RESUMEN
INTRODUCTION: Drugs that block the renin-angiotensin system (RAS) are widely used for treating hypertension, heart and kidney failure, and the harmful effects of diabetes. Components of the RAS have been identified in various organs, but little is known of their effects on bone remodeling. The aim of this study was to evaluate whether the blockage of the RAS influences strain-induced bone remodeling in a model of orthodontic tooth movement. METHODS: An orthodontic appliance was placed in C57BL6/J mice that were randomly divided into 2 groups: vehicle-treated mice (VH) and mice treated with losartan (an angiotensin II receptor blocker). Orthodontic tooth movement and the number of tartrate-resistant acid phosphatase-positive cells were determined by histopathologic analysis. The expression of mediators involved in bone remodeling was evaluated by quantitative real-time polymerase chain reaction. Blood pressure was measured before and during the experimental period. RESULTS: Orthodontic tooth movement and tartrate-resistant acid phosphatase-positive cells were significantly reduced in the losartan group compared with the VH group. mRNA levels of osteoclast markers (RANK, RANKL, cathepsin K, and metalloproteinase 13) were lower in the losartan mice than in the VH group, whereas the expressions of osteoblast markers and negative regulators of bone resorption (periostin, dentin matrix protein, alkaline phosphatase, collagen 1A1, semaphorin 3A3, metalloproteinase 2, and osteoprotegerin) were higher in the VH group. CONCLUSIONS: Blockage of the RAS system decreases osteoclast differentiation and activity and, consequently, results in decreased strain-induced bone remodeling in orthodontic tooth movement.
Asunto(s)
Antagonistas de Receptores de Angiotensina/farmacología , Remodelación Ósea/efectos de los fármacos , Losartán/farmacología , Maxilar/efectos de los fármacos , Técnicas de Movimiento Dental/métodos , Fosfatasa Ácida/análisis , Fosfatasa Alcalina/análisis , Animales , Presión Sanguínea/efectos de los fármacos , Catepsina K/análisis , Moléculas de Adhesión Celular/análisis , Colágeno Tipo I/análisis , Cadena alfa 1 del Colágeno Tipo I , Proteínas de la Matriz Extracelular/análisis , Isoenzimas/análisis , Masculino , Metaloproteinasa 13 de la Matriz/análisis , Metaloproteinasa 2 de la Matriz/análisis , Ratones , Ratones Endogámicos C57BL , Modelos Animales , Osteoblastos/efectos de los fármacos , Osteoclastos/efectos de los fármacos , Osteoprotegerina/análisis , Ligando RANK/análisis , Distribución Aleatoria , Receptor Activador del Factor Nuclear kappa-B/análisis , Semaforina-3A/análisis , Fosfatasa Ácida Tartratorresistente , Técnicas de Movimiento Dental/instrumentaciónRESUMEN
During orthodontic tooth movement (OTM), alveolar bone is resorbed by osteoclasts in compression sites (CS) and is deposited by osteoblasts in tension sites (TS). The aim of this study was to develop a standardized OTM protocol in mice and to investigate the expression of bone resorption and deposition markers in CS and TS. An orthodontic appliance was placed in C57BL6/J mice. To define the ideal orthodontic force, the molars of the mice were subjected to forces of 0.1N, 0.25 N, 0.35 N and 0.5 N. The expression of mediators that are involved in bone remodeling at CS and TS was analyzed using a Real-Time PCR. The data revealed that a force of 0.35 N promoted optimal OTM and osteoclast recruitment without root resorption. The levels of TNF-α, RANKL, MMP13 and OPG were all altered in CS and TS. Whereas TNF-α and Cathepsin K exhibited elevated levels in CS, RUNX2 and OCN levels were higher in TS. Our results suggest that 0.35 N is the ideal force for OTM in mice and has no side effects. Moreover, the expression of bone remodeling markers differed between the compression and the tension areas, potentially explaining the distinct cellular migration and differentiation patterns in each of these sites.
Asunto(s)
Remodelación Ósea/fisiología , Estrés Mecánico , Técnicas de Movimiento Dental , Animales , Catepsina K/genética , Subunidad alfa 1 del Factor de Unión al Sitio Principal/genética , Interleucina-10/genética , Metaloproteinasa 13 de la Matriz/genética , Ratones , Ratones Endogámicos C57BL , Osteocalcina/genética , Osteoprotegerina/genética , Ligando RANK/genética , ARN Mensajero/metabolismo , Receptor Activador del Factor Nuclear kappa-B/genética , Factor de Necrosis Tumoral alfa/genéticaRESUMEN
INTRODUCTION: Cytokines and chemokines regulate bone remodeling during orthodontic tooth movement. CC chemokine ligand 2 (CCL2) is involved in osteoclast recruitment and activity, and its expression is increased in periodontal tissues under mechanical loading. In this study, we investigated whether the CC chemokine receptor 2 (CCR2)-CCL2 axis influences orthodontic tooth movement. METHODS: A coil spring was placed in CCR2-deficient (CCR2(-/-)), wild-type, vehicle-treated, and P8A-treated (CCL2 analog) mice. In a histopathologic analysis, the amounts of orthodontic tooth movement and numbers of osteoclasts were determined. The expression of mediators involved in bone remodeling was evaluated by real-time polymerase chain reaction. RESULTS: Orthodontic tooth movement and the number of TRAP-positive cells were significantly decreased in CCR2(-/-) and P8A-treated mice in relation to wild-type and vehicle-treated mice, respectively. The expressions of RANKL, RANK, and osteoblasts markers (COL-1 and OCN) were lower in CCR2(-/-) than in wild-type mice. No significant difference was found in osteoprotegerin levels between the groups. CONCLUSIONS: These data suggested a reduction of osteoclast and osteoblast activities in the absence of CCR2. The CCR2-CCL2 axis is positively associated with osteoclast recruitment, bone resorption, and orthodontic tooth movement. Therefore, blockage of the CCR2-CCL2 axis might be used in the future for modulating the extent of orthodontic tooth movement.
Asunto(s)
Receptores CCR2/fisiología , Técnicas de Movimiento Dental , Fosfatasa Ácida/análisis , Animales , Biomarcadores/análisis , Remodelación Ósea/fisiología , Resorción Ósea/patología , Recuento de Células , Quimiocina CCL2/fisiología , Quimiotaxis de Leucocito/fisiología , Colágeno Tipo I/análisis , Isoenzimas/análisis , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos , Ratones Noqueados , Alambres para Ortodoncia , Osteoblastos/patología , Osteocalcina/análisis , Osteoclastos/patología , Osteoprotegerina/análisis , Ligando RANK/análisis , Receptor Activador del Factor Nuclear kappa-B/análisis , Fosfatasa Ácida Tartratorresistente , Técnicas de Movimiento Dental/instrumentaciónRESUMEN
OBJECTIVE: Orthodontic tooth movement (OTM) is achieved by alveolar bone remodelling induced by mechanical loading. Whilst interleukin-1 (IL-1) is directly involved in OTM, the role of interleukin-1 receptor antagonist (IL-1Ra), a naturally occurring IL-1 antagonist, is not completely defined. Therefore, the aim of this study was to investigate the effects of IL-1Ra on OTM. METHODS: An orthodontic appliance was placed in C57BL6 mice treated with vehicle or IL-1Ra (10 mg/kg/day). OTM and TRAP-positive osteoclasts were evaluated after 12 days of mechanical loading and the levels of cytokines on periodontal tissues were analysed by ELISA after 12 and 72 h. RESULTS: Mice treated with IL-1Ra showed diminished OTM and decreased numbers of TRAP-positive osteoclasts. In line with this, lower levels of IL-1ß and TNF-α, and higher levels of IL-10, were observed on periodontal tissues of IL-1Ra-treated mice in relation to the vehicle-treated group. CONCLUSION: The present study suggests that IL-1Ra downregulates OTM, probably by its anti-inflammatory actions.
Asunto(s)
Proteína Antagonista del Receptor de Interleucina 1/farmacología , Técnicas de Movimiento Dental , Análisis de Varianza , Animales , Citocinas/metabolismo , Regulación hacia Abajo , Ensayo de Inmunoadsorción Enzimática , Ratones , Ratones Endogámicos C57BL , Aparatos Ortodóncicos , Distribución AleatoriaRESUMEN
O perfil dos pacientes que procuram tratamento ortodôntico mudou nas últimas décadas. O número de pacientes adultos e idosos do sexo feminino cresceu consideravelmente. Esta mudança na demanda trouxe desafios biológicos para o atendimento ortodôntico, por muitas vezes tratarem-se de pacientes com alterações sistêmicas ou sob uso de medicamentos controlados. Dentre estes, podese citar a deficiência de estrógeno e a osteoporose, comuns nessa faixa etária, e que podem interferir na movimentação dentária ortodôntica (MDO). Esta revisão de literatura se propõe a descrever os aspectos biológicos da movimentação ortodôntica e a identificar como a deficiência de estrógeno e a osteoporose podem interferir na remodelação óssea e, consequentemente, na MDO. Este artigo objetiva ainda alertar o ortodontista da importância de se avaliar cuidadosamente a condição sistêmica dos pacientes com possível deficiência de estrógeno/osteoporose, para um correto diagnóstico e elaboração do plano de tratamento.
An increasing number of adult patients are seeking for orthodontic treatment in the last decades, especially postmenopausal women. This represents a biological challenge for the orthodontic treatment, since these patients more often present systemic disorders or are routinely using controlling medication. Among them, estrogen deficiency and osteoporosis are commonly reported in elderly women. This review article elucidates the biological aspects of orthodontic tooth movement, emphasizing how the estrogen deficiency may interfere with this process. This literature review suggests that estrogen deficiency and the use of drugs for osteoporosis treatment may alter the bone remodeling and, consequently, the orthodontic tooth movement. The orthodontist must be aware of the patients systemic condition to better elaborate the correct treatment plan.