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1.
Head Face Med ; 17(1): 4, 2021 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-33546715

RESUMO

BACKGROUND: The purpose of this study was to analyze the relationship between body posture and sagittal dental overjet in children before and after early orthodontic treatment with removable functional orthodontic appliances. METHODS: Angle Class II patients (mean age 8.2 ± 1.2 years; 29 males and 25 females) with a distinctly enlarged overjet (> 9 mm) were retrospectively examined regarding body posture parameters before and after early orthodontic treatment. In addition, changes in overjet were investigated with the aid of plaster models. Forms of transverse dysgnathism (crossbite, lateral malocclusions) and open bite cases were excluded. Body posture parameters kyphosis, lordosis, surface rotation, pelvic tilt, pelvic torsion and trunk imbalance were analyzed by means of rasterstereographical photogrammetry to determine, if the orthodontic overjet correction is associated with specific changes in posture patterns. RESULTS: In nearly all patients an overjet correction and an improvement regarding all body posture and back parameters could be noted after early orthodontic treatment. Overjet reduction (- 3.9 mm ± 2.1 mm) and pelvic torsion (- 1.28° ± 0,44°) were significantly (p < 0.05) and moderately correlated (R = 0.338) with no significant associations found for the other posture and back parameters (p > 0.05). CONCLUSION: Overjet reduction during early orthodontic treatment may be associated with a detectable effect on pelvic torsion.


Assuntos
Má Oclusão de Angle Classe II , Má Oclusão , Aparelhos Ortodônticos Funcionais , Criança , Feminino , Humanos , Masculino , Má Oclusão/diagnóstico por imagem , Má Oclusão/terapia , Má Oclusão de Angle Classe II/diagnóstico por imagem , Má Oclusão de Angle Classe II/terapia , Postura , Estudos Retrospectivos
2.
Ann Anat ; 236: 151702, 2021 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-33607226

RESUMO

BACKGROUND: There is some evidence that estrogen regulates the expression of several genes in different cells, including dental cells. Therefore, the aim of this study was to investigate the role of estrogen deficiency during tooth development regarding tooth structure morphology and its impact on the expression of odontogenesis-related genes. METHODS: A total of 40 female Wistar rats was divided into OVX (estrogen deficiency) and Sham (control) groups. Bilateral ovariectomy was performed in the OVX group, while Sham surgery was performed in the control group at the age of 21 days. At an age of 56 days, 16 rats were euthanized for gene expression analyses of Bmp4, Smad6, Tgfb1 and Runx2. At the age of 63 days, the remaining rats were euthanized for histological and morphometric analyses of teeth. The mandibles of the rats were submitted to µCT analysis. Tooth structures (enamel, dentin and dental pulp) were analyzed. T test was used to compare the mean differences between groups (p<0.05). RESULTS: In the µCT analysis, enamel and dentin thickness were significantly increased in the control group (p<0.0001). Pulp dimensions were significantly larger in the OVX group (p<0.0001). A reduction of tooth structures in the OVX group was confirmed in HE staining. Smad6 was differentially expressed in the OVX group (p=0.04). CONCLUSION: Estrogen deficiency affects gene expression in the odontogenic region and tooth structure morphology.

3.
Cells ; 10(2)2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33535605

RESUMO

Genetic predisposition, traumatic events, or excessive mechanical exposure provoke arthritic changes in the temporomandibular joint (TMJ). We analysed the impact of mechanical stress that might be involved in the development and progression of TMJ osteoarthritis (OA) on murine synovial fibroblasts (SFs) of temporomandibular origin. SFs were subjected to different protocols of mechanical stress, either to a high-frequency tensile strain for 4 h or to a tensile strain of varying magnitude for 48 h. The TMJ OA induction was evaluated based on the gene and protein secretion of inflammatory factors (Icam-1, Cxcl-1, Cxcl-2, Il-1ß, Il-1ra, Il-6, Ptgs-2, PG-E2), subchondral bone remodelling (Rankl, Opg), and extracellular matrix components (Col1a2, Has-1, collagen and hyaluronic acid deposition) using RT-qPCR, ELISA, and HPLC. A short high-frequency tensile strain had only minor effects on inflammatory factors and no effects on the subchondral bone remodelling induction or matrix constituent production. A prolonged tensile strain of moderate and advanced magnitude increased the expression of inflammatory factors. An advanced tensile strain enhanced the Ptgs-2 and PG-E2 expression, while the expression of further inflammatory factors were decreased. The tensile strain protocols had no effects on the RANKL/OPG expression, while the advanced tensile strain significantly reduced the deposition of matrix constituent contents of collagen and hyaluronic acid. The data indicates that the application of prolonged advanced mechanical stress on SFs promote PG-E2 protein secretion, while the deposition of extracellular matrix components is decreased.

4.
Int J Mol Sci ; 22(3)2021 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-33513808

RESUMO

There is little known about the effect of the periodontopathogen Filifactor alocis on macrophages as key cells of the innate immune defense in the periodontium. Therefore, the aim of the present study was to investigate the effect of F. alocis and additionally of the pro-inflammatory cytokine tumor necrosis factor-alpha (TNFα) on visfatin and other pro-inflammatory and proteolytic molecules associated with periodontitis in human macrophages. The presence of macrophage markers CD14, CD86, CD68, and CD163 was examined in gingival biopsies from healthy individuals and periodontitis patients. Human macrophages were incubated with F. alocis and TNFα for up to 2 d. The effects of both stimulants on macrophages were determined by real-time PCR, ELISA, immunocytochemistry, and immunofluorescence. F. alocis was able to significantly stimulate the synthesis of visfatin by human macrophages using TLR2 and MAPK pathways. In addition to visfatin, F. alocis was also able to increase the synthesis of cyclooxygenase 2, TNFα, and matrix metalloproteinase 1. Like F. alocis, TNFα was also able to stimulate the production of these proinflammatory and proteolytic molecules. Our results highlight the pathogenetic role of F. alocis in periodontal diseases and also underline the involvement of visfatin in the aetiopathogenesis of periodontitis.

5.
Int J Mol Sci ; 22(2)2021 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-33435280

RESUMO

Dietary salt uptake and inflammation promote sodium accumulation in tissues, thereby modulating cells like macrophages and fibroblasts. Previous studies showed salt effects on periodontal ligament fibroblasts and on bone metabolism by expression of nuclear factor of activated T-cells-5 (NFAT-5). Here, we investigated the impact of salt and NFAT-5 on osteoclast activity and orthodontic tooth movement (OTM). After treatment of osteoclasts without (NS) or with additional salt (HS), we analyzed gene expression and the release of tartrate-resistant acid phosphatase and calcium phosphate resorption. We kept wild-type mice and mice lacking NFAT-5 in myeloid cells either on a low, normal or high salt diet and inserted an elastic band between the first and second molar to induce OTM. We analyzed the expression of genes involved in bone metabolism, periodontal bone loss, OTM and bone density. Osteoclast activity was increased upon HS treatment. HS promoted periodontal bone loss and OTM and was associated with reduced bone density. Deletion of NFAT-5 led to increased osteoclast activity with NS, whereas we detected impaired OTM in mice. Dietary salt uptake seems to accelerate OTM and induce periodontal bone loss due to reduced bone density, which may be attributed to enhanced osteoclast activity. NFAT-5 influences this reaction to HS, as we detected impaired OTM and osteoclast activity upon deletion.

6.
Int J Mol Sci ; 22(2)2021 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-33435582

RESUMO

The aim of the study was to clarify whether orthodontic forces and periodontitis interact with respect to the anti-apoptotic molecules superoxide dismutase 2 (SOD2) and baculoviral IAP repeat-containing protein 3 (BIRC3). SOD2, BIRC3, and the apoptotic markers caspases 3 (CASP3) and 9 (CASP9) were analyzed in gingiva from periodontally healthy and periodontitis subjects by real-time PCR and immunohistochemistry. SOD2 and BIRC3 were also studied in gingiva from rats with experimental periodontitis and/or orthodontic tooth movement. Additionally, SOD2 and BIRC3 levels were examined in human periodontal fibroblasts incubated with Fusobacterium nucleatum and/or subjected to mechanical forces. Gingiva from periodontitis patients showed significantly higher SOD2, BIRC3, CASP3, and CASP9 levels than periodontally healthy gingiva. SOD2 and BIRC3 expressions were also significantly increased in the gingiva from rats with experimental periodontitis, but the upregulation of both molecules was significantly diminished in the concomitant presence of orthodontic tooth movement. In vitro, SOD2 and BIRC3 levels were significantly increased by F. nucleatum, but this stimulatory effect was also significantly inhibited by mechanical forces. Our study suggests that SOD2 and BIRC3 are produced in periodontal infection as a protective mechanism against exaggerated apoptosis. In the concomitant presence of orthodontic forces, this protective anti-apoptotic mechanism may get lost.


Assuntos
Proteína 3 com Repetições IAP de Baculovírus/genética , Regulação da Expressão Gênica , Ligamento Periodontal/metabolismo , Periodonto/metabolismo , Superóxido Dismutase/genética , Animais , Apoptose/genética , Proteína 3 com Repetições IAP de Baculovírus/metabolismo , Caspase 3/genética , Caspase 3/metabolismo , Caspase 9/genética , Caspase 9/metabolismo , Células Cultivadas , Fibroblastos/citologia , Fibroblastos/metabolismo , Fusobacterium nucleatum/fisiologia , Gengiva/citologia , Gengiva/metabolismo , Interações Hospedeiro-Patógeno , Humanos , Ligamento Periodontal/citologia , Ligamento Periodontal/microbiologia , Periodonto/citologia , Periodonto/microbiologia , Ratos , Superóxido Dismutase/metabolismo
7.
Biomedicines ; 8(12)2020 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-33302395

RESUMO

Many patients regularly take histamine receptor antagonists, such as cetirizine, to prevent allergic reactions, but these antiallergic drugs may have inadvertent effects on orthodontic treatment. In previous studies, histamine has been shown to modulate the sterile inflammatory reaction underlying orthodontic tooth movement. Pertinent effects of histamine antagonization via cetirizine during orthodontic treatment, however, have not been adequately investigated. We thus treated male Fischer344 rats either with tap water (control group) or cetirizine by daily oral gavage corresponding to the clinically used human dosage adjusted to the rat metabolism (0.87 mg/kg) or to a previously published high dosage of cetirizine (3 mg/kg). Experimental anterior movement of the first upper left molar was induced by insertion of a nickel-titanium (NiTi) coil spring (0.25 N) between the molar and the upper incisors. Cone-beam computed tomography (CBCT), micro-computed tomography (µCT) images, as well as histological hematoxylin-eosin (HE), and tartrate-resistant acid phosphatase (TRAP) stainings were used to assess the extent of tooth movement, cranial growth, periodontal bone loss, root resorptions, and osteoclast activity in the periodontal ligament. Both investigated cetirizine dosages had no impact on the weight gain of the animals and, thus, animal welfare. Neither the extent of tooth movement, nor cranial growth, nor root resorption, nor periodontal bone loss were significantly influenced by the cetirizine dosages investigated. We, thus, conclude that histamine receptor antagonist cetirizine can be used during orthodontic treatment to prevent allergic reactions without clinically relevant side effects on orthodontic tooth movement.

8.
J Orofac Orthop ; 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-33258981

RESUMO

PURPOSE: Evaluation of tooth movement after retainer debonding in retainer-associated misalignment cases. METHODS: This pilot study is based on a retrospective data analysis. Adult patients (age 25.5 ± 4.9 years) wearing fixed twistflex retainers and having visible retainer-associated misalignment were included and examined for tooth movement after retainer debonding. Orthodontic study models were taken at retainer debonding (t0) and 14 (±1) weeks later (t1). They were digitally superimposed using 2D/3D dental imaging software and tooth movement was analyzed in all three dimensions. RESULTS: A total of 23 teeth (12 upper teeth: 10 incisors, 2 canines; 11 lower teeth: 7 incisors, 4 canines) were analyzed. Mean overall tipping was 1.11 ± 0.82° in the mesial/distal direction (angulation, x­axis), 2.02 ± 1.9° in the buccal/lingual direction (inclination, y­axis) and 1.28 ± 0.99° around the tooth axis (z-axis). Mean overall bodily movement was 0.30 ± 0.31 mm in the mesial/distal direction (angulation, x­axis), 0.10 ± 0.13 mm in the buccal/lingual direction (inclination, y­axis), and mean in- or extrusion 0.22 ± 0.24 mm (z-axis). Mean tipping and bodily movement were more pronounced in the upper jaw. CONCLUSION: The present data shows that tooth movement after debonding of twistflex retainers can be expected in misalignment cases.

9.
Int J Mol Sci ; 21(24)2020 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-33322510

RESUMO

Autophagy (cellular self-consumption) is a crucial adaptation mechanism during cellular stress conditions. This study aimed to examine how this important process is regulated in human periodontal ligament (PDL) fibroblasts by mechanical and inflammatory stress conditions and whether the mammalian target of rapamycin (mTOR) signaling pathway is involved. Autophagy was quantified by flow cytometry. Qualitative protein phosphorylation profiling of the mTOR pathway was carried out. Effects of mTOR regulation were assessed by quantification of important synthesis product collagen 1, cell proliferation and cell death with real-time PCR and flow cytometry. Autophagy as a response to mechanical or inflammatory treatment in PDL fibroblasts was dose and time dependent. In general, autophagy was induced by stress stimulation. Phosphorylation analysis of mTOR showed regulatory influences of mechanical and inflammatory stimulation on crucial target proteins. Regulation of mTOR was also detectable via changes in protein synthesis and cell proliferation. Physiological pressure had cell-protective effects (p = 0.025), whereas overload increased cell death (p = 0.003), which was also promoted in long-term inflammatory treatment (p < 0.001). Our data provide novel insights about autophagy regulation by mechanical and inflammatory stress conditions in human PDL fibroblasts. Our results suggest some involvement of the mTOR pathway in autophagy and cell fate regulation under the named conditions.


Assuntos
Autofagia/fisiologia , Estresse Mecânico , Morte Celular/fisiologia , Células Cultivadas , Fibroblastos/metabolismo , Fibroblastos/fisiologia , Humanos , Inflamação/metabolismo , Inflamação/fisiopatologia , Transdução de Sinais/fisiologia
10.
Int J Mol Sci ; 21(24)2020 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-33333756

RESUMO

Orthodontic tooth movement (OTM) creates compressive and tensile strain in the periodontal ligament, causing circulation disorders. Hypoxia-inducible factor 1α (HIF-1α) has been shown to be primarily stabilised by compression, but not hypoxia in periodontal ligament fibroblasts (PDLF) during mechanical strain, which are key regulators of OTM. This study aimed to elucidate the role of heparan sulfate integrin interaction and downstream kinase phosphorylation for HIF-1α stabilisation under compressive and tensile strain and to which extent downstream synthesis of VEGF and prostaglandins is HIF-1α-dependent in a model of simulated OTM in PDLF. PDLF were subjected to compressive or tensile strain for 48 h. In various setups HIF-1α was experimentally stabilised (DMOG) or destabilised (YC-1) and mechanotransduction was inhibited by surfen and genistein. We found that HIF-1α was not stabilised by tensile, but rather by compressive strain. HIF-1α stabilisation had an inductive effect on prostaglandin and VEGF synthesis. As expected, HIF-1α destabilisation reduced VEGF expression, whereas prostaglandin synthesis was increased. Inhibition of integrin mechanotransduction via surfen or genistein prevented stabilisation of HIF-1α. A decrease in VEGF expression was observed, but not in prostaglandin synthesis. Stabilisation of HIF-1α via integrin mechanotransduction and downstream phosphorylation of kinases seems to be essential for the induction of VEGF, but not prostaglandin synthesis by PDLF during compressive (but not tensile) orthodontic strain.


Assuntos
Fibroblastos/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Mecanotransdução Celular , Ligamento Periodontal/metabolismo , Adolescente , Adulto , Células Cultivadas , Feminino , Fibroblastos/efeitos dos fármacos , Quinase 1 de Adesão Focal/antagonistas & inibidores , Genisteína/farmacologia , Glicina/análogos & derivados , Glicina/farmacologia , Glicosaminoglicanos/antagonistas & inibidores , Humanos , Indazóis/farmacologia , Integrinas/antagonistas & inibidores , Masculino , Mecanotransdução Celular/efeitos dos fármacos , Mecanotransdução Celular/genética , Ligamento Periodontal/citologia , Ligamento Periodontal/efeitos dos fármacos , Fosforilação , Prostaglandina-Endoperóxido Sintases/genética , Prostaglandina-Endoperóxido Sintases/metabolismo , Prostaglandinas/biossíntese , Prostaglandinas/metabolismo , Estabilidade Proteica/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Estresse Mecânico , Técnicas de Movimentação Dentária , Ureia/análogos & derivados , Ureia/farmacologia , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo
11.
Ann Anat ; 234: 151648, 2020 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-33221386

RESUMO

OBJECTIVE: The aim of the present study was to evaluate the expressions of CXCL5, CXCL8, and CXCL10 in periodontal cells and tissues in response to microbial signals and/or biomechanical forces. METHODS: Human gingival biopsies from inflamed and healthy sites were used to examine the chemokine expressions and protein levels by real-time PCR and immunohistochemistry. The chemokines were also investigated in gingival biopsies from rats submitted to experimental periodontitis and/or tooth movement. Furthermore, chemokine levels were determined in human periodontal fibroblasts stimulated by the periodontopathogen Fusobacterium nucleatum and/or constant tensile forces (CTS) by real-time PCR and ELISA. Additionally, gene expressions were evaluated in periodontal fibroblasts exposed to F. nucleatum and/or CTS in the presence and absence of a MAPK inhibitor by real-time PCR. RESULTS: Increased CXCL5, CXCL8, and CXCL10 levels were observed in human and rat gingiva from sites of inflammation as compared with periodontal health. The rat experimental periodontitis caused a significant (p<0.05) increase in alveolar bone resorption, which was further enhanced when combined with tooth movement. In vitro, F. nucleatum caused a significant upregulation of CXCL5, CXCL8, and CXCL10 at 1 day. Once the cells were exposed simultaneously to F. nucleatum and CTS, the chemokines regulation was significantly enhanced. The transcriptional findings were also observed at protein level. Pre-incubation with the MEK1/2 inhibitor significantly (p<0.05) inhibited the stimulatory actions of F. nucleatum either alone or in combination with CTS on the expression levels of CXCL5, CXCL8, and CXCL10 at 1d. CONCLUSIONS: Our data provide original evidence that biomechanical strain further increases the stimulatory actions of periodontal bacteria on the expressions of these chemokines. Therefore, biomechanical loading in combination with periodontal infection may lead to stronger recruitment of immunoinflammatory cells to the periodontium, which might result in an aggravation of periodontal inflammation and destruction.

12.
Int J Mol Sci ; 21(21)2020 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-33153049

RESUMO

The human oral microbiota consists of over 700 widespread taxa colonizing the oral cavity in several anatomically diverse oral niches. Lately, sequencing of the 16S rRNA genes has become an acknowledged, culture-independent method to characterize the oral microbiota. However, only a small amount of data are available concerning microbial differences between oral niches in periodontal health and disease. In the context of periodontitis, the cytokine expression in the gingival crevicular fluid has been studied in detail, whereas little is known about the cytokine profile in hard and soft tissue biofilms. In order to characterize oral niches in periodontal health, the oral microbiota and cytokine pattern were analyzed at seven different sites (plaque (P), gingival crevicular fluid (GCF), saliva (S), tongue (T), hard palate (HP), cheek (C) and sublingual area (U)) of 20 young adults using next-generation sequencing and multiplex immunoassays. Site-specific microbial compositions were detected, which clustered into three distinct metaniches ("P-GCF", "S-T-HP" and "C-U") and were associated with niche-/metaniche-specific cytokine profiles. Our findings allow the definition of distinct metaniches according to their microbial composition, partly reflected by their cytokine profile, and provide new insights into microenvironmental similarities between anatomical diverse oral niches.

13.
Clin Oral Investig ; 2020 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-33099705

RESUMO

OBJECTIVES: The aim of this study was investigate the cranium dimensions of adult female rats, who suffered estrogen deficiency during the prepubertal stage, to assess the impact of estrogen deficiency on craniofacial morphology. MATERIAL AND METHODS: Twenty-two female Wistar rats were divided into ovariectomy (OVX) (n = 11) and sham-operated control (n = 11) groups. Bilateral ovariectomy were performed in both groups at 21 days old (prepubertal stage), and rats were euthanized at an age of 63 days (post-pubertal stage). Micro-CT scans were performed with rat skulls, and the cranium morphometric landmark measurements were taken in the dorsal, lateral, and ventral view positions. Differences in measurements between the OVX and sham control groups were assessed using t test with an established alpha error of 5%. RESULTS: The measures of the rats' skull showed that the inter-zygomatic arch width and anterior cranial base length were significantly larger in OVX group (p = 0.020 and p = 0.050, respectively), whereas the length of parietal bone was significantly higher in the sham group (p = 0.026). For the remaining measurements no significant differences between groups were detected (p > 0.05). CONCLUSION: This study provides evidence that ovariectomized rats had alterations in cranial bone dimensions, demonstrating that estrogens during puberty are important for skull morphology. CLINICAL RELEVANCE: To understand the role of estrogen on the postnatal cranium development will impact the clinical diagnose and therapy during childhood and adolescence.

14.
Clin Oral Investig ; 2020 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-33033920

RESUMO

OBJECTIVES: The aims of this study were to investigate the antimicrobial efficacy of antiseptics in saliva-derived microcosm biofilms, and to examine phenotypic adaption of bacteria upon repeated exposure to sub-inhibitory antiseptic concentrations. METHODS: Saliva-derived biofilms were formed mimicking caries- or gingivitis-associated conditions, respectively. Microbial compositions were analyzed by semiconductor-based 16S rRNA sequencing. Biofilms were treated with CHX, CPC, BAC, ALX, and DQC for 1 or 10 min, and colony forming units (CFU) were evaluated. Phenotypic adaptation of six selected bacterial reference strains toward CHX, CPC, and BAC was assessed by measuring minimum inhibitory concentrations (MICs) over 10 passages of sub-inhibitory exposure. Protein expression profiles were investigated by SDS-PAGE. RESULTS: Both biofilms showed outgrowth of streptococci and Veillonella spp., while gingivitis biofilms also showed increased relative abundances of Actinomyces, Granulicatella, and Gemella spp. Antiseptic treatment for 1 min led to no relevant CFU-reductions despite for CPC. When treated for 10 min, CPC was most effective followed by BAC, ALX, CHX, and DQC. Stable adaptations with up to fourfold MIC increases were found in E. coli toward all tested antiseptics, in E. faecalis toward CHX and BAC, and in S. aureus toward CPC. Adapted E. coli strains showed different protein expression as compared with the wildtype strain. CONCLUSION: Antiseptics showed limited antimicrobial efficacy toward mature biofilms when applied for clinically relevant treatment periods. Bacteria showed phenotypic adaptation upon repeated sub-inhibitory exposure. CLINICAL RELEVANCE: Clinicians should be aware that wide-spread use of antiseptics may pose the risk of inducing resistances in oral bacteria.

15.
Eur J Orthod ; 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33043973

RESUMO

BACKGROUND: In orthodontic tooth movement (OTM), pseudo-inflammatory processes occur that are similar to those of nicotine-induced periodontitis. Previous studies have shown that nicotine accelerates OTM, but induces periodontal bone loss and dental root resorption via synergistically increased osteoclastogenesis. This study aimed to investigate the role of hypoxia-inducible factor 1 alpha (HIF-1α) in nicotine-induced osteoclastogenesis during OTM. MATERIALS/METHODS: Male Fischer-344 rats were treated with l-Nicotine (1.89 mg/kg/day s.c., N = 10) or NaCl solution (N = 10). After a week of premedication, a NiTi spring was inserted to mesialize the first upper left molar. The extent of dental root resorption, osteoclastogenesis, and HIF-1α protein expression was determined by (immuno)histology, as well as bone volume (BV/TV) and trabecular thickness (TbTh) using µCT. Receptor activator of nuclear factor of activated B-cells ligand (RANK-L), osteoprotegerin (OPG), and HIF-1α expression were examined at the protein level in periodontal ligament fibroblasts (PDLF) exposed to pressure, nicotine and/or hypoxia, as well as PDLF-induced osteoclastogenesis in co-culture experiments with osteoclast progenitor cells. RESULTS: Nicotine favoured dental root resorptions and osteoclastogenesis during OTM, while BV/TV and TbTh were only influenced by force. This nicotine-induced increase does not appear to be mediated by HIF-1α, since HIF-1α was stabilized by force application and hypoxia, but not by nicotine. The in vitro data showed that the hypoxia-induced increase in RANK-L/OPG expression ratio and PDLF-mediated osteoclastogenesis was less pronounced than the nicotine-induced increase. CONCLUSIONS: Study results indicate that the nicotine-induced increase in osteoclastogenesis and periodontal bone resorption during OTM may not be mediated by hypoxic effects or HIF-1α stabilization in the context of nicotine-induced vasoconstriction, but rather by an alternative mechanism.

16.
Orthod Craniofac Res ; 2020 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-33068497

RESUMO

OBJECTIVE: To investigate SNPs in bone- and cartilage-related genes and their interaction in the aetiology of sagittal and vertical skeletal malocclusions. SETTINGS AND SAMPLE POPULATION: This study included 143 patients and classified as follows: skeletal class I (n = 77), class II (n = 47) and class III (n = 19); maxillary retrusion (n = 39), protrusion (n = 52) and well-positioned maxilla (n = 52); mandibular retrognathism (n = 50), prognathism (n = 50) and well-positioned mandible (n = 43); normofacial (n = 72), dolichofacial (n = 55) and brachyfacial (n = 16). MATERIALS AND METHODS: Steiner's ANB, SNA, SNB angles and Ricketts' NBa-PtGn angle were measured to determine the skeletal malocclusion and the vertical pattern. Nine SNPs in BMP2, BMP4, SMAD6, RUNX2, WNT3A and WNT11 were genotyped. Chi-squared test was used to compare genotypes among the groups. Multifactor dimensionality reduction (MDR) and binary logistic regression analysis, both using gender and age as co-variables, were also used. We performed Bonferroni correction for multiple testing. RESULTS: Significant associations at P < .05 were observed for SNPs rs1005464 (P = .042) and rs235768 (P = .021) in BMP2 with mandibular retrognathism and for rs59983488 (RUNX2) with maxillary protrusion (P = .04) as well as for rs708111 (WNT3A) with skeletal class III (P = .02; dominant model), rs1533767 (WNT11) with a brachyfacial skeletal pattern (P = .01, OR = 0.10; dominant model) and for rs3934908 (SMAD6) with prognathism (P = .02; recessive model). After the Bonferroni correction, none of the SNPs remained associated. The MDR predicted some interaction for skeletal class II, dolichofacial and brachyfacial phenotypes. CONCLUSION: Our results suggest that SNPs in BMP2, BMP4, SMAD6, RUNX2, WNT3A and WNT11 could be involved in the aetiology of sagittal and vertical malocclusions.

17.
Ann Anat ; : 151607, 2020 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-33027688

RESUMO

Anencephaly is the most severe form of a neural tube defect resulting from the incomplete occlusion of the anterior neuropore in the fourth week of development and associated with a severely underdeveloped brain mass. As desmal ossification of the neurocranium is induced by the presence of soft tissues (brain), no bone develops as direct consequence of the missing brain. The cranial base, by contrast, is formed by chondral ossification, which is genetically determined, and thus present also in anencephaly. Morphometric characteristics of anencephalic skulls, however, have not yet been investigated in sufficient detail before. In this study we therefore comparatively assessed macroscopic morphological-anatomical and cephalometric CT data on structures and dimensions of 11 macerated anencephalic and 4 normal neonatal skulls highlighting skeletal morphological differences. The most striking results were the missing skullcap and the greatly changed morphology of the existing skull bones, which were reduced in size. The parameters of the skull base, the transverse orbital diameter and maxillary width were significantly smaller in anencephalic skulls. The morphology of the viscerocranium appeared similar to that of normal neonatal skulls. The results of this study can be used in diagnosis and skeletal classification for anencephaly. This can help identify bones that are incomplete, fragmented and taphonomically altered, which is often the case in historical and forensic studies.

18.
Int J Mol Sci ; 21(21)2020 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-33120924

RESUMO

The periodontal ligament (PDL) is exposed to different kinds of mechanical stresses such as bite force or orthodontic tooth movement. A simple and efficient model to study molecular responses to mechanical stress is the application of compressive force onto primary human periodontal ligament fibroblasts via glass disks. Yet, this model suffers from the need for primary cells from human donors which have a limited proliferative capacity. Here we show that an immortalized cell line, PDL-hTERT, derived from primary human periodontal ligament fibroblasts exhibits characteristic responses to glass disk-mediated compressive force resembling those of primary cells. These responses include induction and secretion of pro-inflammatory markers, changes in expression of extracellular matrix-reorganizing genes and induction of genes related to angiogenesis, osteoblastogenesis and osteoclastogenesis. The fact that PDL-hTERT cells can easily be transfected broadens their usefulness, as molecular gain- and loss-of-function studies become feasible.

19.
Immunol Cell Biol ; 2020 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-32888231

RESUMO

Myeloid cells regulate bone density in response to increased salt (NaCl) intake via the osmoprotective transcription factor, nuclear factor of activated T cells-5 (NFAT-5). Because orthodontic tooth movement (OTM) is a pseudoinflammatory immunological process, we investigated the influence of NaCl and NFAT-5 on the expression pattern of macrophages in a model of simulated OTM. RAW264.7 macrophages were exposed for 4 h to 2 g cm-2 compressive or 16% tensile or no mechanical strain (control), with or without the addition of 40 mm NaCl. We analyzed the expression of inflammatory genes and proteins [tumor necrosis factor (TNF), interleukin (IL)-6 and prostaglandin endoperoxide synthase-2 (Ptgs-2)/prostaglandin E2 (PG-E2)] by real-time-quantitative PCR and ELISA. To investigate the role of NFAT-5 in these responses, NFAT-5 was both constitutively expressed and silenced. Salt and compressive strain, but not tensile strain increased the expression of NFAT-5 and most tested inflammatory factors in macrophages. NaCl induced the expression of Ptgs-2/PG-E2 and TNF, whereas secretion of IL-6 was inhibited. Similarly, a constitutive expression of NFAT-5 reduced IL-6 expression, while increasing Ptgs-2/PG-E2 and TNF expression. Silencing of NFAT-5 upregulated IL-6 and reduced Ptgs-2/PG-E2 and TNF expression. Salt had an impact on the expression profile of macrophages as a reaction to compressive and tensile strain that occur during OTM. This was mediated via NFAT-5, which surprisingly also seems to play a regulatory role in mechanotransduction of compressive strain. Sodium accumulation in the periodontal ligament caused by dietary salt consumption might propagate local osteoclastogenesis via increased local inflammation and thus OTM velocity, but possibly also entail side effects such as dental root resorptions or periodontal bone loss.

20.
Ann Anat ; 232: 151585, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32818660

RESUMO

OBJECTIVES: The non-steroidal anti-inflammatory drug etoricoxib is the most highly selective inhibitor of cyclooxygenase-2 available (344:1) and has been approved for postoperative pain therapy following dental interventions in Europe. At clinically relevant doses it has been reported to only have marginal effects on the velocity of orthodontic tooth movement (OTM). Its effects on associated dental root resorptions, osteoclastogenesis, trabecular number in the alveolar bone and periodontal bone loss during OTM, however, have not yet been investigated. MATERIAL AND METHODS: 40 male Fischer344 rats were divided into four groups: 1.5ml tap water/day p.o. (control, 1), additional 7.8mg/kg/day etoricoxib (normal dose) for three (2) or seven (3) days/week and 13.1mg/kg/day (high dose) for seven days/week, respectively (4). After a week of premedication, OTM in anterior direction of the first left upper molar was performed for 28 days by means of a nickel-titanium coil spring (0.25N). We quantified OTM-associated dental root resorptions, osteoclastogenesis, trabecular number and periodontal bone loss by histomorphometrical, histochemical and µCT analyses of the disected tooth-bearing upper jaw sections. RESULTS: After 28 days of OTM, associated reduction of trabecular number seemed to be slightly alleviated by high doses of etoricoxib, whereas no significant other etoricoxib effects in the doses administered could be detected regarding OTM-induced or -associated dental root resorptions, osteoclastogenesis or periodontal bone loss. CONCLUSIONS: Dental root resorptions, osteoclastogenesis and periodontal bone loss during OTM in rats were not significantly affected by etoricoxib in the clinically relevant dosages investigated with only a slight inhibitory effect on bone remodelling to be expected at high dosages. Etoricoxib is therefore not suitable for the prevention of these detrimental effects, but could be a suitable analgesic during OTM, as it has been reported not to affect tooth movement.

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