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1.
Am J Orthod Dentofacial Orthop ; 165(1): 64-72.e12, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37715755

RESUMO

INTRODUCTION: Little is known about how precisely orthodontists in the United States (US) assess crowding or at what range of crowding they recommend extraction. This study aimed to assess the relationship between estimated crowding in patients with a Class I relationship and extraction recommendation by orthodontists in the US. The secondary aims were to evaluate the accuracy and precision of clinician estimations and determine if clinician background traits play a role in extraction decision-making. METHODS: An electronic survey was prepared using 4 patients with a Class I relationship with anterior crowding selected from a University Orthodontics Clinic and was sent to approximately 10,400 subjects through Facebook and the American Association of Orthodontists Partners in Research program. RESULTS: From the 297 responses received, most clinicians recommended extraction once crowding reached 9-10 mm in either the maxilla or the mandible. The data from 2 patients suggest this decision was more strongly correlated with mandibular crowding. Clinician estimations varied widely but, on average, were precise within approximately 2 mm of objective measurements. There was a tendency to overestimate crowding, especially by Northeastern practitioners. Clinicians who reported routinely measuring crowding or who reported that they recommended extractions to >10% of their patients were 1.2-2.0 and 1.4-1.6 times more likely, respectively, to recommend extraction in the patients. CONCLUSIONS: Crowding estimation was highly subjective and varied widely among clinicians. Most clinicians recommended extraction once maxillary or mandibular crowding approximated 9-10 mm. Some clinician demographics were correlated with the precision and accuracy of estimations and the likelihood of extraction in the patients.


Assuntos
Má Oclusão , Ortodontia , Humanos , Extração Dentária , Má Oclusão/terapia , Assistência Odontológica , Ortodontistas , Mandíbula
2.
Am J Orthod Dentofacial Orthop ; 165(6): 680-688.e4, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38573295

RESUMO

INTRODUCTION: This study used digital intraoral scans to evaluate how clear aligner treatment affects occlusal contacts and to determine the influence of sex and age on contact changes. Results were compared with contact changes that occur during fixed appliance therapy. METHODS: Patients included in this study were treated in a University setting and private practice. Inclusion criteria were a Class I malocclusion treated nonextraction with clear aligners and the presence of pretreatment and posttreatment digital intraoral scans. Scans were imported into specialized software, and occlusal contacts were analyzed. The effects of age and sex on contact changes during clear aligner treatment were determined. Changes in occlusal contacts were compared with changes that occur during nonextraction treatment of patients with a Class I relationship using fixed edgewise appliances. RESULTS: A total of 45 clear aligner patients fit the eligibility criteria. Clear aligner treatment reduced the percentage of tight, near, and approximating contacts, whereas the percentage of open and no contacts increased. These changes in occlusal contacts were greater for the older age group studied. Genderinfluenced occlusal contact changes in the anterior dentition only where the decrease in near contacts and increase in open contacts were greater for males. These results for patients treated with clear aligners were similar to those for patients treated with fixed appliances; both treatment modalities reduced close occlusal contacts at the time active treatment was completed. CONCLUSIONS: These results indicated that when clear aligners or fixed appliances are used to treat a Class I malocclusion, the resulting occlusion immediately after debonding is not as "tight" as it was at pretreatment.


Assuntos
Oclusão Dentária , Má Oclusão Classe I de Angle , Modelos Dentários , Humanos , Masculino , Feminino , Estudos Retrospectivos , Má Oclusão Classe I de Angle/terapia , Adolescente , Adulto , Fatores Etários , Adulto Jovem , Fatores Sexuais , Criança , Aparelhos Ortodônticos Removíveis , Desenho de Aparelho Ortodôntico
3.
Am J Orthod Dentofacial Orthop ; 158(2): 237-246.e4, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32746975

RESUMO

INTRODUCTION: Patients may express views about their orthodontic care by posting publicly available reviews on the Internet. This study analyzed online reviews of orthodontists with an emphasis on the types and frequency of complaints expressed in negative reviews. METHODS: A random sample of 10.6% of the American Association of Orthodontists membership was evaluated to identify members practicing in a North American office that is limited to orthodontics and has an online presence. Information regarding those orthodontists and their offices was collected. For offices with Google and/or Yelp reviews, all negative (1- or 2-star) reviews were saved for content analysis. If an office posted a response to a negative review, those responses were also collected for analysis. RESULTS: Of the 807 eligible orthodontists, 92.4% had reviews on Google and/or Yelp. Average ratings of orthodontists were very positive (ie, 4- and 5-star reviews constituted >97% of Google reviews and >88% of Yelp reviews), yielding an average orthodontist rating of 4.72 on Google and 4.42 on Yelp. However, approximately half of those orthodontists (50.9%) also had at least 1 negative review. The 3 most frequently mentioned categories of complaints were regarding quality of care and/or service, interpersonal interactions, and money and/or financial issues. An analysis of the specific kinds of complaints is described. Orthodontists posting responses to negative reviews had significantly better average ratings than those who did not, but this association does not demonstrate a causal relationship. CONCLUSIONS: Understanding the complaints orthodontic patients express in online reviews may suggest strategies to improve patient satisfaction and an orthodontist's online reputation.


Assuntos
Ortodontia , Ortodontistas , Humanos , Satisfação do Paciente
4.
Am J Orthod Dentofacial Orthop ; 158(6): e121-e136, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33250105

RESUMO

INTRODUCTION: This article evaluates and reports on the satisfaction of adult patients across the United States who received orthodontic treatment for anterior open bite malocclusion. The factors that influence satisfaction are also described. METHODS: Practitioners were recruited from the National Dental Practice-Based Research Network. On joining the Network, practitioner demographics and information on their practices were acquired. Practitioners enrolled their adult patients in active treatment for anterior open bite. Patient demographics, patient dentofacial characteristics, and details regarding previous and current treatment were collected through questionnaires at enrollment (T1). Pretreatment lateral cephalograms and intraoral frontal photographs were submitted. Treatment performed, and details related to treatment outcome were recorded through questionnaires at the end of active treatment (T2). Posttreatment lateral cephalograms and intraoral frontal photographs were submitted. Patient satisfaction at T2 was assessed using a 5-point Likert-type scale and open-ended responses. Predictive univariate models were developed to evaluate the factors that affect patient satisfaction. Open-ended responses were reviewed for general trends. RESULTS: T2 data were received for 260 patients, and 248 of these patients completed and returned the patient satisfaction questionnaires. High levels of satisfaction were found in this sample of adult patients receiving treatment for anterior open bite malocclusion. Specifically, 96% of the sample reported being very or somewhat satisfied. Only 10 patients (4%) were not satisfied with the treatment provided or an element of the final result. Successful open bite closure, treatment modality, and certain patient characteristics may affect patient satisfaction. However, there was insufficient power to demonstrate statistical significance because of the very low number of dissatisfied patients. Open-ended responses directly associated with patient satisfaction were received from 23 patients (9%). They relayed positive, neutral, and negative feelings about the treatment received and final results. Additional responses regarding the orthodontic treatment in general, but not specifically linked to patient satisfaction, were received from 119 patients (48%). These comments depict an overwhelmingly positive experience. CONCLUSIONS: Adult patients who received orthodontic treatment for anterior open bite malocclusion were generally satisfied with the treatment provided, as well as the final esthetic and functional results.


Assuntos
Má Oclusão , Mordida Aberta , Adulto , Estética Dentária , Humanos , Má Oclusão/terapia , Mordida Aberta/terapia , Satisfação do Paciente , Inquéritos e Questionários , Resultado do Tratamento
5.
Am J Orthod Dentofacial Orthop ; 158(6): e137-e150, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33250106

RESUMO

INTRODUCTION: Anterior open bite (AOB) continues to be a challenging malocclusion for orthodontists to treat and retain long-term. There is no consensus on which treatment modality is most successful. This study reports on the overall success rate of AOB orthodontic treatment in the adult population across the United States, as well as 4 major treatment modalities and other factors that may influence treatment success. METHODS: Practitioners and their adult patients with AOB were recruited through the National Dental Practice-Based Research Network. Patient dentofacial and demographic characteristics, practitioner demographic and practice characteristics, and factors relating to orthodontic treatment were reported. Treatment success was determined from posttreatment (T2) lateral cephalometric films and intraoral frontal photographs. Treatment was categorized into 4 main groups: aligners, fixed appliances, temporary anchorage devices (TADs), and orthognathic surgery. Extractions were also evaluated. Bivariate and multivariable models were used to investigate the association between treatment success and treatment modality, pretreatment (T1) dentofacial characteristics, patient and practitioner demographics, and practice characteristics, adjusting for clustering of patients within practice. RESULTS: A total of 254 patients, enrolled by 84 practitioners, contributed to T2 data for this study. There were 29 patients in the aligner group, 152 in fixed appliances, 20 in TADs, and 53 in surgery. A total of 49 patients underwent extractions of teeth other than third molars. Ninety-three percent finished treatment with a positive overbite on the T2 lateral cephalogram, and 84% finished with a positive vertical overlap of all incisors. The small number of aligners and TAD patients limited the ability to compare success rates in these groups. Patients treated with orthognathic surgery had a higher rate of success compared with those treated with fixed appliances only. Treatment success was also associated with academic practice setting, T1 mandibular plane angle ≤30°, no to mild T1 crowding, and treatment duration <30 months. CONCLUSIONS: The overall success of orthodontic treatment in adult patients with AOB who participated in this study was very high. Orthognathic surgery was the only treatment modality that exhibited a statistically higher odds of successful outcomes. Some T1 dentofacial characteristics and treatment factors were associated with the successful closure of AOB.


Assuntos
Má Oclusão Classe II de Angle , Mordida Aberta , Sobremordida , Adulto , Cefalometria , Humanos , Mandíbula , Mordida Aberta/terapia
7.
Am J Orthod Dentofacial Orthop ; 156(6): 727-734, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31784006

RESUMO

INTRODUCTION: Tooth size and morphology of anterior teeth influence interarch relationships. The Bolton analysis uses tooth width to calculate a sum of mandibular to maxillary tooth width ratios necessary for proper occlusion. Several parameters not factored in the Bolton analysis influence occlusion, such as tooth thickness. This study sought to use 3D modeling to develop and assess a tooth size analysis that encompasses labioligual thickness as well as mesiodistal width of anterior teeth. METHODS: The role of tooth thickness in interarch relationships was studied using simulations in a 3D modeling software (Suresmile). To develop a new chart of interarch ratios based on tooth thickness, a series of simulations were produced with varying tooth thicknesses and widths. The new ratios were evaluated on records from 50 patients. RESULTS: Findings from the simulations suggest that the ideal tooth thickness remains approximately 2 mm if the overall tooth width of the dentition increases and the interarch anterior ratio is maintained. The thickness-adjusted anterior mandibular to maxillary tooth ratio ranges from 0.70-0.79 depending on the tooth thickness. This thickness-adjusted ratio provides a superior prediction for the sum of anterior tooth width compared with the Bolton analysis. CONCLUSION: Tooth thickness affects interarch tooth width ratios and anterior occlusion. A thickness-adjusted ratio can be used to more accurately predict anterior tooth dimensions necessary to achieve proper occlusion.


Assuntos
Oclusão Dentária , Maxila , Dente , Humanos , Mandíbula , Odontometria
8.
Am J Orthod Dentofacial Orthop ; 151(4): 691-699.e2, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28364892

RESUMO

INTRODUCTION: Most of the published literature on the management of overbite with the Invisalign appliance (Align Technology, Santa Clara, Calif) consists of case reports and case series. METHODS: In this retrospective study of 120 patients, we sought to assess the nature of overbite changes with the Invisalign appliance. Records were collected from 3 practitioners, all experienced with the Invisalign technique. The patients were consecutively treated adults (>18 years old) who underwent orthodontic treatment only with the Invisalign appliance. Patients with major transverse or anteroposterior changes or extraction treatment plans were excluded. The study sample included 68 patients with normal overbites, 40 with deepbites, and 12 with open bites. Their median age was 33 years, and 70% of the patients were women. RESULTS: Cephalometric analyses indicated that the deepbite patients had a median overbite opening of 1.5 mm, whereas the open bite patients had a median deepening of 1.5 mm. The median change for the normal overbite patients was 0.3 mm. Changes in incisor position were responsible for most of the improvements in the deepbite and open bite groups. Minimal changes in molar vertical position and mandibular plane angle were noted. CONCLUSIONS: The Invisalign appliance appears to manage the vertical dimension relatively well, and the primary mechanism is via incisor movements.


Assuntos
Aparelhos Ortodônticos , Ortodontia Corretiva/métodos , Sobremordida/terapia , Adulto , Cefalometria , Feminino , Humanos , Masculino , Ortodontia Corretiva/instrumentação , Estudos Retrospectivos
10.
Mediators Inflamm ; 2013: 728987, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24068858

RESUMO

Obesity has become a worldwide health burden in the last two decades. Obesity has been associated with increased comorbidities, such as coronary artery disease, diabetes, and destructive periodontal disease. Obesity is also part of a group of risk factors occurring together in an individual, which is referred to as metabolic syndrome. Clinical studies have shown higher risk for destructive periodontal disease in obesity and metabolic syndrome. However, the role of obesity and metabolic syndrome in the onset and development of destructive periodontal disease has not yet been fully understood. In this review, we discuss a working model, which focuses on interorgan inflammation as a common etiological factor for destructive periodontal disease associated with obesity and metabolic syndrome. Specifically, we suggest that elevated levels of tumor necrosis factor- α (TNF- α ) or interleukin 6 (IL-6)--both adipokines and known risk factors for destructive periodontal disease--in obesity and metabolic syndrome contribute to the onset and development of destructive periodontal disease. The connections between destructive periodontal disease and systemic conditions, such as obesity or metabolic syndrome, are complex and potentially multidirectional. This review largely focuses on TNF- α and IL-6, inflammatory mediators, as potential common risk factors and does not exclude other biological mechanisms.


Assuntos
Inflamação/metabolismo , Interleucina-6/metabolismo , Síndrome Metabólica/metabolismo , Obesidade/metabolismo , Doenças Periodontais/complicações , Doenças Periodontais/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Adipocinas/metabolismo , Animais , Comorbidade , Humanos , Síndrome Metabólica/complicações , Obesidade/complicações , Doenças Periodontais/imunologia , Fatores de Risco
12.
J Clin Periodontol ; 36(4): 301-7, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19426176

RESUMO

AIM: To investigate whether adiposity is associated with gingival crevicular fluid (GCF) tumour necrosis factor-alpha (TNF-alpha) levels in children. We also examined whether this relationship is mediated through plasma fasting insulin. MATERIALS AND METHODS: This preliminary study used cross-sectional data from the baseline-visit of the Quebec Adipose and Lifestyle InvesTigation in Youth cohort, which is an ongoing longitudinal study investigating the natural history of obesity in Quebec children. Study participants (76 girls and 102 boys) include children aged 8-10 years and their families, living in the Montreal and Quebec City areas. TNF-alpha level was measured in pooled samples (N=4) for each child by enzyme-linked immunosorbant assay. Height and weight were measured. Body mass index (BMI) was calculated as weight/height(2) (kg/m(2)). Sex/age-specific BMI was categorized into normal (<85th percentile), overweight (85th-95th percentile) and obese (>or=95th percentile) defined by the 2000 US-CDC growth charts. Insulin resistance was measured using fasting plasma insulin in children. Data analysis involved descriptive and multiple linear regression analyses. RESULTS: Our results suggest that obesity in boys was associated with a 37% increase of GCF-TNF-alpha level. However, when accounting for insulin resistance this association was reduced and disappeared while the model's goodness of fit improved. CONCLUSIONS: These findings provide support for the link between adiposity in children and GCF-TNF-alpha level, which appears to be mediated by insulin resistance.


Assuntos
Adiposidade/fisiologia , Líquido do Sulco Gengival/química , Fator de Necrose Tumoral alfa/biossíntese , Índice de Massa Corporal , Criança , Estudos Transversais , Feminino , Humanos , Insulina/sangue , Resistência à Insulina/fisiologia , Modelos Lineares , Masculino , Classe Social , Fator de Necrose Tumoral alfa/análise
13.
Angle Orthod ; 88(6): 675-683, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30207487

RESUMO

OBJECTIVES:: To describe the demographic and practice characteristics of the clinicians enrolled in a large, prospective cohort study examining recommendations and treatment for adult anterior open bite (AOB) and the relationship between these characteristics and practitioners' self-reported treatment preferences. The characteristics of the AOB patients recruited were also described. MATERIALS AND METHODS:: Practitioners were recruited from the National Dental Practice-Based Research Network. Participants in the study consisted of practitioners and their adult AOB patients in active treatment. Upon enrollment, practitioners completed questionnaires enquiring about demographics, treatment preferences for adult AOB patients, and treatment recommendations for each patient. Patients completed questionnaires on demographics and factors related to treatment. RESULTS:: Ninety-one practitioners and 347 patients were recruited. Demographic characteristics of recruited orthodontists were similar to those of American Association of Orthodontists members. The great majority of practitioners reported using fixed appliances and elastics frequently for adult AOB patients. Only a third of practitioners reported using aligners frequently for adult AOB patients, and 10% to 13% frequently recommended temporary anchorage devices (TADs) or orthognathic surgery. Seventy-four percent of the patients were female, and the mean age was 31.4 years. The mean pretreatment overbite was -2.4 mm, and the mean mandibular plane angle was 38.8°. Almost 40% of patients had undergone orthodontic treatment previously. CONCLUSIONS:: This article presents the demographic data for 91 doctors and 347 adult AOB patients, as well as the practitioners' self-reported treatment preferences.


Assuntos
Mordida Aberta/terapia , Ortodontistas/estatística & dados numéricos , Padrões de Prática Odontológica/estatística & dados numéricos , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mordida Aberta/epidemiologia , Estados Unidos/epidemiologia , Adulto Jovem
14.
Angle Orthod ; 87(5): 641-650, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28686094

RESUMO

OBJECTIVE: To determine whether, in Class I borderline cases, experienced orthodontists choose nonextraction treatment more frequently than do orthodontists with less experience. A secondary aim was to evaluate whether clinicians' gender and place of education play a role in extraction decision making. MATERIALS AND METHODS: An online survey was developed using three Class I borderline patient cases. The survey included questions about clinicians' demographics as well as questions about the selected cases. The survey was distributed to approximately 2000 clinicians through the American Association of Orthodontics. RESULTS: Of the 253 responses collected, a trend was observed wherein clinicians with more than 15 years of experience preferred an extraction treatment option more frequently than did clinicians with less than 5 years of experience. There was no association between gender and place of education and the decision to extract in the selected borderline cases. Crowding, patient's profile, and mandibular incisor inclination were among the top three reasons chosen by clinicians for both the extraction and nonextraction treatment decisions. CONCLUSIONS: A trend was observed in which clinicians with more experience chose an extraction treatment option more frequently in borderline cases than did those with less experience. Clinicians' gender did not play a role in extraction decision making.


Assuntos
Tomada de Decisões , Má Oclusão Classe I de Angle/terapia , Ortodontia Corretiva/métodos , Ortodontia , Extração Dentária , Adolescente , Criança , Pré-Escolar , Estética Dentária , Feminino , Humanos , Incisivo , Masculino , Mandíbula , Variações Dependentes do Observador , Sistemas On-Line , Ortodontia/estatística & dados numéricos , Ortodontia Corretiva/estatística & dados numéricos , Ortodontistas/educação , Ortodontistas/psicologia , Projetos Piloto , Padrões de Prática Médica , Fatores Sexuais , Inquéritos e Questionários , Extração Dentária/estatística & dados numéricos , Washington
15.
J Cell Commun Signal ; 9(1): 19-26, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25186349

RESUMO

Diabetes diminishes bone healing and ossification. Reduced bone formation in intramembranous ossification is known, yet the mechanism(s) behind impaired intramembranous bone healing are unclear. Here we report the formation of a fibrotic matrix during healing of intramembranous calvarial bone defects that appears to exclude new bone growth. Our histological analyses of 7-day and 14-day calvaria bone healing tissue in chemically-induced diabetic mice and non-diabetic mice showed the accumulation of a non-mineralized fibrotic matrix, likely as a consequence of unresolved hematomas under diabetic conditions. Elevated mRNA and enzyme activity levels of lysyl oxidase on day 7 in diabetic bone healing tissues also supports that the formation of a fibrotic matrix occurs in these tissues. Based on these findings, we propose that elevated fibroblast proliferation and formation of a non-mineralized fibrotic extracellular matrix in diabetes contributes to deficient intramembranous bone healing in diabetes. A greater understanding of this process has relevance to managing dental procedures in diabetics in which successful outcomes depend on intramembranous bone formation.

16.
Bone ; 58: 33-41, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24120383

RESUMO

Diabetes increases the risk of bone fracture. Organic and inorganic bone extracellular matrix components determine bone strength. Previous studies indicate that in diabetes, glycation of collagen causes abnormal arrangements of collagen molecules and fragile bones. Diabetic bone fragility is additionally attributed to reduced levels of lysyl oxidase enzyme-dependent collagen cross-links. The mechanism underlying the presence of lower enzymatic collagen cross-links in diabetic bone has not been directly investigated. Here we determine in primary osteoblast cultures the regulation of lysyl oxidase protein by type I collagen and collagen modified by carboxymethylation (CML-collagen), a form of advanced glycation endproducts. Data indicate that non-glycated collagen up-regulates lysyl oxidase levels both in primary non-differentiated and in differentiating mouse and rat osteoblast cultures, while CML-collagen fails to regulate lysyl oxidase in these cells. Collagen binding to Discoidin Domain Receptor-2 (DDR2) mediates lysyl oxidase increases, determined in DDR2 shRNA knockdown studies. DDR2 binding and activation were disrupted by collagen glycation, pointing to a mechanism for the diminished levels of lysyl oxidase and consequently low lysyl oxidase-derived cross-links in diabetic bone. Our studies indicate that collagen-integrin interactions may not play a major role in up-regulating lysyl oxidase. Furthermore, non-collagenous ligands for the receptor for advanced glycation end products (RAGE) failed to alter lysyl oxidase levels. Taken together with published studies a new understanding emerges in which diabetes- and age-dependent inhibition of normal collagen-stimulated DDR2- and integrin-signaling, and independent advanced glycation-stimulated RAGE-signaling, each contributes to different aspects of diabetic osteopenia.


Assuntos
Colágeno/farmacologia , Produtos Finais de Glicação Avançada/farmacologia , Osteoblastos/efeitos dos fármacos , Osteoblastos/enzimologia , Proteína-Lisina 6-Oxidase/biossíntese , Receptores Proteína Tirosina Quinases/metabolismo , Receptores Mitogênicos/metabolismo , Animais , Bovinos , Diferenciação Celular/efeitos dos fármacos , Receptores com Domínio Discoidina , Regulação para Baixo/efeitos dos fármacos , Indução Enzimática/efeitos dos fármacos , Integrinas/metabolismo , Ligantes , Camundongos , Ratos , Receptor para Produtos Finais de Glicação Avançada , Receptores Imunológicos/metabolismo , Transdução de Sinais , Regulação para Cima/efeitos dos fármacos
17.
PLoS One ; 9(6): e100669, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24971753

RESUMO

Lysyl oxidase is a multifunctional enzyme required for collagen biosynthesis. Various growth factors regulate lysyl oxidase during osteoblast differentiation, subject to modulation by cytokines such as TNF-α in inflammatory osteopenic disorders including diabetic bone disease. Canonical Wnt signaling promotes osteoblast development. Here we investigated the effect of Wnt3a and TNF-α on lysyl oxidase expression in pluripotent C3H10T1/2 cells, bone marrow stromal cells, and committed osteoblasts. Lysyl oxidase was up-regulated by a transcriptional mechanism 3-fold in C3H10T1/2 cells, and 2.5-fold in bone marrow stromal cells. A putative functional TCF/LEF element was identified in the lysyl oxidase promoter. Interestingly, lysyl oxidase was not up-regulated in committed primary rat calvarial- or MC3T3-E1 osteoblasts. TNF-α down-regulated lysyl oxidase both in Wnt3a-treated and in non-treated C3H10T1/2 cells by a post-transcriptional mechanism mediated by miR203. Non-differentiated cells do not produce a collagen matrix; thus, a novel biological role for lysyl oxidase in pluripotent cells was investigated. Lysyl oxidase shRNAs effectively silenced lysyl oxidase expression, and suppressed the growth of C3H10T1/2 cells by 50%, and blocked osteoblast differentiation. We propose that interference with lysyl oxidase expression under excess inflammatory conditions such as those that occur in diabetes, osteoporosis, or rheumatoid arthritis can result in a diminished pool of pluripotent cells which ultimately contributes to osteopenia.


Assuntos
Doenças Ósseas Metabólicas/enzimologia , Doenças Ósseas Metabólicas/patologia , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/enzimologia , Proteína-Lisina 6-Oxidase/metabolismo , Animais , Sequência de Bases , Doenças Ósseas Metabólicas/epidemiologia , Diferenciação Celular , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Meios de Cultivo Condicionados/farmacologia , Regulação para Baixo/efeitos dos fármacos , Inflamação/patologia , Células-Tronco Mesenquimais/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/genética , MicroRNAs/metabolismo , Dados de Sequência Molecular , Osteoblastos/citologia , Osteoblastos/enzimologia , Osteoblastos/metabolismo , Osteogênese , Proteína-Lisina 6-Oxidase/antagonistas & inibidores , Proteína-Lisina 6-Oxidase/genética , RNA Interferente Pequeno/metabolismo , Ratos , Transdução de Sinais/efeitos dos fármacos , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Fator de Necrose Tumoral alfa/farmacologia , Regulação para Cima/efeitos dos fármacos , Proteína Wnt3A/genética , Proteína Wnt3A/metabolismo , Proteína Wnt3A/farmacologia
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