scholarly journals Oleic acid-related anti-inflammatory effects in force-stressed PdL fibroblasts are mediated by H3 lysine acetylation associated with altered IL10 expression

2022 ◽  
Author(s):  
Lisa Schuldt ◽  
Katrin von Brandenstein ◽  
Collin Jacobs ◽  
Judit Symmank
Keyword(s):  
Oleic Acid ◽  
Inflammatory Response ◽  
Alveolar Bone ◽  
Tooth Movement ◽  
Orthodontic Tooth Movement ◽  
Epigenetic Mark ◽  
Lysine Acetylation ◽  
Dependent Manner ◽  
Alternative Source ◽  
Anti Inflammatory

The initiation of a spatially and temporally limited inflammation is essential for tissue and bone remodeling by the periodontal ligament (PdL) located between teeth and alveolar bone. Obesity-associated hyperlipidemic changes may impair PdL fibroblast (PdLF) functions, disturbing their inflammatory response to mechanical stress such as those occurring during orthodontic tooth movement (OTM). Recently, we reported an attenuated pro inflammatory response of human PdLF (HPdLF) to compressive forces when stimulated with monounsaturated oleic acid (OA). Fatty acids, including OA, could serve as alternative source of acetyl-CoA, thereby affecting epigenetic histone marks such as histone 3 lysine acetylation (H3Kac) in a lipid metabolism-dependent manner. In this study, we therefore aimed to investigate the extent to which OA exerts its anti-inflammatory effect via changes in H3Kac. Six-hour compressed HPdLF showed increased H3Kac when cultured with OA. Inhibition of histone deacetylases resulted in a comparable IL10 increase as observed in compressed OA cultures. In contrast, inhibition of histone acetyltransferases, particularly p300/CBP, in compressed HPdLF exposed to OA led to an inflammatory response comparable to compressed control cells. OA-dependent increased association of H3Kac to IL10 promoter regions in force-stressed HPdLF further strengthened the assumption that OA exhibits its anti-inflammatory properties via modulation of this epigenetic mark. In conclusion, our study strongly suggests that obesity-related hyperlipidemia affect the functions of PdL cells via alterations in their epigenetic code. Since epigenetic inhibitors are already widely used clinically, they may hold promise for novel approaches to limit obesity-related risks during OTM.

scholarly journals Parathyroid hormone increases alveolar bone homoeostasis during orthodontic tooth movement in rats with periodontitis via crosstalk between STAT3 and β-catenin

2020 ◽  
Vol 12 (1) ◽  
Author(s):  
Cheng Zhang ◽  
Tiancheng Li ◽  
Chenchen Zhou ◽  
Li Huang ◽  
Yuyu Li ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Bone Loss ◽  
Alveolar Bone ◽  
Tooth Movement ◽  
Orthodontic Tooth Movement ◽  
Underlying Mechanism ◽  
Osteoblastic Differentiation ◽  
Alveolar Bone Loss ◽  
Dependent Manner ◽  
Transcription 3

AbstractPeriodontitis patients are at risk of alveolar bone loss during orthodontic treatment. The aim of this study was to investigate whether intermittent parathyroid hormone (1–34) treatment (iPTH) could reduce alveolar bone loss during orthodontic tooth movement (OTM) in individuals with periodontitis and the underlying mechanism. A rat model of OTM in the context of periodontitis was established and alveolar bone loss was observed. The control, iPTH and iPTH + stattic groups received injections of vehicle, PTH and vehicle, or PTH and the signal transducer and activator of transcription 3 (STAT3) inhibitor stattic, respectively. iPTH prevented alveolar bone loss by enhancing osteogenesis and suppressing bone resorption in the alveolar bone during OTM in rats with periodontitis. This effect of iPTH was along with STAT3 activation and reduced by a local injection of stattic. iPTH promoted osteoblastic differentiation and might further regulate the Wnt/β-catenin pathway in a STAT3-dependent manner. The findings of this study suggest that iPTH might reduce alveolar bone loss during OTM in rats with periodontitis through STAT3/β-catenin crosstalk.

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 The role of inhibition of osteocyte apoptosis in mediating orthodontic tooth movement and periodontal remodeling: a pilot study

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Michele Kaplan ◽  
Zana Kalajzic ◽  
Thomas Choi ◽  
Imad Maleeh ◽  
Christopher L. Ricupero ◽  
...  
Keyword(s):  
Bone Density ◽  
Alveolar Bone ◽  
Tooth Movement ◽  
Orthodontic Tooth Movement ◽  
Tartrate Resistant Acid Phosphatase ◽  
Osteocyte Apoptosis ◽  
Saline Administration ◽  
Group 2 ◽  
Group 1

Abstract Background Orthodontic tooth movement (OTM) has been shown to induce osteocyte apoptosis in alveolar bone shortly after force application. However, how osteocyte apoptosis affects orthodontic tooth movement is unknown. The goal of this study was to assess the effect of inhibition of osteocyte apoptosis on osteoclastogenesis, changes in the alveolar bone density, and the magnitude of OTM using a bisphosphonate analog (IG9402), a drug that affects osteocyte and osteoblast apoptosis but does not affect osteoclasts. Material and methods Two sets of experiments were performed. Experiment 1 was used to specifically evaluate the effect of IG9402 on osteocyte apoptosis in the alveolar bone during 24 h of OTM. For this experiment, twelve mice were divided into two groups: group 1, saline administration + OTM24-h (n=6), and group 2, IG9402 administration + OTM24-h (n=6). The contralateral unloaded sides served as the control. The goal of experiment 2 was to evaluate the role of osteocyte apoptosis on OTM magnitude and osteoclastogenesis 10 days after OTM. Twenty mice were divided into 4 groups: group 1, saline administration without OTM (n=5); group 2, IG9402 administration without OTM (n=5); group 3, saline + OTM10-day (n=6); and group 4, IG9402 + OTM10-day (n=4). For both experiments, tooth movement was achieved using Ultra Light (25g) Sentalloy Closed Coil Springs attached between the first maxillary molar and the central incisor. Linear measurements of tooth movement and alveolar bone density (BVF) were assessed by MicroCT analysis. Cell death (or apoptosis) was assessed by terminal dUTP nick-end labeling (TUNEL) assay, while osteoclast and macrophage formation were assessed by tartrate-resistant acid phosphatase (TRAP) staining and F4/80+ immunostaining. Results We found that IG9402 significantly blocked osteocyte apoptosis in alveolar bone (AB) at 24 h of OTM. At 10 days, IG9402 prevented OTM-induced loss of alveolar bone density and changed the morphology and quality of osteoclasts and macrophages, but did not significantly affect the amount of tooth movement. Conclusion Our study demonstrates that osteocyte apoptosis may play a significant role in osteoclast and macrophage formation during OTM, but does not seem to play a role in the magnitude of orthodontic tooth movement.

scholarly journals Interaction of periodontitis and orthodontic tooth movement—an in vitro and in vivo study

2021 ◽  
Author(s):  
Birgit Rath-Deschner ◽  
Andressa V. B. Nogueira ◽  
Svenja Beisel-Memmert ◽  
Marjan Nokhbehsaim ◽  
Sigrun Eick ◽  
...  
Keyword(s):  
Alveolar Bone ◽  
Tooth Movement ◽  
Mechanical Strain ◽  
Orthodontic Tooth Movement ◽  
Fusobacterium Nucleatum ◽  
In Vivo Study ◽  
Rt Pcr ◽  
Periodontal Inflammation

Abstract Objectives The aim of this in vitro and in vivo study was to investigate the interaction of periodontitis and orthodontic tooth movement on interleukin (IL)-6 and C-X-C motif chemokine 2 (CXCL2). Materials and methods The effect of periodontitis and/or orthodontic tooth movement (OTM) on alveolar bone and gingival IL-6 and CXCL2 expressions was studied in rats by histology and RT-PCR, respectively. The animals were assigned to four groups (control, periodontitis, OTM, and combination of periodontitis and OTM). The IL-6 and CXCL2 levels were also studied in human gingival biopsies from periodontally healthy and periodontitis subjects by RT-PCR and immunohistochemistry. Additionally, the synthesis of IL-6 and CXCL2 in response to the periodontopathogen Fusobacterium nucleatum and/or mechanical strain was studied in periodontal fibroblasts by RT-PCR and ELISA. Results Periodontitis caused an increase in gingival levels of IL-6 and CXCL2 in the animal model. Moreover, orthodontic tooth movement further enhanced the bacteria-induced periodontal destruction and gingival IL-6 gene expression. Elevated IL-6 and CXCL2 gingival levels were also found in human periodontitis. Furthermore, mechanical strain increased the stimulatory effect of F. nucleatum on IL-6 protein in vitro. Conclusions Our study suggests that orthodontic tooth movement can enhance bacteria-induced periodontal inflammation and thus destruction and that IL-6 may play a pivotal role in this process. Clinical relevance Orthodontic tooth movement should only be performed after periodontal therapy. In case of periodontitis relapse, orthodontic therapy should be suspended until the periodontal inflammation has been successfully treated and thus the periodontal disease is controlled again.

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.

scholarly journals Osteoclastic effects of mBMMSCs under compressive pressure during orthodontic tooth movement

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jing Wang ◽  
Delong Jiao ◽  
Xiaofeng Huang ◽  
Yuxing Bai
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Normal Saline ◽  
Periodontal Ligament ◽  
Alveolar Bone ◽  
Tooth Movement ◽  
Orthodontic Tooth Movement ◽  
Mouse Bone Marrow ◽  
Micro Ct ◽  
Tail Vein

Abstract Background During orthodontic tooth movement (OTM), alveolar bone remodelling is closely related to mechanical force. It is unclear whether stem cells can affect osteoclastogenesis to promote OTM. This study aimed to investigate the role of mouse bone marrow mesenchymal stem cells (mBMMSCs) under compression load in OTM. Methods A mouse OTM model was established, and GFP-labelled mBMMSCs and normal saline were injected into different groups of mice by tail vein injection. OTM distance was measured using tissue specimens and micro-computed tomography (micro-CT). The locations of mBMMSCs were traced using GFP immunohistochemistry. Haematoxylin-eosin staining, tartrate-resistant acid phosphate (TRAP) staining and immunohistochemistry of Runx2 and lipoprotein lipase were used to assess changes in the periodontal ligament during OTM. mBMMSCs under compression were co-cultured with mouse bone marrow-derived macrophages (mBMMs), and the gene expression levels of Rankl, Mmp-9, TRAP, Ctsk, Alp, Runx2, Ocn and Osterix were determined by RT-PCR. Results Ten days after mBMMSCs were injected into the tail vein of mice, the OTM distance increased from 176 (normal saline) to 298.4 μm, as determined by tissue specimen observation, and 174.2 to 302.6 μm, as determined by micro-CT metrological analysis. GFP-labelled mBMMSCs were mostly located on the compressed side of the periodontal ligament. Compared to the saline group, the number of osteoclasts in the alveolar bone increased significantly (P < 0.01) on the compressed side in the mBMMSC group. Three days after mBMMSC injection, the number of Runx2-GFP double-positive cells on the tension side was significantly higher than that on the compression side. After applying compressive force on the mBMMSCs in vitro for 2 days, RANKL expression was significantly higher than in the non-compression cells, but expression of Alp, Runx2, Ocn and Osterix was significantly decreased (P < 0.05). The numbers of osteoclasts differentiated in response to mBMMs co-cultured with mBMMSCs under pressure load and expression of osteoclast differentiation marker genes (Mmp-9, TRAP and Ctsk) were significantly higher than those in mBMMs stimulated by M-CSF alone (P < 0.05). Conclusions mBMMSCs are not only recruited to the compressed side of the periodontal ligament but can also promote osteoclastogenesis by expressing Rankl, improving the efficiency of OTM.

scholarly journals Is Inflammation a Friend or Foe for Orthodontic Treatment?: Inflammation in Orthodontically Induced Inflammatory Root Resorption and Accelerating Tooth Movement

2021 ◽  
Vol 22 (5) ◽  
pp. 2388
Author(s):  
Masaru Yamaguchi ◽  
Shinichi Fukasawa
Keyword(s):  
Inflammatory Mediators ◽  
Orthodontic Treatment ◽  
Alveolar Bone ◽  
Tooth Movement ◽  
Root Resorption ◽  
Orthodontic Tooth Movement ◽  
Tnf Α ◽  
Orthodontic Forces ◽  
Necrosis Factor

The aim of this paper is to provide a review on the role of inflammation in orthodontically induced inflammatory root resorption (OIIRR) and accelerating orthodontic tooth movement (AOTM) in orthodontic treatment. Orthodontic tooth movement (OTM) is stimulated by remodeling of the periodontal ligament (PDL) and alveolar bone. These remodeling activities and tooth displacement are involved in the occurrence of an inflammatory process in the periodontium, in response to orthodontic forces. Inflammatory mediators such as prostaglandins (PGs), interleukins (Ils; IL-1, -6, -17), the tumor necrosis factor (TNF)-α superfamily, and receptor activator of nuclear factor (RANK)/RANK ligand (RANKL)/osteoprotegerin (OPG) are increased in the PDL during OTM. OIIRR is one of the accidental symptoms, and inflammatory mediators have been detected in resorbed roots, PDL, and alveolar bone exposed to heavy orthodontic force. Therefore, these inflammatory mediators are involved with the occurrence of OIIRR during orthodontic tooth movement. On the contrary, regional accelerating phenomenon (RAP) occurs after fractures and surgery such as osteotomies or bone grafting, and bone healing is accelerated by increasing osteoclasts and osteoblasts. Recently, tooth movement after surgical procedures such as corticotomy, corticision, piezocision, and micro-osteoperforation might be accelerated by RAP, which increases the bone metabolism. Therefore, inflammation may be involved in accelerated OTM (AOTM). The knowledge of inflammation during orthodontic treatment could be used in preventing OIIRR and AOTM.

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.

Surgical Repositioning of the Premaxilla in Combination with Two-Stage Alveolar Bone Grafting in Bilateral Cleft Lip and Palate

1998 ◽  
Vol 35 (4) ◽  
pp. 304-309 ◽  
Author(s):  
Mitsuyoshi Iino ◽  
Tomokazu Sasaki ◽  
Shoko Kochi ◽  
Masayuki Fukuda ◽  
Tetsu Takahashi ◽  
...  
Keyword(s):  
Bone Grafting ◽  
Surgical Procedure ◽  
Cleft Lip ◽  
Cleft Lip And Palate ◽  
Alveolar Bone ◽  
Tooth Movement ◽  
Orthodontic Tooth Movement ◽  
Two Stage ◽  
Alveolar Bone Grafting ◽  
Bilateral Cleft Lip

Objective This paper introduces a surgical technique for premaxillary repositioning in combination with two-stage alveolar bone grafting for the correction of the premaxillary deformity of patients with bilateral cleft lip and palate (BCLP). The paper also reports on two patients with BCLP who underwent this surgical management. Surgical Procedure The operation is usually performed when the patient is 8 to 14 years of age. In the first stage of surgery, the side more accessible to the septopremaxillary junction is selected, and an osteotomy of the premaxilla and unilateral alveolar bone grafting are performed. Approximately 4 to 12 months after the first stage of surgery, contralateral alveolar bone grafting is carried out. Conclusion We have found that this surgical procedure is highly effective, because it ensures the blood supply to the premaxilla and minimizes the potential for surgical failure. Moreover, it affords wide exposure of the premaxillary bone surface, facilitating sufficient boney bridging and allowing for orthodontic tooth movement.

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