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International Journal of Medical... 2018The tooth root transmits and balances occlusal forces through the periodontium to the alveolar bone. The periodontium, including the gingiva, the periodontal ligament,...
The tooth root transmits and balances occlusal forces through the periodontium to the alveolar bone. The periodontium, including the gingiva, the periodontal ligament, the cementum and the partial alveolar bone, derives from the dental follicle (DF), except for the gingiva. In the early developmental stages, the DF surrounds the tooth germ as a sphere and functions to promote tooth eruption. However, the morphological dynamics and factors regulating the differentiation of the DF during root elongation remain largely unknown. Miniature pigs are regarded as a useful experimental animal for modeling in craniofacial research because they are similar to humans with respect to dentition and mandible anatomy. In the present study, we used the third deciduous incisor of miniature pig as the model to investigate the factors influencing DF differentiation during root development. We found that the DF was shaped like a crescent and was located between the root apical and the alveolar bone. The expression levels of WNT5a, β-Catenin, and COL-I gradually increased from the center of the DF (beneath the apical foramen) to the lateral coronal corner, where the DF differentiates into the periodontium. To determine the potential regulatory role of the apical papilla on DF cell differentiation, we co-cultured dental follicle stem cells (DFSCs) with stem cells of the apical papilla (SCAPs). The osteogenesis and fibrogenesis abilities of DFSCs were inhibited when being co-cultured with SCAPs, suggesting that the fate of the DF can be regulated by signals from the apical papilla. The apical papilla may sustain the undifferentiated status of DFSCs before root development finishes. These data yield insight into the interaction between the root apex and surrounding DF tissues in root and periodontium development and shed light on the future study of root regeneration in large mammals.
Topics: Alveolar Bone Grafting; Animals; Cell Differentiation; Cells, Cultured; Dental Cementum; Dental Sac; Humans; Odontogenesis; Osteogenesis; Periodontal Ligament; Stem Cells; Swine; Swine, Miniature; Tooth Root
PubMed: 29511365
DOI: 10.7150/ijms.22495 -
Journal of Orthopaedic Surgery and... Jun 2023Human periodontal ligament stem cells (hPDLSCs) have a superior ability to promote the formation of new bones and achieve tissue regeneration. However, mesenchymal stem...
BACKGROUND
Human periodontal ligament stem cells (hPDLSCs) have a superior ability to promote the formation of new bones and achieve tissue regeneration. However, mesenchymal stem cells (MSCs) are placed in harsh environments after transplantation, and the hostile microenvironment reduces their stemness and hinders their therapeutic effects. Klotho is an antiaging protein that participates in the regulation of stress resistance. In our previous study, we demonstrated the protective ability of Klotho in hPDLSCs.
METHODS
A cranial bone defect model of rats was constructed, and the hPDLSCs with or without Klotho pretreatment were transplanted into the defects. Histochemical staining and micro-computed tomography were used to detect cell survival, osteogenesis, and immunoregulatory effects of hPDLSCs after transplantation. The in vitro capacity of hPDLSCs was measured by a macrophage polarization test and the inflammatory level of macrophages. Furthermore, we explored autophagy activity in hPDLSCs, which may be affected by Klotho to regulate cell homeostasis.
RESULTS
Pretreatment with the recombinant human Klotho protein improved cell survival after hPDLSC transplantation and enhanced their ability to promote bone regeneration. Furthermore, Klotho pretreatment can promote stem cell immunomodulatory effects in macrophages and modulate cell autophagy activity, in vivo and in vitro.
CONCLUSION
These findings suggest that the Klotho protein protects hPDLSCs from stress after transplantation to maintain stem cell function via enhancing the immunomodulatory ability of hPDLSCs and inhibiting cell autophagy.
Topics: Humans; Rats; Animals; Periodontal Ligament; X-Ray Microtomography; Stem Cells; Osteogenesis; Bone Regeneration; Proteins; Autophagy; Cell Differentiation; Cells, Cultured; Cell Proliferation
PubMed: 37264407
DOI: 10.1186/s13018-023-03849-8 -
Molecular Medicine Reports Mar 2021The periodontium is a highly dynamic microenvironment constantly adapting to changing external conditions. In the processes of periodontal tissue formation and... (Review)
Review
The periodontium is a highly dynamic microenvironment constantly adapting to changing external conditions. In the processes of periodontal tissue formation and remodeling, certain molecules may serve an essential role in maintaining periodontal homeostasis. Wnt family member 5a (Wnt5a), as a member of the Wnt family, has been identified to have extensive biological roles in development and disease, predominantly through the non‑canonical Wnt signaling pathway or through interplay with the canonical Wnt signaling pathway. An increasing number of studies has also demonstrated that it serves crucial roles in periodontal tissues. Wnt5a participates in the development of periodontal tissues, maintains a non‑mineralized state of periodontal ligament, and regulates bone homeostasis. In addition, Wnt5a is involved in the pathogenesis of periodontitis. Recently, it has been shown to serve a positive role in the regeneration of integrated periodontal complex. The present review article focuses on recent research studies of Wnt5a and its functions in development, maintenance, and pathological disorders of periodontal tissues, as well as its potential effect on periodontal regeneration.
Topics: Animals; Humans; Periodontal Ligament; Periodontitis; Regeneration; Wnt-5a Protein
PubMed: 33398377
DOI: 10.3892/mmr.2020.11806 -
Tissue Engineering. Part A Jun 2021Rebuilding the tooth-supporting tissues (periodontium) destroyed by periodontitis remains a clinical challenge. Periodontal ligament cells (PDLCs), multipotent cells...
Rebuilding the tooth-supporting tissues (periodontium) destroyed by periodontitis remains a clinical challenge. Periodontal ligament cells (PDLCs), multipotent cells within the periodontal ligament (PDL), differentiate and form new PDL and mineralized tissues (cementum and bone) during native tissue repair in response to specific extracellular matrix (ECM) cues. Thus, harnessing ECM cues to control PDLC activity , and ultimately, to design a PDLC delivery vehicle for tissue regeneration is an important goal. In this study, poly(ethylene glycol) hydrogels were used as a synthetic PDL ECM to interrogate the roles of cell-matrix interactions and cell-mediated matrix remodeling in controlling PDLC activity. Results showed that PDLCs within matrix metalloproteinase (MMP)-degradable hydrogels expressed key PDL matrix genes and showed a six to eightfold increase in alkaline phosphatase (ALP) activity compared with PDLCs in nondegradable hydrogel controls. The increase in ALP activity, commonly considered an early marker of cementogenic/osteogenic differentiation, occurred independent of the presentation of the cell-binding ligand RGD or soluble media cues and remained elevated when inhibiting PDLC-matrix binding and intracellular tension. ALP activity was further increased in softer hydrogels regardless of degradability and was accompanied by an increase in PDLC volume. However, scaffolds that fostered PDLC ALP activity did not necessarily promote hydrogel ECM mineralization. Rather, matrix mineralization was greatest in stiffer, MMP-degradable hydrogels and required the presence of soluble media cues. These divergent outcomes illustrate the complexity of the PDLC response to ECM cues and the limitations of current scaffold materials. Nevertheless, key biomaterial design principles for controlling PDLC activity were identified for incorporation into scaffolds for periodontal tissue regeneration. Impact statement Engineered scaffolds are an attractive approach for delivering periodontal ligament cells (PDLCs) to rebuild the tooth-supporting tissues. Replicating key extracellular matrix (ECM) cues within tissue engineered scaffolds may maximize PDLC potential. However, the identity of important ECM cues and how they can be harnessed to control PDLC activity is still unknown. In this study, matrix degradability, cell-matrix binding, and stiffness were varied using synthetic poly(ethylene glycol) hydrogels for three-dimensional PDLC culture. PDLCs exhibited dramatic and divergent responses to these cues, supporting further investigation of ECM-replicating scaffolds for control of PDLC behavior and periodontal tissue regeneration.
Topics: Cell Differentiation; Hydrogels; Osteogenesis; Periodontal Ligament; Tissue Scaffolds
PubMed: 33107404
DOI: 10.1089/ten.TEA.2020.0278 -
Journal of Periodontal Research Apr 2020The Sharpey's fibers of periodontal ligament (PDL) anchor the PDL to alveolar bone and cementum and are essential for the function of PDL. While qualitative analyses of...
BACKGROUND AND OBJECTIVE
The Sharpey's fibers of periodontal ligament (PDL) anchor the PDL to alveolar bone and cementum and are essential for the function of PDL. While qualitative analyses of the Sharpey's fibers have been widely explored, a comprehensive quantitative characterization of the Sharpey's fibers is not available. In this work, we selected rat molars as a model and comprehensively characterized the PDL Sharpey's fibers (diameter, density, length, embedding angle, and insertion angle).
MATERIALS AND METHODS
A total of 24 rat mandibular molars, eight maxillary first molars, and their surrounding alveolar bone were harvested, fixed, rendered anorganic and observed under scanning electron microscopy (SEM). The mandibles and maxillae (n = 4) were harvested, processed, sectioned, and stained with Sirius red for histological observation. SEM images were used for quantitative analyses of diameters and densities of the Sharpey's fibers, while Sirius red staining images were used to measure lengths and angles. The Sharpey's fibers were comprehensively characterized in terms of positions (cervical, middle, and apical thirds), PDL fiber groups (alveolar crest, horizontal, oblique, apical, and interradicular groups), sides (cementum and bone sides), and teeth (mandibular first, second, third molars, and maxillary first molar).
RESULTS
Our results showed that the characteristic parameters of the Sharpey's fibers varied in different positions, fiber groups, sides, and teeth. Specifically, the median diameter of the Sharpey's fibers on the bone side was significantly greater than that on the cementum side, while the median density of the Sharpey's fibers on the bone side was significantly lower than that on the cementum side, regardless of the positions and teeth. For the same tooth, the median length of the embedded Sharpey's fibers on the bone side was more than two times greater than that on the cementum side. Among all fiber groups, the alveolar crest group had the maximum length of the Sharpey's fibers on the bone side and the minimal length of the Sharpey's fibers on the cementum side. There is an approximate 5-15° difference between the embedding angle and the insertion angle in each group. The oblique group had the smallest embedding angles on both the bone and cementum sides.
CONCLUSION
This study provides a comprehensive and quantitative characterization of the Sharpey's fibers using rat molars as a model. Overall, these parameters varied according to different vertical positions, fiber groups, teeth, and jawbones. The quantitative information of the Sharpey's fibers presented in this work facilitates our understanding of PDL functions and advances the development of biomimetic materials for periodontal tissue regeneration.
Topics: Alveolar Process; Animals; Dental Cementum; Molar; Periodontal Ligament; Rats
PubMed: 31788804
DOI: 10.1111/jre.12716 -
Hua Xi Kou Qiang Yi Xue Za Zhi = Huaxi... Dec 2022The expression of osteoprotegerin (OPG) and receptor activator of nuclear factor-κB ligand (RANKL) in human periodontal ligament cells (HPDLCs) was investigated by cell...
OBJECTIVES
The expression of osteoprotegerin (OPG) and receptor activator of nuclear factor-κB ligand (RANKL) in human periodontal ligament cells (HPDLCs) was investigated by cell culture under continuous static pressure.
METHODS
HPDLCs were primarily cultured by tissue explant method and divided into three groups: group A (13-18 years old), group B (19-29 years old), and group C (30-44 years old). CCK-8 was used to detect the proliferation of HPDLCs. The senescence of HPDLCs was detected by senescence-associated β-galactosidase staining. Cells in the three groups were respectively given 0, 1.5, 3, 6, 12, 24, 48, and 72 h of continuous static pressure . The expression of OPG and RANKL in the supernatant was detected by enzyme-linked immunosorbent assay.
RESULTS
After continuous static pressure for stimulation, the expression of OPG and RANKL changed. The expression of OPG increased with time and age (<0.01). The expression of RANKL increased with time and decreased with age (<0.01). The ratio of OPG/RANKL initially decreased, increased with time, and then continued to rise with age (<0.01).
CONCLUSIONS
Aging could increase the expression of OPG and the ratio of OPG/RANKL and decrease the expression of RANKL in HPDLCs under continuous static pressure .
Topics: Humans; Adolescent; Young Adult; Adult; Osteoprotegerin; RANK Ligand; Periodontal Ligament; Cells, Cultured; Aging
PubMed: 36416317
DOI: 10.7518/hxkq.2022.06.005 -
Cellular Microbiology Apr 2018Host-derived matrix metalloproteinases (MMPs) and bacterial proteases mediate destruction of extracellular matrices and supporting alveolar bone in periodontitis. The...
Host-derived matrix metalloproteinases (MMPs) and bacterial proteases mediate destruction of extracellular matrices and supporting alveolar bone in periodontitis. The Treponema denticola dentilisin protease induces MMP-2 expression and activation in periodontal ligament (PDL) cells, and dentilisin-mediated activation of pro-MMP-2 is required for cellular fibronectin degradation. Here, we report that T. denticola regulates MMP-2 expression through epigenetic modifications in the periodontium. PDL cells were treated with epigenetic enzyme inhibitors before or after T. denticola challenge. Fibronectin fragmentation, MMP-2 expression, and activation were assessed by immunoblot, zymography, and qRT-PCR, respectively. Chromatin modification enzyme expression in T. denticola-challenged PDL cells and periodontal tissues were evaluated using gene arrays. Several classes of epigenetic enzymes showed significant alterations in transcription in diseased tissue and T. denticola-challenged PDL cells. T. denticola-mediated MMP-2 expression and activation were significantly reduced in PDL cells treated with inhibitors of aurora kinases and histone deacetylases. In contrast, DNA methyltransferase inhibitors had little effect, and inhibitors of histone acetyltransferases, methyltransferases, and demethylases exacerbated T. denticola-mediated MMP-2 expression and activation. Chronic epigenetic changes in periodontal tissues mediated by T. denticola or other oral microbes may contribute to the limited success of conventional treatment of chronic periodontitis and may be amenable to therapeutic reversal.
Topics: Cells, Cultured; Epigenesis, Genetic; Histone Code; Humans; Matrix Metalloproteinase 2; Matrix Metalloproteinase Inhibitors; Periodontal Ligament; Treponema denticola
PubMed: 29205773
DOI: 10.1111/cmi.12815 -
International Journal of Molecular... Jun 2021During orthodontic tooth movement (OTM), applied orthodontic forces cause an extensive remodeling of the extracellular matrix (ECM) in the periodontal ligament (PDL).... (Review)
Review
During orthodontic tooth movement (OTM), applied orthodontic forces cause an extensive remodeling of the extracellular matrix (ECM) in the periodontal ligament (PDL). This is mainly orchestrated by different types of matrix metalloproteinases (MMPs) and their tissue inhibitors of matrix metalloproteinases (TIMPs), which are both secreted by periodontal ligament (PDL) fibroblasts. Multiple in vitro and in vivo studies already investigated the influence of applied orthodontic forces on the expression of MMPs and TIMPs. The aim of this systematic review was to explore the expression levels of MMPs and TIMPs during OTM and the influence of specific orthodontic force-related parameters. Electronic article search was performed on PubMed and Web of Science until 31 January 2021. Screenings of titles, abstracts and full texts were performed according to PRISMA, whereas eligibility criteria were defined for in vitro and in vivo studies, respectively, according to the PICO schema. Risk of bias assessment for in vitro studies was verified by specific methodological and reporting criteria. For in vivo studies, risk of bias assessment was adapted from the Joanna Briggs Institute Critical Appraisal Checklist for analytical cross-sectional study. Electronic article search identified 3266 records, from which 28 in vitro and 12 in vivo studies were included. The studies showed that orthodontic forces mainly caused increased MMPs and TIMPs expression levels, whereas the exact effect may depend on various intervention and sample parameters and subject characteristics. This systematic review revealed that orthodontic forces induce a significant effect on MMPs and TIMPs in the PDL. This connection may contribute to the controlled depletion and formation of the PDLs' ECM at the compression and tension site, respectively, and finally to the highly regulated OTM.
Topics: Animals; Cross-Sectional Studies; Humans; Matrix Metalloproteinases; Periodontal Ligament; Stress, Mechanical; Tissue Inhibitor of Metalloproteinases
PubMed: 34203475
DOI: 10.3390/ijms22136967 -
Medicina (Kaunas, Lithuania) Aug 2023This numerical analysis investigated the biomechanical behavior of the mandibular bone as a structure subjected to 0.5 N of orthodontic force during periodontal...
This numerical analysis investigated the biomechanical behavior of the mandibular bone as a structure subjected to 0.5 N of orthodontic force during periodontal breakdown. Additionally, the suitability of the five most used failure criteria (Von Mises (VM), Tresca (T), maximum principal (S1), minimum principal (S3), and hydrostatic pressure (HP)) for the study of bone was assessed, and a single criterion was identified for the study of teeth and the surrounding periodontium (by performing correlations with other FEA studies). The finite element analysis (FEA) employed 405 simulations over eighty-one mandibular models with variable levels of bone loss (0-8 mm) and five orthodontic movements (intrusion, extrusion, tipping, rotation, and translation). For the numerical analysis of bone, the ductile failure criteria are suitable (T and VM are adequate for the study of bone), with Tresca being more suited. S1, S3, and HP criteria, due to their distinctive design dedicated to brittle materials and liquids/gas, only occasionally correctly described the bone stress distribution. Only T and VM displayed a coherent and correlated gradual stress increase pattern for all five movements and levels of the periodontal breakdown. The quantitative values provided by T and VM were the highest (for each movement and level of bone loss) among all five criteria. The MHP (maximum physiological hydrostatic pressure) was exceeded in all simulations since the mandibular bone is anatomically less vascularized, and the ischemic risks are reduced. Only T and VM displayed a correlated (both qualitative and quantitative) stress increase for all five movements. Both T and VM displayed rotation and translation, closely followed by tipping, as stressful movements, while intrusion and extrusion were less stressful for the mandibular bone. Based on correlations with earlier numerical studies on the same models and boundary conditions, T seems better suited as a single unitary failure criterion for the study of teeth and the surrounding periodontium.
Topics: Humans; Cancellous Bone; Finite Element Analysis; Periodontal Ligament; Bone Diseases, Metabolic; Mandible
PubMed: 37629752
DOI: 10.3390/medicina59081462 -
Journal of Dental Research Sep 2022Periodontal disease is a significant public health problem worldwide. Excess unresolved chronic inflammation destroys the periodontal tissues that surround and support...
Periodontal disease is a significant public health problem worldwide. Excess unresolved chronic inflammation destroys the periodontal tissues that surround and support the teeth, and efforts to control inflammation by removal of bacterial deposits on the teeth have limited long-term impact. Likewise, procedures aimed at regeneration of the periodontal tissues have shown limited success. Recent advances in stem cell research have shown promising novel prospects for the use of periodontal ligament stem cells (PDLSCs) in tissue regeneration; however, control of inflammation remains a barrier. Human PDLSCs have been shown to release specialized proresolving lipid mediators (SPMs) that modulate the immune response and promote resolution of inflammation, tissue repair, and regeneration. Studies on stem cell biology in periodontology have also been limited by the lack of a good large animal model. Herein, we describe PDLSC biology of the Yorkshire pig (pPDLSCs). pPDLSCs were isolated and characterized. Using lipid mediator profiling, we demonstrate for the first time that pPDLSCs biosynthesize cysteinyl-containing SPMs (cys-SPMs), specifically, maresin conjugates in tissue regeneration 3 (MCTR3) and its authentication using liquid chromatography/tandem mass spectrometry. The exogenous addition of the n-3 precursor docosahexaenoic acid enhances MCTR3 biosynthesis. Using immunocytochemistry, we show that pPDLSCs express 4 of the SPM biosynthetic pathway enzymes necessary for SPM biosynthesis, including 5-lipoxygenase, 12-lipoxygenase, and 15-lipoxygenase-1. In addition, we identified and quantified the cytokine/chemokine profile of pPDLSCs using a 13-plex immunology multiplex assay and found that the pretreatment of pPDLSCs with MCTR3 in an inflammatory environment reduced the production of acute and chronic proinflammatory cytokines/chemokines. Together, these results suggest that enhancing resolution of inflammation pathways and mediators may be a possible key early event in predictable periodontal regeneration.
Topics: Animals; Docosahexaenoic Acids; Humans; Inflammation; Periodontal Ligament; Stem Cells; Swine; Wound Healing
PubMed: 35428422
DOI: 10.1177/00220345221090879