scholarly journals Molecular Basis for Periodontal Ligament Adaptation to In Vivo Loading

2019 ◽  
Vol 98 (3) ◽  
pp. 331-338 ◽  
Author(s):  
X. Zhang ◽  
X. Yuan ◽  
Q. Xu ◽  
M. Arioka ◽  
L.A. Van Brunt ◽  
...  
Keyword(s):  
Wnt Signaling ◽  
Periodontal Ligament ◽  
Molecular Basis ◽  
Alveolar Bone ◽  
Adaptive Responses ◽  
Soft Diet ◽  
In Vivo Loading ◽  
First Time ◽  
Responsive Cell

A soft food diet leads to changes in the periodontal ligament (PDL). These changes, which have been recognized for more than a century, are ascribed to alterations in mechanical loading. While these adaptive responses have been well characterized, the molecular, cellular, and mechanical mechanisms underlying the changes have not. Here, we implicate Wnt signaling in the pathoetiology of PDL responses to underloading. We show that Wnt-responsive cells and their progeny in the PDL space exhibit a burst in proliferation in response to mastication. If an animal is fed a soft diet from the time of weaning, then this burst in Wnt-responsive cell proliferation is quelled; as a consequence, both the PDL and the surrounding alveolar bone undergo atrophy. Returning these animals to a hard food diet restores the Wnt signaling in PDL. These data provide, for the first time, a molecular mechanism underlying the adaptive response of the PDL to loading.

Mechano‐adaptive Responses of Alveolar Bone to Implant Hyper‐loading in a pre‐clinical in vivo model

2020 ◽  
Vol 31 (12) ◽  
pp. 1159-1172 ◽  
Author(s):  
Ye Tian ◽  
Zhijun Li ◽  
Jinlong Chen ◽  
Xue Yuan ◽  
Steven J. Sadowsky ◽  
...  
Keyword(s):  
Alveolar Bone ◽  
In Vivo Model ◽  
Adaptive Responses

scholarly journals Wnt Signaling in Periodontal Disease

2021 ◽  
Vol 2 ◽  
Author(s):  
David González-Quintanilla ◽  
Nicolás Abásolo ◽  
Pablo Astudillo
Keyword(s):  
Periodontal Disease ◽  
Wnt Signaling ◽  
Periodontal Ligament ◽  
Chronic Condition ◽  
Wnt Pathway ◽  
Alveolar Bone ◽  
Canonical Pathways ◽  
Canonical Wnt ◽  
Proper Balance

Periodontitis is a multifactorial and chronic condition associated with the formation of a dysbiotic biofilm, leading to a pro-inflammatory environment that can modulate cell signaling. The Wnt pathway plays fundamental roles during homeostasis and disease, and emerging evidence suggests its involvement in the maintenance of the periodontium and the development of periodontitis. Here, we summarize the role of the Wnt/β-catenin and non-canonical Wnt signaling pathways in periodontitis. The accumulated data suggests specific roles for each branch of the Wnt pathway. Wnt5a emerges as a critical player promoting periodontal ligament remodeling and impairing regenerative responses modulated by the Wnt/β-catenin pathway, such as alveolar bone formation. Collectively, the evidence suggests that achieving a proper balance between the Wnt/β-catenin and non-canonical pathways, rather than their independent modulation, might contribute to controlling the progression and severity of the periodontal disease.

scholarly journals A bilayered tissue engineered in vitro model simulating the tooth periodontium

2021 ◽  
Vol 42 ◽  
pp. 232-245
Author(s):  
A Khadre ◽  
ELM Raif ◽  
S Junaid ◽  
OM Goudouri ◽  
W Refaat ◽  
...  
Keyword(s):  
Gene Expression ◽  
Periodontal Ligament ◽  
Alveolar Bone ◽  
Cell Attachment ◽  
Human Tooth ◽  
Periodontal Ligament Cells ◽  
Collagen Membrane ◽  
Tissue Component

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.

Time-dependent mechanical behaviour of the periodontal ligament

2000 ◽  
Vol 214 (5) ◽  
pp. 497-504 ◽  
Author(s):  
W D van Driel ◽  
E J van Leeuwen ◽  
J W Von den Hoff ◽  
J C Maltha ◽  
A M Kuijpers-Jagtman
Keyword(s):  
Finite Element ◽  
Finite Element Model ◽  
Mechanical Behaviour ◽  
Periodontal Ligament ◽  
Alveolar Bone ◽  
Element Model ◽  
Time Dependent ◽  
Step Response ◽  
In Vivo Experiments

The process of tooth displacement in response to orthodontic forces is thought to be induced by the stresses and strains in the periodontium. The mechanical force on the tooth is transmitted to the alveolar bone through a layer of soft connective tissue, the periodontal ligament. Stress and/or strain distribution in this layer must be derived from mathematical models, such as the finite element method, because it cannot be measured directly in a non-destructive way. The material behaviour of the constituent tissues is required as an input for such a model. The purpose of this study was to determine the time-dependent mechanical behaviour of the periodontal ligament due to orthodontic loading of a tooth. Therefore, in vivo experiments were performed on beagle dogs. The experimental configuration was simulated in a finite element model to estimate the poroelastic material properties for the periodontal ligament. The experiments showed a two-step response: an instantaneous displacement of 14.10 ± 3.21 μm within 4 s and a more gradual (creep) displacement reaching a maximum of 60.00 ± 9.92 μm after 5 h. This response fitted excellently in the finite element model when 21 per cent of the ligament volume was assigned a permeability of 1.0 × 10−14m4/Ns, the remaining 97 per cent was assigned a permeability of 2.5 × 10−17 m4/N s. A tissue elastic modulus of 0.015 ± 0.001 MPa was estimated. Our results indicate that fluid compartments within the periodontal ligament play an important role in the transmission and damping of forces acting on teeth.

scholarly journals Molecular Basis of p53 Functional Inactivation by the Leukemic Protein MLL-ELL

2003 ◽  
Vol 23 (12) ◽  
pp. 4230-4246 ◽  
Author(s):  
Dmitri Wiederschain ◽  
Hidehiko Kawai ◽  
JiJie Gu ◽  
Ali Shilatifard ◽  
Zhi-Min Yuan
Keyword(s):  
Molecular Basis ◽  
Molecular Mechanisms ◽  
Cellular Transformation ◽  
Wild Type ◽  
Efficient Inhibitor ◽  
C Terminus ◽  
Functional Inactivation ◽  
Necessary And Sufficient ◽  
First Time

ABSTRACT The Eleven Lysine-rich Leukemia (ELL) gene undergoes translocation and fuses in frame to the Multiple Lineage Leukemia (MLL) gene in a substantial proportion of patients suffering from acute forms of leukemia. Molecular mechanisms of cellular transformation by the MLL-ELL fusion are not well understood. Although both MLL-ELL and wild-type ELL can reduce functional activity of p53 tumor suppressor, our data reveal that MLL-ELL is a much more efficient inhibitor of p53 than is wild-type ELL. We also demonstrate for the first time that ELL extreme C terminus [ELL(eCT)] is required for the recruitment of p53 into MLL-ELL nuclear foci and is both necessary and sufficient for the MLL-ELL inhibition of p53-mediated induction of p21 and apoptosis. Finally, our results demonstrate that MLL-ELL requires the presence of intact ELL(eCT) in order to disrupt p53 interactions with p300/CBP coactivator and thus significantly reduce p53 acetylation in vivo. Since ELL(eCT) has recently been shown to be both necessary and sufficient for MLL-ELL-mediated transformation of normal blood progenitors, our data correlate ELL(eCT) contribution to MLL-ELL transformative effects with its ability to functionally inhibit p53.

scholarly journals Transglutaminase Type 2 regulates the Wnt/β-catenin pathway in vertebrates

2021 ◽  
Vol 12 (3) ◽  
Author(s):  
Federica Rossin ◽  
Roberto Costa ◽  
Matteo Bordi ◽  
Manuela D’Eletto ◽  
Luca Occhigrossi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Wnt Signaling ◽  
Wnt Pathway ◽  
Rna Seq ◽  
Cellular Processes ◽  
Lower Vertebrates ◽  
First Time ◽  
Cellular Transcriptome

AbstractTG2 is a multifunctional enzyme involved in several cellular processes and has emerging as a potential regulator of gene expression. In this regard, we have recently shown that TG2 is able to activate HSF1, the master transcriptional regulator of the stress‐responsive genes; however, its effect on the overall gene expression remains unclear. To address this point, we analyzed, by RNA-seq, the effect of TG2 on the overall transcriptome as well as we characterized the TG2 interactome in the nucleus. The data obtained from these omics approaches reveal that TG2 markedly influences the overall cellular transcriptome profile and specifically the Wnt and HSF1 pathways. In particular, its ablation leads to a drastic downregulation of many key members of these pathways. Interestingly, we found that key components of the Wnt/β-catenin pathway are also downregulated in cells lacking HSF1, thus confirming that TG2 regulates the HSF1 and this axis controls the Wnt signaling. Mechanistic studies revealed that TG2 can regulate the Wnt pathway by physically interacts with β-catenin and its nuclear interactome includes several proteins known to be involved in the regulation of the Wnt signaling. In order to verify whether this effect is playing a role in vivo, we ablated TG2 in Danio rerio. Our data show that the zebrafish lacking TG2 cannot complete the development and their death is associated with an evident downregulation of the Wnt pathway and a defective heat-shock response. Our findings show for the first time that TG2 is essential for the correct embryonal development of lower vertebrates, and its action is mediated by the Wnt/HSF1 axis.

scholarly journals Mechanoadaptive Responses in the Periodontium Are Coordinated by Wnt

2019 ◽  
Vol 98 (6) ◽  
pp. 689-697 ◽  
Author(s):  
Q. Xu ◽  
X. Yuan ◽  
X. Zhang ◽  
J. Chen ◽  
Y. Shi ◽  
...  
Keyword(s):  
Alveolar Bone ◽  
Extensive Literature ◽  
Mechanical Forces ◽  
Stress Distributions ◽  
Adaptive Responses ◽  
Direct Response ◽  
Physical Loading ◽  
Restricted Pattern ◽  
Formation Phase

Despite an extensive literature documenting the adaptive changes of bones and ligaments to mechanical forces, our understanding of how tissues actually mount a coordinated response to physical loading is astonishingly inadequate. Here, using finite element (FE) modeling and an in vivo murine model, we demonstrate the stress distributions within the periodontal ligament (PDL) caused by occlusal hyperloading. In direct response, a spatially restricted pattern of apoptosis is triggered in the stressed PDL, the temporal peak of which is coordinated with a spatially restricted burst in PDL cell proliferation. This culminates in increased collagen deposition and a thicker, stiffer PDL that is adapted to its new hyperloading status. Meanwhile, in the adjacent alveolar bone, hyperloading activates bone resorption, the peak of which is followed by a bone formation phase, leading ultimately to an accelerated rate of mineral apposition and an increase in alveolar bone density. All of these adaptive responses are orchestrated by a population of Wnt-responsive stem/progenitor cells residing in the PDL and bone, whose death and revival are ultimately responsible for directly giving rise to new PDL fibers and new bone.

scholarly journals Regeneration of the zebrafish retinal pigment epithelium after widespread genetic ablation

2018 ◽  
Author(s):  
Nicholas J. Hanovice ◽  
Lyndsay L. Leach ◽  
Kayleigh Slater ◽  
Ana E. Gabriel ◽  
Dwight Romanovicz ◽  
...  
Keyword(s):  
Retinal Pigment Epithelium ◽  
Wnt Signaling ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Age Related Macular Degeneration ◽  
Rpe Cells ◽  
Genetic Ablation ◽  
Age Related ◽  
First Time

ABSTRACTThe retinal pigment epithelium (RPE) is a specialized monolayer of pigmented cells within the eye that is critical for maintaining visual system function. Diseases affecting the RPE have dire consequences for vision, and the most prevalent of these is atrophic (dry) age-related macular degeneration (AMD), which is thought to result from RPE dysfunction and degeneration. An intriguing possibility for treating RPE degenerative diseases like atrophic AMD is the stimulation of endogenous RPE regeneration; however, very little is known about the mechanisms driving successful RPE regeneration in vivo. Here, we developed a zebrafish transgenic model (rpe65a:nfsB-GFP) that enabled ablation of large swathes of mature RPE. RPE ablation resulted in rapid RPE degeneration, as well as degeneration of Bruch’s membrane and underlying photoreceptors. Using this model, we demonstrate for the first time that larval and adult zebrafish are capable of regenerating a functional RPE monolayer after RPE ablation. Regenerated RPE cells first appear at the periphery of the RPE, and regeneration proceeds in a peripheral-to-central fashion. RPE ablation elicits a robust proliferative response in the remaining RPE. Subsequently, proliferative cells move into the injury site and differentiate into RPE. BrdU pulse-chase analyses demonstrate that the regenerated RPE is likely derived from remaining peripheral RPE cells. Pharmacological inhibition of Wnt signaling significantly reduces cell proliferation in the RPE and delays overall RPE recovery. These data demonstrate that the zebrafish RPE possesses a robust capacity for regeneration and highlight a potential mechanism through which endogenous RPE regenerate in vivo.SIGNIFICANCE STATEMENTDiseases resulting in RPE degeneration are among the leading causes of blindness worldwide, and no therapy exists that can replace RPE or restore lost vision. One intriguing possibility is the development of therapies focused on stimulating endogenous RPE regeneration. For this to be possible, we must first gain a deeper understanding of the mechanisms underlying RPE regeneration. Here, we ablate mature RPE in zebrafish and demonstrate that zebrafish regenerate RPE after widespread injury. Injury-adjacent RPE proliferate and regenerate RPE, suggesting that they are the source of regenerated tissue. Finally, we demonstrate that Wnt signaling is required for RPE regeneration. These findings establish an in vivo model through which the molecular and cellular underpinnings of RPE regeneration can be further characterized.

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 ◽  
...  
Keyword(s):  
Periodontal Ligament ◽  
Alveolar Bone ◽  
Key Factors ◽  
Active Chromatin ◽  
Periodontal Ligament Fibroblasts ◽  
Chromatin Region ◽  
Transcriptional Alterations ◽  
Pparγ Agonists

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.

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