Dynamic simulation of alveolar bone remodeling based on viscoelastic constitutive model of periodontal ligament

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

The Angle Orthodontist ◽

10.2319/032213-234.1 ◽

2013 ◽

Vol 84 (2) ◽

pp. 297-303 ◽

Cited By ~ 31

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.

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

Journal of Dental Research ◽

10.1177/00220345970760070501 ◽

1997 ◽

Vol 76 (7) ◽

pp. 1357-1366 ◽

Cited By ~ 62

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.

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

Journal of Dental Research ◽

10.1177/00220345211019949 ◽

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.

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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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