scholarly journals D-Mannose Enhanced Immunomodulation of Periodontal Ligament Stem Cells via Inhibiting IL-6 Secretion

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Lijia Guo ◽  
Yanan Hou ◽  
Liang Song ◽  
Siying Zhu ◽  
Feiran Lin ◽  
...  
Keyword(s):  
T Cell ◽  
Periodontal Ligament ◽  
Alveolar Bone ◽  
Periodontal Regeneration ◽  
Treg Cells ◽  
Cell Number ◽  
Periodontal Ligament Stem Cells ◽  
Periodontal Tissues ◽  
Periodontal Tissue Regeneration ◽  
Periodontal Ligament Stem Cell

Periodontal ligament stem cell- (PDLSC-) mediated periodontal tissue regeneration has recently been proposed for the new therapeutic method to regenerate lost alveolar bone and periodontal ligament. It was reported that both autogenic and allogeneic PDLSCs could reconstruct damaged periodontal tissues but the regeneration effects were not consistent. The effective methods to improve the properties of PDLSCs should be further considered. In this study, we investigated if D-mannose could affect the immunomodulatory properties of hPDLSCs. After being pretreated with D-mannose, hPDLSCs could inhibit T cell proliferation and affect T cell differentiation into Treg cells. We found that less IL-6 could be detected in D-mannose-pretreated hPDLSCs. In the D-mannose pretreatment group, induced Treg cell number would decrease if increased IL-6 levels could be detected. Our data uncovered a previously unrecognized function of D-mannose to regulate the immunomodulatory function of PDLSCs and that IL-6 might play a key role in this process. The results provided a property method to improve PDLSC-based periodontal regeneration.

scholarly journals EZH2 Regulates Lipopolysaccharide-Induced Periodontal Ligament Stem Cell Proliferation and Osteogenesis through TLR4/MyD88/NF-κB Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Pengcheng Wang ◽  
Huan Tian ◽  
Zheng Zhang ◽  
Zuomin Wang
Keyword(s):  
Cell Proliferation ◽  
Periodontal Ligament ◽  
Underlying Mechanism ◽  
Chronic Inflammatory Disease ◽  
Periodontal Ligament Stem Cells ◽  
Western Blot Assay ◽  
Alizarin Red ◽  
Protein Levels ◽  
Periodontal Tissues ◽  
Periodontal Ligament Stem Cell

Background. Periodontitis induced by bacteria especially Gram-negative bacteria is the most prevalent chronic inflammatory disease worldwide. Emerging evidence supported that EZH2 plays a significant role in the inflammatory response of periodontal tissues. However, little information is available regarding the underlying mechanism of EZH2 in periodontitis. This study is aimed at determining the potential role and underlying mechanism of EZH2 in periodontitis. Methods. The protein levels of EZH2, H3K27ME, p-p65, p-IKB, TLR4, MyD88, Runx2, and OCN were examined by western blot assay. Proliferation was evaluated by CCK8 assay. The levels of TNFα, IL1β, and IL6 were detected by ELISA assay. Migration was detected by wound healing assay. The distribution of p65 was detected by immunofluorescence. The formation of mineralized nodules was analyzed using alizarin red staining. Results. LPS stimulation significantly promoted EZH2 and H3K27me3 expression in primary human periodontal ligament stem cells (PDLSCs). Targeting EZH2 prevented LPS-induced upregulation of the inflammatory cytokines and inhibition of cell proliferation and migration. Furthermore, EZH2 knockdown attenuated the TLR4/MyD88/NF-κB signaling to facilitate PDLSC osteogenesis. Conclusions. Modulation of the NF-κB pathway through the inhibition of EZH2 may offer a new perspective on the treatment of chronic apical periodontitis.

scholarly journals The Role of Noncoding RNAs in Osteogenic Differentiation of Human Periodontal Ligament Stem Cells

2021 ◽  
Vol 6 ◽  
pp. 247275122199922
Author(s):  
Paras Ahmad ◽  
Martin J. Stoddart ◽  
Elena Della Bella
Keyword(s):  
Stem Cells ◽  
Osteogenic Differentiation ◽  
Periodontal Ligament ◽  
Noncoding Rna ◽  
Molecular Mechanisms ◽  
Alveolar Bone ◽  
Noncoding Rnas ◽  
Tissue Destruction ◽  
Periodontal Ligament Stem Cells ◽  
Periodontal Tissues

Chronic inflammatory diseases, including periodontitis, are the most common causes of bone tissue destruction. Periodontitis often leads to loss of connective tissue homeostasis and reduced alveolar bone levels. Human periodontal ligament stem cells (PDLSCs), a population of multipotent stem cells derived from periodontal ligament tissues, are considered as candidate cells for the regeneration of alveolar bone and periodontal tissues. Periodontitis impairs the osteogenic differentiation of human PDLSCs. Noncoding RNAs (ncRNAs), including long noncoding RNA (lncRNA), microRNA (miRNA), and circular RNA (circRNA), have been proposed as vital regulators influencing several differentiation processes including bone regeneration. Still, the molecular mechanisms of ncRNAs regulating osteogenic differentiation of human PDLSCs remain poorly understood. Exploring the influence of ncRNAs in the process of osteogenic differentiation of human PDLSCs may provide novel therapeutic strategies for tissue regeneration as the regeneration of the lost periodontium is the ultimate goal of periodontal therapy.

Tissue engineering in periodontology: Biological mediators for periodontal regeneration

2019 ◽  
Vol 42 (5) ◽  
pp. 241-257 ◽  
Author(s):  
Daniela Carmagnola ◽  
Gaia Pellegrini ◽  
Claudia Dellavia ◽  
Lia Rimondini ◽  
Elena Varoni
Keyword(s):  
Tissue Engineering ◽  
Periodontal Ligament ◽  
Alveolar Bone ◽  
State Of The Art ◽  
Periodontal Regeneration ◽  
Functional System ◽  
Bioactive Molecules ◽  
Comprehensive Review ◽  
Periodontal Tissues ◽  
Temporal And Spatial

Teeth and the periodontal tissues represent a highly specialized functional system. When periodontal disease occurs, the periodontal complex, composed by alveolar bone, root cementum, periodontal ligament, and gingiva, can be lost. Periodontal regenerative medicine aims at recovering damaged periodontal tissues and their functions by different means, including the interaction of bioactive molecules, cells, and scaffolds. The application of growth factors, in particular, into periodontal defects has shown encouraging effects, driving the wound healing toward the full, multi-tissue periodontal regeneration, in a precise temporal and spatial order. The aim of the present comprehensive review is to update the state of the art concerning tissue engineering in periodontology, focusing on biological mediators and gene therapy.

Regeneration of Periodontal Tissues in Non-human Primates with rhGDF-5 and Beta-Tricalcium Phosphate

2011 ◽  
Vol 90 (12) ◽  
pp. 1416-1421 ◽  
Author(s):  
K.B. Emerton ◽  
S.J. Drapeau ◽  
H. Prasad ◽  
M. Rohrer ◽  
P. Roffe ◽  
...  
Keyword(s):  
Tissue Regeneration ◽  
Tricalcium Phosphate ◽  
Alveolar Bone ◽  
Periodontal Regeneration ◽  
Human Growth ◽  
Graft Material ◽  
Periodontal Tissue ◽  
Periodontal Tissues ◽  
Beta Tricalcium Phosphate ◽  
Periodontal Tissue Regeneration

The application of growth factors has been advocated in support of periodontal regeneration. Recombinant human growth and differentiation factor-5 (rhGDF-5), a member of the bone morphogenetic protein family, has been used to encourage periodontal tissue regeneration. This study evaluated the dose response of rhGDF-5 lyophilized onto beta-tricalcium phosphate (bTCP) granules for periodontal tissue regeneration in a baboon model. Periodontal defects were created bilaterally in 12 baboons by a split-mouth design. Plaque was allowed to accumulate around wire ligatures to create chronic disease. After 2 mos, the ligatures were removed, and a notch was placed at the base of the defect. Two teeth on each side of the mouth were randomly treated with bTCP only, 0.5, 1.0, or 2.0 mg rhGDF-5/g bTCP. Animals were sacrificed 5 mos post-treatment, with micro-CT and histomorphometric analysis performed. After 5 mos, analysis showed alveolar bone, cementum, and periodontal ligament formation in all treatment groups, with a dose-dependent increase in rhGDF-5-treated groups. Height of periodontal tissues also increased with the addition of rhGDF-5, and the amount of residual graft material decreased with rhGDF-5 treatment. Therefore, rhGDF-5 delivered on bTCP demonstrated effective regeneration of all 3 tissues critical for periodontal repair.

scholarly journals Periodontal Inflammation-Triggered by Periodontal Ligament Stem Cell Pyroptosis Exacerbates Periodontitis

2021 ◽  
Vol 9 ◽  
Author(s):  
Qin Chen ◽  
Xingguang Liu ◽  
Dingyu Wang ◽  
Jisi Zheng ◽  
Lu Chen ◽  
...  
Keyword(s):  
Periodontal Ligament ◽  
Alveolar Bone ◽  
Gingival Crevicular Fluid ◽  
Inflammatory Diseases ◽  
Periodontal Ligament Stem Cells ◽  
Tissue Microenvironment ◽  
Periodontal Bacteria ◽  
Periodontal Inflammation ◽  
Periodontal Ligament Stem Cell ◽  
Crevicular Fluid

Periodontitis is an immune inflammatory disease that leads to progressive destruction of bone and connective tissue, accompanied by the dysfunction and even loss of periodontal ligament stem cells (PDLSCs). Pyroptosis mediated by gasdermin-D (GSDMD) participates in the pathogenesis of inflammatory diseases. However, whether pyroptosis mediates PDLSC loss, and inflammation triggered by pyroptosis is involved in the pathological progression of periodontitis remain unclear. Here, we found that PDLSCs suffered GSDMD-dependent pyroptosis to release interleukin-1β (IL-1β) during human periodontitis. Importantly, the increased IL-1β level in gingival crevicular fluid was significantly correlated with periodontitis severity. The caspase-4/GSDMD-mediated pyroptosis caused by periodontal bacteria and cytoplasmic lipopolysaccharide (LPS) dominantly contributed to PDLSC loss. By releasing IL-1β into the tissue microenvironment, pyroptotic PDLSCs inhibited osteoblastogenesis and promoted osteoclastogenesis, which exacerbated the pathological damage of periodontitis. Pharmacological inhibition of caspase-4 or IL-1β antibody blockade in a rat periodontitis model lead to the significantly reduced loss of alveolar bone and periodontal ligament damage. Furthermore, Gsdmd deficiency alleviated periodontal inflammation and bone loss in mouse experimental periodontitis. These findings indicate that GSDMD-driven PDLSC pyroptosis and loss plays a pivotal role in the pathogenesis of periodontitis by increasing IL-1β release, enhancing inflammation, and promoting osteoclastogenesis.

scholarly journals The Fate of Transplanted Periodontal Ligament Stem Cells in Surgically Created Periodontal Defects in Rats

2019 ◽  
Vol 20 (1) ◽  
pp. 192 ◽  
Author(s):  
Kengo Iwasaki ◽  
Keiko Akazawa ◽  
Mizuki Nagata ◽  
Motohiro Komaki ◽  
Izumi Honda ◽  
...  
Keyword(s):  
Stem Cells ◽  
Periodontal Disease ◽  
Periodontal Ligament ◽  
Periodontal Regeneration ◽  
Cell Transfer ◽  
Periodontal Ligament Stem Cells ◽  
Sequence Detection ◽  
Periodontal Tissues ◽  
Alu Sequence ◽  
Novel Method

Periodontal disease is chronic inflammation that leads to the destruction of tooth-supporting periodontal tissues. We devised a novel method (“cell transfer technology”) to transfer cells onto a scaffold surface and reported the potential of the technique for regenerative medicine. The aim of this study is to examine the efficacy of this technique in periodontal regeneration and the fate of transplanted cells. Human periodontal ligament stem cells (PDLSCs) were transferred to decellularized amniotic membrane and transplanted into periodontal defects in rats. Regeneration of tissues was examined by microcomputed tomography and histological observation. The fate of transplanted PDLSCs was traced using PKH26 and human Alu sequence detection by PCR. Imaging showed more bone in PDLSC-transplanted defects than those in control (amnion only). Histological examination confirmed the enhanced periodontal tissue formation in PDLSC defects. New formation of cementum, periodontal ligament, and bone were prominently observed in PDLSC defects. PKH26-labeled PDLSCs were found at limited areas in regenerated periodontal tissues. Human Alu sequence detection revealed that the level of Alu sequence was not increased, but rather decreased. This study describes a novel stem cell transplantation strategy for periodontal disease using the cell transfer technology and offers new insight for cell-based periodontal regeneration.

scholarly journals Biocompatible Nanocomposite Enhanced Osteogenic and Cementogenic Differentiation of Periodontal Ligament Stem Cells In Vitro for Periodontal Regeneration

Materials ◽  
2020 ◽  
Vol 13 (21) ◽  
pp. 4951 ◽  
Author(s):  
Jin Liu ◽  
Quan Dai ◽  
Michael D. Weir ◽  
Abraham Schneider ◽  
Charles Zhang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Periodontal Ligament ◽  
Periodontal Regeneration ◽  
Gingival Recession ◽  
Dental Composite ◽  
Periodontal Ligament Stem Cells ◽  
Related Transcription Factor ◽  
Collagen Type 1 ◽  
First Time

Decays in the roots of teeth is prevalent in seniors as people live longer and retain more of their teeth to an old age, especially in patients with periodontal disease and gingival recession. The objectives of this study were to develop a biocompatible nanocomposite with nano-sized calcium fluoride particles (Nano-CaF2), and to investigate for the first time the effects on osteogenic and cementogenic induction of periodontal ligament stem cells (hPDLSCs) from human donors.Nano-CaF2 particles with a mean particle size of 53 nm were produced via a spray-drying machine.Nano-CaF2 was mingled into the composite at 0%, 10%, 15% and 20% by mass. Flexural strength (160 ± 10) MPa, elastic modulus (11.0 ± 0.5) GPa, and hardness (0.58 ± 0.03) GPa for Nano-CaF2 composite exceeded those of a commercial dental composite (p < 0.05). Calcium (Ca) and fluoride (F) ions were released steadily from the composite. Osteogenic genes were elevated for hPDLSCs growing on 20% Nano-CaF2. Alkaline phosphatase (ALP) peaked at 14 days. Collagen type 1 (COL1), runt-related transcription factor 2 (RUNX2) and osteopontin (OPN) peaked at 21 days. Cementogenic genes were also enhanced on 20% Nano-CaF2 composite, promoting cementum adherence protein (CAP), cementum protein 1 (CEMP1) and bone sialoprotein (BSP) expressions (p < 0.05). At 7, 14 and 21 days, the ALP activity of hPDLSCs on 20% Nano-CaF2 composite was 57-fold, 78-fold, and 55-fold greater than those of control, respectively (p < 0.05). Bone mineral secretion by hPDLSCs on 20% Nano-CaF2 composite was 2-fold that of control (p < 0.05). In conclusion, the novel Nano-CaF2 composite was biocompatible and supported hPDLSCs. Nano-CaF2 composite is promising to fill tooth root cavities and release Ca and F ions to enhance osteogenic and cementogenic induction of hPDLSCs and promote periodontium regeneration.

scholarly journals Periodontal Bone-Ligament-Cementum Regeneration via Scaffolds and Stem Cells

Cells ◽  
2019 ◽  
Vol 8 (6) ◽  
pp. 537 ◽  
Author(s):  
Jin Liu ◽  
Jianping Ruan ◽  
Michael D. Weir ◽  
Ke Ren ◽  
Abraham Schneider ◽  
...  
Keyword(s):  
Stem Cells ◽  
Gene Therapy ◽  
Tooth Loss ◽  
Soft Tissues ◽  
Alveolar Bone ◽  
Periodontal Regeneration ◽  
Periodontal Tissues ◽  
Oral And Maxillofacial Region ◽  
And Function ◽  
Bone Remains

Periodontitis is a prevalent infectious disease worldwide, causing the damage of periodontal support tissues, which can eventually lead to tooth loss. The goal of periodontal treatment is to control the infections and reconstruct the structure and function of periodontal tissues including cementum, periodontal ligament (PDL) fibers, and bone. The regeneration of these three types of tissues, including the re-formation of the oriented PDL fibers to be attached firmly to the new cementum and alveolar bone, remains a major challenge. This article represents the first systematic review on the cutting-edge researches on the regeneration of all three types of periodontal tissues and the simultaneous regeneration of the entire bone-PDL-cementum complex, via stem cells, bio-printing, gene therapy, and layered bio-mimetic technologies. This article primarily includes bone regeneration; PDL regeneration; cementum regeneration; endogenous cell-homing and host-mobilized stem cells; 3D bio-printing and generation of the oriented PDL fibers; gene therapy-based approaches for periodontal regeneration; regenerating the bone-PDL-cementum complex via layered materials and cells. These novel developments in stem cell technology and bioactive and bio-mimetic scaffolds are highly promising to substantially enhance the periodontal regeneration including both hard and soft tissues, with applicability to other therapies in the oral and maxillofacial region.

scholarly journals Local Injection of Allogeneic Stem Cells from Apical Papilla Enhanced Periodontal Tissue Regeneration in Minipig Model of Periodontitis

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Guoqing Li ◽  
Nannan Han ◽  
Xiuli Zhang ◽  
Haoqing Yang ◽  
Yangyang Cao ◽  
...  
Keyword(s):  
Stem Cells ◽  
Tissue Regeneration ◽  
Alveolar Bone ◽  
Local Injection ◽  
Swine Model ◽  
Periodontal Tissue ◽  
Clinical Assessments ◽  
Periodontal Tissues ◽  
Periodontal Tissue Regeneration ◽  
Apical Papilla

Background. Discovering suitable seeding cells and simple application technique will be beneficial for MSC-mediated treatment of periodontitis. Stem cells from apical papilla (SCAPs) might be the candidate seeding cell for the periodontal tissues regeneration based on their origin and characters. In this research, we investigated the effect of SCAPs on periodontal tissue regeneration in swine by local injection. Methods. We established experimental periodontitis model in miniature pigs and then treated them with SCAPs by local injection. Clinical assessments, computed tomography (CT) scanning, histologic examination, and quantitative measurements were used to evaluate the effect of periodontal tissues regeneration. Results. At 12 weeks after injection, clinical assessments showed that probing depth, gingival recession, and attachment loss values were 5.44±0.77 mm versus 7.33±1.0 mm (p<0.01), 2.33±0.33 mm versus 2.11±0.69 mm (p>0.05), and 7.78±0.84 mm versus 9.44±1.07 mm (p<0.01) in SCAPs group and 0.9% NaCl group, respectively. CT scan results showed a significant increase of 12.86 mm3 alveolar bone regeneration in SCAPs group compared with 0.9% NaCl group. In addition, histopathology results demonstrated remarkable regeneration in SCAPs group, whereas regeneration of periodontal tissue was hardly found in 0.9% NaCl group. Conclusion. Local injection of SCAPs could effectively restore tissue defects brought about by periodontitis in the swine model. Thus, SCAPs, as an easily accessible dental-deriving stem cell, may serve as an alternative application for periodontitis treatment.

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