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1.
Dent Traumatol ; 39(6): 586-596, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37485754

RESUMO

BACKGROUND/AIM: Mandibular condylar fractures represent 25%-35% of all mandibular fractures. Despite profound research, there is still a controverse debate about treating these fractures conservatively or by open reduction and internal fixation (ORIF). The aim of this study is to analyse the outcome after open and closed treatment of extracapsular mandibular condyle fractures regarding general characteristics, post-treatment malocclusion, facial nerve palsy (FNP), maximum mouth opening (MMO) and parotid complications. METHODS: A retrospective cohort of 377 fractures (350 open, 27 closed treatment) was reviewed by reference to clinical and radiological pre- and postoperative documentation. Follow-up period was 12 months. Pearsons' chi-square-test, correlations, Kruskal-Wallis test and t-test were carried out for statistical analysis. RESULTS: The dominant type of fracture was type II in Spiessl and Schroll classification (50.1%). In the open treated fractures, the most common approach was retromandibular transparotid (91.7%). Post-treatment malocclusion occurred in 18.0% and was significantly increased in bilateral fractures (p = .039), in luxation fractures (p = .016) and in patients with full dentition (p = .004). After open reduction and internal fixation (ORIF), temporary FNP was documented in 7.1% whereas a permanent paresis occurred in 1.7%. FNP was significantly associated with high fractures (p = .001), comminution (p = .028) and increased duration of surgery (p = .040). Parotid complications were significantly associated with revision surgery (p = .009). Post-treatment reduction of MMO mainly occurred in female patients (p < .001) as well as in patients with bilateral fractures (p < .001), high fractures (p = .030) and concomitant mandibular (p = .001) and midfacial fractures (p = .009). CONCLUSION: Malocclusion seems to be the most frequent long-term complication after open reduction and osteosynthesis of extracapsular mandibular condyle fractures. We suggest ORIF by a transparotid approach to be an appropriate treatment with a low complication rate regarding especially FNP for extracapsular fractures of the mandibular condyle.


Assuntos
Traumatismos do Nervo Facial , Má Oclusão , Fraturas Mandibulares , Humanos , Feminino , Côndilo Mandibular/diagnóstico por imagem , Côndilo Mandibular/cirurgia , Estudos Retrospectivos , Traumatismos do Nervo Facial/etiologia , Mandíbula , Fraturas Mandibulares/diagnóstico por imagem , Fraturas Mandibulares/cirurgia , Fixação Interna de Fraturas/efeitos adversos , Má Oclusão/complicações , Resultado do Tratamento
2.
Differentiation ; 114: 20-26, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32473528

RESUMO

Replicative senescence causes a reduced osteogenic differentiation potential of senescent dental follicle cells (DFCs). The transcription factor p53 is often involved in the induction of cellular senescence, but little is known about its role in DFCs. This study examined for the first time the role of p53 compared to its pro-proliferative antagonist E2F-1 in terms of osteogenic differentiation potential and induction of senescence. Protein expression of E2F-1 decreased during cell aging, while p53 was expressed constitutively. Gene silencing of E2F1 (E2F-1) inhibited the proliferation rate of DFCs and increased the induction of cellular senescence. The induction of cellular senescence is regulated independently of the gene expression of TP53 (p53), since its gene expression depends on the expression of E2F1. Moreover, gene silencing of TP53 induced E2F1 gene expression and increased cell proliferation, but did not affect the rate of induction of cellular senescence. TP53 knockdown further induced the alkaline phosphatase and mineralization in DFCs. However, the simultaneous silencing of TP53 and E2F1 did not inhibit the inductive effect of TP53 knockdown on osteogenic differentiation, indicating that this effect is independent of E2F-1. In summary, our results suggest that p53 inhibits osteogenic differentiation and cell proliferation in senescent DFCs, but is not significantly involved in senescence induction.


Assuntos
Diferenciação Celular/genética , Senescência Celular/genética , Saco Dentário/crescimento & desenvolvimento , Fator de Transcrição E2F1/genética , Osteogênese/genética , Proteína Supressora de Tumor p53/genética , Proliferação de Células/genética , Saco Dentário/citologia , Fator de Transcrição E2F1/antagonistas & inibidores , Regulação da Expressão Gênica no Desenvolvimento , Técnicas de Silenciamento de Genes , Inativação Gênica , Humanos
3.
Clin Oral Investig ; 24(9): 3039-3047, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31832793

RESUMO

OBJECTIVES: Definition of implant success is unclear in prosthetic implant-based rehabilitation of head neck cancer patients. MATERIALS AND METHODS: Fifty-two patients with 309 inserted implants were included in this prospective observational study. Implant survival (in situ and loaded) and implant success (modified Albrektsson criteria) at 2-year follow-up were evaluated under the influence of patient- and implant-specific variables. RESULTS: Thirty-nine patients with 234 implants finished the study. Overall implant survival after 2 years was 92.3% (216/234) with an osseointegration rate of 94% (220/234). Implant success was 78.6% (184/234). Main reasons for failure were "bone resorption > 1.7mm" (n = 27, 11.5%) and "implant not in situ or not loaded" (n = 18, 7.7%). Smoking (OR 3.1, p = 0.034), bone grafts (OR 2.4, p = 0.021) and radiation dose > 60 Gy (OR 3.8, p = 0.025) revealed as significant predictors for implant failure. CONCLUSION: Implant survival differs significantly from implant success in head and neck cancer patients. Implant success is mainly determined by radiographic peri-implant bone resorption. CLINICAL RELEVANCE: Dealing with head and neck cancer patients a higher amount of peri-implant bone resorption must be taken into account and warrants for intensified implant monitoring.


Assuntos
Perda do Osso Alveolar , Implantes Dentários , Neoplasias de Cabeça e Pescoço , Implantação Dentária Endóssea , Prótese Dentária Fixada por Implante , Falha de Restauração Dentária , Seguimentos , Neoplasias de Cabeça e Pescoço/reabilitação , Neoplasias de Cabeça e Pescoço/cirurgia , Humanos , Estudos Prospectivos , Resultado do Tratamento
4.
Clin Oral Investig ; 24(10): 3707-3713, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32876748

RESUMO

OBJECTIVES: SARS-CoV-2 is mainly transmitted by inhalation of droplets and aerosols. This puts healthcare professionals from specialties with close patient contact at high risk of nosocomial infections with SARS-CoV-2. In this context, preprocedural mouthrinses with hydrogen peroxide have been recommended before conducting intraoral procedures. Therefore, the aim of this study was to investigate the effects of a 1% hydrogen peroxide mouthrinse on reducing the intraoral SARS-CoV-2 load. METHODS: Twelve out of 98 initially screened hospitalized SARS-CoV-2-positive patients were included in this study. Intraoral viral load was determined by RT-PCR at baseline, whereupon patients had to gargle mouth and throat with 20 mL of 1% hydrogen peroxide for 30 s. After 30 min, a second examination of intraoral viral load was performed by RT-PCR. Furthermore, virus culture was performed for specimens exhibiting viral load of at least 103 RNA copies/mL at baseline. RESULTS: Ten out of the 12 initially included SARS-CoV-2-positive patients completed the study. The hydrogen peroxide mouthrinse led to no significant reduction of intraoral viral load. Replicating virus could only be determined from one baseline specimen. CONCLUSION: A 1% hydrogen peroxide mouthrinse does not reduce the intraoral viral load in SARS-CoV-2-positive subjects. However, virus culture did not yield any indication on the effects of the mouthrinse on the infectivity of the detected RNA copies. CLINICAL RELEVANCE: The recommendation of a preprocedural mouthrinse with hydrogen peroxide before intraoral procedures is questionable and thus should not be supported any longer, but strict infection prevention regimens are of paramount importance. TRIAL REGISTRATION: German Clinical Trials Register (ref. DRKS00022484).


Assuntos
Betacoronavirus , Infecções por Coronavirus , Pandemias , Pneumonia Viral , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19 , Feminino , Humanos , Peróxido de Hidrogênio , Masculino , Pessoa de Meia-Idade , Antissépticos Bucais , Projetos Piloto , Estudos Prospectivos , SARS-CoV-2 , Carga Viral , Adulto Jovem
5.
Mol Cell Biochem ; 455(1-2): 21-28, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30406314

RESUMO

The osteogenic differentiation of dental follicle cells (DFCs) is inhibited by the onset of cellular senescence, but the cause for this is largely unknown. Recently it was shown that WNT5a, which is an inductor of the non-canonical WNT pathway, stimulates both cellular senescence and osteogenic differentiation of different cell types. In this study, we investigated the role of WNT5a for viability and osteogenic differentiation in human DFCs after the induction of cellular senescence. DFCs were cultivated until the induction of cellular senescence. The induction of cellular senescence was confirmed by ß-galactosidase staining, estimation of population doubling time, and slightly telomere length shortening. After induction of cellular senescence, the expression of WNT5A and the potential to induce the osteogenic differentiation decreased. Inhibition of WNT5A by specific siRNAs had significant effect on the viability of DFCs. Cell proliferation was reduced, whereas both cellular senescence and cell death were increased in DFCs. However, an inhibition of WNT5A did only slightly effect the osteogenic differentiation of DFCs. Our results suggest that WNT5A supports viability during both cell proliferation and osteogenic differentiation of DFCs.


Assuntos
Diferenciação Celular , Proliferação de Células , Senescência Celular , Saco Dentário/metabolismo , Osteogênese , Proteína Wnt-5a/metabolismo , Sobrevivência Celular , Saco Dentário/citologia , Humanos
6.
Mol Cell Biochem ; 439(1-2): 45-52, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28770470

RESUMO

Cellular senescence is a restricting factor for regenerative therapies with somatic stem cells. We showed previously that the onset of cellular senescence inhibits the osteogenic differentiation in stem cells of the dental follicle (DFCs), although the mechanism remains elusive. Two different pathways are involved in the induction of the cellular senescence, which are driven either by the cell cycle protein P21 or by the cell cycle protein P16. In this study, we investigated the expression of cell cycle proteins in DFCs after the induction of cellular senescence. The induction of cellular senescence was proved by an increased expression of ß-galactosidase and an increased population doubling time after a prolonged cell culture. Cellular senescence regulated the expression of cell cycle proteins. The expression of cell cycle protein P16 was up-regulated, which correlates with the induction of cellular senescence markers in DFCs. However, the expression of cyclin-dependent kinases (CDK)2 and 4 and the expression of the cell cycle protein P21 were successively decreased in DFCs. In conclusion, our data suggest that a P16-dependent pathway drives the induction of cellular senescence in DFCs.


Assuntos
Senescência Celular , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Saco Dentário/metabolismo , Transdução de Sinais , Células Cultivadas , Quinase 2 Dependente de Ciclina/biossíntese , Quinase 4 Dependente de Ciclina/biossíntese , Inibidor de Quinase Dependente de Ciclina p21/biossíntese , Saco Dentário/citologia , Regulação da Expressão Gênica , Humanos
7.
Clin Oral Implants Res ; 26(7): 831-40, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24713048

RESUMO

OBJECTIVE: The aim of this study was to compare crestal bone-level changes, soft tissue parameters and implant success and survival between small-diameter implants made of titanium/zirconium (TiZr) alloy or of Grade IV titanium (Ti) in edentulous mandibles restored with removable overdentures. MATERIALS AND METHODS: This was a randomized, controlled, double-blind, split-mouth multicenter clinical trial. Patients with edentulous mandibles received two Straumann bone-level implants (diameter 3.3 mm), one of Ti Grade IV (control) and one of TiZr (test), in the interforaminal region. Implants were loaded after 6-8 weeks and removable Locator-retained overdentures were placed within 2 weeks of loading. Modified plaque and sulcus bleeding indices, radiographic bone level, and implant survival and success were evaluated up to 36 months. RESULTS: Of 91 treated patients, 75 completed the three-year follow-up. Three implants were lost (two control and one test implant). The survival rates were 98.7% and 97.3%, and the mean marginal bone level change was -0.78 ± 0.75 and -0.60 ± 0.71 mm for TiZr and Ti Grade IV implants. Most patients had a plaque score of 0 or 1 (54% for test and 51.7% for control), and a sulcus bleeding score of 0 (46.1% for test and 44.9% for control). No significant differences were found between the two implant types for bone-level change, soft tissue parameters, survival and success. CONCLUSIONS: After 36 months, similar outcomes were found between Ti Grade IV and TiZr implants. The results confirm that the results seen at 12 months continue over time.


Assuntos
Implantação Dentária Endóssea/métodos , Implantes Dentários , Mandíbula/cirurgia , Idoso , Ligas Dentárias , Planejamento de Prótese Dentária , Revestimento de Dentadura , Método Duplo-Cego , Feminino , Humanos , Arcada Edêntula/reabilitação , Masculino , Titânio , Resultado do Tratamento , Zircônio
8.
Acta Odontol Scand ; 73(2): 93-100, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25376664

RESUMO

OBJECTIVE: Dental stem cells (SCs) will be increasingly used for bone regeneration in the future. Recently, dental follicle cells (DFCs) from retained human third molars have been isolated and characterized as osteogenic progenitors. Although these results are promising for regenerative dentistry, molecular processes during osteogenic differentiation are not yet well understood. MATERIALS AND METHODS: This study compared DFCs before and during osteogenic differentiation. ALP activity was measured and cells were stained with alizarin red. Real-time RT-PCRs for osteogenic markers were done. The genome-wide expression profile was evaluated using a microarray. RESULTS: DFCs showed strong mineralization and increased expression of osteogenic marker genes during osteogenic differentiation. A microarray analysis showed regulated genes before and in the process of osteogenic differentiation (day 7). Several regulated genes in DFCs were associated with skeletal development. Bioinformatic analysis revealed a number of factors associated with dental follicle osteogenic differentiation. Osteogenic differentiation affected expression levels of the transcriptional regulators FOXC2 and ZNF219. CONCLUSION: In conclusion, the results yielded new objectives for further studies on transcription factors like FOXC2 or ETV1 and their role in dental SCs during osteogenic differentiation.


Assuntos
Saco Dentário/citologia , Perfilação da Expressão Gênica , Células-Tronco/fisiologia , Fosfatase Alcalina/análise , Regeneração Óssea/genética , Calcificação Fisiológica/genética , Cálcio/análise , Técnicas de Cultura de Células , Diferenciação Celular/genética , Proteínas de Ligação a DNA/genética , Fatores de Transcrição Forkhead/genética , Regulação da Expressão Gênica/genética , Marcadores Genéticos/genética , Estudo de Associação Genômica Ampla , Humanos , Análise em Microsséries , Osteogênese/genética , Transcrição Gênica/genética , Dedos de Zinco/genética
9.
Cell Tissue Res ; 357(3): 695-705, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24816988

RESUMO

Dental follicle cells (DFCs) can be artificially differentiated into mineralizing cells. With a dexamethasone-based differentiation protocol, transcription factors ZBTB16 and NR4A3 are highly upregulated but Runx2 and other osteogenic marker genes are not. Previous studies have suggested the involvement of a Runx2-independent differentiation pathway. The objective of this study is to further elucidate this mechanism. Differentiation of DFCs was examined by alkaline phosphatase (ALP) staining and ALP activity measurement, by Alizarin Red S staining and by real-time reverse transcription plus the polymerase chain reaction. ZBTB16 was overexpressed by using a transient transfection method. Resulting genome-wide gene expression changes were assessed by microarray. ZBTB16 and Runx2 were inhibited by short interfering RNA transfection. Promoter binding of ZBTB16 was evaluated by chromatin immunoprecipitation. Downregulation of Runx2 had no effect on dexamethasone-induced differentiation but was effective on BMP2-induced differentiation. Downregulation of ZBTB16, however, impaired dexamethasone-induced differentiation. Genes that were upregulated by dexamethasone induction were also upregulated by ZBTB16 overexpression. Genes that were not upregulated during dexamethasone-induced differentiation were also not regulated by ZBTB16 overexpression. ZBTB16 bound directly to the promoter regions of osterix and NR4A3 but not that of Runx2. Overexpression of ZBTB16 led to changes in the gene expression profile, whereby upregulated genes were overrepresented in osteogenesis-associated biological processes. Our findings suggest that, in DFCs, a Runx2-independent differentiation mechanism exists that is regulated by ZBTB16.


Assuntos
Diferenciação Celular/efeitos dos fármacos , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Saco Dentário/citologia , Saco Dentário/metabolismo , Dexametasona/farmacologia , Fatores de Transcrição Kruppel-Like/metabolismo , Osteogênese/efeitos dos fármacos , Fosfatase Alcalina/metabolismo , Sítios de Ligação , Biomarcadores/metabolismo , Imunoprecipitação da Cromatina , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Saco Dentário/efeitos dos fármacos , Humanos , Fatores de Transcrição Kruppel-Like/antagonistas & inibidores , Fatores de Transcrição Kruppel-Like/genética , Minerais/metabolismo , Regiões Promotoras Genéticas/genética , Proteína com Dedos de Zinco da Leucemia Promielocítica , Ligação Proteica/efeitos dos fármacos , Receptores de Esteroides/genética , Receptores de Esteroides/metabolismo , Receptores dos Hormônios Tireóideos/genética , Receptores dos Hormônios Tireóideos/metabolismo , Fator de Transcrição Sp7 , Fatores de Transcrição/metabolismo , Regulação para Cima/efeitos dos fármacos , Adulto Jovem
10.
Front Oncol ; 14: 1401165, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38933444

RESUMO

Background: The aim of this study was to investigate the effect of antiresorptive agents on the ossification of reconstructed mandibles by free bone grafts for the first time. Methods: A total of 38 reconstructions of the jaw were retrospectively evaluated for ossification between bone segments by two raters based on postoperative panoramic radiographs. The study group (n = 13) had segmental resection of the mandible and free bone flap reconstruction due to medication-related osteonecrosis of the jaw (MRONJ). The control group (noMRONJ, n = 25) comprised segmental mandibular resections and free bone flap reconstructions due to tumors, chronic osteomyelitis, or trauma without any radiation. Ossification time and influencing factors were evaluated. Results: Both duration of surgery (346 ± 90 min. vs. 498 ± 124 min.; p < 0.001) and hospitalization (8.7 ± 2.8 days vs. 13.4 ± 5.3 days, p = 0.006) were shorter in the MRONJ group compared to the noMRONJ group. Ossification after mandibular reconstruction was significantly faster in the MRONJ study group [224 days, interquartile range (IQR) 175-287] compared to the control group (288 days, IQR 194-445; p < 0.001). Moreover, good initial contact between the segments resulted in faster ossification (p < 0.001) in the MRONJ group. Ossification rate between original and grafted bone or between grafted bone segments only did not differ in both the study and control groups (MRONJ, p = 0.705 vs. control, p = 0.292). The type of antiresorptive agent did not show any significance for ossification. The rate of wound healing disturbances did also not differ between the study and control groups (p = 0.69). Conclusion: Advanced MRONJ (stage 3) can be resected and reconstructed safely with free microvascular bone flaps. Antiresorptive agents enhance the ossification of the bone segments. Optimal initial contact of the bone segments accelerates bone healing. Surgery and hospitalization are markedly shortened in this vulnerable group of MRONJ patients compared to oncologic patients.

11.
J Clin Med ; 13(14)2024 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-39064143

RESUMO

Background: The aim of this study was to evaluate the difference between pre- and post-operative radiotherapy on the progress of ossification after free fibula flap reconstruction of the mandible using three-dimensional (3D) analysis. Methods: A total of 38 free fibula reconstructions of the mandible were evaluated retrospectively for ossification between bone segments by measuring Hounsfield Units (HU) in at least two postoperative computer tomography scans (average of 2.4 scans per patient; around the 5th, 12th, 16th, and 19th month postoperative). Three subgroups were created according to the time of irradiation: preoperative radiotherapy (preORT) (n = 11), postoperative radiotherapy (postORT) (n = 16), and patients without any radiation therapy (n = 11) as the control group (noRT). HU in eight regions of interest (ROI) and overlapping surfaces between segments per contact point, as well as influencing factors, were analyzed. Results: The fastest progress in gain of HU ossification with a difference of 0.30 HU/day was observed in noRT compared to preORT (p = 0.002). postORT was -0.24 HU/day slower than preORT (p = 0.005). Original and grafted bone showed a significantly slower HU uptake than between two graft segments with -84.18 HU/day (p < 0.001). Moreover, a larger initial overlapping surface between the segments in cm2 resulted in a higher rise of HU/day (p < 0.001). Conclusions: 3D analysis of post-reconstructive CT scans shows prolonged ossification of mandible reconstructions by free fibula after head and neck radiation. The effect is distinct in cases with post-operative adjuvant radiotherapy. The effects of radiotherapy on ossification may be minimized by a larger initial contact surface and improved operational techniques. Moreover, HU longitudinal measurements and 3D analysis offer new perspectives for clinical evaluation of successful bony healing.

12.
J Clin Med ; 13(5)2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38592235

RESUMO

Background: The aim of this study is to assess patients' subjective perception of treatment outcome after extracapsular fractures of the mandibular condyle. Methods: A questionnaire survey regarding facial nerve palsy (FNP), malocclusion, pain, reduction in maximum mouth opening (MMO) and further discomfort after 3, 6, and 12 months was carried out. Patients aged 18 or more presenting with an extracapsular condylar fracture between 2006 and 2020 were identified by purposive sampling Questionnaires were received from 115 patients. Fractures were classified on the basis of the pre-treatment imaging, the way of treatment was obtained from patients' medical records. Data were analyzed using Pearsons' chi-square-test, descriptive statistics and Student's t-test. Results: 93.0% of the fractures were treated by open reduction and internal fixation (ORIF). MMO reduction was the most common post-treatment complication (55.6%). ORIF was associated with less pain after 3 months (p = 0.048) and lower VAS scores compared to conservative treatment (p = 0.039). Comminuted fractures were more frequently associated with post-treatment malocclusion (p = 0.048), FNP (p = 0.016) and MMO reduction (p = 0.001). Bilateral fractures were significantly accompanied by malocclusion (p = 0.029), MMO reduction (p = 0.038) and pain occurrence (p < 0.001). Conclusions: Patients report less pain after ORIF. Comminuted and bilateral fractures seem to be major risk factors for complications. Subjective perception of complications after extracapsular condylar fractures differs from objectively assessed data.

13.
Differentiation ; 83(1): 10-6, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22099172

RESUMO

Dental follicle is a loose connective tissue that surrounds the developing tooth. Dental follicle cells (DFCs) have a promising potential for tissue engineering applications including periodontal and bone regeneration. However, little is known about the molecular mechanisms underlying osteogenic differentiation. In a previous study we detected that more than 35% of genes that are regulated during osteogenic differentiation of DFCs have promoter binding sites for the transcription factors TP53 and SP1. However, the role of these transcription factors in dental stem cells is still unknown. We hypothesize that both factors influence the processes of cell proliferation and differentiation in dental stem cells. Therefore, we transiently transfected DFCs and dental pulp stem cells (SHED; Stem cells from human exfoliated decidiuous teeth) with expression vectors for these transcription factors. After overexpression of SP1 and TP53, SP1 influenced cell proliferation and TP53 osteogenic differentiation in both dental cell types. The effects on cell proliferation and differentiation were less pronounced after siRNA mediated silencing of TP53 and SP1. This indicates that the effects we observed after TP53 and SP1 overexpression are indirect and subject of complex regulation. Interestingly, upregulated biological processes in DFCs after TP53-overexpression resemble the downregulated biological processes in SHED after SP1-overexpression. Here, regulated processes are involved in cell motility, wound healing and programmed cell death. In conclusion, our study demonstrates that SP1 and TP53 influence cell proliferation and differentiation and similar biological processes in both SHED and DFCs.


Assuntos
Polpa Dentária/citologia , Saco Dentário/citologia , Imunoglobulinas/metabolismo , Células-Tronco/citologia , Proteína Supressora de Tumor p53/metabolismo , Regeneração Óssea , Diferenciação Celular/genética , Proliferação de Células , Células Cultivadas , Polpa Dentária/crescimento & desenvolvimento , Saco Dentário/crescimento & desenvolvimento , Regulação da Expressão Gênica , Inativação Gênica , Humanos , Imunoglobulinas/genética , Osteogênese/genética , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Células-Tronco/metabolismo , Engenharia Tecidual , Esfoliação de Dente/genética , Esfoliação de Dente/metabolismo , Proteína Supressora de Tumor p53/genética
14.
Differentiation ; 84(5): 366-70, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23142732

RESUMO

Stem cell fate can be induced by the grade of stiffness of the extracellular matrix, depending on the developed tissue or complex tissues. For example, a rigid extracellular matrix induces the osteogenic differentiation in bone marrow derived mesenchymal stem cells (MSCs), while a softer surface induces the osteogenic differentiation in dental follicle cells (DFCs). To determine whether differentiation of ectomesenchymal dental precursor cells is supported by similar grades of extracellular matrices (ECMs) stiffness, we examined the influence of the surface stiffness on the proliferation and osteogenic differentiation of stem cells from human exfoliated deciduous teeth (SHED). Cell proliferation of SHED was significantly decreased on cell culture surfaces with a muscle-like stiffness. A dexamethasone-based differentiation medium induced the osteogenic differentiation of SHED on substrates of varying mechanical stiffness. Here, the hardest surface improved the induction of osteogenic differentiation in comparison to that with the softest stiffness. In conclusion, our study showed that the osteogenic differentiation of ectomesenchymal dental precursor cells SHED and DFCs are not supported by similar grades of ECM stiffness.


Assuntos
Diferenciação Celular , Matriz Extracelular/química , Osteogênese , Células-Tronco/citologia , Dente Decíduo/citologia , Linhagem Celular , Saco Dentário/citologia , Dexametasona , Dureza , Humanos
15.
Exp Gerontol ; 172: 112071, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36563529

RESUMO

Dental Follicle Cells (DFCs) are somatic stem cells with a limited lifespan, but little is known about a possible mechanism of cellular senescence. Previous studies have shown that cellular senescence is associated with increased demand of glycolsis or the "glycolytic metabotype", which can be induced by activation of 5' adenosine monophosphate-activated protein kinase (AMPK), and decreased autophagy. This study examined the role of AMPK in inducing senescence in DFCs. During the induction of cellular senescence, AMPK activity was impaired, suggesting a negative impact on senescence induction. In line with this assumption, cellular senescence was induced upon inhibition of AMPK with a specific siRNA. In addition, after this inhibition, autophagy was also inhibited. Moreover, specific inhibition of autophagy promoted cellular senescence. However, inducers of AMPK such as metformin or AICAR surprisingly increased senescence in DFCs. Interestingly, autophagy was impaired after long-term induction of AMPK with AICAR and metformin. Moreover, activation of AMPK induces the consumption of glucose but decreases NAD/NADH ratio in DFCs that suggest not only "glycolytic metabotype" of DFCs but also Mitochondrial Dysfunction Associated Senescence (MiDAS). Both changes are highly associated with the induction of cellular senescence. Hence, both AMPK activation and inhibition promote the induction of cellular senecence of DFCs.


Assuntos
Proteínas Quinases Ativadas por AMP , Metformina , Humanos , Proteínas Quinases Ativadas por AMP/metabolismo , Saco Dentário/metabolismo , Senescência Celular , Metformina/farmacologia , Fosforilação , Autofagia
16.
Arch Oral Biol ; 150: 105676, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36934664

RESUMO

OBJECTIVE: Short telomeres and genomic DNA damage are causes of cellular senescence in dental follicle cells (DFCs). DESIGN: This study examined the role of the DNA damage response (DDR) during cellular senescence of DFCs by ß-galactosidase activity and DNA damage by comet assay. Expression of genes/proteins was determined by Western Blots and reverse transcription-quantitative polymerase chain reaction, while glycolysis was enzymatically estimated. Cell cycle stages and reactive oxygen species (ROS) were investigated by flow cytometry. RESULTS: During the induction of cellular senescence gene expression of DDR genes were down-regulated, while DNA double-strand breaks occurred at the same time. Furthermore, inhibition of DNA protein kinase (DNA-PK) reduced senescence and ROS, both of which are associated with cellular senescence. In contrast, while these data suggest that inhibition of DDR is associated with the induction of cellular senescence, inhibition of DNA-PK did not result in renewal of DFCs, as inhibition resulted in typical features of depleted cells such as increased cell size and reduced cell proliferation rate. DNA-PK repression inhibited both osteogenic differentiation potential and glycolysis, which are typical features of cellular exhaustion. Moreover, DNA-PK affects cellular senescence via activation of AKT1 (protein kinase B). CONCLUSION: Our results suggest that DNA-PK promotes cellular senescence, but DFCs may control the induction of cellular senescence via down-regulation of DDR genes. However, we also showed that inhibition of DNA-PK cannot renew senescent DFCs.


Assuntos
Osteogênese , Proteínas Quinases , Proteínas Quinases/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Polinucleotídeo 5'-Hidroxiquinase/genética , Polinucleotídeo 5'-Hidroxiquinase/metabolismo , Saco Dentário , Senescência Celular , Proteínas/metabolismo , Dano ao DNA , DNA
17.
Oral Maxillofac Surg ; 27(1): 163-168, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35296946

RESUMO

A 50-year-old patient presented with a two-year history of chronic osteomyelitis of the left mandibular body. It was treated by wide segmental resection of the left hemimandible and reconstruction with a free vascularized fibular graft. Six months after surgery, the patient returned with pain, swelling, and moth-like lesions in the transplant in combination with appositional bone formation surrounding the ossified fibular bone. Radiographic and histological examination led to the diagnosis of a recurrent osteomyelitis with proliferative periostitis affecting the resected and reconstructed mandible. Application of ibandronate led to a significant symptom decrease.


Assuntos
Osteomielite , Periostite , Procedimentos de Cirurgia Plástica , Humanos , Periostite/diagnóstico , Periostite/cirurgia , Osteomielite/cirurgia , Mandíbula/cirurgia , Fíbula/transplante , Transplante Ósseo
18.
Biomedicines ; 11(10)2023 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-37893160

RESUMO

When research on osteogenic differentiation in dental follicle cells (DFCs) began, projects focused on bone morphogenetic protein (BMP) signaling. The BMP pathway induces the transcription factor DLX3, whichh in turn induces the BMP signaling pathway via a positive feedback mechanism. However, this BMP2/DLX3 signaling pathway only seems to support the early phase of osteogenic differentiation, since simultaneous induction of BMP2 or DLX3 does not further promote differentiation. Recent data showed that inhibition of classical protein kinase C (PKCs) supports the mineralization of DFCs and that osteogenic differentiation is sensitive to changes in signaling pathways, such as protein kinase B (PKB), also known as AKT. Small changes in the lipidome seem to confirm the participation of AKT and PKC in osteogenic differentiation. In addition, metabolic processes, such as fatty acid biosynthesis, oxidative phosphorylation, or glycolysis, are essential for the osteogenic differentiation of DFCs. This review article attempts not only to bring the various factors into a coherent picture of osteogenic differentiation in DFCs, but also to relate them to recent developments in other types of osteogenic progenitor cells.

19.
J Clin Med ; 12(11)2023 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-37297831

RESUMO

(1) Background: The radial forearm flap (RFF) has evolved as the flap of choice for intraoral mucosal reconstructions, providing thin and pliable skin with a safe blood supply. Perforator flaps such as the anterolateral thigh (ALT) flap are increasingly being discussed for the same applications. (2) Methods: Patient history, treatment details, and outcome of 12 patents with moderate to extended defects of the lip and/or nose area that were reconstructed by a folded radial forearm flap were retrospectively evaluated for oncologic and functional outcomes. (3) Results: The mean oncologic and functional follow-up were 21.1 (min. 3.8; max. 83.3) and 31.2 (min. 6; max. 96) months, respectively. All flaps survived without revision. In eight cases, major lip defects were reconstructed by an RFF; in six patients, the palmaris longus tendon was included for lip suspension. The functional results in terms of eating, drinking, and mouth opening were good in five cases, while three patients were graded as fair due to moderate drooling. In seven cases, the major parts of the nose were reconstructed with two good and five fair (nostril constriction in three cases) functional results. (4) Conclusions: The folded RFF remains a unique free flap option for complex three-dimensional lip and nose reconstructions in terms of flexibility, versatility, and robustness.

20.
Dent J (Basel) ; 11(8)2023 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-37623289

RESUMO

Aim of this study was to demonstrate the diagnostic ability to differentiate odontogenic keratocysts (OKCs) from ameloblastomas (AMs) based on computed tomography (CT) or cone beam computed tomography (CBCT) scans. Preoperative CT and CBCT scans from 2004 to 2019 of OKCs and AMs were analyzed in 51 participants. Lesions were three-dimensionally (3D) assessed and Hounsfield units (HU) as well as gray scale values (GSV) were quantified. Calculated HU spectra were compared within the same imaging modalities using unpaired t-tests and correlated with participants characteristics by calculating Pearsons correlation coefficients. Within the CT scans, AMs had highly significantly higher HU values compared to OKCs (43.52 HU and 19.79 HU, respectively; p < 0.0001). Analogous, within the CBCT scans, AMs had significantly higher GSV compared to OKCs (-413.76 HU and -564.76 HU, respectively; p = 0.0376). These findings were independent from participants' gender and age, anatomical site, and lesion size, indicating that the HU- and GSV-based difference reflects an individual configuration of the lesion. HU and GSV spectra calculated from CT and CBCT scans can be used to discriminate between OKCs and AMs. This diagnostic approach represents a faster and non-invasive option for preoperative diagnosis of such entities and has potential to facilitate therapeutic decision making.

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