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Dental Clinics of North America Oct 2022As a widespread chronical disease, periodontitis progressively destroys tooth-supporting structures (periodontium) and eventually leads to tooth loss. Therefore,... (Review)
Review
As a widespread chronical disease, periodontitis progressively destroys tooth-supporting structures (periodontium) and eventually leads to tooth loss. Therefore, regeneration of damaged/lost periodontal tissues has been a major subject in periodontal research. During periodontal tissue regeneration, biomaterials play pivotal roles in improving the outcome of the periodontal therapy. With the advancement of biomaterial science and engineering in recent years, new biomimetic materials and scaffolding fabrication technologies have been proposed for periodontal tissue regeneration. This article summarizes recent progress in periodontal tissue regeneration from a biomaterial perspective. First, various guide tissue regeneration/guide bone regeneration membranes and grafting biomaterials for periodontal tissue regeneration are overviewed. Next, the recent development of multifunctional scaffolding biomaterials for alveolar bone/periodontal ligament/cementum regeneration is summarized. Finally, clinical care points and perspectives on the use of biomimetic scaffolding materials to reconstruct the hierarchical periodontal tissues are provided.
Topics: Biocompatible Materials; Guided Tissue Regeneration, Periodontal; Humans; Periodontal Ligament; Periodontium; Tissue Engineering
PubMed: 36216452
DOI: 10.1016/j.cden.2022.05.011 -
International Journal of Oral Science Jun 2021Nowadays, orthodontic treatment has become increasingly popular. However, the biological mechanisms of orthodontic tooth movement (OTM) have not been fully elucidated.... (Review)
Review
Nowadays, orthodontic treatment has become increasingly popular. However, the biological mechanisms of orthodontic tooth movement (OTM) have not been fully elucidated. We were aiming to summarize the evidences regarding the mechanisms of OTM. Firstly, we introduced the research models as a basis for further discussion of mechanisms. Secondly, we proposed a new hypothesis regarding the primary roles of periodontal ligament cells (PDLCs) and osteocytes involved in OTM mechanisms and summarized the biomechanical and biological responses of the periodontium in OTM through four steps, basically in OTM temporal sequences, as follows: (1) Extracellular mechanobiology of periodontium: biological, mechanical, and material changes of acellular components in periodontium under orthodontic forces were introduced. (2) Cell strain: the sensing, transduction, and regulation of mechanical stimuli in PDLCs and osteocytes. (3) Cell activation and differentiation: the activation and differentiation mechanisms of osteoblast and osteoclast, the force-induced sterile inflammation, and the communication networks consisting of sensors and effectors. (4) Tissue remodeling: the remodeling of bone and periodontal ligament (PDL) in the compression side and tension side responding to mechanical stimuli and root resorption. Lastly, we talked about the clinical implications of the updated OTM mechanisms, regarding optimal orthodontic force (OOF), acceleration of OTM, and prevention of root resorption.
Topics: Humans; Osteoblasts; Osteoclasts; Periodontal Ligament; Periodontium; Root Resorption; Tooth Movement Techniques
PubMed: 34183652
DOI: 10.1038/s41368-021-00125-5 -
Developmental Cell Sep 2020Teeth are attached to alveolar bone by the periodontal ligament (PDL), which contains stem cells supporting tissue turnover. Here, we identified Gli1+ cells in adult...
Teeth are attached to alveolar bone by the periodontal ligament (PDL), which contains stem cells supporting tissue turnover. Here, we identified Gli1+ cells in adult mouse molar PDL as multi-potential stem cells (PDLSCs) giving rise to PDL, alveolar bone, and cementum. They support periodontium tissue turnover and injury repair. Gli1+ PDLSCs are surrounding the neurovascular bundle and more enriched in the apical region. Canonical Wnt signaling is essential for their activation. Alveolar bone osteocytes negatively regulate Gli1+ PDLSCs activity through sclerostin, a Wnt inhibitor. Blockage of sclerostin accelerates the PDLSCs lineage contribution rate in vivo. Sclerostin expression is modulated by physiological occlusal force. Removal of occlusal force upregulates sclerostin and inhibits PDLSCs activation. In summary, Gli1+ cells are the multipotential PDLSCs in vivo. Osteocytes provide negative feedback to PDLSCs and inhibit their activities through sclerostin. Physiological occlusal force indirectly regulates PDLSCs activities by fine-tuning this feedback loop.
Topics: Animals; Cell Differentiation; Cells, Cultured; Mice, Transgenic; Multipotent Stem Cells; Osteocytes; Periodontal Ligament; Periodontium; Regeneration; Stem Cells; Wnt Signaling Pathway; Zinc Finger Protein GLI1
PubMed: 32652075
DOI: 10.1016/j.devcel.2020.06.006 -
Clinical Oral Investigations Jan 2022The aim of this in vitro and in vivo study was to investigate the interaction of periodontitis and orthodontic tooth movement on interleukin (IL)-6 and C-X-C motif...
OBJECTIVES
The aim of this in vitro and in vivo study was to investigate the interaction of periodontitis and orthodontic tooth movement on interleukin (IL)-6 and C-X-C motif chemokine 2 (CXCL2).
MATERIALS AND METHODS
The effect of periodontitis and/or orthodontic tooth movement (OTM) on alveolar bone and gingival IL-6 and CXCL2 expressions was studied in rats by histology and RT-PCR, respectively. The animals were assigned to four groups (control, periodontitis, OTM, and combination of periodontitis and OTM). The IL-6 and CXCL2 levels were also studied in human gingival biopsies from periodontally healthy and periodontitis subjects by RT-PCR and immunohistochemistry. Additionally, the synthesis of IL-6 and CXCL2 in response to the periodontopathogen Fusobacterium nucleatum and/or mechanical strain was studied in periodontal fibroblasts by RT-PCR and ELISA.
RESULTS
Periodontitis caused an increase in gingival levels of IL-6 and CXCL2 in the animal model. Moreover, orthodontic tooth movement further enhanced the bacteria-induced periodontal destruction and gingival IL-6 gene expression. Elevated IL-6 and CXCL2 gingival levels were also found in human periodontitis. Furthermore, mechanical strain increased the stimulatory effect of F. nucleatum on IL-6 protein in vitro.
CONCLUSIONS
Our study suggests that orthodontic tooth movement can enhance bacteria-induced periodontal inflammation and thus destruction and that IL-6 may play a pivotal role in this process.
CLINICAL RELEVANCE
Orthodontic tooth movement should only be performed after periodontal therapy. In case of periodontitis relapse, orthodontic therapy should be suspended until the periodontal inflammation has been successfully treated and thus the periodontal disease is controlled again.
Topics: Animals; Fusobacterium nucleatum; Gingiva; Periodontal Ligament; Periodontitis; Rats; Tooth Movement Techniques
PubMed: 34024010
DOI: 10.1007/s00784-021-03988-4 -
Scientific Reports Jun 2020To evaluate tooth behaviours under various maxillary incisor retraction protocols for clear aligner therapy. A three-dimensional finite element model of maxillary...
To evaluate tooth behaviours under various maxillary incisor retraction protocols for clear aligner therapy. A three-dimensional finite element model of maxillary dentition was constructed for first premolar extraction. A loading method was developed to mimic the mode of action of clear aligners for incisor en masse retraction. Three protocols with different amounts of retraction and intrusion on incisors were designed. Initial tooth displacements and stresses on periodontal ligaments were analysed with ANSYS software. The central (U) and lateral (U) incisors exhibited uncontrolled lingual tipping and extrusion upon 0.25 mm retraction. U1 exhibited translation movement, while U underwent less tipping during 0.2 mm retraction and 0.15 mm intrusion. Labial tipping and intrusion of U and bodily intrusion of U were observed during 0.1 mm of retraction and 0.23 mm of intrusion. With the additional intrusion on incisors, canine showed extrusion movement, and higher stresses on periodontal ligaments were shifted from U to canines. Incisors also exhibited different mesial-distal angulation in the three simulations, while posterior teeth all suffered mesial inclination. Incorporating intrusion displacement in clear aligners led to a tendency of lingual root movement during incisor retraction. The complexity of tooth movement should be recognized regarding clear aligner therapy.
Topics: Bicuspid; Biomechanical Phenomena; Dentition; Finite Element Analysis; Humans; Incisor; Maxilla; Orthodontic Appliances, Removable; Periodontal Ligament; Printing, Three-Dimensional; Software; Stress, Mechanical; Tooth Mobility; Tooth Movement Techniques
PubMed: 32576935
DOI: 10.1038/s41598-020-67273-2 -
Stem Cell Research & Therapy Nov 2019The inflammation and regeneration process may be accompanied by the shift in the M1/M2 polarization of macrophages to adapt to extracellular signals. How the macrophages...
BACKGROUND
The inflammation and regeneration process may be accompanied by the shift in the M1/M2 polarization of macrophages to adapt to extracellular signals. How the macrophages responded to the altered immunological environment in the periodontal niche after stem cell transplantation has never been explored. The purpose of present study is to investigate whether M1/M2 polarization of macrophages participated in the tissue homeostasis and wound healing during periodontal ligament stem cell (PDLSC)-based periodontal regeneration.
METHODS
A rat periodontal defect model was utilized to observe the regeneration process in the PDLSC transplantation-enhanced periodontal repair. Dynamic changes in the markers of M1/M2 macrophages were observed on days 3, 7, and 21 post surgery. In addition, the outcome of regeneration was analyzed on day 21 after surgery. To further investigate the effect of PDLSCs on macrophage polarization, the conditioned medium of PDLSCs was utilized to treat M0, M1, and M2 macrophages for 24 h; markers of M1/M2 polarization were evaluated in macrophages.
RESULTS
Elevated bone volume and average thickness of bone trabecular was observed in the PDLSC-treated group by micro-computed tomography on day 21. In addition, enhanced periodontal regeneration was observed in the PDLSC-treated group with cementum-like structure regeneration and collagen fiber formation, which inserted into the newly formed cementum. On day 3, PDLSC transplantation increased IL-10 level in the periodontal tissue, while decreased TNF-α in the early stage of periodontal regeneration. On day 7, enhanced CD163+ cell infiltration and heightened expression of markers of M2 macrophages were observed. Furthermore, conditioned medium from PDLSC culture induced macrophage polarization towards the anti-inflammatory phenotype by downregulating TNF-α and upregulating IL-10, Arg-1, and CD163 in vitro.
CONCLUSIONS
PDLSCs could induce macrophage polarization towards the M2 phenotype, and the shift in the polarization towards M2 macrophages in the early stage of tissue repair contributed to the enhanced periodontal regeneration after stem cell transplantation. Therefore, signals from the transplanted PDLSCs might alter the immune microenvironment to enhance periodontal regeneration.
Topics: Animals; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Cell Count; Cell Polarity; Cells, Cultured; Culture Media, Conditioned; Cytokines; Interferon-gamma; Interleukin-4; Lipopolysaccharides; Macrophages; Male; Paracrine Communication; Periodontal Ligament; Rats, Sprague-Dawley; Receptors, Cell Surface; Regeneration; Stem Cells
PubMed: 31730019
DOI: 10.1186/s13287-019-1409-4 -
International Endodontic Journal Oct 2022To assess the cytocompatibility and bioactive potential of the new calcium silicate cement-based sealer AH Plus Bioceramic Sealer (AHPbcs) on human periodontal ligament...
AIM
To assess the cytocompatibility and bioactive potential of the new calcium silicate cement-based sealer AH Plus Bioceramic Sealer (AHPbcs) on human periodontal ligament stem cells (hPDLSCs) compared with the epoxy resin-based sealer AH Plus (AHP) and the calcium silicate cement-based sealer Endosequence BC Sealer (ESbcs).
METHODOLOGY
Standardized sample discs and 1:1, 1:2 and 1:4 eluates of the tested materials were prepared. The following assays were performed: surface element distribution via SEM-EDX, cell attachment and morphology via SEM, cell viability via a MTT assay, cell migration/proliferation via a wound-healing assay, osteo/cemento/odontogenic marker expression via RT-qPCR and cell mineralized nodule formation via Alizarin Red S staining. HPDLSCs were isolated from extracted third molars. Comparisons were made with hPDLSCs cultured in unconditioned (negative control) or osteogenic (positive control) culture media. Statistical significance was established at p < .05.
RESULTS
A higher peak of Ca + was detected from ESbcs compared with AHPbcs and AHP in SEM-EDX. Both AHPbcs and ESbcs showed significantly positive results in the cytocompatibility assays (cell viability, migration/proliferation, attachment and morphology) compared with a negative control group, whilst AHP showed significant negative results. Both AHPbcs and ESbcs exhibited an upregulation of at least one osteo/odonto/cementogenic marker compared with the negative and positive control groups. Both ESbcs and AHPbcs showed a significantly higher calcified nodule formation than the negative and positive control groups, indicative of their biomineralization potential and were also significantly higher than AHP group.
CONCLUSION
AH Plus Bioceramic Sealer exhibited a significantly higher cytocompatibility and bioactive potential than AH Plus and a similar cytocompatibility to that of Endosequence BC Sealer. Endosequence BC Sealer exhibited a significantly higher mineralization potential than the other tested sealers. The results from this in vitro study act as supporting evidence for the use of AH Plus Bioceramic Sealer in root canal treatment.
Topics: Calcium Compounds; Epoxy Resins; Humans; Materials Testing; Periodontal Ligament; Root Canal Filling Materials; Silicates
PubMed: 35950780
DOI: 10.1111/iej.13805 -
Cell Proliferation Oct 2020Mechanical force plays an important role in modulating stem cell fate and behaviours. However, how periodontal ligament stem cells (PDLSCs) perceive mechanical stimulus...
OBJECTIVES
Mechanical force plays an important role in modulating stem cell fate and behaviours. However, how periodontal ligament stem cells (PDLSCs) perceive mechanical stimulus and transfer it into biological signals, and thereby promote alveolar bone remodelling, is unclear.
MATERIALS AND METHODS
An animal model of force-induced tooth movement and a compressive force in vitro was used. After force application, tooth movement distance, mesenchymal stem cell and osteoclast number, and proinflammatory cytokine expression were detected in periodontal tissues. Then, rat primary PDLSCs with or without force loading were isolated, and their stem cell characteristics including clonogenicity, proliferation, multipotent differentiation and immunoregulatory properties were evaluated. Under compressive force in vitro, the effects of the ERK signalling pathway on PDLSC characteristics were evaluated by Western blotting.
RESULTS
Mechanical force in vivo induced PDLSC proliferation, which was accompanied with inflammatory cytokine accumulation, osteoclast differentiation and TRPV4 activation; the force-stimulated PDLSCs showed greater clonogenicity and proliferation, reduced differentiation ability, improved induction of macrophage migration, osteoclast differentiation and proinflammatory factor expression. The biological changes induced by mechanical force could be partially suppressed by TRPV4 inhibition. Mechanistically, force-induced activation of TRPV4 in PDLSCs regulated osteoclast differentiation by affecting the RANKL/OPG system via ERK signalling.
CONCLUSIONS
Taken together, we show here that TRPV4 activation in PDLSCs under mechanical force contributes to changing their stem cell characteristics and modulates bone remodelling during tooth movement.
Topics: Animals; Biomechanical Phenomena; Bone Remodeling; Cell Proliferation; Cells, Cultured; Humans; Male; Osteoclasts; Periodontal Ligament; Rats; Rats, Sprague-Dawley; Stem Cells; Stress, Mechanical; TRPV Cation Channels
PubMed: 32964544
DOI: 10.1111/cpr.12912 -
International Journal of Nanomedicine 2023Dental pulp stem cell-derived exosomes (DPSC-EXO), which have biological characteristics similar to those of metrocytes, have been found to be closely associated with...
Dental Pulp Stem Cell-Derived Exosomes Regulate Anti-Inflammatory and Osteogenesis in Periodontal Ligament Stem Cells and Promote the Repair of Experimental Periodontitis in Rats.
PURPOSE
Dental pulp stem cell-derived exosomes (DPSC-EXO), which have biological characteristics similar to those of metrocytes, have been found to be closely associated with tissue regeneration. Periodontitis is an immune inflammation and tissue destructive disease caused by plaque, resulting in alveolar bone loss and periodontal epithelial destruction. It is not clear whether DPSC-EXO can be used as an effective therapy for periodontal regeneration. The purpose of this study was not only to verify the effect of DPSC-EXO on reducing periodontitis and promoting periodontal tissue regeneration, but also to reveal the possible mechanism.
METHODS
DPSC-EXO was isolated by ultracentrifugation. Then it characterized by transmission electron microscope (TEM), nanoparticle tracking analysis (NTA) and Western Blot. In vitro, periodontal ligament stem cells (PDLSCs) were treated with DPSC-EXO, the abilities of cell proliferation, migration and osteogenic potential were evaluated. Furthermore, we detected the expression of IL-1β, TNF-αand key proteins in the IL-6/JAK2/STAT3 signaling pathway after simulating the inflammatory environment by LPS. In addition, the effect of DPSC-EXO on the polarization phenotype of macrophages was detected. In vivo, the experimental periodontitis in rats was established and treated with DPSC-EXO or PBS. After 4 weeks, the maxillae were collected and detected by micro-CT and histological staining.
RESULTS
DPSC-EXO promoted the proliferation, migration and osteogenesis of PDLSCs in vitro. DPSC-EXO also regulated inflammation by inhibiting the IL-6/JAK2/STAT3 signaling pathway during acute inflammatory stress. In addition, the results showed that DPSC-EXO could polarize macrophages from the M1 phenotype to the M2 phenotype. In vivo, we found that DPSC-EXO could effectively reduce alveolar bone loss and promote the healing of the periodontal epithelium in rats with experimental periodontitis.
CONCLUSION
DPSC-EXO plays an important role in inhibiting periodontitis and promoting tissue regeneration. This study provides a promising acellular therapy for periodontitis.
Topics: Animals; Rats; Periodontal Ligament; Alveolar Bone Loss; Dental Pulp; Exosomes; Interleukin-6; Osteogenesis; Periodontitis; Anti-Inflammatory Agents; Inflammation
PubMed: 37608819
DOI: 10.2147/IJN.S420967 -
Advanced Science (Weinheim,... Oct 2023Periodontium supports teeth in a mechanically stimulated tissue environment, where heterogenous stem/progenitor populations contribute to periodontal homeostasis. In...
Periodontium supports teeth in a mechanically stimulated tissue environment, where heterogenous stem/progenitor populations contribute to periodontal homeostasis. In this study, Leptin receptor+ (Lepr+) cells are identified as a distinct periodontal ligament stem cell (PDLSC) population by single-cell RNA sequencing and lineage tracing. These Lepr+ PDLSCs are located in the peri-vascular niche, possessing multilineage potential and contributing to tissue repair in response to injury. Ablation of Lepr+ PDLSCs disrupts periodontal homeostasis. Hyper-loading and unloading of occlusal forces modulate Lepr+ PDLSCs activation. Piezo1 is demonstrated that mediates the mechanosensing of Lepr+ PDLSCs by conditional Piezo1-deficient mice. Meanwhile, Yoda1, a selective activator of Piezo1, significantly accelerates periodontal tissue growth via the induction of Lepr+ cells. In summary, Lepr marks a unique multipotent PDLSC population in vivo, to contribute toward periodontal homeostasis via Piezo1-mediated mechanosensing.
Topics: Animals; Mice; Receptors, Leptin; Cell Differentiation; Periodontal Ligament; Tooth; Stem Cells; Ion Channels
PubMed: 37553778
DOI: 10.1002/advs.202303291