scholarly journals PPARγ-Induced Global H3K27 Acetylation Maintains Osteo/Cementogenic Abilities of Periodontal Ligament Fibroblasts

2021 ◽  
Vol 22 (16) ◽  
pp. 8646
Author(s):  
Hang Yuan ◽  
Shigeki Suzuki ◽  
Shizu Hirata-Tsuchiya ◽  
Akiko Sato ◽  
Eiji Nemoto ◽  
...  

The periodontal ligament is a soft connective tissue embedded between the alveolar bone and cementum, the surface hard tissue of teeth. Periodontal ligament fibroblasts (PDLF) actively express osteo/cementogenic genes, which contribute to periodontal tissue homeostasis. However, the key factors maintaining the osteo/cementogenic abilities of PDLF remain unclear. We herein demonstrated that PPARγ was expressed by in vivo periodontal ligament tissue and its distribution pattern correlated with alkaline phosphate enzyme activity. The knockdown of PPARγ markedly reduced the osteo/cementogenic abilities of PDLF in vitro, whereas PPARγ agonists exerted the opposite effects. PPARγ was required to maintain the acetylation status of H3K9 and H3K27, active chromatin markers, and the supplementation of acetyl-CoA, a donor of histone acetylation, restored PPARγ knockdown-induced decreases in the osteo/cementogenic abilities of PDLF. An RNA-seq/ChIP-seq combined analysis identified four osteogenic transcripts, RUNX2, SULF2, RCAN2, and RGMA, in the PPARγ-dependent active chromatin region marked by H3K27ac. Furthermore, RUNX2-binding sites were selectively enriched in the PPARγ-dependent active chromatin region. Collectively, these results identified PPARγ as the key transcriptional factor maintaining the osteo/cementogenic abilities of PDLF and revealed that global H3K27ac modifications play a role in the comprehensive osteo/cementogenic transcriptional alterations mediated by PPARγ.

2006 ◽  
Vol 327 (1) ◽  
pp. 25-31 ◽  
Author(s):  
Heung-Joong Kim ◽  
Yong Seok Choi ◽  
Moon-Jin Jeong ◽  
Byung-Ock Kim ◽  
Sung-Hoon Lim ◽  
...  

2003 ◽  
Vol 82 (8) ◽  
pp. 641-645 ◽  
Author(s):  
T. Yamamoto ◽  
F. Myokai ◽  
F. Nishimura ◽  
T. Ohira ◽  
N. Shiomi ◽  
...  

Genes expressed by human periodontal ligament fibroblasts (HPFs) are likely to be associated with specific functions of the ligament. The aim of this study is to profile genes expressed highly by HPFs. A library (6 × 103 pfu) was constructed, followed by subtraction of HPF cDNAs with human gingival fibroblast (HGF) cDNAs. Reverse-dot hybridization revealed that 33 clones expressed higher levels of specific mRNAs in HPFs than in HGFs. These were mRNAs for known genes, including several associated with maturation and differentiation of cells. None had been reported in PFs. One clone, PDL-29, identified as a COX assembly factor, showed much stronger mRNA expression in HPFs than in HGFs in culture. In rat periodontium, however, PDL-29 mRNA expression was similar in PFs and GFs. These results suggest that HPFs express many previously unreported genes associated with maturation and differentiation, but expression can differ in vitro and in vivo.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Judit Symmank ◽  
Martin Chorus ◽  
Sophie Appel ◽  
Jana Marciniak ◽  
Isabel Knaup ◽  
...  

Abstract Alveolar bone (AB) remodeling is necessary for the adaption to mechanical stimuli occurring during mastication and orthodontic tooth movement (OTM). Thereby, bone degradation and assembly are strongly regulated processes that can be altered in obese patients. Further, increased fatty acids (FA) serum levels affect bone remodeling cells and we, therefore, investigated whether they also influence the function of periodontal ligament fibroblast (PdLF). PdLF are a major cell type regulating the differentiation and function of osteoblasts and osteoclasts localized in the AB. We stimulated human PdLF (HPdLF) in vitro with palmitic (PA) or oleic acid (OA) and analyzed their metabolic activity, growth, survival and expression of osteogenic markers and calcium deposits. Our results emphasize that PA increased cell death of HPdLF, whereas OA induced their osteoblastic differentiation. Moreover, quantitative expression analysis of OPG and RANKL revealed altered levels in mechanically stimulated PA-treated HPdLF. Furthermore, osteoclasts stimulated with culture medium of mechanical stressed FA-treated HPdLF revealed significant changes in cell differentiation upon FA-treatment. For the first time, our results highlight a potential role of specific FA in the function of HPdLF-modulated AB remodeling and help to elucidate the complex interplay of bone metabolism, mechanical stimulation and obesity-induced alterations.


2021 ◽  
Vol 42 ◽  
pp. 232-245
Author(s):  
A Khadre ◽  
ELM Raif ◽  
S Junaid ◽  
OM Goudouri ◽  
W Refaat ◽  
...  

Due to the complexity of the structure of the tooth periodontium, regeneration of the full tooth attachment is not a trivial task. There is also a gap in models that can represent human tooth attachment in vitro and in vivo. The aim of this study was to develop a bilayered in vitro construct that simulated the tooth periodontal ligament and attached alveolar bone, for the purpose of tissue regeneration and investigation of physiological and orthodontic loading. Two types of materials were used to develop this construct: sol-gel 60S10Mg derived scaffold, representing the hard tissue component of the periodontium, and commercially available Geistlich Bio-Gide® collagen membrane, representing the soft tissue component of the tooth attachment. Each scaffold was dynamically seeded with human periodontal ligament cells (HPDLCs). Scaffolds were either cultured separately, or combined in a bilayered construct, for 2 weeks. Characterisation of the individual scaffolds and the bilayered constructs included biological characterisation (cell viability, scanning electron microscopy to confirm cell attachment, gene expression of periodontium regeneration markers), and mechanical characterisation of scaffolds and constructs. HPDLCs enjoyed a biocompatible 3-dimensional environment within the bilayered construct components. There was no drop in cellular gene expression in the bilayered construct, compared to the separate scaffolds.


2007 ◽  
Vol 27 (12) ◽  
pp. 4306-4316 ◽  
Author(s):  
Svetlana N. Popova ◽  
Malgorzata Barczyk ◽  
Carl-Fredrik Tiger ◽  
Wouter Beertsen ◽  
Paola Zigrino ◽  
...  

ABSTRACT The fibroblast integrin α11β1 is a key receptor for fibrillar collagens. To study the potential function of α11 in vivo, we generated a null allele of the α11 gene. Integrin α11−/− mice are viable and fertile but display dwarfism with increased mortality, most probably due to severely defective incisors. Mutant incisors are characterized by disorganized periodontal ligaments, whereas molar ligaments appear normal. The primary defect in the incisor ligament leads to halted tooth eruption. α11β1-defective embryonic fibroblasts displayed severe defects in vitro, characterized by (i) greatly reduced cell adhesion and spreading on collagen I, (ii) reduced ability to retract collagen lattices, and (iii) reduced cell proliferation. Analysis of matrix metalloproteinase in vitro and in vivo revealed disturbed MMP13 and MMP14 synthesis in α11−/− cells. We show that α11β1 is the major receptor for collagen I on mouse embryonic fibroblasts and suggest that α11β1 integrin is specifically required on periodontal ligament fibroblasts for cell migration and collagen reorganization to help generate the forces needed for axial tooth movement. Our data show a unique role for α11β1 integrin during tooth eruption.


1981 ◽  
Vol 50 (1) ◽  
pp. 299-314
Author(s):  
C.G. Bellows ◽  
A.H. Melcher ◽  
J.E. Aubin

Monkey periodontal ligament fibroblasts (MPLF cells), human gingival fibroblasts (HGF cells), rat embryonic calvaria cells (REC cells), porcine periodontal ligament epithelial cells (PPLE cells) and rat osteosarcoma 17/2 cells (ROS cells) were incorporated into 3-dimensional collagen gels plated in 60 mm Petri dishes in order: first, to measure the capacity of these cell types to contract; second, to investigate cell-collagen and intercellular relationships during contraction; and third, to define the cellular contribution to tissue contraction in an in vitro system. Measurements at times up to 72 h on 3 ml gels containing 5 × 10(5) cells and with a collagen concentration of 1.20 mg/ml showed that MPLF cells contracted the gels at a significantly greater rate (P less than 0.001) than did the other cell types. In addition, contraction started sooner and was of greater extent than with the other cells. HGF cells contracted the gels more rapidly than REC and PPLE cells, while ROS cells caused no contraction. Several stages of gel compaction could be defined: (1) the attachment of cells to collagen; (2) cellular spreading within the collagen fibre matrix; (3) organization and alignment of collagen fibres by cell processes; (4) cell migration; (5) establishment of intercellular contacts; and (6) the development of a cellular reticular arrangement within the gel and the extension of this arrangement into a 3-dimensional, tissue-like, honeycomb network. Electron microscopic observations on 0.1 ml gels containing MPLF cells showed that, in the early contractile phase, numerous cell processes attached to or enclosed collagen fibrils. These processes contained microfilamentous material and few organelles. In compacted gels, the cells contained an increased amount of distended rough endoplasmic reticulum and Golgi membranes. Since MPLF cells have the capacity for vigorous contraction of the collagen gels and since they develop a reticular, 3-dimensional structure in compacted gels that is reminiscent of the relationship of periodontal ligament fibroblasts to collagen fibres in vivo, it is suggested that they could provide the major force necessary for tooth eruption in vivo. This system also provides a well-defined in vitro model to study the sequential stages that occur during contraction processes.


2021 ◽  
Vol 15 (1) ◽  
pp. 417-423
Author(s):  
Fabio Schemann-Miguel ◽  
Antonio Carlos Aloise ◽  
Silvana Gaiba ◽  
Lydia Masako Ferreira

Background: The application of static compressive forces to periodontal ligament fibroblasts (PDLFs) in vivo or in vitro has been linked to the expression of biochemical agents and local tissue modifications that could be involved in maintaining homeostasis during orthodontic movement. An approach used for identifying mesenchymal cells, or a subpopulation of progenitor cells in both tumoral and normal tissues, involves determining the activity of aldehyde dehydrogenase (ALDH). However, the role of subpopulations of PDLF-derived undifferentiated cells in maintaining homeostasis during tooth movement remains unclear. Objective: This study aimed at analyzing the effect of applying a static compressive force to PDLFs on the activity of ALDH in these cells. Methods: PDLFs were distributed into two groups: control group (CG), where fibroblasts were not submitted to compression, and experimental group (EG), where fibroblasts were submitted to a static compressive force of 4 g/mm2 for 6 hours. The compressive force was applied directly to the cells using a custom-built device. ALDH activity in the PDLFs was evaluated by a flow cytometry assay. Results: ALDH activity was observed in both groups, but was significantly lower in EG than in CG after the application of a static compressive force in the former. Conclusion: Application of a static compressive force to PDLFs decreased ALDH activity.


Antioxidants ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 1221
Author(s):  
Eun-Nam Kim ◽  
Tae-Young Kim ◽  
Eui Kyun Park ◽  
Jae-Young Kim ◽  
Gil-Saeng Jeong

Periodontitis is an infectious inflammatory disease of tissues around teeth that destroys connective tissues and is characterized by the loss of periodontal ligaments and alveolar bone. A new treatment strategy is needed owing to the limitations of the current surgical treatment method and the side effects of anti-inflammatory drugs. Therefore, here, we assessed whether Panax ginseng fruit extract (PGFE) is a new therapeutic agent for periodontitis in vitro and in vivo. According to the results, PGFE suppressed pro-inflammatory cytokines such as tumor necrosis factor-α, interleukin (IL)-1β, and IL-6, and pro-inflammatory mediators such as inducible nitric oxide synthase and cyclooxygenase-2 through heme oxygenase-1 expression in human periodontal ligament cells stimulated with Porphyromonas gingivalis lipopolysaccharide (PG-LPS). In addition, the osteogenic induction of human periodontal ligament cells was inhibited by PG-LPS, and protein and mRNA levels of osteogenic markers such as alkaline phosphatase, collagen type 1 (COL1), osteopontin (OPN), and runt-related transcription factor 2 (RUNX2) were increased. The efficacy of PGFE for inhibiting periodontitis in vitro was demonstrated in a representative in vitro model of periodontitis induced by ligature and PG-LPS. Subsequently, hematoxylin and eosin staining and micro-computed tomography of the euthanized experimental animal model confirmed suppressed periodontal inflammation, which is an important strategy for treating periodontitis and for recovering the resulting alveolar bone loss. Therefore, PGFE is a potential, novel therapeutic agent for periodontal diseases.


2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Syed Taufiqul Islam ◽  
Yoshihito Kurashige ◽  
Erika Minowa ◽  
Koki Yoshida ◽  
Durga Paudel ◽  
...  

AbstractThe epithelial cell rests of Malassez (ERM) are essential in preventing ankylosis between the alveolar bone and the tooth (dentoalveolar ankylosis). Despite extensive research, the mechanism by which ERM cells suppress ankylosis remains uncertain; perhaps its varied population is to reason. Therefore, in this study, eighteen unique clones of ERM (CRUDE) were isolated using the single-cell limiting dilution and designated as ERM 1–18. qRT-PCR, ELISA, and western blot analyses revealed that ERM-2 and -3 had the highest and lowest amelogenin expression, respectively. Mineralization of human periodontal ligament fibroblasts (HPDLF) was reduced in vitro co-culture with CRUDE ERM, ERM-2, and -3 cells, but recovered when an anti-amelogenin antibody was introduced. Transplanted rat molars grown in ERM-2 cell supernatants produced substantially less bone than those cultured in other cell supernatants; inhibition was rescued when an anti-amelogenin antibody was added to the supernatants. Anti-Osterix antibody staining was used to confirm the development of new bones. In addition, next-generation sequencing (NGS) data were analysed to discover genes related to the distinct roles of CRUDE ERM, ERM-2, and ERM-3. According to this study, amelogenin produced by ERM cells helps to prevent dentoalveolar ankylosis and maintain periodontal ligament (PDL) space, depending on their clonal diversity.


2020 ◽  
Vol 17 ◽  
Author(s):  
Reem Habib Mohamad Ali Ahmad ◽  
Marc Fakhoury ◽  
Nada Lawand

: Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by the progressive loss of neurons leading to cognitive and memory decay. The main signs of AD include the irregular extracellular accumulation of amyloidbeta (Aβ) protein in the brain and the hyper-phosphorylation of tau protein inside neurons. Changes in Aβ expression or aggregation are considered key factors in the pathophysiology of sporadic and early-onset AD and correlate with the cognitive decline seen in patients with AD. Despite decades of research, current approaches in the treatment of AD are only symptomatic in nature and are not effective in slowing or reversing the course of the disease. Encouragingly, recent evidence revealed that exposure to electromagnetic fields (EMF) can delay the development of AD and improve memory. This review paper discusses findings from in vitro and in vivo studies that investigate the link between EMF and AD at the cellular and behavioural level, and highlights the potential benefits of EMF as an innovative approach for the treatment of AD.


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