Axin2+ PDL Cells Directly Contribute to New Alveolar Bone Formation in Response to Orthodontic Tension Force

2022 ◽  
pp. 002203452110625
Author(s):  
K. Wang ◽  
C. Xu ◽  
X. Xie ◽  
Y. Jing ◽  
P.J. Chen ◽  
...  
Keyword(s):  
Bone Formation ◽  
Progenitor Cells ◽  
Alveolar Bone ◽  
Tooth Movement ◽  
Critical Role ◽  
Tension Force ◽  
Mineral Apposition Rate ◽  
Moderate Degree ◽  
Cell Numbers ◽  
Pdl Cells

Wnt–β-catenin signaling plays a key role in orthodontic tooth movement (OTM), a common clinical practice for malocclusion correction. However, its targeted periodontal ligament (PDL) progenitor cells remain largely unclear. In this study, we first showed a synchronized increase in Wnt–β-catenin levels and Axin2+ PDL progenitor cell numbers during OTM using immunostaining of β-catenin in wild-type mice and X-gal staining in the Axin2-LacZ knock-in line. Next, we demonstrated time-dependent increases in Axin2+ PDL progenitors and their progeny cell numbers within PDL and alveolar bones during OTM using a one-time tamoxifen-induced Axin2 tracing line ( Axin2CreERT2/+; R26RtdTomato/+). Coimmunostaining images displayed both early and late bone markers (such as RUNX2 and DMP1) in the Axin2Lin PDL cells. Conversely, ablation of Axin2+ PDL cells via one-time tamoxifen-induced diphtheria toxin subunit A (DTA) led to a drastic decrease in osteogenic activity (as reflected by alkaline phosphatase) in PDL and alveolar bone. There was also a decrease in new bone mass and a significant reduction in the mineral apposition rate on both the control side (to a moderate degree) and the OTM side (to a severe degree). Thus, we conclude that the Axin2+ PDL cells (the Wnt-targeted key cells) are highly sensitive to orthodontic tension force and play a critical role in OTM-induced PDL expansion and alveolar bone formation. Future drug development targeting the Axin2+ PDL progenitor cells may accelerate alveolar bone formation during orthodontic treatment.

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.

Compressive Force Induces VEGF Production in Periodontal Tissues

2009 ◽  
Vol 88 (8) ◽  
pp. 752-756 ◽  
Author(s):  
A. Miyagawa ◽  
M. Chiba ◽  
H. Hayashi ◽  
K. Igarashi
Keyword(s):  
Alveolar Bone ◽  
Tooth Movement ◽  
Vascular System ◽  
Orthodontic Tooth Movement ◽  
Compressive Force ◽  
Vegf Mrna ◽  
Angiogenic Activity ◽  
Periodontal Tissues ◽  
Pdl Cells

During orthodontic tooth movement, the activation of the vascular system in the compressed periodontal ligament (PDL) is an indispensable process in tissue remodeling. We hypothesized that compressive force would induce angiogenesis of PDL through the production of vascular endothelial growth factor (VEGF). We examined the localization of VEGF in rat periodontal tissues during experimental tooth movement in vivo, and the effects of continuous compressive force on VEGF production and angiogenic activity in human PDL cells in vitro. PDL cells adjacent to hyalinized tissue and alveolar bone on the compressive side showed marked VEGF immunoreactivity. VEGF mRNA expression and production in PDL cells increased, and conditioned medium stimulated tube formation. These results indicate that continuous compressive force enhances VEGF production and angiogenic activity in PDL cells, which may contribute to periodontal remodeling, including angiogenesis, during orthodontic tooth movement.

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

1994 ◽  
Vol 266 (5) ◽  
pp. E731-E738 ◽  
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.

Tooth Movement

1991 ◽  
Vol 2 (4) ◽  
pp. 411-450 ◽  
Author(s):  
Zeev Davidovitch
Keyword(s):  
Alveolar Bone ◽  
Tooth Movement ◽  
Bone Cells ◽  
Biological Response ◽  
Mechanical Forces ◽  
Clinical Environment ◽  
Isolated Cells ◽  
Streaming Potentials ◽  
Pdl Cells ◽  
New Findings

This article reviews the evolution of concepts regarding the biological foundation of force-induced tooth movement. Nineteenth century hypotheses proposed two mechanisms: application of pressure and tension to the periodontal ligament (PDL), and bending of the alveolar bone. Histologic investigations in the early and middle years of the 20th century revealed that both phenomena actually occur concomitantly, and that cells, as well as extracellular components of the PDL and alveolar bone, participate in the response to applied mechanical forces, which ultimately results in remodeling activities. Experiments with isolated cells in culture demonstrated that shape distortion might lead to cellular activation, either by opening plasma membrane ion channels, or by crystallizing cytoskeletal filaments. Mechanical distortion of collagenous matrices, mineralized or non-mineralized, may, on the other hand, evoke the development of bioelectric phenomena (stress-generated potentials and streaming potentials) that are capable of stimulating cells by altering the electric charge on their membrane or their fluid envelope. In intact animals, mechanical perturbations on the order of about 1 min/d are apparently sufficient to cause profound osteogenic responses, perhaps due to matrix proteoglycan-related "strain memory". Enzymatically isolated human PDL cells respond biochemically to mechanical and chemical signals. The latter include endocrines, autocrines, and paracrines. Histochemical and immunohistochemical studies showed that during the early places of tooth movement, PDL fluids are shifted, and cells and matrix are distorted. Vasoactive neurotransmitters are released from periodontal nerve terminals, causing leukocytes to migrate out of adjacent capillaries. Cytokines and growth factors are secreted by these cells, stimulating PDL cells and alveolar bone lining cells to remodel their related matrices. This remodeling activity facilitates movement of teeth into areas in which bone had been resorbed. This emerging information suggests that in the living mammal, many cell types are involved in the biological response to applied mechanical stress to teeth, and thereby to bone. Essentially, cells of the nervous, immune, and endocrine systems become involved in the activation and response of PDL and alveolar bone cells to applied stresses. This fact implies that research in the area of the biological response to force application to teeth should be sufficiently broad to include explorations of possible associations between physical, cellular, and molecular phenomena. The goals of this investigative field should continue to expound on fundamental principles, particularly on extrapolating new findings to the clinical environment, where millions of patients are subjected annually to applications of mechanical forces to their teeth for long periods of time in an effort to improve their position in the oral cavity. Recently developed research tools such as cell culture techniques and immunologic probes, are the best hope for enhancing this development.

scholarly journals Diabetes Enhances Periodontal Bone Loss through Enhanced Resorption and Diminished Bone Formation

2006 ◽  
Vol 85 (6) ◽  
pp. 510-514 ◽  
Author(s):  
R. Liu ◽  
H.S. Bal ◽  
T. Desta ◽  
N. Krothapalli ◽  
M. Alyassi ◽  
...  
Keyword(s):  
Bone Loss ◽  
Bone Formation ◽  
Alveolar Bone ◽  
Diabetic Rats ◽  
New Bone Formation ◽  
Periodontal Ligament Fibroblasts ◽  
Zdf Rat ◽  
Pdl Cells ◽  
Periodontal Bone Loss

Using a ligature-induced model in type-2 Zucker diabetic fatty (ZDF) rat and normoglycemic littermates, we investigated whether diabetes primarily affects periodontitis by enhancing bone loss or by limiting osseous repair. Diabetes increased the intensity and duration of the inflammatory infiltrate (P < 0.05). The formation of osteoclasts and percent eroded bone after 7 days of ligature placement was similar, while four days after removal of ligatures, the type 2 diabetic group had significantly higher osteoclast numbers and activity (P < 0.05). The amount of new bone formation following resorption was 2.4- to 2.9-fold higher in normoglycemic vs. diabetic rats (P < 0.05). Diabetes also increased apoptosis and decreased the number of bone-lining cells, osteoblasts, and periodontal ligament fibroblasts (P < 0.05). Thus, diabetes caused a more persistent inflammatory response, greater loss of attachment and more alveolar bone resorption, and impaired new bone formation. The latter may be affected by increased apoptosis of bone-lining and PDL cells.

scholarly journals TGF-Beta Receptor II Is Critical for Osteogenic Progenitor Cell Proliferation and Differentiation During Postnatal Alveolar Bone Formation

2021 ◽  
Vol 12 ◽  
Author(s):  
Chunmei Xu ◽  
Xudong Xie ◽  
Hu Zhao ◽  
Yafei Wu ◽  
Jun Wang ◽  
...  
Keyword(s):  
Bone Formation ◽  
Transforming Growth Factor Beta ◽  
Matrix Protein ◽  
Transforming Growth Factor ◽  
Alveolar Bone ◽  
Extracellular Matrix Protein ◽  
Mineral Density ◽  
Tgfβ Signaling ◽  
Cell Numbers ◽  
Proliferation And Differentiation

Transforming growth factor beta (TGFβ) signaling plays an important role during osteogenesis. However, most research in this area focuses on cortical and trabecular bone, whereas alveolar bone is largely overlooked. To address the role of TGFβR2 (the key receptor for TGFβ signaling) during postnatal alveolar bone development, we conditionally deleted Tgfβr2 in early mesenchymal progenitors by crossing Gli1-CreERT2; Tgfβr2flox/flox; R26RtdTomato mice (named early cKO) or in osteoblasts by crossing 3.2kb Col1-CreERT2; Tgfβr2flox/flox; R26RtdTomato mice (named late cKO). Both cKO lines were induced at postnatal day 5 (P5) and mice were harvested at P28. Compared to the control littermates, early cKO mice exhibited significant reduction in alveolar bone mass and bone mineral density, with drastic defects in the periodontal ligament (PDL); conversely, the late cKO mice displayed very minor changes in alveolar bone. Mechanism studies showed a significant reduction in PCNA+ PDL cell numbers and OSX+ alveolar bone cell numbers, as well as disorganized PDL fibers with a great reduction in periostin (the most abundant extracellular matrix protein) on both mRNA and protein levels. We also showed a drastic reduction in β-catenin in the early cKO PDL and a great increase in SOST (a potent inhibitor of Wnt signaling). Based on these findings, we conclude that TGFβ signaling plays critical roles during early alveolar bone formation via the promotion of PDL mesenchymal progenitor proliferation and differentiation mechanisms.

The Effect of Amitriptyline and Sertraline on the Tooth Movement, Root Resorption and Alveolar Bone Remodeling After Load Application in Dogs

2021 ◽  
Author(s):  
Mehdi Rafiei ◽  
Sousan Sadeghian
Keyword(s):  
Bone Formation ◽  
Bone Remodeling ◽  
Alveolar Bone ◽  
Tooth Movement ◽  
Root Resorption ◽  
Load Application ◽  
Control Group ◽  
P Value ◽  
External Root Resorption ◽  
Alveolar Bone Remodeling

Introduction: Antidepressant drugs are the most commonly prescribed classes of pharmacologic agents in the public. The drugs have been shown to have a role in the regulation of bone cell function and as a result affecting the orthodontic tooth movements. The aim of this study was to determine the effect of Amitriptyline and Sertraline on the tooth movement, root resorption and alveolar bone remodeling after load application in dogs.   Materials and Methods: In this experimental study, 9 male dogs were randomly divided into three groups, first group sertraline, second group Amitriptyline and the control group (normal saline). A nickel titanium spring (200 gr) was used between second premolar and canine after 1st premolar extraction. After 2 months, the reduction of distance between 2nd premolar and canine was measured. The percentages of root resorption and bone formation were determined. The data were analyzed using repeated measures analysis at significance level of 0.05.   Results: In the three groups of amitriptyline, sertraline and control, the mean of teeth movement (p value = 0.483), external root resorption (p value = 0.608), total bone mineral density (p value = 0.078), bone formation percentage (p value = 0.616) and immature and lamellar bone formation (p value = 0.083), there was no statistical difference in any group and in premolar teeth Conclusions: The rate of tooth movement and the percentages of bone formation and root resorption in dogs decreased with systemic administration of amitriptyline and sertraline; although this reduction was not statistically significant in comparison with control group. 

scholarly journals Tension force-induced bone formation in orthodontic tooth movement via modulation of the GSK-3β/β-catenin signaling pathway

2017 ◽  
Vol 49 (1) ◽  
pp. 75-84 ◽  
Author(s):  
Yelin Mao ◽  
Liangliang Wang ◽  
Ye Zhu ◽  
Yu Liu ◽  
Hongwei Dai ◽  
...  
Keyword(s):  
Bone Formation ◽  
Signaling Pathway ◽  
Tooth Movement ◽  
Orthodontic Tooth Movement ◽  
Tension Force ◽  
Gsk 3Β

Effects of Occlusal Stimuli on Alveolar/Jaw Bone Formation

2007 ◽  
Vol 86 (1) ◽  
pp. 47-51 ◽  
Author(s):  
Y. Shimomoto ◽  
C.J. Chung ◽  
Y. Iwasaki-Hayashi ◽  
T. Muramoto ◽  
K. Soma
Keyword(s):  
Bone Formation ◽  
Bone Growth ◽  
Alveolar Bone ◽  
Growth Period ◽  
Mineral Apposition Rate ◽  
Bone Apposition ◽  
Jaw Bone ◽  
Growing Rats ◽  
The Relationship ◽  
Craniofacial Complex

Occlusion is known to influence the growth and development of the craniofacial complex. However, the consequences of occlusal hypofunction, or its recovery, on the amount of formation and development of alveolar bone and the jaw are not fully understood. Therefore, the present study was designed to elucidate the relationship between the occlusal stimuli and alveolar and jaw bone growth by the use of a hypofunction/recovered occlusal function model in growing rats. Bone histomorphometric analyses, including bone apposition rate and mineral apposition rate, were evaluated in double-labeled frontal sections of mandibular second molars. Results showed that occlusal hypofunction significantly suppressed alveolar and jaw bone formation compared with that in animals growing normally (p < 0.05). However, recovered occlusal function induced an enhancement in jaw bone formation. These results indicate the influence of occlusal function on alveolar and jaw bone formation during the growth period.

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