scholarly journals Mechanistic Insight into Orthodontic Tooth Movement Based on Animal Studies: A Critical Review

2021 ◽  
Vol 10 (8) ◽  
pp. 1733
Author(s):  
Hyeran Helen Jeon ◽  
Hellen Teixeira ◽  
Andrew Tsai

Alveolar bone remodeling in orthodontic tooth movement (OTM) is a highly regulated process that coordinates bone resorption by osteoclasts and new bone formation by osteoblasts. Mechanisms involved in OTM include mechano-sensing, sterile inflammation-mediated osteoclastogenesis on the compression side and tensile force-induced osteogenesis on the tension side. Several intracellular signaling pathways and mechanosensors including the cilia and ion channels transduce mechanical force into biochemical signals that stimulate formation of osteoclasts or osteoblasts. To date, many studies were performed in vitro or using human gingival crevicular fluid samples. Thus, the use of transgenic animals is very helpful in examining a cause and effect relationship. Key cell types that participate in mediating the response to OTM include periodontal ligament fibroblasts, mesenchymal stem cells, osteoblasts, osteocytes, and osteoclasts. Intercellular signals that stimulate cellular processes needed for orthodontic tooth movement include receptor activator of nuclear factor-κB ligand (RANKL), tumor necrosis factor-α (TNF-α), dickkopf Wnt signaling pathway inhibitor 1 (DKK1), sclerostin, transforming growth factor beta (TGF-β), and bone morphogenetic proteins (BMPs). In this review, we critically summarize the current OTM studies using transgenic animal models in order to provide mechanistic insight into the cellular events and the molecular regulation of OTM.

2021 ◽  
pp. 002203452110199
Author(s):  
Y. Xie ◽  
Q. Tang ◽  
S. Yu ◽  
W. Zheng ◽  
G. Chen ◽  
...  

Orthodontic tooth movement (OTM) depends on periodontal ligament cells (PDLCs) sensing biomechanical stimuli and subsequently releasing signals to initiate alveolar bone remodeling. However, the mechanisms by which PDLCs sense biomechanical stimuli and affect osteoclastic activities are still unclear. This study demonstrates that the core circadian protein aryl hydrocarbon receptor nuclear translocator–like protein 1 (BMAL1) in PDLCs is highly involved in sensing and delivering biomechanical signals. Orthodontic force upregulates BMAL1 expression in periodontal tissues and cultured PDLCs in manners dependent on ERK (extracellular signal–regulated kinase) and AP1 (activator protein 1). Increased BMAL1 expression can enhance secretion of CCL2 (C-C motif chemokine 2) and RANKL (receptor activator of nuclear factor–κB ligand) in PDLCs, which subsequently promotes the recruitment of monocytes that differentiate into osteoclasts. The mechanistic delineation clarifies that AP1 induced by orthodontic force can directly interact with the BMAL1 promoter and activate gene transcription in PDLCs. Localized administration of the ERK phosphorylation inhibitor U0126 or the BMAL1 inhibitor GSK4112 suppressed ERK/AP1/BMAL1 signaling. These treatments dramatically reduced osteoclastic activity in the compression side of a rat orthodontic model, and the OTM rate was almost nonexistent. In summary, our results suggest that force-induced expression of BMAL1 in PDLCs is closely involved in controlling osteoclastic activities during OTM and plays a vital role in alveolar bone remodeling. It could be a useful therapeutic target for accelerating the OTM rate and controlling pathologic bone-remodeling activities.


1994 ◽  
Vol 266 (5) ◽  
pp. E731-E738 ◽  
Author(s):  
C. Dolce ◽  
J. Anguita ◽  
L. Brinkley ◽  
P. Karnam ◽  
M. Humphreys-Beher ◽  
...  

Effects on bone remodeling have been attributed to epidermal growth factor (EGF). Sialoadenectomy (SX) removes the major source of EGF in rodents and decreases both salivary and serum EGF levels. EGF effects on rat alveolar bone remodeling manifested by molar drift (MD) and orthodontic tooth movement (OTM) were examined using the following two approaches: 1) EGF depletion by SX and replacement by orally administered EGF (50 micrograms.animal-1.day-1); 2) sham rats supplemented with matching amounts of EGF. MD and OTM were measured using cephalometric radiographs; bone formation was measured histomorphometrically using tetracycline labeling. Normal MD was not detected after SX, and alveolar bone formation was significantly reduced both around the tooth and in nondental sites. Replacement EGF given to SX rats and supplemental EGF administered to sham rats changed the direction and enhanced the rate of MD. A mesially directed orthodontic force applied to the molars of SX animals increased bone formation on the distal aspect of the tooth roots. Supplemental EGF did not significantly affect OTM. EGF affects alveolar bone remodeling, as manifested clinically by alterations in normal maxillary MD.


2017 ◽  
Vol 758 ◽  
pp. 255-263 ◽  
Author(s):  
Ananto Ali Alhasyimi ◽  
Pinandi Sri Pudyani ◽  
Widya Asmara ◽  
Ika Dewi Ana

Relapse is considered a significant failure after orthodontic treatment. In response to relapse, RANKL expressions will increase, while OPG expressions will decrease. CHA is thought to be one of an ideal candidate for enhancing bone formation. Moreover, a-PRF is a source high levels of growth factors that play a central role in the bone remodeling. This research was intended to investigate the effect of hydrogel CHA-aPRF in preventing relapse. Hydrogel-CHA was initially designed, with its degradation profile and FTIR (Fourie’s Transform Infrared) spectra were investigated as the basis to find out optimum formulation before incorporated with aPRF. Hydrogel-CHA microspheres were prepared in 3 different compositions: those were encoded 30-CHA, 40-CHA, and 50-CHA. After the hydrogel formulation and characterization were completed, 10 mL blood samples were collected, then centrifuged at 1500 rpm for 14 min. At the end of the centrifugation process, the aPRF clot was isolated and then pressed to obtain their releasate. The releasate aPRF was then loaded into the best formulation candidate of hydrogel CHA. The hydrogel incorporated aPRF was then gently injected on the mesial side of incisor gingival sulcus of the rabbit after orthodontic tooth movement. The FTIR analysis showed that carbonated apatite was successfully developed during the fabrication process of hydrogel-CHA microspheres. It was also known that degradation profile of 30-CHA was considered ideal compared to the other compositions. The application of CHA-aPRF (group C) was proven to significantly prevent relapse, indicated by lowest percentage of relapse 21 days after debonding (29.95±3.91%) compared to control group. Furthermore, it has been found that expressions of RANKL were significantly lowest (p<0.05) in group C on day 0, 3, and 7, while OPG expressions showed significantly highest (p<0.05) in group C on day 14 and 21 after debonding. These results indicate that incorporation of hydrogel-CHA has potential effect to enhance alveolar bone remodeling and prevent orthodontic relapse by stimulates OPG expression and suppresses RANKL expression.


2017 ◽  
Vol 5 (2) ◽  
pp. 90
Author(s):  
Herniyati Herniyati

Background: Orthodontic tooth movement depends on bone remodeling. VEGF plays an important role in bone remodeling in both pressure area and tension area. Robusta coffee contains caffeine, chlorogenic acid and caffeic acid. Caffeine may increase osteoclastogenesis, and caffeic acid has antioxidant effects that may reduce oxidative stress in osteoblasts Objective: To analysis of VEGF of orthodontic tooth movement post robusta coffeesteeping administration. Material and methods: The experimental laboratories research used 16rats  were divided into 2 groups. Group A: the rats were applied with  orthodontic mechanical force (OMF) and group B: OMF + coffee steeping of 20mg /100 g of BW. OMF was conducted by applying  ligature wire with a diameter of 0.20 mm on the molar-1 (M-1) and both incivus of right maxilla. Subsequently, M-1 of right maxilla was moved to mesial  with Niti closed coil spring. Observations were made on days 15 and 22 by taking the gingival crevicular fluid by putting paper point on the gingival sulcus of mesio-and disto-palatal area of M-1 of right maxilla to determine the levels of VEGF using ELISA method. Results: the administration of Robusta coffee steeping increased the levels of VEGF in both compression area and tension area (p <0.05).The levels of VEGF in tension area larger than the compression area(p >0.05).Conclusion: the Robusta coffee steeping administration increased the levels of VEGF oforthodontic tooth movement ,therefore it may improve alveolar bone remodeling process and it may be an alternative to accelerate orthodontic treatment.


2017 ◽  
Vol 50 (2) ◽  
pp. 91
Author(s):  
H. Herniyati

Background: The application of orthodontic forces subjects blood capillaries to considerable pressure, resulting in hypoxia on the pressure side. Vascular endothelial growth factor (VEGF), expressed in osteoblasts represents an important mitogen that induces angiogenesis. Osteoblasts and blood capillaries play an important role in bone formation. Robusta coffee contains chlorogenic acid and caffeic acid both of which produce antioxidant effects capable of reducing oxidative stress in osteoblasts. Purpose: The aim of this study was to analyze the effects of Robusta coffee extract on the number of osteoblasts and blood capillaries in orthodontic tooth movement. Methods: This research constituted a laboratory-based experimental study involving the use of sixteen male rodents divided into two groups, namely; control group (C) consisting of eight mice given orthodontic mechanical force (OMF) and a treatment group (T) containing eight mice administered OMF and dried Robusta coffee extract at a dose of 20mg/ 100 g BW. The OMF was performed by installing a ligature wire on the maxillary right first molar and both maxillary incisors. In the following stage, the maxillary right first molar was moved to the mesial using Tension Gauze with a Nickel Titanium Orthodontic closed coil spring. Observation was subsequently undertaken on the 15th day by extracting the maxillary right first and second molar with their periodontal tissues. Thereafter, histological examination was performed using hematoxylin-eosin (HE) staining technique to measure the number of osteoblasts and blood capillaries on the mesial and distal periodontal ligaments of the maxillary right first molar. Results: The administration of Robusta coffee extract increases the number of blood capillaries and osteoblasts on both the pressure and tension sides were found to be significantly higher in the T group compared to the C group (p<0,05). Conclusion: Robusta coffee extract increase the number of osteoblasts and blood capillaries, thereby playing a role in improving the alveolar bone remodeling process in orthodontic tooth movement.


2021 ◽  
Vol 12 ◽  
Author(s):  
Yukun Jiang ◽  
Yuzhe Guan ◽  
Yuanchen Lan ◽  
Shuo Chen ◽  
Tiancheng Li ◽  
...  

Orthodontic tooth movement (OTM) is a process depending on the remodeling of periodontal tissues surrounding the roots. Orthodontic forces trigger the conversion of mechanical stimuli into intercellular chemical signals within periodontal ligament (PDL) cells, activating alveolar bone remodeling, and thereby, initiating OTM. Recently, the mechanosensitive ion channel Piezo1 has been found to play pivotal roles in the different types of human cells by transforming external physical stimuli into intercellular chemical signals. However, the function of Piezo1 during the mechanotransduction process of PDL cells has rarely been reported. Herein, we established a rat OTM model to study the potential role of Piezo1 during the mechanotransduction process of PDL cells and investigate its effects on the tension side of alveolar bone remodeling. A total of 60 male Sprague-Dawley rats were randomly assigned into three groups: the OTM + inhibitor (INH) group, the OTM group, and the control (CON) group. Nickel-titanium orthodontic springs were applied to trigger tooth movement. Mice were sacrificed on days 0, 3, 7, and 14 after orthodontic movement for the radiographic, histological, immunohistochemical, and molecular biological analyses. Our results revealed that the Piezo1 channel was activated by orthodontic force and mainly expressed in the PDL cells during the whole tooth movement period. The activation of the Piezo1 channel was essential for maintaining the rate of orthodontic tooth movement and facilitation of new alveolar bone formation on the tension side. Reduced osteogenesis-associated transcription factors such as Runt-related transcription factor 2 (RUNX2), Osterix (OSX), and receptor activator of nuclear factor-kappa B ligand (RANKL)/osteoprotegerin (OPG) ratio were examined when the function of Piezo1 was inhibited. In summary, Piezo1 plays a critical role in mediating both the osteogenesis and osteoclastic activities on the tension side during OTM.


2006 ◽  
Vol 190 (1) ◽  
pp. 141-150 ◽  
Author(s):  
Sílvia Emiko Matsuo ◽  
Suzana Garcia Leoni ◽  
Alison Colquhoun ◽  
Edna Teruko Kimura

Transforming growth factor-beta 1 (TGF-β1) and activin A (ActA) induce similar intracellular signaling mediated by the mothers against decapentaplegic homolog (SMAD) proteins. TGF-β1 is a potent antimitogenic factor for thyroid follicular cells, while the role of ActA is not clear. In our study, the proliferation of TPC-1, the papillary thyroid carcinoma cell line, was reduced by both recombinant ActA and TGF-β1. Due to the concomitant expression of TGF-β1 and ActA in thyroid tumors, we investigated the effects of either TGF-β1 or ActA gene silencing by RNA interference in TPC-1 cells in order to distinguish the specific participation of each in proliferation and intracellular signaling. An increased proliferation and reduced SMAD2, SMAD3, and SMAD4 mRNA expression were observed in both TGF-β1 and ActA knockdown cells. Recombinant TGF-β1 and ActA increased the expression of inhibitory SMAD7, whereas they reduced c-MYC. Accordingly, we detected a reduction in SMAD7 expression in knockdown cells while, unexpectedly, c-MYC was reduced. Our data indicate that both TGF-β1 and ActA generate SMADs signaling with each regulating the expression of their target genes, SMAD7 and c-MYC. Furthermore, TGF-β1 and ActA have an antiproliferative effect on thyroid papillary carcinoma cell, exerting an important role in the control of thyroid tumorigenesis.


2019 ◽  
Vol 13 (01) ◽  
pp. 102-107 ◽  
Author(s):  
Ida Bagus Narmada ◽  
Muhammad Rubianto ◽  
Suhartono Taat Putra

Abstract Objective The aim of this study is to analyze the low-intensity laser therapy (LILT) biostimulation mechanism as adjuvant therapy within orthodontic treatment as a means of accelerating bone remodeling by transforming growth factor β1 (TGF-β1), bone alkaline phosphatase (BALP), and osteocalcin (OSC) expression. Materials and Methods An analytical experimental method incorporating a posttest only randomized the control group design. The sample consisted of 24 3- to 4-month-old male Cavia porcellus weighing between 300 and 500 g divided into three groups (group 1: control, group 2: received orthodontic treatment, and group 3: received orthodontic treatment with irradiation LILT). LILT biostimulation at a dose of 4 joule/cm2 was performed daily for 3 min on the mesial-distal labial-palatal of the first dextra and sinistra incisor for 2 weeks. The TGF-β1, BALP, and OSC expression was subjected to immunohistochemical analysis. An analysis of variance with multiple comparison, a Tukey's honestly significant difference test, a Kruskal–Wallis test, and a Wilcoxon–Mann–Whitney test were all performed (p < 0.05). Results TGF-β1 expression was significantly different (p = 0.047; p < 0.05) in the tension area, but not in the compression side (p = 0.154; p > 0.05). BALP expression was significantly different in both the tension (p = 0.009) and compression areas (p = 0.005; p < 0.05). OSC expression was significantly different (p = 0.034; p < 0.05) in the tension side, but not in the compression area (p = 1.194; p > 0.05). Conclusion LILT biostimulation can increase TGF-β1, BALP, and OSC expression during orthodontic tooth movement.


2012 ◽  
Vol 17 (6) ◽  
pp. 20e1-20e5
Author(s):  
Luegya Amorim Henriques Knop ◽  
Ricardo Lima Shintcovsk ◽  
Luciana Borges Retamoso ◽  
Ana Maria Trindade Grégio ◽  
Orlando Tanaka

INTRODUCTION: Tooth movement is initially characterized by an acute sterile inflammation, followed by sequential multiple reactions in the periodontal ligament in response to biomechanical forces. Pharmacological agents such as corticosteroids may affect the course of orthodontic movement. Scientific studies show antagonistic actions of these drugs on bone resorption during tooth movement. OBJECTIVE: To review the literature about the effect of corticosteroids on orthodontic tooth movement. CONCLUSION: Patients should be questioned regarding the use of these drugs in the orthodontic practice and for those who use them, the orthodontic treatment should be differentiated, with longer intervals between visits and periodic X-rays due to the delay in bone formation observed in some scientific studies.


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