DNA Changes in Mechanically Deformed Osteoblasts: A New Hypothesis

1993 ◽  
Vol 20 (1) ◽  
pp. 1-11 ◽  
Author(s):  
Jonathan R. Sandy

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.

Author(s):  
Birgit Rath-Deschner ◽  
Andressa V. B. Nogueira ◽  
Svenja Beisel-Memmert ◽  
Marjan Nokhbehsaim ◽  
Sigrun Eick ◽  
...  

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.


2020 ◽  
Vol 24 (10) ◽  
pp. 3661-3670 ◽  
Author(s):  
Birgit Rath-Deschner ◽  
Svenja Memmert ◽  
Anna Damanaki ◽  
Marjan Nokhbehsaim ◽  
Sigrun Eick ◽  
...  

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.


2021 ◽  
pp. 002203452098477
Author(s):  
S. Wald ◽  
A. Leibowitz ◽  
Y. Aizenbud ◽  
Y. Saba ◽  
K. Zubeidat ◽  
...  

Sustained mechanical forces applied to tissue are known to shape local immunity. In the oral mucosa, mechanical stress, either naturally induced by masticatory forces or externally via mechanical loading during orthodontic tooth movement (OTM), is translated, in part, by T cells to alveolar bone resorption. Nevertheless, despite being considered critical for OTM, depletion of CD4+ and CD8+ T cells is reported to have no impact on tooth movement, thus questioning the function of αβT cells in OTM-associated bone resorption. To further address the role of T cells in OTM, we first characterized the leukocytes residing in the periodontal ligament (PDL), the tissue of interest during OTM, and compared it to the neighboring gingiva. Unlike the gingiva, monocytes and neutrophils represent the major leukocytes of the PDL. These myeloid cells were also the main leukocytes in the PDL of germ-free mice, although at lower levels than SPF mice. T lymphocytes were more enriched in the gingiva than the PDL, yet in both tissues, the relative fraction of the γδT cells was higher than the αβ T cells. We thus sought to examine the role of γδT cells in OTM. γδT cells residing in the PDL were mainly Vγ6+ and produced interleukin (IL)–17A but not interferon-γ. Using Tcrd-GDL mice allowing conditional ablation of γδT cells in vivo, we demonstrate that OTM was greatly diminished in the absence of γδT cells. Further analysis revealed that ablation of γδT cells decreased early IL-17A expression, monocyte and neutrophil recruitment, and the expression of the osteoclastogenic molecule receptor activator of nuclear factor–κβ ligand. This, eventually, resulted in reduced numbers of osteoclasts in the pressure site during OTM. Collectively, our data suggest that γδT cells are essential in OTM for translating orthodontic mechanical forces to bone resorption, required for relocating the tooth in the alveolar bone.


2020 ◽  
Vol 21 (24) ◽  
pp. 9530
Author(s):  
Christian Kirschneck ◽  
Magdalena Thuy ◽  
Alexandra Leikam ◽  
Svenja Memmert ◽  
James Deschner ◽  
...  

Orthodontic tooth movement (OTM) creates compressive and tensile strain in the periodontal ligament, causing circulation disorders. Hypoxia-inducible factor 1α (HIF-1α) has been shown to be primarily stabilised by compression, but not hypoxia in periodontal ligament fibroblasts (PDLF) during mechanical strain, which are key regulators of OTM. This study aimed to elucidate the role of heparan sulfate integrin interaction and downstream kinase phosphorylation for HIF-1α stabilisation under compressive and tensile strain and to which extent downstream synthesis of VEGF and prostaglandins is HIF-1α-dependent in a model of simulated OTM in PDLF. PDLF were subjected to compressive or tensile strain for 48 h. In various setups HIF-1α was experimentally stabilised (DMOG) or destabilised (YC-1) and mechanotransduction was inhibited by surfen and genistein. We found that HIF-1α was not stabilised by tensile, but rather by compressive strain. HIF-1α stabilisation had an inductive effect on prostaglandin and VEGF synthesis. As expected, HIF-1α destabilisation reduced VEGF expression, whereas prostaglandin synthesis was increased. Inhibition of integrin mechanotransduction via surfen or genistein prevented stabilisation of HIF-1α. A decrease in VEGF expression was observed, but not in prostaglandin synthesis. Stabilisation of HIF-1α via integrin mechanotransduction and downstream phosphorylation of kinases seems to be essential for the induction of VEGF, but not prostaglandin synthesis by PDLF during compressive (but not tensile) orthodontic strain.


Author(s):  
Maximilian G. Decker ◽  
Cita Nottmeier ◽  
Julia Luther ◽  
Anke Baranowsky ◽  
Bärbel Kahl-Nieke ◽  
...  

2003 ◽  
Vol 82 (8) ◽  
pp. 646-651 ◽  
Author(s):  
I. Takahashi ◽  
M. Nishimura ◽  
K. Onodera ◽  
J.-W. Bae ◽  
H. Mitani ◽  
...  

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.


2020 ◽  
Vol 5 (3) ◽  
pp. 65 ◽  
Author(s):  
Giovanna Vermiglio ◽  
Antonio Centofanti ◽  
Giovanni Matarese ◽  
Angela Militi ◽  
Marco Matarese ◽  
...  

The orthodontic tooth movement is the last step of several biological processes that take place after the application of external forces. During this process, dental pulp tissue is subjected to structural and protein expression modifications in order to maintain their integrity and functional morphology. The purpose of the present work was to perform an in vivo study, evaluating protein expression modifications in the human dental pulp of patients that have undergone orthodontic tooth movement due to pre-calibrated light force application for 30 days. Dental pulp samples were extracted from molars and premolars of the control group and after 7 and 30 days of treatment; the samples were then processed for immunofluorescence reactions using antibodies against fibronectin, collagen I and vascular endothelial growth factor (VEGF). Our results show that, after 7 days of treatment, all tested proteins change their pattern expression and will reset after 30 days. These data demonstrate that the dental pulp does not involve any irreversible iatrogenic alterations, supporting the efficacy and safety of using pre-calibrated force application to induce orthodontic tooth movement in clinical practice.


2016 ◽  
Vol 62 (2) ◽  
pp. 328-334 ◽  
Author(s):  
Klaus Pantel ◽  
Catherine Alix-Panabières

AbstractBACKGROUNDResearch on circulating tumor cells (CTCs) as new biomarkers has received great attention over the past decade. In particular, the capture and analysis of CTCs as “liquid biopsies” provides the possibility to avoid invasive tissue biopsies, with obvious implications in cancer diagnostics.CONTENTThe focus of this review is to describe and discuss how functional studies on viable CTCs can enlarge the spectrum of applications of liquid biopsies, with emphasis on breast, prostate, colon, and lung cancer as the major tumor entities in industrialized countries. The low number of CTCs in the peripheral blood of most cancer patients makes challenging the in vitro culture of CTCs. Epithelial tumor cells are difficult to culture, even when starting with millions of tumor cells. Recently, several groups have achieved important advances in the in vitro and in vivo expansion of CTCs from cancer patients at very advanced stages with higher amounts of CTCs. Here, we present current technologies to enrich and detect viable human CTCs, including positive and negative enrichment strategies that are based on antigen expression and physical properties of CTCs. We also discuss published data about functional studies on CTCs that use in vitro and in vivo models.SUMMARYFunctional analyses on CTCs offer the possibility to identify the biological properties of metastatic cells, including the identification of metastasis-initiating cells. Moreover, CTC-derived cell lines and xenografts might reveal new therapeutic targets and can be used for drug screening.


2012 ◽  
Vol 3 (1) ◽  
pp. 56-61
Author(s):  
Fraser McDonald

Many theories are advanced with respect to the behaviour of bone under external loading. Essentially they divide into external loading (with respect to tension and compression), tissue-fluid-based theories and electrical-based theories. While this appears to be a distinct classification with regard to an understanding of these theories, it must be emphasised that each theory has a significant inter-relationship with the others. It is also essential to differentiate that, while an effect can be identified at the cellular level, the relative importance and significance of this can be limited in vivo and its relative role and importance overwhelmed by other loading issues. In this article consideration is given to a possible basis of orthodontic tooth movement and like so many other hypotheses it is difficult to directly evaluate and measure; it must be considered by deduction of current known facts. The concept was initially reported when comparing bone remodelling in a femur with orthodontic tooth movement;1 further data is now available although the concept is not completely acceptable. It does, however, produce an explanation for some clinical findings which assist us in our orthodontic care delivery.


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