Orthodontic Force–Induced BMAL1 in PDLCs Is a Vital Osteoclastic Activator

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.

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Mechanosensitive Piezo1 in Periodontal Ligament Cells Promotes Alveolar Bone Remodeling During Orthodontic Tooth Movement

Frontiers in Physiology ◽

10.3389/fphys.2021.767136 ◽

2021 ◽

Vol 12 ◽

Author(s):

Yukun Jiang ◽

Yuzhe Guan ◽

Yuanchen Lan ◽

Shuo Chen ◽

Tiancheng Li ◽

...

Keyword(s):

Bone Remodeling ◽

Periodontal Ligament ◽

Alveolar Bone ◽

Tooth Movement ◽

Critical Role ◽

Orthodontic Tooth Movement ◽

Chemical Signals ◽

Periodontal Tissues ◽

Alveolar Bone Remodeling ◽

Pdl Cells

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.

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PROFIL OSTEOBLAS DAN OSTEOKLAS TULANG ALVEOLAR PADA MODEL TIKUS DIABETES TAHAP AWAL DENGAN APLIKASIGAYA ORTODONTI YANG BERBEDA

el–Hayah ◽

10.18860/elha.v5i2.3025 ◽

2015 ◽

Vol 5 (2) ◽

pp. 97

Author(s):

Nuzulul Hikmah

Keyword(s):

Bone Remodeling ◽

Wistar Rats ◽

Alveolar Bone ◽

Tooth Movement ◽

Early Stage ◽

Orthodontic Tooth Movement ◽

Orthodontic Force ◽

Force Application ◽

Alveolar Bone Remodeling ◽

Diabetic Treatment

Orthodontic tooth movement is obtained through alveolar bone remodeling. Alveolar bone remodeling includes resorption process that played by osteoclasts and bone formed process that played by osteoblasts. Diabetes affects on orthodontic tooth movement. The magnitude of orthodontic force that applied in the early stages of diabetic conditions, would be a consideration of the alveolar bone remodeling process. The purpose of this study was to determine osteoblast and osteoclast profile in early stage of rat diabetic models with different orthodontic force application. 24 Wistar rats were divided into three groups of controls andthree groups of early stage of diabetic treatment with different orthodontic force application (10, 20, and 30 gramforce/grf). The results showed an increased of osteoclast numbers in early stage of diabetes and will be increased along with the increased of orthodontic force. The results also showed a decreased of osteoblast number in early stage of diabetes, but it would be increased along with the increased of orthodontic force.

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Effects of sialoadenectomy and exogenous EGF on molar drift and orthodontic tooth movement in rats

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1994.266.5.e731 ◽

1994 ◽

Vol 266 (5) ◽

pp. E731-E738 ◽

Cited By ~ 2

Author(s):

C. Dolce ◽

J. Anguita ◽

L. Brinkley ◽

P. Karnam ◽

M. Humphreys-Beher ◽

...

Keyword(s):

Bone Formation ◽

Bone Remodeling ◽

Alveolar Bone ◽

Tooth Movement ◽

Orthodontic Tooth Movement ◽

Alveolar Bone Remodeling ◽

Tooth Roots ◽

Epidermal Growth ◽

Tetracycline Labeling ◽

Distal Aspect

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.

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Locally Inhibition of Orthodontic Relapse by Injection of Carbonated Hydroxy Apatite-Advanced Platelet Rich Fibrin in a Rabbit Model

Key Engineering Materials ◽

10.4028/www.scientific.net/kem.758.255 ◽

2017 ◽

Vol 758 ◽

pp. 255-263 ◽

Cited By ~ 3

Author(s):

Ananto Ali Alhasyimi ◽

Pinandi Sri Pudyani ◽

Widya Asmara ◽

Ika Dewi Ana

Keyword(s):

Bone Remodeling ◽

Alveolar Bone ◽

Tooth Movement ◽

Rabbit Model ◽

Orthodontic Tooth Movement ◽

Potential Effect ◽

Control Group ◽

Hydroxy Apatite ◽

Carbonated Apatite ◽

Alveolar Bone Remodeling

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.

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ANALISIS VEGF PADA PERGERAKAN GIGI ORTODONTI SETELAH PEMBERIAN SEDUHAN KOPI ROBUSTA ( COFFEACANEPHORA)

Jurnal Teknosains ◽

10.22146/teknosains.22992 ◽

2017 ◽

Vol 5 (2) ◽

pp. 90

Author(s):

Herniyati Herniyati

Keyword(s):

Bone Remodeling ◽

Caffeic Acid ◽

Alveolar Bone ◽

Tooth Movement ◽

Gingival Crevicular Fluid ◽

Orthodontic Tooth Movement ◽

Robusta Coffee ◽

Alveolar Bone Remodeling ◽

Group B ◽

Compression Area

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.

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The increased number of osteoblasts and capillaries in orthodontic tooth movement post-administration of Robusta coffee extract

Dental Journal (Majalah Kedokteran Gigi) ◽

10.20473/j.djmkg.v50.i2.p91-96 ◽

2017 ◽

Vol 50 (2) ◽

pp. 91

Author(s):

H. Herniyati

Keyword(s):

Alveolar Bone ◽

Tooth Movement ◽

Orthodontic Tooth Movement ◽

Staining Technique ◽

Control Group ◽

Blood Capillaries ◽

Second Molar ◽

Periodontal Tissues ◽

Robusta Coffee ◽

Alveolar Bone Remodeling

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.

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The Effects of Systemic Prescription of Amitriptyline on Orthodontic Tooth Movement Rate, Root Resorption and Alveolar Bone Remodeling in Dog

Biomedical & Pharmacology Journal ◽

10.13005/bpj/1263 ◽

2017 ◽

Vol 10 (3) ◽

pp. 1537-1544

Author(s):

Sara Siadat ◽

Soosan Sadeghian ◽

Majid Heidarpour ◽

Sayed Mohammad Razavi ◽

Seyed Sadra Izadi

Keyword(s):

Bone Remodeling ◽

Alveolar Bone ◽

Tooth Movement ◽

Root Resorption ◽

Orthodontic Tooth Movement ◽

Movement Rate ◽

Alveolar Bone Remodeling ◽

Tooth Movement Rate

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Effects of Corticision on Paradental Remodeling in Orthodontic Tooth Movement

The Angle Orthodontist ◽

10.2319/020308-60.1 ◽

2009 ◽

Vol 79 (2) ◽

pp. 284-291 ◽

Cited By ~ 96

Author(s):

Su-Jung Kim ◽

Young-Guk Park ◽

Seung-Goo Kang

Keyword(s):

Alveolar Bone ◽

Tooth Movement ◽

Orthodontic Tooth Movement ◽

Control Group ◽

Orthodontic Force ◽

Alveolar Bone Remodeling ◽

Biologic Effects ◽

Group A ◽

Group B ◽

Tissue Specimens

Abstract Objective: To investigate the biologic effects of Corticision on alveolar remodeling in orthodontic tooth movement. Materials and Methods: In this study, 16 cats were divided into 3 groups: group A, only orthodontic force (control); group B, orthodontic force plus Corticision; and group C, orthodontic force plus Corticision and periodic mobilization. Histologic and histomorphometric studies were performed on tissue specimens on days 7, 14, 21, and 28. Results: Extensive direct resorption of bundle bone with less hyalinization and more rapid removal of hyalinized tissue were observed in group B. The accumulated mean apposition area of new bone on day 28 was observed to be 3.5-fold higher in group B than in the control group A. Conclusions: Corticision might be an efficient procedure for accelerating orthodontic tooth movement accompanied with alveolar bone remodeling.

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FOXO3 Mediates Tooth Movement by Regulating Force-Induced Osteogenesis

Journal of Dental Research ◽

10.1177/00220345211021534 ◽

2021 ◽

pp. 002203452110215

Author(s):

A. Jin ◽

Y. Hong ◽

Y. Yang ◽

H. Xu ◽

X. Huang ◽

...

Keyword(s):

Bone Remodeling ◽

Alveolar Bone ◽

Tooth Movement ◽

Orthodontic Tooth Movement ◽

Osteoblastic Differentiation ◽

Mechanical Force ◽

Bone Mesenchymal Stem Cells ◽

Efficient Manner ◽

Alveolar Bone Remodeling

The high prevalence of malocclusion and dentofacial malformations means that the demand for orthodontic treatments has been increasing rapidly. As the biological basis of orthodontic treatment, the mechanism of mechanical force–induced alveolar bone remodeling during orthodontic tooth movement (OTM) has become the key scientific issue of orthodontics. It has been demonstrated that bone mesenchymal stem cells (BMSCs) are crucial for bone remodeling and exhibit mechanical sensing properties. Mechanical force can promote osteoblastic differentiation of BMSCs and osteogenesis, but the key factor that mediates mechanical force–induced osteogenesis during OTM remains unclear. In this study, by performing reverse-phase protein arrays on BMSCs exposed to mechanical force, we found that the expression level of forkhead box O3 (FOXO3) was significantly upregulated during the mechanical force–induced osteoblastic differentiation of BMSCs. The number of FOXO3-positive cells was consistently higher on the OTM side as compared with the control side and accompanied by the enhancement of osteogenesis. Remarkably, inhibiting FOXO3 with repaglinide delayed OTM by severely impairing mechanical force–induced bone formation in vivo. Moreover, knockdown of FOXO3 effectively inhibited the mechanical force–induced osteoblastic differentiation of BMSCs, whereas the overexpression of FOXO3 enhanced this effect. Mechanistically, we revealed a novel regulatory model in which FOXO3 promoted osteocalcin transcription by activating its promoter in cooperation with runt-related transcription factor 2 (RUNX2). We collectively obtained the first evidence that FOXO3 is critical for OTM, where it responds to mechanical force and directly regulates downstream osteoblastic differentiation in an efficient manner.

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PENGARUH EKSTRAK KOPI ROBUSTA TERHADAP EKSPRESI OSTEOKALSIN PADA OSTEOBLAS SELAMA PERGERAKAN GIGI ORTODONTI

Jurnal Teknosains ◽

10.22146/teknosains.23158 ◽

2017 ◽

Vol 6 (1) ◽

pp. 31

Author(s):

Herniyati Herniyati

Keyword(s):

Bone Remodeling ◽

Alveolar Bone ◽

Tooth Movement ◽

Orthodontic Tooth Movement ◽

Mechanical Force ◽

Coil Spring ◽

Immunohistochemical Examination ◽

Robusta Coffee ◽

Alveolar Bone Remodeling ◽

Compression Area

The objective of research is to determine the expression of osteocalcin on osteoblasts during orthodontic tooth movement after administration robusta coffee extract. Materials and Methods: 16 rats were divided into 2 groups: group K: rats applied with orthodontic mechanical force (OMF) and group P: OMF + coffee robusta extract of 20mg /100 g of BW. OMF was conducted by applying ligature wire on permanent maxillary right first molar and both permanent maxillary incisivus. Subsequently, the permanent maxillary right first molar moved to mesial with Ni-Ti orthodontic closed coil spring. Observations were made on day 15 by immunohistochemical examination to determine the expression of osteocalcin. Results: Robusta coffee extract improved the expression of osteocalcin in the compression and tension areas (p <0.05). Expression of osteocalcin in tension area larger than that in compression area (p <0.05). Conclusion: The administration of Robusta coffee extract increases the expression of osteocalcin, which can increase alveolar bone remodeling.

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