scholarly journals Wnt1 Promotes Cementum and Alveolar Bone Growth in a Time-Dependent Manner

2021 ◽  
pp. 002203452110123
Author(s):  
C. Nottmeier ◽  
N. Liao ◽  
A. Simon ◽  
M.G. Decker ◽  
J. Luther ◽  
...  
Keyword(s):  
Bone Growth ◽  
Alveolar Bone ◽  
Bone Volume ◽  
Dependent Manner ◽  
Micro Computed Tomography ◽  
Noncollagenous Proteins ◽  
Ectopic Mineralization ◽  
Regenerative Dentistry ◽  
Wnt1 Expression

The WNT/β-catenin signaling pathway plays a central role in the biology of the periodontium, yet the function of specific extracellular WNT ligands remains poorly understood. By using a Wnt1-inducible transgenic mouse model targeting Col1a1-expressing alveolar osteoblasts, odontoblasts, and cementoblasts, we demonstrate that the WNT ligand WNT1 is a strong promoter of cementum and alveolar bone formation in vivo. We induced Wnt1 expression for 1, 3, or 9 wk in Wnt1Tg mice and analyzed them at the age of 6 wk and 12 wk. Micro–computed tomography (CT) analyses of the mandibles revealed a 1.8-fold increased bone volume after 1 and 3 wk of Wnt1 expression and a 3-fold increased bone volume after 9 wk of Wnt1 expression compared to controls. In addition, the alveolar ridges were higher in Wnt1Tg mice as compared to controls. Nondecalcified histology demonstrated increased acellular cementum thickness and cellular cementum volume after 3 and 9 wk of Wnt1 expression. However, 9 wk of Wnt1 expression was also associated with periodontal breakdown and ectopic mineralization of the pulp. The composition of this ectopic matrix was comparable to those of cellular cementum as demonstrated by quantitative backscattered electron imaging and immunohistochemistry for noncollagenous proteins. Our analyses of 52-wk-old mice after 9 wk of Wnt1 expression revealed that Wnt1 expression affects mandibular bone and growing incisors but not molar teeth, indicating that Wnt1 influences only growing tissues. To further investigate the effect of Wnt1 on cementoblasts, we stably transfected the cementoblast cell line (OCCM-30) with a vector expressing Wnt1-HA and performed proliferation as well as differentiation experiments. These experiments demonstrated that Wnt1 promotes proliferation but not differentiation of cementoblasts. Taken together, our findings identify, for the first time, Wnt1 as a critical regulator of alveolar bone and cementum formation, as well as provide important insights for harnessing the WNT signal pathway in regenerative dentistry.

Micro-Computed Tomography Analysis on Administration of Mesenchymal Stem Cells - Bovine Teeth Scaffold Composites for Alveolar Bone Tissue Engineering

2021 ◽  
Vol 52 ◽  
pp. 86-96
Author(s):  
Desi Sandra Sari ◽  
Fourier Dzar Eljabbar Latief ◽  
Ferdiansyah ◽  
Ketut Sudiana ◽  
Fedik Abdul Rantam
Keyword(s):  
Computed Tomography ◽  
Tissue Engineering ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Bone Regeneration ◽  
Bone Growth ◽  
Alveolar Bone ◽  
Micro Computed Tomography ◽  
Freeze Dried ◽  
Significant Difference

The tissue engineering approach for periodontal tissue regeneration using a combination of stem cells and scaffold has been vastly developed. Mesenchymal Stem Cells (MSCs) seeded with Bovine Teeth Scaffold (BTSc) can repair alveolar bone damage in periodontitis cases. The alveolar bone regeneration process was analyzed by micro-computed tomography (µ-CT) to observe the structure of bone growth and to visualize the scaffold in 3-Dimensional (3D). The purpose of this study is to analyze alveolar bone regeneration by µ-CT following the combination of MSCs and bovine teeth scaffold (MSCs-BTSc) implantation in the Wistar rat periodontitis model. Methods. MSCs were cultured from adipose-derived mesenchymal stem cells of rats. BTSc was taken from bovine teeth and freeze-dried with a particle size of 150-355 µm. MSCs were seeded on BTSc for 24 hours and transplanted in a rat model of periodontitis. Thirty-five Wistar rats were made as periodontitis models with LPS induction from P. gingivalis injected to the buccal section of interproximal gingiva between the first and the second mandibular right-molar teeth for six weeks. There were seven groups (control group, BTSc group on day 7, BTSc group on day 14, BTSc group on day 28, MSCs-BTSc group on day 7, MSCs-BTSc group on day 14, MSCs-BTSc group on day 28). The mandibular alveolar bone was analyzed and visualized in 3D with µ-CT to observe any new bone growth. Statistical Analysis. Group data were subjected to the Kruskal Wallis test followed by the Mann-Whitney (p <0.05). The µ-CT qualitative analysis shows a fibrous structure, which indicates the existence of new bone regeneration. Quantitative analysis of the periodontitis model showed a significant difference between the control model and the model with the alveolar bone resorption (p <0.05). The bone volume and density measurements revealed that the MSCs-BTSc group on day 28 formed new bone compared to other groups (p <0.05). Administration of MSCs-BTSc combination has the potential to form new alveolar bone.

scholarly journals Activation of the STAT1 Pathway Accelerates Periodontitis in Nos3-/- Mice

2019 ◽  
Vol 98 (9) ◽  
pp. 1027-1036 ◽  
Author(s):  
W. Wei ◽  
X. Xiao ◽  
J. Li ◽  
H. Ding ◽  
W. Pan ◽  
...  
Keyword(s):  
Gene Knockout ◽  
L929 Cell ◽  
Cytokine Expression ◽  
Macrophage Infiltration ◽  
Dependent Manner ◽  
Tissue Destruction ◽  
Micro Computed Tomography ◽  
Underlying Mechanisms

Early studies on the etiology and pathogenesis of hypertension have shown that it has a considerable association with inflammation and the immune response as well as periodontitis. Clinical studies have also shown that hypertension can promote the periodontal tissue destruction caused by periodontitis. However, the underlying mechanisms remain unclear. This study aimed to explore the possible mechanisms of how hypertension aggravates periodontitis. Treatment with or without the signal transducer and activator of transcription 1 (STAT1) inhibitor fludarabine was performed in an endothelial nitric oxide synthase gene knockout-related ( Nos3-/-) mouse model with the hypertension phenotype of periodontitis induced by bacteria. Micro–computed tomography, immunohistochemistry, Western blot, quantitative reverse transcription polymerase chain reaction, immunofluorescence, and ELISA were performed. We demonstrated that Nos3-/--related hypertension increases bone resorption and periodontal destruction in periodontitis lesion areas, which can be inhibited by the STAT1 inhibitor. Experimental data also showed that Nos3-/- significantly increased macrophage infiltration and proinflammatory cytokine expression in the periodontitis lesion area, which is dependent on the angiotensin II–induced STAT1 pathway. Inhibition of STAT1 in vivo can decrease the expression of proinflammatory cytokines and macrophage infiltration. Furthermore, data in this study showed that Nos3-/--related hypertension further downregulated the STAT3 anti-inflammatory function and its downstream chemokine expression in a STAT1-dependent manner. By applying RAW 264.7 and L929 cell lines and monocytes isolated from Nos3-/- mice, we confirmed that activation of the STAT1 pathway inhibits STAT3 and its downstream pathway and promotes inflammatory cytokine expression in vitro. Collectively, our current study demonstrated that STAT1 plays an indispensable role in the Nos3-/--related hypertension with aggravation of periodontitis, suggesting that STAT1 may be a key target for the treatment of periodontitis with hypertension.

scholarly journals In vivo microcomputed tomography evaluation of rat alveolar bone and root resorption during orthodontic tooth movement

2012 ◽  
Vol 83 (3) ◽  
pp. 402-409 ◽  
Author(s):  
Nan Ru ◽  
Sean Shih-Yao Liu ◽  
Li Zhuang ◽  
Song Li ◽  
Yuxing Bai
Keyword(s):  
Alveolar Bone ◽  
Tooth Movement ◽  
Root Resorption ◽  
Volume Fraction ◽  
Orthodontic Tooth Movement ◽  
Bone Volume ◽  
Structure Model ◽  
Bone Volume Fraction ◽  
Trabecular Thickness

ABSTRACT Objective: To observe the real-time microarchitecture changes of the alveolar bone and root resorption during orthodontic treatment. Materials and Methods: A 10 g force was delivered to move the maxillary left first molars mesially in twenty 10-week-old rats for 14 days. The first molar and adjacent alveolar bone were scanned using in vivo microcomputed tomography at the following time points: days 0, 3, 7, and 14. Microarchitecture parameters, including bone volume fraction, structure model index, trabecular thickness, trabecular number, and trabecular separation of alveolar bone, were measured on the compression and tension side. The total root volume was measured, and the resorption crater volume at each time point was calculated. Univariate repeated measures analysis of variance with Bonferroni corrections were performed to compare the differences in each parameter between time points with significance level at P &lt; .05. Results: From day 3 to day 7, bone volume fraction, structure model index, trabecular thickness, and trabecular separation decreased significantly on the compression side, but the same parameters increased significantly on the tension side from day 7 to day 14. Root resorption volume of the mesial root increased significantly on day 7 of orthodontic loading. Conclusions: Real-time root and bone resorption during orthodontic movement can be observed in 3 dimensions using in vivo micro-CT. Alveolar bone resorption and root resorption were observed mostly in the apical third on day 7 on the compression side; bone formation was observed on day 14 on the tension side during orthodontic tooth movement.

The anabolic effect of 17β-oestradiol on the trabecular bone of adult rats is suppressed by indomethacin

1992 ◽  
Vol 133 (2) ◽  
pp. 189-195 ◽  
Author(s):  
J. W. M. Chow ◽  
J. M. Lean ◽  
T. Abe ◽  
T. J. Chambers
Keyword(s):  
Bone Formation ◽  
Trabecular Bone ◽  
Bone Growth ◽  
Formation Rate ◽  
Bone Volume ◽  
Female Rats ◽  
Mineral Apposition Rate ◽  
Adult Rats ◽  
Bone Formation Rate

ABSTRACT We have previously demonstrated that administration of oestrogen, at doses sufficient to raise serum concentrations to those seen in late pregnancy, increases trabecular bone formation in the metaphysis of adult rats. To determine whether prostaglandins (PGs), which have been shown to induce osteogenesis in vivo, play a role in the induction of bone formation by oestrogen, 13-week-old female rats were given daily doses of 4 mg 17β-oestradiol (OE2)/kg for 17 days, alone or with indomethacin (1 mg/kg). The rats were also given double fluorochrome labels and at the end of the experiment tibias were subjected to histomorphometric assessment. Treatment with OE2 suppressed longitudinal bone growth and increased uterine wet weight, as expected, and neither response was affected by indomethacin. Oestrogen also induced a threefold increase in trabecular bone formation in the proximal tibial metaphysis, which resulted in a substantial increase in trabecular bone volume. As previously observed, the increase in bone formation was predominantly due to an increase in osteoblast recruitment (as judged by an increase in the percentage of bone surface showing double fluorochrome labels), with only a minor increase in the activity of mature osteoblasts (as judged by the mineral apposition rate). Indomethacin abolished the increase in osteoblastic recruitment, but the activity of mature osteoblastic cells remained high. The bone formation rate and bone volume remained similar to controls. The results suggest that PG production may be necessary for the increased osteoblastic recruitment induced by oestrogen, but not to mediate the effects of oestrogen on the activity of mature osteoblasts. Journal of Endocrinology (1992) 133, 189–195

scholarly journals Deferoxamine Reduces Inflammation and Osteoclastogenesis in Avulsed Teeth

2021 ◽  
Vol 22 (15) ◽  
pp. 8225
Author(s):  
Ko Eun Lee ◽  
Mijeong Jeon ◽  
Seunghan Mo ◽  
Hyo-Seol Lee ◽  
Je Seon Song ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Alveolar Bone ◽  
Root Surface ◽  
Tartrate Resistant Acid Phosphatase ◽  
Micro Ct ◽  
Sprague Dawley ◽  
Micro Computed Tomography ◽  
Model Cell

Replacement and inflammatory resorption are serious complications associated with the delayed replantation of avulsed teeth. In this study, we aimed to assess whether deferoxamine (DFO) can suppress inflammation and osteoclastogenesis in vitro and attenuate inflammation and bone resorption in a replanted rat tooth model. Cell viability and inflammation were evaluated in RAW264.7 cells. Osteoclastogenesis was confirmed by tartrate-resistant acid phosphatase staining, reactive oxygen species (ROS) measurement, and quantitative reverse transcriptase–polymerase chain reaction in teeth exposed to different concentrations of DFO. In vivo, molars of 31 six-week-old male Sprague–Dawley rats were extracted and stored in saline (n = 10) or DFO solution (n = 21) before replantation. Micro-computed tomography (micro-CT) imaging and histological analysis were performed to evaluate inflammation and root and alveolar bone resorption. DFO downregulated the genes related to inflammation and osteoclastogenesis. DFO also reduced ROS production and regulated specific pathways. Furthermore, the results of the micro-CT and histological analyses provided evidence of the decrease in inflammation and hard tissue resorption in the DFO group. Overall, these results suggest that DFO reduces inflammation and osteoclastogenesis in a tooth replantation model, and thus, it has to be further investigated as a root surface treatment option for an avulsed tooth.

scholarly journals Sustained Release of Bone Morphogenetic Protein-2 through Alginate Microbeads Enhances Bone Regeneration in Rabbit Tibial Metaphyseal Defect Model

Materials ◽  
2021 ◽  
Vol 14 (10) ◽  
pp. 2600
Author(s):  
Junhyung Kim ◽  
Seoyun Lee ◽  
Yonghyun Choi ◽  
Jonghoon Choi ◽  
Byung-Jae Kang
Keyword(s):  
Sustained Release ◽  
Bone Regeneration ◽  
Bone Morphogenetic Protein ◽  
Bone Volume ◽  
Bone Morphogenetic Protein 2 ◽  
Enzyme Linked Immunosorbent Assay ◽  
Micro Computed Tomography ◽  
Combined Application ◽  
Morphogenetic Protein

Bone morphogenetic protein-2 (BMP-2) is widely used to enhance bone regeneration. However, because of its short half-life and rapid disappearance, large amounts of BMP-2 are needed, leading to unintended side effects. In this study, BMP-2-encapsulated alginate microbeads (AM) were used to enhance bone regeneration. Enzyme-linked immunosorbent assay confirmed the sustained release of BMP-2 from AM. Vascular endothelial growth factor (VEGF)-adsorbing aptamer-conjugated hydroxyapatite (Apt-HA) was used for osteoconduction and dual delivery of VEGF and BMP-2. For in vivo bone regeneration evaluation, the grafts (1) Apt-HA + phosphate-buffered saline (PBS), (2) Apt-HA + AM without BMP-2, (3) Apt-HA + BMP-2, and (4) Apt-HA + AM encapsulated with BMP-2 were implanted into rabbit tibial metaphyseal defects. After four weeks, micro-computed tomography (CT), histological, and histomorphometric analyses were performed to evaluate bone regeneration. The Apt-HA + AM with BMP-2 group revealed a significantly higher new bone volume and bone volume/total volume (BV/TV) in both cortical and trabecular bone than the others. Furthermore, as evaluated by histomorphometric analysis, BMP-2 AM exhibited a significantly higher bone formation area than the others, indicating that AM could be used to efficiently deliver BMP-2 through sustained release. Moreover, the combined application of BMP-2-encapsulated Apt-HA + AM may effectively promote bone regeneration.

scholarly journals Antibody to Receptor Activator of NF-κB Ligand Ameliorates T Cell-Mediated Periodontal Bone Resorption

2010 ◽  
Vol 79 (2) ◽  
pp. 911-917 ◽  
Author(s):  
Xiaoping Lin ◽  
Xiaozhe Han ◽  
Toshihisa Kawai ◽  
Martin A. Taubman
Keyword(s):  
T Cell ◽  
Bone Resorption ◽  
Alveolar Bone ◽  
Immune Cell ◽  
Significant Inhibition ◽  
Dependent Manner ◽  
Igg Antibody ◽  
Receptor Activator

ABSTRACTActivated T and B lymphocytes in periodontal disease lesions express receptor activator of NF-κB ligand (RANKL), which induces osteoclastic bone resorption. The objective of this study was to evaluate the effects of anti-RANKL antibody on periodontal bone resorptionin vitroandin vivo. Aggregatibacter actinomycetemcomitansouter membrane protein 29 (Omp29) andA. actinomycetemcomitanslipopolysaccharide (LPS) were injected into 3 palatal gingival sites, and Omp29-specific T clone cells were transferred into the tail veins of rats. Rabbit anti-RANKL IgG antibody or F(ab′)2antibody fragments thereof were injected into the palatal sites in each rat (days −1, 1, and 3). Anti-RANKL IgG antibody significantly inhibited soluble RANKL (sRANKL)-induced osteoclastogenesisin vitro, in a dose-dependent manner, but also gave rise to a rat antibody response to rabbit IgGin vivo, with no significant inhibition of periodontal bone resorption detected. Lower doses (1.5 and 0.15 μg/3 sites) of F(ab′)2antibody were not immunogenic in the context of the experimental model. Periodontal bone resorption was inhibited significantly by injection of the anti-RANKL F(ab′)2antibody into gingivae. The sRANKL concentrations for the antibody-treated groups were decreased significantly compared to those for the untreated group. Osteoclasts on the alveolar bone surface were also diminished significantly after antibody injection. Gingival sRANKL concentration and bone loss showed a significant correlation with one another in animals receiving anti-RANKL F(ab′)2antibody. These results suggest that antibody to RANKL can inhibitA. actinomycetemcomitans-specific T cell-induced periodontal bone resorption by blockade and reduction of tissue sRANKL, providing an immunological approach to ameliorate immune cell-mediated periodontal bone resorption.

scholarly journals Periodontitis and vascular inflammatory biomarkers: an experimental in vivo study in rats

Odontology ◽  
2019 ◽  
Vol 108 (2) ◽  
pp. 202-212
Author(s):  
Yago Leira ◽  
Ramón Iglesias-Rey ◽  
Noemí Gómez-Lado ◽  
Pablo Aguiar ◽  
Tomás Sobrino ◽  
...  
Keyword(s):  
Alveolar Bone ◽  
Vascular Diseases ◽  
Serum Levels ◽  
Systemic Circulation ◽  
Inflammatory Biomarkers ◽  
In Vivo Study ◽  
Micro Computed Tomography ◽  
Periodontal Inflammation ◽  
Experimental Periodontitis

Abstract The objective of this preclinical in vivo study was to determine changes in vascular inflammatory biomarkers in systemic circulation after injection of lipopolysaccharide (LPS) from Porphyromonas gingivalis (Pg) in rats. Experimental periodontitis was induced by injections of Pg-LPS. Gingival soft and hard tissues changes were analysed by means of magnetic resonance imaging and micro computed tomography. Serum levels of interleukin (IL)-6, IL-10, pentraxin (PTX) 3, and soluble fragment of tumor necrosis factor-like weak inducer of apoptosis (sTWEAK) were determined at baseline and 24 h, 7, 14, and 21 days after periodontal induction. Significant periodontal inflammation and alveolar bone loss were evident at the end of periodontal induction. Experimental periodontitis posed an acute systemic inflammatory response with increased serum levels of IL-6 and PTX3 at 24 h post-induction, followed by a significant overexpression of sTWEAK at 7 days. This inflammatory state was maintained until the end of the experiment (21 days). As expected, IL-10 serum levels were significantly lower during the follow-up compared to baseline concentrations. In the present animal model, experimental periodontitis is associated with increased systemic inflammation. Further studies are needed to confirm whether PTX3 and sTWEAK could be useful biomarkers to investigate potential mechanisms underlying the relationship between periodontitis and atherosclerotic vascular diseases.

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