responses from soft and hard tissues as well as the soft tissue-to-bone interfaces. Inspired by the hierarchical structure of native periodontal tissues, tissue engineering technology provides unique opportunities to coordinate multiple cell types into scaffolds that mimic the natural periodontal structure in vitro. In this study, we designed and fabricated highly ordered multicompartmental scaffolds by melt electrowriting, an advanced 3-dimensional (3D) printing technique. This strategy attempted to mimic the characteristic periodontal microenvironment through multicompartmental constructs comprising 3 tissue-specific regions: 1) a bone compartment with dense mesh structure, 2) a ligament compartment mimicking the highly aligned periodontal ligaments (PDLs), and 3) a transition region that bridges the bone and ligament, a critical feature that differentiates this system from mono- or bicompartmental alternatives. The multicompartmental constructs successfully achieved coordinated proliferation and differentiation of multiple cell types in vitro within short time, including both ligamentous- and bone-derived cells. Long-term 3D coculture of primary human osteoblasts and PDL fibroblasts led to a mineral gradient from calcified to uncalcified regions with PDL-like insertions within the transition region, an effect that is challenging to achieve with mono- or bicompartmental platforms. This process effectively recapitulates the key feature of interfacial tissues in periodontium. Collectively, this tissue-engineered approach offers a fundament for engineering periodontal tissue constructs with characteristic 3D microenvironments similar to native tissues. This multicompartmental 3D printing approach is also highly compatible with the design of next-generation scaffolds, with both highly adjustable compartmentalization properties and patient-specific shapes, for multitissue engineering in complex periodontal defects.
Topics: Humans; Tissue Engineering; Tissue Scaffolds; Periodontium; Printing, Three-Dimensional; Periodontal Ligament
PubMed: 35689382
DOI: 10.1177/00220345221099823