RESUMO
BACKGROUND: We previously found the conditions of supplementary vibration that accelerated tooth movement and induced bone resorption in an experimental rat tooth movement model. However, the molecular biological mechanisms underlying supplementary vibration-induced orthodontic tooth movement are not fully understood. Transforming growth factor (TGF)-ß upregulates osteoclastogenesis via induction of the receptor activator of nuclear factor kappa B ligand expression, thus TGF-ß is considered an essential cytokine to induce bone resorption. OBJECTIVES: The aim of this study is to examine the role of TGF-ß during the acceleration of orthodontic tooth movement by supplementary vibration. MATERIALS AND METHODS: In experimental tooth movement, 15 g of orthodontic force was loaded onto the maxillary right first molar for 28 days. Supplementary vibration (3 g, 70 Hz) was applied to the maxillary first molar for 3 min on days 0, 7, 14, and 21. TGF-ß receptor inhibitor SB431542 was injected into the submucosal palatal and buccal areas of the maxillary first molars once every other day. The co-culture of RAW264.7 cells and MLO-Y4 cells was used as an in vitro osteoclastogenesis model. RESULTS: SB431542 suppressed the acceleration of tooth movement and the increase in the number of osteoclasts by supplementary vibration in our experimental rat tooth movement model. Immunohistochemical analysis showed supplementary vibration increased the number of TGF-ß1-positive osteocytes in the alveolar bone on the compression side during the experimental tooth movement. Moreover, vibration-upregulated TGF-ß1 in MLO-Y4 cells induced osteoclastogenesis. CONCLUSIONS: Orthodontic tooth movement was accelerated by supplementary vibration through the promotion of the production of TGF-ß1 in osteocytes and subsequent osteoclastogenesis.
Assuntos
Reabsorção Óssea , Técnicas de Movimentação Dentária , Ratos , Animais , Osteócitos/metabolismo , Osteogênese/fisiologia , Fator de Crescimento Transformador beta1/metabolismo , Vibração , Fator de Crescimento Transformador beta/metabolismo , Osteoclastos , Fatores de Crescimento Transformadores/metabolismoRESUMO
OBJECTIVES: The most typical maxillofacial feature of patients with acromegaly is mandibular protrusion. This study aimed to determine differences in maxillofacial morphology between skeletal Class III patients with and without acromegaly using cephalometric analysis. METHODS: Cephalograms of 37 patients with acromegaly (Acro), 37 age-matched non-acromegalic patients with skeletal Class III malocclusion (C-III), and 37 age-matched Class I malocclusion patients (C-I; control) were retrospectively collected. The skeletal and dental morphology of each group was analyzed using cephalometric analysis, which included linear and angular measurements and facial profilograms. In addition, we analyzed diagnostic performance and cutoff values for discriminating acromegaly from skeletal Class III malocclusion using receiver operating characteristic (ROC) curve analysis. RESULTS: The mandibular ramus height was larger in the Acro group than in the other groups. The increase in L1/MP in the Acro group, which represented labial inclination of the mandibular central incisors, was the most characteristic feature in this study. ROC curve analysis indicated that a cutoff value of 88.4° for L1/MP had the highest diagnostic performance in discriminating acromegaly from non-acromegalic Class III malocclusion. CONCLUSIONS: Acromegaly was characterized by a greater degree of bimaxillary prognathism than was non-acromegalic Class III malocclusion. Focusing on labial inclination of the mandibular central incisors would be the most useful way to differentiate acromegaly from non-acromegalic Class III malocclusion.
Assuntos
Acromegalia , Má Oclusão Classe III de Angle , Acromegalia/diagnóstico por imagem , Cefalometria , Humanos , Má Oclusão Classe III de Angle/diagnóstico por imagem , Projetos Piloto , Estudos RetrospectivosRESUMO
In vertebrates, new bone formation via intramembranous osteogenesis is a critical biological event for development, remodeling, and fracture healing of bones. Chemotaxis of osteoblast lineage cells is an essential cellular process in new bone formation. Connective tissue growth factor (CTGF) is known to exert chemotactic properties on various cells; however, details of CTGF function in the chemotaxis of osteoblast lineage cells and underlying molecular biological mechanisms have not been clarified. The aim of the present study was to evaluate the chemotactic properties of CTGF and its underlying mechanisms during active bone formation through intramembranous osteogenesis. In our mouse tensile force-induced bone formation model, preosteoblasts were aggregated at the osteogenic front of calvarial bones. CTGF was expressed at the osteogenic front, and functional inhibition of CTGF using a neutralizing antibody suppressed the aggregation of preosteoblasts. In vitro experiments using µ-slide chemotaxis chambers showed that a gradient of CTGF induced chemotaxis of preosteoblastic MC3T3-E1 cells, while a neutralizing integrin α5 antibody and a Ras inhibitor inhibited the CTGF-induced chemotaxis of MC3T3-E1 cells. These findings suggest that the CTGF-integrin α5-Ras axis is an essential molecular mechanism to promote chemotaxis of preosteoblasts during new bone formation through intramembranous osteogenesis.
Assuntos
Quimiotaxia , Fator de Crescimento do Tecido Conjuntivo/metabolismo , Integrina alfa5/genética , Osteoblastos/metabolismo , Osteogênese/fisiologia , Resistência à Tração , Proteínas ras/genética , Células 3T3 , Animais , Biomarcadores , Osso e Ossos , Diferenciação Celular , Quimiotaxia/efeitos dos fármacos , Quimiotaxia/genética , Fator de Crescimento do Tecido Conjuntivo/farmacologia , Imunofluorescência , Imuno-Histoquímica , Integrina alfa5/metabolismo , Camundongos , Osteoblastos/citologia , Transdução de Sinais , Proteínas ras/metabolismoRESUMO
Tenascin-like molecule major (Ten-m)/odd Oz (Odz), a type II transmembrane molecule, is well known to modulate neural development. We have reported that Ten-m/Odz3 is expressed in cartilaginous tissues and cells. Actin cytoskeleton and its regulator ras homolog gene family member A (RhoA) are closely associated with chondrogenesis. The present study aimed to evaluate the function and molecular mechanism of Ten-m/Odz3 during chondrogenesis, focusing on RhoA and the actin cytoskeleton. Ten-m/Odz3 was expressed in precartilaginous condensing mesenchyme in mouse limb buds. Ten-m/Odz3 knockdown in ATDC5 induced actin cytoskeleton reorganization and change of cell shape through modulation of RhoA activity and FGF2 expression. Ten-m/Odz3 knockdown suppressed ATDC5 migration and expression of genes associated with chondrogenesis, such as Sox9 and type II collagen, via RhoA. On the other hand, Ten-m/Odz3 knockdown inhibited proliferation of ATDC5 in a RhoA-independent manner. These findings suggest that Ten-m/Odz3 plays an important role in early chondrogenesis regulating RhoA-mediated actin reorganization.
Assuntos
Diferenciação Celular , Movimento Celular , Condrócitos/citologia , Condrócitos/metabolismo , Condrogênese , Proteínas de Membrana/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Proteína rhoA de Ligação ao GTP/metabolismo , Citoesqueleto de Actina/efeitos dos fármacos , Citoesqueleto de Actina/metabolismo , Actinas/metabolismo , Animais , Diferenciação Celular/genética , Linhagem Celular , Movimento Celular/genética , Proliferação de Células , Forma Celular , Condrogênese/genética , Fator 2 de Crescimento de Fibroblastos/metabolismo , Regulação da Expressão Gênica , Humanos , Camundongos Endogâmicos C57BLRESUMO
To shorten the duration of orthodontic treatment it is important not only to reduce risks such as dental caries, periodontal disease, and root resorption, but also to decrease pain and discomfort caused by a fixed appliance. Several studies have investigated the effect of vibration applied to fixed appliances to accelerate tooth movement. Although it was reported that vibration accelerates orthodontic tooth movement by enhancing alveolar bone resorption, the underlying cellular and molecular mechanisms remain unclear. In this study, we investigated the effects of vibration on osteoclastogenesis in vitro and in vivo. Vibration applied to pre-osteoclast cell line RAW264.7 cells enhanced cell proliferation but did not affect their differentiation into osteoclasts. Osteocytes in bone are known to be mechanosensitive and to act as receptor activator of nuclear factor kappa B (NF-κB) ligand (RANKL). Therefore, in the present study, vibration was applied to cells from the osteocyte-like cell line MLO-Y4. In MLO-Y4 cells, vibration induced phosphorylation of the inhibitor of NF-κB (IκB) and caused nuclear localization of NF-κB p65. Additionally, vibration increased RANKL mRNA expression, but did not affect osteoprotegerin (OPG) mRNA expression in MLO-Y4 cells, thus resulting in an increased RANKL/OPG ratio. Consistent with these findings, vibration applied during experimental tooth movement increased NF-κB activation and RANKL expression in osteocytes on the compression side of alveolar bone in vivo, whereas vibration had no such effects on the tension side. Furthermore, in a co-culture of MLO-Y4 cells and RAW264.7 cells, vibration applied to MLO-Y4 cells enhanced osteoclastogenesis. These findings suggest that vibration could accelerate orthodontic tooth movement by enhancing osteoclastogenesis through increasing the number of pre-osteoclasts and up-regulating RANKL expression in osteocytes on the compression side of alveolar bone via NF-κB activation.
Assuntos
NF-kappa B/metabolismo , Osteócitos/metabolismo , Osteogênese/fisiologia , Ligante RANK/biossíntese , Transdução de Sinais/fisiologia , Vibração , Processo Alveolar/metabolismo , Animais , Técnicas de Cocultura , Expressão Gênica , Masculino , Camundongos , Osteoclastos/metabolismo , Ligante RANK/genética , Células RAW 264.7 , Ratos , Ratos WistarRESUMO
Several recent prospective clinical trials have investigated the effect of supplementary vibration applied with fixed appliances in an attempt to accelerate tooth movement and shorten the duration of orthodontic treatment. Among them, some studies reported an increase in the rate of tooth movement, but others did not. This technique is still controversial, and the underlying cellular and molecular mechanisms remain unclear. In the present study, we developed a new vibration device for a tooth movement model in rats, and investigated the efficacy and safety of the device when used with fixed appliances. The most effective level of supplementary vibration to accelerate tooth movement stimulated by a continuous static force was 3 gf at 70 Hz for 3 minutes once a week. Furthermore, at this optimum-magnitude, high-frequency vibration could synergistically enhance osteoclastogenesis and osteoclast function via NF-κB activation, leading to alveolar bone resorption and finally, accelerated tooth movement, but only when a static force was continuously applied to the teeth. These findings contribute to a better understanding of the mechanism by which optimum-magnitude high-frequency vibration accelerates tooth movement, and may lead to novel approaches for the safe and effective treatment of malocclusion.
Assuntos
Aceleração , Osteoclastos/citologia , Eletricidade Estática , Estresse Mecânico , Técnicas de Movimentação Dentária/instrumentação , Técnicas de Movimentação Dentária/métodos , Vibração , Animais , Fenômenos Biomecânicos , Masculino , Osteogênese , Ligamento Periodontal/citologia , Ratos , Ratos WistarRESUMO
Sutures are fibrous tissues that connect bones in craniofacial skeletal complexes. Cranio- and dentofacial skeletal deformities in infant and adolescent patients can be treated by applying tensile force to sutures to induce sutural bone formation. The early gene expression induced by mechanical stress is essential for bone formation in long bones; however, early gene expression during sutural bone formation induced by tensile force is poorly characterized. In vivo studies are essential to evaluate molecular responses to mechanical stresses in heterogeneous cell populations, such as sutures. In this paper we examined in vivo early gene expression and the underlying regulatory mechanism for this expression in tensile-force-applied cranial sutures, focusing on genes involved in vascularization. Tensile force upregulated expression of vascular factors, such as vascular endothelial growth factor (Vegf) and endothelial cell markers, in sutures within 3 h. The expression of connective tissue growth factor (Ctgf) and Rho-associated coiled-coil containing protein kinase 2 (Rock2) was also upregulated by tensile force. A CTGF-neutralizing antibody and the ROCK inhibitor, Y-27632, abolished tensile-force-induced Vegf expression. Moreover, tensile force activated extracellular signal-related kinase 1/2 (ERK1/2) signaling in sagittal sutures, and the ERK1/2 inhibitor, U0126, partially inhibited tensile-force-induced Ctgf expression. These results indicate that tensile force induces in vivo gene expression associated with vascularization early in tensile-force-induced sutural bone formation. Moreover, the early induction of Vegf gene expression is regulated by CTGF and ROCK2.
Assuntos
Suturas Cranianas , Regulação da Expressão Gênica/fisiologia , Sistema de Sinalização das MAP Quinases/fisiologia , Neovascularização Fisiológica/fisiologia , Resistência à Tração/fisiologia , Fator A de Crescimento do Endotélio Vascular/biossíntese , Adolescente , Animais , Fator de Crescimento do Tecido Conjuntivo/metabolismo , Suturas Cranianas/irrigação sanguínea , Suturas Cranianas/metabolismo , Humanos , Lactente , Masculino , Camundongos , Camundongos Endogâmicos ICR , Estresse Mecânico , Quinases Associadas a rho/metabolismoRESUMO
This is a case report about the successful orthodontic treatment of a bilateral cleft lip and palate patient by using a combination of bone grafting and subsequent prosthodontic rehabilitation. An adult patient with a bilateral cleft lip and palate presented with a concave profile, anterior and lateral crossbite, a markedly deep overbite, and residual bilateral alveolar clefts. His jaw movement patterns were unstable and irregular due to his collapsed bite. Orthodontic treatment with bilateral bone grafting improved his concave profile by downward and backward rotation of the mandible within the freeway space, and optimum occlusion and functionally stable and smooth jaw movements were obtained. After a 6-year retention period, no skeletal relapse could be detected, and his occlusal stability was satisfactory.
Assuntos
Transplante Ósseo , Fenda Labial/terapia , Fissura Palatina/terapia , Má Oclusão Classe II de Angle/terapia , Ortodontia Corretiva/métodos , Procedimentos de Cirurgia Plástica , Adulto , Anodontia/diagnóstico por imagem , Anodontia/terapia , Cefalometria , Fenda Labial/diagnóstico por imagem , Fissura Palatina/diagnóstico por imagem , Terapia Combinada , Humanos , Masculino , Má Oclusão Classe II de Angle/diagnóstico por imagem , Modelos Dentários , Radiografia PanorâmicaAssuntos
Dermatite Atópica/epidemiologia , Adulto , Distribuição por Idade , Idoso , Povo Asiático/genética , Dermatite Atópica/etiologia , Dermatite Atópica/genética , Dermatite Atópica/patologia , Feminino , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Exame Físico , Prevalência , Índice de Gravidade de DoençaRESUMO
Necrolytic migratory erythema (NME) is an uncommon inflammatory dermatosis with a distinctive clinical and histological appearance. It shows irregular erythema, bullae, erosion, crusts and pigmentation. While it is typically associated with glucagonoma, some cases of NME without glucagonoma have been reported. Herein, we report a case of necrolytic migratory erythema associated with malabsorption 30 years after ileocolectomy. She presented erosive erythema with scale or partly flaccid bullae on her intergluteal cleft, buttock and extremities. Her laboratory data revealed essential amino acid deficiency and a slightly decreased serum zinc level, while her plasma glucagon level was low. With diagnosis of non-glucagonoma-associated NME with malabsorption due to short-bowel syndrome, she was treated and improved by i.v. amino acid supplement. Histological findings of NME include necrotic changes of keratinocytes in the upper epidermis, proliferation of those in the lower epidermis and inflammatory cell infiltration of upper dermis. We also examined the expression pattern of epidermal keratins (K6, K10) and Ki-67, one of the markers of proliferative activity, to assess the proliferation and differentiation of keratinocytes in a NME lesion by immunostaining. The findings with these immunostainings support the characteristics of HE-staining, and suggest hyponutrition may induce changing differentiation/proliferation of keratinocytes.
Assuntos
Eritema/etiologia , Síndrome do Intestino Curto/complicações , Diferenciação Celular , Proliferação de Células , Eritema/patologia , Feminino , Humanos , Queratinócitos/patologia , Queratinócitos/fisiologia , Queratinas/metabolismo , Pessoa de Meia-IdadeRESUMO
Both CCL27 and CCL28 are ligands for CCR10 and attract CCR10(+) lymphocytes. We previously demonstrated that CCL27 and CCL28 were strongly expressed in sera and lesional keratinocytes of patients with atopic dermatitis and psoriasis vulgaris. However, the regulation of CCL27 and CCL28 production in keratinocytes has not been well documented. In this study, we showed that CCL27 and CCL28 expression and production by a human keratinocyte cell line, HaCaT cells, were strongly induced by inflammatory cytokines tumor necrosis factor-alpha and interleukin-1beta. CCL27 production was downregulated by inhibitors of p38 mitogen-activated protein kinase and nuclear factor-kappa B (NF-kappaB). By contrast, CCL28 production was downregulated by inhibitors of extracellular signal-regulated kinase and NF-kappaB. Our study results suggest that CCL28 produced by keratinocytes is mediated by different signal pathways from CCL27 and that both CCL27 and CCL28 are involved in the pathogenesis of inflammatory skin diseases.