scholarly journals Force-induced Adrb2 in Periodontal Ligament Cells Promotes Tooth Movement

2014 ◽  
Vol 93 (11) ◽  
pp. 1163-1169 ◽  
Author(s):  
H. Cao ◽  
X. Kou ◽  
R. Yang ◽  
D. Liu ◽  
X. Wang ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Periodontal Ligament ◽  
Alveolar Bone ◽  
Tooth Movement ◽  
Osteoclast Differentiation ◽  
Compressive Force ◽  
Mechanical Force ◽  
Periodontal Ligament Cells ◽  
Force Application ◽  
Alveolar Bone Remodeling

The sympathetic nervous system (SNS) regulates bone resorption through β-2 adrenergic receptor (Adrb2). In orthodontic tooth movement (OTM), mechanical force induces and regulates alveolar bone remodeling. Compressive force-associated osteoclast differentiation and alveolar bone resorption are the rate-limiting steps of tooth movement. However, whether mechanical force can activate Adrb2 and thus contribute to OTM remains unknown. In this study, orthodontic nickel-titanium springs were applied to the upper first molars of rats and Adrb1/2-/- mice to confirm the role of SNS and Adrb2 in OTM. The results showed that blockage of SNS activity in the jawbones of rats by means of superior cervical ganglion ectomy reduced OTM distance from 860 to 540 μm after 14 d of force application. In addition, the injection of nonselective Adrb2 agonist isoproterenol activated the downstream signaling of SNS to accelerate OTM from 300 to 540 μm after 7 d of force application. Adrb1/2-/- mice showed significantly reduced OTM distance (19.5 μm) compared with the wild-type mice (107.6 μm) after 7 d of force application. Histopathologic analysis showed that the number of Adrb2-positive cells increased in the compressive region of periodontal ligament after orthodontic force was applied on rats. Mechanistically, mechanical compressive force upregulated Adrb2 expression in primary-cultured human periodontal ligament cells (PDLCs) through the elevation of intracellular Ca2+ concentration. Activation of Adrb2 in PDLCs increased the RANKL/OPG ratio and promoted the peripheral blood mononuclear cell differentiation to osteoclasts in the cocultured system. Upregulation of Adrb2 in PDLCs promoted osteoclastogenesis, which accelerated OTM through Adrb2-enhanced bone resorption. In summary, this study suggests that mechanical force-induced Adrb2 activation in PDLCs contributes to SNS-regulated OTM.

Role of Osteocyte-PDL Crosstalk in Tooth Movement via SOST/Sclerostin

2018 ◽  
Vol 97 (12) ◽  
pp. 1374-1382 ◽  
Author(s):  
N. Odagaki ◽  
Y. Ishihara ◽  
Z. Wang ◽  
E. Ei Hsu Hlaing ◽  
M. Nakamura ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Bone Remodeling ◽  
Alveolar Bone ◽  
Tooth Movement ◽  
Control Level ◽  
Compressive Force ◽  
Mechanical Stimuli ◽  
Independent Manner ◽  
Alveolar Bone Remodeling

Sclerostin (Scl) negatively regulates bone formation and favors bone resorption. Osteocytes, the cells responsible for mechanosensing, are known as the primary source of Scl and are a key regulator of bone remodeling through the induction of receptor activator of NF-κB ligand (RANKL). However, the spatiotemporal patterns of Scl in response to mechanical stimuli and their regulatory mechanisms remain unknown. We investigated the regulatory dynamics of the SOST/Scl expression generated by orthodontic tooth movement (OTM) in vivo and in vitro. In 8-wk-old male mice, coil springs were used to move the first molar mesially for 0, 1, 5, or 10 d. A regional histogram and the distribution patterns of the Scl expression showed that the Scl expression in the alveolar bone was increased on the compression side and peaked on day 5, with a gradual increase in the degree of significance. On day 10, the expression around the periodontal ligament (PDL)–alveolar bone boundary returned to the control level. Conversely, the expression of Scl on the tension side was only significantly decreased on day 1. Compressive force biphasically modulated the SOST/Scl expression in the isolated human PDL and thereby upregulated osteocytic SOST via paracrine activation in an osteocyte-PDL co-culture system designed to mimic OTM. This system did not affect the RANKL or OPG expression in osteocytes, suggesting that the bone resorption pathways are acted upon in a PDL-dependent and osteocyte-independent manner through RANKL/OPG signaling. Moreover, sclerostin neutralizing antibody significantly attenuated the upregulation of SOST that was induced by compressive force. In conclusion, our results provide evidence to support that factors secreted by the PDL, including SOST/Scl, control alveolar bone remodeling through osteocytic SOST/Scl in OTM.

Expression of Connexin 43 in Rat Mandibular Bone and Periodontal Ligament (PDL) Cells during Experimental Tooth Movement

1997 ◽  
Vol 76 (7) ◽  
pp. 1357-1366 ◽  
Author(s):  
M. Su ◽  
J.L. Borke ◽  
H.J. Donahue ◽  
Z. Li ◽  
N.M. Warshawsky ◽  
...  
Keyword(s):  
Bone Remodeling ◽  
Periodontal Ligament ◽  
Connexin 43 ◽  
Alveolar Bone ◽  
Tooth Movement ◽  
Cdna Probe ◽  
Periodontal Ligament Cells ◽  
Alveolar Bone Remodeling ◽  
Junction Protein ◽  
Experimental Tooth Movement

Bone remodeling in response to force requires the coordinated action of osteoblasts, osteoclasts, osteocytes, and periodontal ligament cells. Coordination among these cells may be mediated, in part, by cell-to-cell communication via gap junctions. This study tests the hypothesis that the regulation of expression of connexin 43, a gap junction protein, is part of the transduction mechanism between force as applied to bone during orthodontic tooth movement and bone remodeling. To test this hypothesis, we examined connexin 43 expression in a rat model system of experimental tooth movement. To establish the model, we extracted maxillary first molars to initiate supra-eruption of opposing mandibular molars. The rats were killed at 0, 6, 12, 24, and 48 hrs post-extraction. The mandibles were removed, demineralized, and embedded in paraffin. To localize connexin 43 protein and mRNA, we used a specific antibody for immunohistochemistry and a specific cDNA probe for in situ hybridization. Western and Northern blot analyses were used to assess the specificity of the connexin 43 antibody and cDNA probe, respectively. We found connexin 43 protein expressed by osteoclasts (++++) and periodontal ligament cells (+++) in compression zones, and by osteoblasts (++++) and osteocytes (++++) in tension zones of the periodontal ligament. In addition, connexin 43 mRNA was found in some bone and periodontal ligament cells. Connexin 43 protein was found, by densitometric analysis, to be higher in the periodontal ligament after exposure to force compared with controls (P < 0.001). The number of osteocytes expressing connexin 43 48 hrs after molar extraction was also significantly greater in bone subjected to tension when compared with controls (P < 0.001). The results of this study support the hypothesis that connexin 43 plays a role in the coordination of events during experimentally induced alveolar bone remodeling.

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

2021 ◽  
pp. 002203452110199
Author(s):  
Y. Xie ◽  
Q. Tang ◽  
S. Yu ◽  
W. Zheng ◽  
G. Chen ◽  
...  
Keyword(s):  
Bone Remodeling ◽  
Alveolar Bone ◽  
Tooth Movement ◽  
Orthodontic Tooth Movement ◽  
Nuclear Factor Κb ◽  
Periodontal Ligament Cells ◽  
Orthodontic Force ◽  
Periodontal Tissues ◽  
Alveolar Bone Remodeling ◽  
Biomechanical Stimuli

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.

scholarly journals Force-induced decline of FOXM1 in human periodontal ligament cells contributes to osteoclast differentiation

2019 ◽  
Vol 89 (5) ◽  
pp. 804-811 ◽  
Author(s):  
Qian Li ◽  
Jianyun Zhang ◽  
Dawei Liu ◽  
Yunan Liu ◽  
Yanheng Zhou
Keyword(s):  
Transcription Factors ◽  
Periodontal Ligament ◽  
Osteoclast Differentiation ◽  
Specific Inhibitor ◽  
Compressive Force ◽  
Nuclear Factor Κb ◽  
Periodontal Ligament Cells ◽  
Tartrate Resistant Acid Phosphatase ◽  
Proliferation Capacity ◽  
Human Periodontal Ligament Cells

ABSTRACT Objectives: To investigate whether Forkhead family transcription factors are responsive to mechanical force and the resulting influence on the osteoclast differentiation mediated by human periodontal ligament cells (PDLCs). Materials and Methods: A high-throughput RNA sequencing assay was performed in compressive force–stimulated and control human PDLCs. Alteration of FOXM1, a member of the Forkhead family transcription factors, was further confirmed by Western blotting and quantitative reverse-transcription polymerase chain reaction. Expression of FOXM1 was inhibited by either small interfering RNA (siRNA) transfection or addition of its specific inhibitor Siomycin A. Then, cells were exposed to compressive force and co-cultured with the murine macrophage cell line Raw264.7, followed by tartrate-resistant acid phosphatase staining assay. Expression changes of receptor activator of nuclear factor κB ligand (RANKL) and osteoprotegetin (OPG) caused by FOXM1 suppression were measured. Alkaline phosphatase (ALP) staining, ALP activity assay, and crystal violet staining assay were performed after FOXM1 inhibition. Results: FOXM1 transcription decreased after mechanical stimulation in PDLCs. Inhibition of FOXM1 promoted force-induced osteoclast differentiation of RAW264.7 and upregulated the RANKL/OPG ratio in PDLCs. Interference of FOXM1 led to promoted osteogenic differentiation but decreased proliferation of PDLCs. Conclusions: FOXM1 is a novel mechano-responsive gene in human PDLCs. Suppressing FOXM1 expression could promote osteoclast differentiation as well as RANKL/OPG in human PDLCs. FOXM1 also plays a role in controlling PDLC differentiation and proliferation capacity.

scholarly journals Compression and hypoxia play independent roles while having combinative effects in the osteoclastogenesis induced by periodontal ligament cells

2015 ◽  
Vol 86 (1) ◽  
pp. 66-73 ◽  
Author(s):  
Mei Le Li ◽  
Jianru Yi ◽  
Yan Yang ◽  
Xuan Zhang ◽  
Wei Zheng ◽  
...  
Keyword(s):  
Gene Expression ◽  
Periodontal Ligament ◽  
Tooth Movement ◽  
Thin Sheet ◽  
Orthodontic Tooth Movement ◽  
Compressive Force ◽  
Periodontal Ligament Cells ◽  
Tartrate Resistant Acid Phosphatase ◽  
Hypoxia Group ◽  
Polymerase Chain

ABSTRACT Objective:  To investigate the isolated and combined effects of compression and hypoxia on the osteoclastogenesis induced by periodontal ligament cells (PDLCs). Materials and Methods:  A periodontal ligament tissue model (PDLtm) was established by 3-D culturing human PDLCs on a thin sheet of poly lactic-co-glycolic acid scaffold. The PDLtm was treated with hypoxia and/or compression for 6, 24, or 72 hours. After that, a real-time polymerase chain reaction was used for gene expression analysis. The conditioned media were used for the coculture of osteoblast and osteoclast (OC) precursors; tartrate-resistant acid phosphatase staining was done to examine OC formation. Results:  Either compression or hypoxia alone significantly up-regulated the gene expression of pro-osteoclastogenic cytokines in the PDLtm and enhanced osteoclastogenesis in the cocultures, and the combination of the two had significantly stronger effects than either stimulation alone. In addition, comparing the two stimulants, we found that the osteoclastogenic property of the PDLCs peaked earlier (at 6 hours) in the compression group than in the hypoxia group (at 24 hours). Conclusions:  Both compressive force and hypoxia may take part in initiating osteoclastogenesis in orthodontic tooth movement and may have combinatory effects, which could update our concepts of the mechanisms involved in the initiation of bone resorption on the pressure side of the tooth in question.

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

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.

scholarly journals Porphyromonas gingivalis GroEL Induces Osteoclastogenesis of Periodontal Ligament Cells and Enhances Alveolar Bone Resorption in Rats

PLoS ONE ◽  
2014 ◽  
Vol 9 (7) ◽  
pp. e102450 ◽  
Author(s):  
Feng-Yen Lin ◽  
Fung-Ping Hsiao ◽  
Chun-Yao Huang ◽  
Chun-Ming Shih ◽  
Nai-Wen Tsao ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Porphyromonas Gingivalis ◽  
Periodontal Ligament ◽  
Alveolar Bone ◽  
Periodontal Ligament Cells

scholarly journals Effect of cyclical forces on the periodontal ligament and alveolar bone remodeling during orthodontic tooth movement

2013 ◽  
Vol 84 (2) ◽  
pp. 297-303 ◽  
Author(s):  
Zana Kalajzic ◽  
Elizabeth Blake Peluso ◽  
Achint Utreja ◽  
Nathaniel Dyment ◽  
Jun Nihara ◽  
...  
Keyword(s):  
Bone Remodeling ◽  
Periodontal Ligament ◽  
Structural Integrity ◽  
Alveolar Bone ◽  
Tooth Movement ◽  
Volume Fraction ◽  
Tartrate Resistant Acid Phosphatase ◽  
Vibratory Stimulus ◽  
Bone Volume Fraction ◽  
Alveolar Bone Remodeling

ABSTRACT Objective: To investigate the effect of externally applied cyclical (vibratory) forces on the rate of tooth movement, the structural integrity of the periodontal ligament, and alveolar bone remodeling. Methods: Twenty-six female Sprague-Dawley rats (7 weeks old) were divided into four groups: CTRL (unloaded), VBO (molars receiving a vibratory stimulus only), TMO (molars receiving an orthodontic spring only), and TMO+VB (molars receiving an orthodontic spring and the additional vibratory stimulus). In TMO and TMO+VB groups, the rat first molars were moved mesially for 2 weeks using Nickel-Titanium coil spring delivering 25 g of force. In VBO and TMO+VB groups, cyclical forces at 0.4 N and 30 Hz were applied occlusally twice a week for 10 minutes. Microfocus X-ray computed tomography analysis and tooth movement measurements were performed on the dissected rat maxillae. Tartrate-resistant acid phosphatase staining and collagen fiber assessment were performed on histological sections. Results: Cyclical forces significantly inhibited the amount of tooth movement. Histological analysis showed marked disorganization of the collagen fibril structure of the periodontal ligament during tooth movement. Tooth movement caused a significant increase in osteoclast parameters on the compression side of alveolar bone and a significant decrease in bone volume fraction in the molar region compared to controls. Conclusions: Tooth movement was significantly inhibited by application of cyclical forces.

scholarly journals Mechanical stimulation induced osteogenic differentiation of BMSCs through TWIST/E2A/p21 axis

2020 ◽  
Vol 40 (5) ◽  
Author(s):  
Qingyuan Guo ◽  
Ying Liu ◽  
Renhao Sun ◽  
Fang Yang ◽  
Pengyan Qiao ◽  
...  
Keyword(s):  
Osteogenic Differentiation ◽  
Bone Remodeling ◽  
Mechanical Stimulation ◽  
Alveolar Bone ◽  
Tooth Movement ◽  
Dynamic Change ◽  
Mechanical Force ◽  
Alveolar Bone Remodeling ◽  
Underlying Mechanisms ◽  
Cyclical Stretch

Abstract The relationship between mechanical force and alveolar bone remodeling is an important issue in orthodontics because tooth movement is dependent on the response of bone tissue to the mechanical force induced by the appliances used. Mechanical cyclical stretch plays an essential role in the cell osteogenic differentiation involved in bone remodeling. However, the underlying mechanisms are unclear, particularly the molecular pathways regulated by mechanical stimulation. In the present study, we reported a dynamic change of p21 level in response to mechanical cyclical stretch, and shRNA-p21 in bone marrow mesenchymal stem cells (BMSCs) induced osteogenic differentiation. The mechanism was mediated through TWIST/E2A/p21 axis. These results supported the mechanical stimulation-induced osteogenic differentiation is negatively regulated by p21.

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