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 ◽  
...  

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.

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 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.


2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Huaming Huang ◽  
Ruili Yang ◽  
Yan-heng Zhou

Periodontal ligament stem cells (PDLSCs) possess self-renewal, multilineage differentiation, and immunomodulatory properties. They play a crucial role in maintaining periodontal homeostasis and also participated in orthodontic tooth movement (OTM). Various studies have applied controlled mechanical stimulation to PDLSCs and investigated the effects of orthodontic force on PDLSCs. Physical stimuli can regulate the proliferation and differentiation of PDLSCs. During the past decade, a variety of studies has demonstrated that applied forces can activate different signaling pathways in PDLSCs, including MAPK, TGF-β/Smad, and Wnt/β-catenin pathways. Besides, recent advances have highlighted the critical role of orthodontic force in PDLSC fate through mediators, such as IL-11, CTHRC1, miR-21, and H2S. This perspective review critically discusses the PDLSC fate to physical forcein vitroand orthodontic forcein vivo, as well as the underlying molecular mechanism involved in OTM.


2021 ◽  
Vol 2021 ◽  
pp. 1-20
Author(s):  
Yuanbo Liu ◽  
Yilong Ai ◽  
Xuan Sun ◽  
Bowen Meng ◽  
Xi Chen ◽  
...  

Objectives. Bones constitute organs that are engaged in constant self-remodelling. Osteoblast and osteoclast homeostasis during remodelling contribute to overall skeletal status. Orthodontics is a clinical discipline that involves the investigation and implementation of moving teeth through the bone. The application of mechanical force to the teeth causes an imbalance between osteogenesis and osteogenesis in alveolar bone, leading to tooth movement. Osteoimmunology comprises the crosstalk between the immune and skeletal systems that regulate osteoclast–osteoblast homeostasis. Interleukin- (IL-) 20, an IL-10 family member, is regarded as a proinflammatory factor for autoimmune diseases and has been implicated in bone loss disease. However, the mechanism by which IL-20 regulates osteoclast differentiation and osteoclastogenesis activation remains unclear. This study investigated the effects of IL-20 on osteoclast differentiation in a rat model; it explored the underlying molecular mechanism in vitro and the specific effects on orthodontic tooth movement in vivo. Methods. For in vitro analyses, primary rat bone marrow-derived macrophages (BMMs) were prepared from Sprague–Dawley rats for osteoclast induction. After BMMs had been treated with combinations of recombinant IL-20 protein, siRNA, and plasmids, the expression levels of osteoclast-specific factors and signalling pathway proteins were detected through real-time polymerase chain reaction, western blotting, and immunofluorescence staining. For in vivo analyses, IL-20 was injected into the rat intraperitoneal cavity after the establishment of a rat orthodontic tooth movement (OTM) model. OTM distance was detected by Micro-CT and HE staining; the expression levels of protein were detected through immunofluorescence staining. Results. In vitro analyses showed that a low concentration of IL-20 promoted preosteoclast proliferation and osteoclastogenesis. However, a high concentration of IL-20 inhibited BMM proliferation and osteoclastogenesis. IL-20 knockdown decreased the expression of osteoclast specific-markers, while IL-20 overexpression increased the expression of osteoclast specific-markers. Furthermore, IL-20 regulated osteoclast differentiation through the OPG/RANKL/RANK pathway. Overexpression of IL-20 could significantly upregulate RANKL-mediated osteoclast differentiation and osteoclast specific-marker expression; moreover, RANKL/NF-κB/NFATc1 acted as downstream signalling molecule for IL-20. In vivo analysis showed that OTM speed was significantly increased after intraperitoneal injection of IL-20; additionally, mechanical stress sensing proteins were markedly activated. Conclusions. IL-20 augments osteoclastogenesis and osteoclast-mediated bone erosion through the RANKL/NF-κB/NFATc1 signalling pathway. IL-20 inhibition can effectively reduce osteoclast differentiation and diminish bone resorption. Furthermore, IL-20 can accelerate orthodontic tooth movement and activate mechanical stress sensing proteins.


2019 ◽  
Vol 14 (6) ◽  
pp. 504-518 ◽  
Author(s):  
Dilcele Silva Moreira Dziedzic ◽  
Bassam Felipe Mogharbel ◽  
Priscila Elias Ferreira ◽  
Ana Carolina Irioda ◽  
Katherine Athayde Teixeira de Carvalho

This systematic review evaluated the transplantation of cells derived from adipose tissue for applications in dentistry. SCOPUS, PUBMED and LILACS databases were searched for in vitro studies and pre-clinical animal model studies using the keywords “ADIPOSE”, “CELLS”, and “PERIODONTAL”, with the Boolean operator “AND”. A total of 160 titles and abstracts were identified, and 29 publications met the inclusion criteria, 14 in vitro and 15 in vivo studies. In vitro studies demonstrated that adipose- derived cells stimulate neovascularization, have osteogenic and odontogenic potential; besides adhesion, proliferation and differentiation on probable cell carriers. Preclinical studies described improvement of bone and periodontal healing with the association of adipose-derived cells and the carrier materials tested: Platelet Rich Plasma, Fibrin, Collagen and Synthetic polymer. There is evidence from the current in vitro and in vivo data indicating that adipose-derived cells may contribute to bone and periodontal regeneration. The small quantity of studies and the large variation on study designs, from animal models, cell sources and defect morphology, did not favor a meta-analysis. Additional studies need to be conducted to investigate the regeneration variability and the mechanisms of cell participation in the processes. An overview of animal models, cell sources, and scaffolds, as well as new perspectives are provided for future bone and periodontal regeneration study designs.


Biomolecules ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 932
Author(s):  
Julia Brockhaus ◽  
Rogerio B. Craveiro ◽  
Irma Azraq ◽  
Christian Niederau ◽  
Sarah K. Schröder ◽  
...  

Human Periodontal Ligament Fibroblasts (hPDLF), as part of the periodontal apparatus, modulate inflammation, regeneration and bone remodeling. Interferences are clinically manifested as attachment loss, tooth loosening and root resorption. During orthodontic tooth movement (OTM), remodeling and adaptation of the periodontium is required in order to enable tooth movement. hPDLF involvement in the early phase-OTM compression side was investigated for a 72-h period through a well-studied in vitro model. Changes in the morphology, cell proliferation and cell death were analyzed. Specific markers of the cell cycle were investigated by RT-qPCR and Western blot. The study showed that the morphology of hPDLF changes towards more unstructured, unsorted filaments under mechanical compression. The total cell numbers were significantly reduced with a higher cell death rate over the whole observation period. hPDLF started to recover to pretreatment conditions after 48 h. Furthermore, key molecules involved in the cell cycle were significantly reduced under compressive force at the gene expression and protein levels. These findings revealed important information for a better understanding of the preservation and remodeling processes within the periodontium through Periodontal Ligament Fibroblasts during orthodontic tooth movement. OTM initially decelerates the hPDLF cell cycle and proliferation. After adapting to environmental changes, human Periodontal Ligament Fibroblasts can regain homeostasis of the periodontium, affecting its reorganization.


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.


2021 ◽  
Vol 11 (9) ◽  
pp. 3824
Author(s):  
Ioana-Andreea Sioustis ◽  
Mihai Axinte ◽  
Marius Prelipceanu ◽  
Alexandra Martu ◽  
Diana-Cristala Kappenberg-Nitescu ◽  
...  

Finite element analysis studies have been of interest in the field of orthodontics and this is due to the ability to study the stress in the bone, periodontal ligament (PDL), teeth and the displacement in the bone by using this method. Our study aimed to present a method that determines the effect of applying orthodontic forces in bodily direction on a healthy and reduced periodontium and to demonstrate the utility of finite element analysis. Using the cone-beam computed tomography (CBCT) of a patient with a healthy and reduced periodontium, we modeled the geometric construction of the contour of the elements necessary for the study. Afterwards, we applied a force of 1 N and a force of 0.8 N in order to achieve bodily movement and to analyze the stress in the bone, in the periodontal ligament and the absolute displacement. The analysis of the applied forces showed that a minimal ligament thickness is correlated with the highest value of the maximum stress in the PDL and a decreased displacement. This confirms the results obtained in previous clinical practice, confirming the validity of the simulation. During orthodontic tooth movement, the morphology of the teeth and of the periodontium should be taken into account. The effect of orthodontic forces on a particular anatomy could be studied using FEA, a method that provides real data. This is necessary for proper treatment planning and its particularization depends on the patient’s particular situation.


2021 ◽  
Vol 138 ◽  
pp. 111495
Author(s):  
Nancy Y. Guerrero-Pepinosa ◽  
María C. Cardona-Trujillo ◽  
Sandra C. Garzón-Castaño ◽  
Luz Angela Veloza ◽  
Juan C. Sepúlveda-Arias

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Lihua Yin ◽  
Wenxiao Cheng ◽  
Zishun Qin ◽  
Hongdou Yu ◽  
Zhanhai Yu ◽  
...  

This study is to explore the osteogenesis potential of the human periodontal ligament stem cells (hPDLSCs) induced by naringin in vitro and in vitro. The results confirmed that 1 μM naringin performs the best effect and a collection of bone-related genes (RUNX2,COL1A2, OPN, and OCN) had significantly higher expression levels compared to the control group. Furthermore, a typical trabecular structure was observed in vivo, surrounded by a large amount of osteoblasts. These results demonstrated that naringin, at a concentration of 1 μM, can efficiently promote the proliferation and differentiation of hPDLSCs both in vitro and in vivo.


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