scholarly journals CXCL1, CCL2, and CCL5 modulation by microbial and biomechanical signals in periodontal cells and tissues—in vitro and in vivo studies

2020 ◽  
Vol 24 (10) ◽  
pp. 3661-3670 ◽  
Author(s):  
Birgit Rath-Deschner ◽  
Svenja Memmert ◽  
Anna Damanaki ◽  
Marjan Nokhbehsaim ◽  
Sigrun Eick ◽  
...  
Keyword(s):  
Tooth Movement ◽  
Orthodontic Tooth Movement ◽  
In Vivo Studies ◽  
Mechanical Forces ◽  
Rt Pcr ◽  
Mechanical Signals ◽  
Periodontal Infection ◽  
Experimental Periodontitis

Abstract Objectives This study was established to investigate whether the chemokines CXCL1, CCL2, and CCL5 are produced in periodontal cells and tissues and, if so, whether their levels are regulated by microbial and/or mechanical signals. Materials and methods The chemokine expression and protein levels in gingival biopsies from patients with and without periodontitis were analyzed by RT-PCR and immunohistochemistry. The chemokines were also analyzed in gingival biopsies from rats subjected to experimental periodontitis and/or orthodontic tooth movement. Additionally, chemokine levels were determined in periodontal fibroblasts exposed to the periodontopathogen Fusobacterium nucleatum and mechanical forces by RT-PCR and ELISA. Results Higher CXCL1, CCL2, and CCL5 levels were found in human and rat gingiva from sites of periodontitis as compared with periodontally healthy sites. In the rat experimental periodontitis model, the bacteria-induced upregulation of these chemokines was significantly counteracted by orthodontic forces. In vitro, F. nucleatum caused a significant upregulation of all chemokines at 1 day. When the cells were subjected simultaneously to F. nucleatum and mechanical forces, the upregulation of chemokines was significantly inhibited. The transcriptional findings were paralleled at protein level. Conclusions This study provides original evidence in vitro and in vivo that the chemokines CXCL1, CCL2, and CCL5 are regulated by both microbial and mechanical signals in periodontal cells and tissues. Furthermore, our study revealed that biomechanical forces can counteract the stimulatory actions of F. nucleatum on these chemokines. Clinical relevance Mechanical loading might aggravate periodontal infection by compromising the recruitment of immunoinflammatory cells.

scholarly journals Regulation of Anti-Apoptotic SOD2 and BIRC3 in Periodontal Cells and Tissues

2021 ◽  
Vol 22 (2) ◽  
pp. 591
Author(s):  
Birgit Rath-Deschner ◽  
Andressa Vilas Boas Nogueira ◽  
Svenja Memmert ◽  
Marjan Nokhbehsaim ◽  
Joni Augusto Cirelli ◽  
...  
Keyword(s):  
Tooth Movement ◽  
Orthodontic Tooth Movement ◽  
Fusobacterium Nucleatum ◽  
Protective Mechanism ◽  
Mechanical Forces ◽  
Periodontal Infection ◽  
Experimental Periodontitis ◽  
Orthodontic Forces ◽  
Superoxide Dismutase 2

The aim of the study was to clarify whether orthodontic forces and periodontitis interact with respect to the anti-apoptotic molecules superoxide dismutase 2 (SOD2) and baculoviral IAP repeat-containing protein 3 (BIRC3). SOD2, BIRC3, and the apoptotic markers caspases 3 (CASP3) and 9 (CASP9) were analyzed in gingiva from periodontally healthy and periodontitis subjects by real-time PCR and immunohistochemistry. SOD2 and BIRC3 were also studied in gingiva from rats with experimental periodontitis and/or orthodontic tooth movement. Additionally, SOD2 and BIRC3 levels were examined in human periodontal fibroblasts incubated with Fusobacterium nucleatum and/or subjected to mechanical forces. Gingiva from periodontitis patients showed significantly higher SOD2, BIRC3, CASP3, and CASP9 levels than periodontally healthy gingiva. SOD2 and BIRC3 expressions were also significantly increased in the gingiva from rats with experimental periodontitis, but the upregulation of both molecules was significantly diminished in the concomitant presence of orthodontic tooth movement. In vitro, SOD2 and BIRC3 levels were significantly increased by F. nucleatum, but this stimulatory effect was also significantly inhibited by mechanical forces. Our study suggests that SOD2 and BIRC3 are produced in periodontal infection as a protective mechanism against exaggerated apoptosis. In the concomitant presence of orthodontic forces, this protective anti-apoptotic mechanism may get lost.

scholarly journals Interaction of periodontitis and orthodontic tooth movement—an in vitro and in vivo study

2021 ◽  
Author(s):  
Birgit Rath-Deschner ◽  
Andressa V. B. Nogueira ◽  
Svenja Beisel-Memmert ◽  
Marjan Nokhbehsaim ◽  
Sigrun Eick ◽  
...  
Keyword(s):  
Alveolar Bone ◽  
Tooth Movement ◽  
Mechanical Strain ◽  
Orthodontic Tooth Movement ◽  
Fusobacterium Nucleatum ◽  
In Vivo Study ◽  
Rt Pcr ◽  
Periodontal Inflammation

Abstract 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.

scholarly journals MMPs and TIMPs Expression Levels in the Periodontal Ligament during Orthodontic Tooth Movement: A Systematic Review of In Vitro and In Vivo Studies

2021 ◽  
Vol 22 (13) ◽  
pp. 6967
Author(s):  
Christian Behm ◽  
Michael Nemec ◽  
Fabian Weissinger ◽  
Marco Aoqi Rausch ◽  
Oleh Andrukhov ◽  
...  
Keyword(s):  
Systematic Review ◽  
Periodontal Ligament ◽  
Tooth Movement ◽  
Orthodontic Tooth Movement ◽  
In Vivo Studies ◽  
Bias Assessment ◽  
Expression Levels ◽  
Orthodontic Forces

Background: 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. Methods: 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. Results: 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. Conclusion: 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.

Expression of MMP-8 and MMP-13 Genes in the Periodontal Ligament during Tooth Movement in Rats

2003 ◽  
Vol 82 (8) ◽  
pp. 646-651 ◽  
Author(s):  
I. Takahashi ◽  
M. Nishimura ◽  
K. Onodera ◽  
J.-W. Bae ◽  
H. Mitani ◽  
...  
Keyword(s):  
Gene Expression ◽  
Periodontal Ligament ◽  
Tooth Movement ◽  
Orthodontic Tooth Movement ◽  
Polymerase Chain Reaction Analysis ◽  
Tension And Compression ◽  
Polymerase Chain

Periodontal ligament tissue is remodeled on both the tension and compression sides of moving teeth during orthodontic tooth movement. The present study was designed to clarify the hypothesis that the expression of MMP-8 and MMP-13 mRNA is promoted during the remodeling of periodontal ligament tissue in orthodontic tooth movement. We used the in situ hybridization method and semi-quantitative reverse-transcription/polymerase chain-reaction analysis to elucidate the gene expression of MMP-8 and MMP-13 mRNA. Expression of MMP-8 and MMP-13 mRNA transiently increased on both the compression and tension sides during active tooth movement in vivo. The gene expression of MMP-8 and MMP-13 was induced by tension, while compression indirectly promoted the gene expression of MMP-8 and MMP-13 through soluble factors in vitro. Thus, we concluded that the expression of MMP-8 and MMP-13 is differentially regulated by tension and compression, and plays an important role in the remodeling of the periodontal ligament.

An Anti-c-Fms Antibody Inhibits Orthodontic Tooth Movement

2008 ◽  
Vol 87 (4) ◽  
pp. 396-400 ◽  
Author(s):  
H. Kitaura ◽  
M. Yoshimatsu ◽  
Y. Fujimura ◽  
T. Eguchi ◽  
H. Kohara ◽  
...  
Keyword(s):  
Mechanical Loading ◽  
Tooth Movement ◽  
Bone Erosion ◽  
Orthodontic Tooth Movement ◽  
Movement Model ◽  
Tnf Α ◽  
Macrophage Colony ◽  
Factor Α

Orthodontic force induces osteoclastogenesis in vivo. It has recently been reported that administration of an antibody against the macrophage-colony-stimulating factor (M-CSF) receptor c-Fms blocks osteoclastogenesis and bone erosion induced by tumor necrosis factor-α (TNF-α) administration. This study aimed to examine the effect of an anti-c-Fms antibody on mechanical loading-induced osteoclastogenesis and osteolysis in an orthodontic tooth movement model in mice. Using TNF receptor 1- and 2-deficient mice, we showed that orthodontic tooth movement was mediated by TNF-α. We injected anti-c-Fms antibody daily into a local site, for 12 days, during mechanical loading. The anti-c-Fms antibody significantly inhibited orthodontic tooth movement, markedly reduced the number of osteoclasts in vivo, and inhibited TNF-α-induced osteoclastogenesis in vitro. These findings suggest that M-CSF plays an important role in mechanical loading-induced osteoclastogenesis and bone resorption during orthodontic tooth movement mediated by TNF-α.

Alteration of Bone’s Nonlinear Elastic and Viscoelastic Nanomechanical Properties Is Triggered by Low Intensity Pulsed Ultrasound

2009 ◽  
Author(s):  
Suzanne Ferreri ◽  
Yi-Xian Qin
Keyword(s):  
Mechanical Strength ◽  
Material Properties ◽  
Signal Intensity ◽  
In Vivo Studies ◽  
Dynamic Mechanical ◽  
Mechanical Signals ◽  
Ultrasound Signal ◽  
Ultrasound Signals

Dynamic mechanotransduction, particularly under high frequency, low amplitude signals, has been proven effective in mediating bone loss and improving mechanical strength for tissues affected by estrogen deficient osteopenia. Ultrasound, which behaves as an alternating pressure wave in bone, may offer an effective, non-invasive technology for delivery of anabolic signals. In vitro, dynamic mechanical signals delivered using ultrasound have been shown to increase osteoblast proliferation [1], and in vivo studies have established ultrasound as an effective treatment for delayed and non-union fractures [2]. Previously, we showed that ultrasound signals similar to those currently used in a clinical setting for fracture healing were effective in mediating decreases in bone volume and mechanical strength at the millimeter length-scale in response to estrogen deficient osteopenia [3]. Due to bone’s inherent viscoelasticity and the dynamic nature of the applied ultrasound signals, it is particularly important to consider both elastic and viscous components of bone’s adaptive response to applied loads. In light of these findings, the goal of this study was to determine the role of therapeutic ultrasound signal intensity in modulating changes in bone’s nanoscale elastic and viscoelastic material properties associated with estrogen deficient osteopenia. We hypothesize that bone is sensitive to dynamic mechanical signals delivered via ultrasound and that bone’s tissue level nano-scale material properties, particularly nonlinear viscoelastic properties, are sensitive to ultrasound signal intensity.

scholarly journals Attenuation of Spatial Memory in 5xFAD Mice by Halting Cholinesterases, Oxidative Stress and Neuroinflammation Using a Cyclopentanone Derivative

2020 ◽  
Vol 13 (10) ◽  
pp. 318
Author(s):  
Rahim Ullah ◽  
Gowhar Ali ◽  
Nisar Ahmad ◽  
Muhammad Akram ◽  
Geeta Kumari ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Open Field ◽  
Inflammatory Cytokines ◽  
In Vivo Studies ◽  
Cholinesterase Inhibition ◽  
Rt Pcr ◽  
Y Maze ◽  
5Xfad Mice

Alzheimer’s disease (AD) is an irreversible and chronic neurological disorder that gradually destroys memory and thinking skills. The research study was designed to investigate the underlying molecular signaling involved in the neuroprotective effects of cyclopentanone derivative i.e., 2-(hydroxyl-(3-nitrophenyl)methyl)cyclopentanone (3NCP) as a therapeutic agent for AD. In this study, In vivo studies were carried out on a well-known 5xFAD mice model using different behavioural test models such as open field, rotarod, Morris water maze (MWM), and Y-maze tests. Furthermore, in vitro cholinesterase inhibition activity assays were carried out. The frontal cortex (FC) and hippocampus (HC) homogenates were tested for the levels/activities of cholinesterases, glutathione (GSH), glutathione S-transferase (GST), and catalase. Furthermore, the hippocampal expression of inflammatory cytokines was observed via RT-PCR and western blot. The results of in vivo studies show an enhancement in the learning behavior. The 3NCP treatment reduced latency time in MWM and Y-maze tests, also increase spontaneous alternation indicate significant effect of 3NCP on memory. Furthermore, open field and rotarod studies revealed that 3NCP does not cause motor coordination deficit. The results of the in vitro studies revealed that the IC50 values of the 3NCP against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) were 16.17 and 20.51 µg/mL, respectively. This decline in AChE and BChE was further supported by ex vivo studies. Further, the 3NCP mitigates the GSH level, GST, and catalase activities in HC and FC. The mRNA and protein expression of inflammatory cytokines (IL-1β, IL-6, TNF-α) markedly declined in RT-PCR and western blotting. The results of the current study conclusively demonstrate that 3NCP reduces oxidative stress and mitigates neuroinflammation in 5xFAD mice, implying that 3NCP may be a potential therapeutic candidate for AD treatment in the future.

DNA Changes in Mechanically Deformed Osteoblasts: A New Hypothesis

1993 ◽  
Vol 20 (1) ◽  
pp. 1-11 ◽  
Author(s):  
Jonathan R. Sandy
Keyword(s):  
Dna Synthesis ◽  
Tooth Movement ◽  
Mechanical Strain ◽  
Orthodontic Tooth Movement ◽  
Published Data ◽  
Mechanical Forces ◽  
In Vivo Models ◽  
Potent Inducer ◽  
New Hypothesis

The available evidence strongly implicates the osteoblast as the key regulator of bone remodelling activity. Since orthodontic tooth movement is a potent inducer of such activity it is relevant to study the effect of mechanical forces on this cell population. The development of a model for mechanically deforming monolayer cultures of cells is described. The effect of mechanical forces on osteoblast-like cells was examined by a number of parameters. Changes in DNA synthesis seen in short-term experiments were at variance with previous published data. The data derived from longer term experiments was in close agreement with in vivo models; intermittent forces producing an increase in DNA synthesis when compared to static or continuous forces. These changes are discussed in relation to current perspectives of second messenger activation by mechanical strain. Prostaglandins did not appear to mediate these events. There was also no evidence that synthesis of the cytokine, interleukin-I (IL-1), or the metalloproteinase, collagenase was altered by mechanical forces.

scholarly journals Direct 3D Printing of Clear Orthodontic Aligners: Current State and Future Possibilities

Materials ◽  
2021 ◽  
Vol 14 (7) ◽  
pp. 1799
Author(s):  
Gianluca M. Tartaglia ◽  
Andrea Mapelli ◽  
Cinzia Maspero ◽  
Tommaso Santaniello ◽  
Marco Serafin ◽  
...  
Keyword(s):  
3D Printing ◽  
New Technologies ◽  
Tooth Movement ◽  
In Vivo Studies ◽  
Orthodontic Appliances ◽  
Complex Method ◽  
Suitable Alternative ◽  
Current State

The recent introduction of three-dimensional (3D) printing is revolutionizing dentistry and is even being applied to orthodontic treatment of malocclusion. Clear, personalized, removable aligners are a suitable alternative to conventional orthodontic appliances, offering a more comfortable and efficient solution for patients. Including improved oral hygiene and aesthetics during treatment. Contemporarily, clear aligners are produced by a thermoforming process using various types of thermoplastic materials. The thermoforming procedure alters the properties of the material, and the intraoral environment further modifies the properties of a clear aligner, affecting overall performance of the material. Direct 3D printing offers the creation of highly precise clear aligners with soft edges, digitally designed and identically reproduced for an entire set of treatment aligners; offering a better fit, higher efficacy, and reproducibility. Despite the known benefits of 3D printing and the popularity of its dental applications, very limited technical and clinical data are available in the literature about directly printed clear aligners. The present article discusses the advantages of 3D printed aligners in comparison to thermoformed ones, describes the current state of the art, including a discussion of the possible road blocks that exist such as a current lack of approved and marketed materials and limited existence of aligner specific software. The present review suggests the suitability of 3D direct printed aligners is superior to that of thermoformed manufactured aligners because of the prior’s increased accuracy, load resistance, and lower deformation. It is an overall more stable way to produce an aligner where submillimeter movements can make a difference in treatment outcome. Direct 3D printing represents a complex method to control the thickness of the aligner and therefore has a better ability to control the force vectors that are used to produce tooth movement. There is currently no other approved material on the market that can do this. The conclusion of this article is that we encourage further in vitro and in vivo studies to test these new technologies and materials.

scholarly journals Effect of TNF-α-Induced Sclerostin on Osteocytes during Orthodontic Tooth Movement

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Fumitoshi Ohori ◽  
Hideki Kitaura ◽  
Aseel Marahleh ◽  
Akiko Kishikawa ◽  
Saika Ogawa ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Alveolar Bone ◽  
Tooth Movement ◽  
Orthodontic Tooth Movement ◽  
Osteoclast Formation ◽  
Rankl Expression ◽  
Bone Maintenance ◽  
Tnf Α

Osteocytes are abundant cells in bone, which contribute to bone maintenance. Osteocytes express receptor activator of nuclear factor kappa-B ligand (RANKL) and regulate osteoclast formation. Orthodontic tooth movement (OTM) occurs by osteoclast resorption of alveolar bone. Osteocyte-derived RANKL is critical in bone resorption during OTM. Additionally, tumor necrosis factor-α (TNF-α) is important in osteoclastogenesis during OTM. Sclerostin has been reported to enhance RANKL expression in the MLO-Y4 osteocyte-like cell line. This study investigated the effect of TNF-α on sclerostin expression in osteocytes during OTM. In vitro analysis of primary osteocytes, which were isolated from DMP1-Topaz mice by sorting the Topaz variant of GFP-positive cells, revealed that SOST mRNA expression was increased when osteocytes were cultured with TNF-α and that RANKL mRNA expression was increased when osteocytes were cultured with sclerostin. Moreover, the number of TRAP-positive cells was increased in osteocytes and osteoclast precursors cocultured with sclerostin. In vivo analysis of mouse calvariae that had been subcutaneously injected with phosphate-buffered saline (PBS) or TNF-α revealed that the number of TRAP-positive cells and the percentage of sclerostin-positive osteocytes were higher in the TNF-α group than in the PBS group. Furthermore, the level of SOST mRNA was increased by TNF-α. As an OTM model, a Ni-Ti closed-coil spring connecting the upper incisors and upper-left first molar was placed to move the first molar to the mesial direction in wild-type (WT) mice and TNF receptor 1- and 2-deficient (TNFRsKO) mice. After 6 days of OTM, the percentage of sclerostin-positive osteocytes on the compression side of the first molar in TNFRsKO mice was lower than that in WT mice. In this study, TNF-α increased sclerostin expression in osteocytes, and sclerostin enhanced RANKL expression in osteocytes. Thus, TNF-α may play an important role in sclerostin expression in osteocytes and enhance osteoclast formation during OTM.

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