scholarly journals Interleukin-20 Acts as a Promotor of Osteoclastogenesis and Orthodontic Tooth Movement

2021 ◽  
Vol 2021 ◽  
pp. 1-20
Author(s):  
Yuanbo Liu ◽  
Yilong Ai ◽  
Xuan Sun ◽  
Bowen Meng ◽  
Xi Chen ◽  
...  
Keyword(s):  
Mechanical Stress ◽  
Tooth Movement ◽  
Osteoclast Differentiation ◽  
Orthodontic Tooth Movement ◽  
Signalling Pathway ◽  
Immunofluorescence Staining ◽  
Expression Levels ◽  
Stress Sensing

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.

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.

scholarly journals Tumour-derived exosomal lncRNA-SOX2OT promotes bone metastasis of non-small cell lung cancer by targeting the miRNA-194-5p/RAC1 signalling axis in osteoclasts

2021 ◽  
Vol 12 (7) ◽  
Author(s):  
Jianjiao Ni ◽  
Xiaofei Zhang ◽  
Juan Li ◽  
Zhiqin Zheng ◽  
Junhua Zhang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Bone Metastasis ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Osteoclast Differentiation ◽  
Small Cell ◽  
Signalling Pathway ◽  
Small Cell Lung

AbstractBone is a frequent metastatic site of non-small cell lung cancer (NSCLC), and bone metastasis (BoM) presents significant challenges for patient survival and quality of life. Osteolytic BoM is characterised by aberrant differentiation and malfunction of osteoclasts through modulation of the TGF-β/pTHrP/RANKL signalling pathway, but its upstream regulatory mechanism is unclear. In this study, we found that lncRNA-SOX2OT was highly accumulated in exosomes derived from the peripheral blood of NSCLC patients with BoM and that patients with higher expression of exosomal lncRNA-SOX2OT had significantly shorter overall survival. Additionally, exosomal lncRNA-SOX2OT derived from NSCLC cells promoted cell invasion and migration in vitro, as well as BoM in vivo. Mechanistically, we discovered that NSCLC cell-derived exosomal lncRNA-SOX2OT modulated osteoclast differentiation and stimulated BoM by targeting the miRNA-194-5p/RAC1 signalling axis and TGF-β/pTHrP/RANKL signalling pathway in osteoclasts. In conclusion, exosomal lncRNA-SOX2OT plays a crucial role in promoting BoM and may serve as a promising prognostic biomarker and treatment target in metastatic NSCLC.

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.

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.

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.

Mechanical Stretching of Mouse Calvarial Osteoblasts In Vitro Models Changes in MMP-2 and MMP-9 Expression at the Bone-Implant Interface

2016 ◽  
Vol 42 (2) ◽  
pp. 138-144 ◽  
Author(s):  
Richard A. Nichols ◽  
Frank D. Niagro ◽  
James L. Borke ◽  
Michael F. Cuenin
Keyword(s):  
Mechanical Stress ◽  
Mechanical Loading ◽  
Tooth Movement ◽  
Active Form ◽  
Orthodontic Tooth Movement ◽  
Biological Response ◽  
Gelatin Zymography ◽  
Joint Disease ◽  
Mechanical Stretching

Bone to mechanical loading elicits a biological response that has clinical significance for several areas in dental medicine, including orthodontic tooth movement, tempromandibular joint disease, and endosseous dental implant osseointegration. Human orthopedic studies of failed hip implant sites have identified increased mRNA expression of several collagen-degrading matrix metalloproteinases (MMPs), while in vitro experiments have shown increases in MMP secretion after exposure to inflammatory mediators. This investigation evaluates the effects of mechanical deformation on in vitro osteoblasts by assessing changes in MMP gene expression and enzyme activity. We seeded mouse neonatal calvarial osteoblasts onto flexible 6-well plates and subjected to continuous cyclic mechanical stretching. The expression and activity of mRNA for several MMPs (2, 3, 9, and 10) was assessed. When subjected to mechanical stress in culture, only mRNA specific for MMP-9 was significantly increased compared to nonstretched controls (P < .005). Measurement of MMP activity by gelatin zymography demonstrated that none of the MMPs showed increased activity with stretching; however, MMP-2 activity decreased. Our results suggest that in response to stretch, MMP-2 responds rapidly by inhibiting conversion of a MMP-2 to the active form, while a slower up-regulation of MMP-9 may play a role in the long-term remodeling of extracellular matrix in response to continuous mechanical loading. This study suggests that the regulation of metalloproteinases at both the mRNA and protein level are important in the response of bone to mechanical stress.

scholarly journals In Vitro Weight-Loaded Cell Models for Understanding Mechanodependent Molecular Pathways Involved in Orthodontic Tooth Movement: A Systematic Review

2018 ◽  
Vol 2018 ◽  
pp. 1-17 ◽  
Author(s):  
Mila Janjic ◽  
Denitsa Docheva ◽  
Olivera Trickovic Janjic ◽  
Andrea Wichelhaus ◽  
Uwe Baumert
Keyword(s):  
Systematic Review ◽  
Mechanical Stress ◽  
Tooth Movement ◽  
Orthodontic Tooth Movement ◽  
Compressive Force ◽  
Cell Types ◽  
Dental Stem Cells ◽  
Protein Protein Interaction ◽  
Different Cell Types

Cells from the mesenchymal lineage in the dental area, including but not limited to PDL fibroblasts, osteoblasts, and dental stem cells, are exposed to mechanical stress in physiological (e.g., chewing) and nonphysiological/therapeutic (e.g., orthodontic tooth movement) situations. Close and complex interaction of these different cell types results in the physiological and nonphysiological adaptation of these tissues to mechanical stress. Currently, different in vitro loading models are used to investigate the effect of different types of mechanical loading on the stress adaptation of these cell types. We performed a systematic review according to the PRISMA guidelines to identify all studies in the field of dentistry with focus on mechanobiology using in vitro loading models applying uniaxial static compressive force. Only studies reporting on cells from the mesenchymal lineage were considered for inclusion. The results are summarized regarding gene expression in relation to force duration and magnitude, and the most significant signaling pathways they take part in are identified using protein-protein interaction networks.

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.

Biological and Molecular Evidences for the Antitumor Potential of EGb 761 in Glioma Cells In Vitro and In Vivo

2021 ◽  
Vol 15 (5) ◽  
pp. 685-692
Author(s):  
Xin Sui ◽  
Jia Zhou ◽  
Yan Xu ◽  
Yuchen Wang ◽  
Guangfu Lv ◽  
...  
Keyword(s):  
Growth Factor ◽  
Caspase 3 ◽  
Glioma Cells ◽  
Signalling Pathway ◽  
Migration And Invasion ◽  
Egb 761 ◽  
Western Blots ◽  
Expression Levels

EGb 761, the standardized extract from the Ginkgo biloba leaves, has therapeutic effect on many diseases. However, its mechanisms on glioma remain to be fully established. This study aims to investigate the possible effects of EGb 761 on glioma cells, to explore its potential mechanism. The glioma cells SHG44 and U251 were used as materials, the proliferation, migration and invasion were assessed by the MTT, the scratch-wound and Transwell assays were performed respectively. Levels of insulin-like growth factor-1, Bcl-2, p53, Smad2/3, Bax, cleaved caspase-3 and p-Smad2/3 were determined by western blots. The development and progression of U251 glioma cell were measured in vivo, and the apoptosis was evaluated. The results showed that EGb 761 could inhibit the proliferation, migration, and invasion of SHG-44 and U251 cells in vitro. Meanwhile, the expression levels of IGF-1 and Bcl-2, and the transforming growth factor-β (TGF-β) signaling were inhibited. In contrast, the expression levels of p53, Bax, and cleaved caspase-3 were increased significantly. In conclusion, this study suggested that EGb 761 could suppress the growth of glioma cells in vitro and in vivo, possibly by inhibiting the TGF-β signalling pathway and activating the p53 signalling pathway.

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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