Bundling of collagen fibrils influences osteocyte network formation during bone modeling.

Osteocytes form a cellular network by gap junctions between their cell processes. This network is important since intercellular communication via the network is essential for bone metabolism. However, the factors that influence the formation of this osteocyte network remain unknown. As the early stage of osteocyte network formation occurs on the bone surface, we observed a newly formed trabecular bone surface by orthogonal focused ion beam-scanning electron microscopy. The embedding late osteoblast processes tended to avoid bundled collagen fibrils and elongate into sparse collagen fibrils. Then, we examined whether the inhibition of bundling of collagen fibrils using a potent lysyl oxidase inhibitor, ß-aminopropionitrile (BAPN) changed the cellular network of the chick calvaria. The osteocyte shape of the control group was spindle-shape, while that of the BAPN group was sphere-shaped. In addition, the osteocyte processes of the control group were elongated vertically to the long axis of the cell body, whereas the osteocyte processes of the BAPN group were elongated radially. Therefore, it was suggested that the bundling of collagen fibrils influences normal osteocyte network formation during bone modeling.

Age-related changes in the effect of rapid maxillary expansion on the position of labially impacted maxillary canines: A case-control study.

INTRODUCTION: The early diagnosis and interception of potential maxillary canine impaction is the most desirable approach for correcting their path of eruption. However, there is still a lack of evidence regarding the effect of rapid maxillary expansion (RME) on labially impacted canines. This study aimed to investigate the age-related effect of RME on labially impacted maxillary canines in order to reduce the risk of their impaction in the mixed dentition and to examine the proper timing of interceptive treatment. METHODS: All patients aged 7-10 years were treated with an RME appliance using the same protocol. The distance to the occlusal plane, axis to the midline, and distribution in different sectors-depending on the patients' age-were evaluated for maxillary canines before and after treatment on panoramic radiographs in order to detect changes in the position of the impacted canines. These geometric measurements in the impacted canines were also validated by observing the nontreated canines at each age. RESULTS: Significant differences existed between the impacted canines and the erupted canines in all 3 categories in all age groups. RME treatment modulated the position of the impacted canines in all age groups. Interestingly, a statistically significant difference before and after RME in all categories was detected in patients aged <8 years. A discriminant analysis also showed a positive association of RME treatment with the risk of labially impacted canines. The standardized regression coefficients showed that the angulation of the maxillary canine was the most important predictor for impaction. CONCLUSIONS: Our findings indicate that RME treatment in the early mixed dentition was effective for managing labially impacted maxillary canines. An age of 7-8 years with early mixed dentition might be the most appropriate timing for therapeutic intervention on the basis of RME treatment for buccal canine impaction.

Changes in the intra- and peri-cellular sclerostin distribution in lacuno-canalicular system induced by mechanical unloading.

INTRODUCTION: Mechanical stimuli regulate Sclerostin (Scl), a negative regulator of bone formation, expression in osteocytes. However, the detailed Scl distribution in osteocytes in response to mechanical unloading remains unclear. MATERIALS AND METHODS: Twelve-week-old male rats were used. The sciatic and femoral nerves on the right side were excised as mechanical unloading treatment. A sham operation was performed on the left side. One week after neurotrauma, the bone density of the femora was evaluated by peripheral quantitative computed tomography, and immunofluorescence was performed in coronal sections of the femoral diaphysis. The mean fluorescence intensity and fluorescent profile of Scl from the marrow to the periosteal side were analyzed to estimate the Scl expression and determine to which side (marrow or periosteal) the Scl prefers to distribute in response to mechanical unloading. The most sensitive region indicated by the immunofluorescence results was further investigated by transmission electron microscopy (TEM) with immunogold staining to show the Scl expression changes in different subcellular structures. RESULTS: In femur distal metaphysis, neurotrauma-induced mechanical unloading significantly decreased the bone density, made the distribution of Scl closer to the marrow on the anterior and medial side, and increased the Scl expression only on the lateral side. TEM findings showed that only the expression of Scl in canaliculi was increased by mechanical unloading. CONCLUSIONS: Our results showed that even short-term mechanical unloading is enough to decrease bone density, and mechanical unloading not only regulated the Scl expression but also changed the Scl distribution in both the osteocyte network and subcellular structures.

The Analysis of Gap Junctional Intercellular Communication Among Osteocytes in Chick Calvariae by Fluorescence Recovery After Photobleaching.

This chapter describes the use of fluorescence recovery after photobleaching (FRAP) for analyzing gap junctional intercellular communication (GJIC) among osteocytes in chick calvariae by confocal laser scanning microscope.

Loading history changes the morphology and compressive force-induced expression of receptor activator of nuclear factor kappa B ligand/osteoprotegerin in MLO-Y4 osteocytes.

BACKGROUND: In this study, we investigated the effect of the mechanical loading history on the expression of receptor activator of nuclear factor kappa B ligand (RANKL) and osteoprotegerin (OPG) in MLO-Y4 osteocyte-like cells. METHODS: Three hours after MLO-Y4 osteocytes were seeded, a continuous compressive force (CCF) of 31 dynes/cm2 with or without additional CCF (32 dynes/cm2) was loaded onto the osteocytes. After 36 h, the additional CCF (loading history) was removed for a recovery period of 10 h. The expression of RANKL, OPG, RANKL/OPG ratio, cell numbers, viability and morphology were time-dependently examined at 0, 3, 6 and 10 h. Then, the same additional CCF was applied again for 1 h to all osteocytes with or without the gap junction inhibitor to examine the expression of RANKL, OPG, the RANKL/OPG ratio and other genes that essential to characterize the phenotype of MLO-Y4 cells. Fluorescence recovery after photobleaching technique was also applied to test the differences of gap-junctional intercellular communications (GJIC) among MLO-Y4 cells. RESULTS: The expression of RANKL and OPG by MLO-Y4 osteocytes without a loading history was dramatically decreased and increased, respectively, in response to the 1-h loading of additional weight. However, the expression of RANKL, OPG and the RANKL/OPG ratio were maintained at the same level as in the control group in the MLO-Y4 osteocytes with a loading history but without gap junction inhibitor treatment. Treatment of loading history significantly changed the capacity of GJIC and protein expression of connexin 43 (Cx43) but not the mRNA expression of Cx43. No significant difference was observed in the cell number or viability between the MLO-Y4 osteocyte-like cells with and without a loading history or among different time checkpoints during the recovery period. The cell morphology showed significant changes and was correlated with the expression of OPG, Gja1 and Dmp1 during the recovery period. CONCLUSION: Our findings indicated that the compressive force-induced changes in the RANKL/OPG expression could be habituated within at least 11 h by 36-h CCF exposure. GJIC and cell morphology may play roles in response to loading history in MLO-Y4 osteocyte-like cells.

The expression and regulation of Wnt1 in tooth movement-initiated mechanotransduction.

INTRODUCTION: The Wnt signaling pathway acts as a key regulator of skeletal development and its homeostasis. However, the potential role of Wnt1 in the mechanotransduction machinery of orthodontic tooth movement-initiated bone remodeling is still unclear. Hence, this study focused on the regulatory dynamics of the Wnt1 expression in both the periodontal ligament (PDL) and osteocytes in vivo and in vitro. METHODS: The Wnt1 expression in the orthodontically moved maxillary first molar in mice was assessed at 0, 1, and 5 days, on both the compression and tension sides. Primary isolated human PDL (hPDL) fibroblasts, as well as murine long-bone osteocyte-Y4 (MLO-Y4) cells, were exposed to continuous compressive force and static tensile force. RESULTS: The relative quantification of immunodetection showed that orthodontic tooth movement significantly stimulated the Wnt1 expression in both the PDL and alveolar osteocytes on the tension side on day 5, whereas the expression on the compression side did not change. This increase in the Wnt1 expression, shown in vivo, was also noted after the application of 12% static tensile force in isolated hPDL fibroblasts and 20% in MLO-Y4 cells. In contrast, a compressive force led to the attenuation of the Wnt1 gene expression in both hPDL fibroblasts and MLO-Y4 cells in a force-dependent manner. In the osteocyte-PDL coculture system, recombinant sclerostin attenuated Wnt1 in PDL, whereas the antisclerostin antibody upregulated its gene expression, indicating that mechanically-driven Wnt1 signaling in PDL might be regulated by osteocytic sclerostin. CONCLUSIONS: Our findings provide that Wnt1 signaling plays a vital role in tooth movement-initiated bone remodeling via innovative mechanotransduction approaches.

Comprehensive approach to simultaneous molar intrusion and canine retraction in the treatment of Class II anterior open bite using miniscrew anchorage.

INTRODUCTION: Anterior open bite is one of the most difficult malocclusions to correct in orthodontic treatment. Molar intrusion using miniscrew anchorage has been developed as a new strategy for open bite correction; however, this procedure still has an important concern about prolonged treatment duration in the patient with anteroposterior discrepancy due to the separate step-by-step movement of anterior and posterior teeth. OBJECTIVE: This article illustrates a comprehensive orthodontic approach for dentoalveolar open bite correction of an adult patient, by using miniscrew. CASE REPORT: A woman 19 years and 5 months of age had chief complaints of difficulty chewing with the anterior teeth and maxillary incisor protrusion. An open bite of -2.0 mm caused by slight elongation of the maxillary molars was found. The patient was diagnosed with Angle Class II malocclusion with anterior open bite due to the vertical elongation of maxillary molars. After extraction of the maxillary first premolars, concurrent movements of molar intrusion and canine retraction were initiated with the combined use of sectional archwires, elastic chains and miniscrews. RESULTS: At 4 months after the procedure, positive overbite was achieved subsequent to the intrusion of maxillary molars by 1.5 mm and without undesirable side effects. Class I canine relation was also achieved at the same time. The total active treatment period was 21 months. The resultant occlusion and satisfactory facial profile were maintained after 54 months of retention. CONCLUSION: The presented treatment shows the potential to shorten the treatment duration and to contribute to the long-term stability for open bite correction.

Occlusal reconstruction of a patient with ameloblastoma ablation using alveolar distraction osteogenesis: a case report.

BACKGROUND: Ameloblastoma is one of the most common benign odontogenic neoplasms. Its surgical excision has the potential to lead to postoperative malocclusion. In this case report, we describe the successful interdisciplinary orthodontic treatment of a patient with ameloblastoma who underwent marginal mandibulectomy. CASE PRESENTATION: A woman of 20-year-old was diagnosed with ameloblastoma, and underwent marginal mandibulectomy when she was 8 years of age. She had an excessive overjet (11.5 mm) and a mild open bite (- 1.5 mm) with a severely resorbed atrophic edentulous ridge in the area around the mandibular left lateral incisor, canine and first premolar. An alveolar bone defect associated with tumor resection was regenerated by vertical distraction osteogenesis (DO). Subsequently, 3 dental implants were placed into the reconstructed mandible. Orthodontic treatment using implant-anchored mechanics provided a proper facial profile with significantly improved occlusal function. The occlusion appeared stable for a 7-year retention period. CONCLUSIONS: These results suggest that surgically assisted and implant anchored-orthodontic approaches might be effective for the correction of such malocclusions.

Comprehensive approach to simultaneous molar intrusion and canine retraction in the treatment of Class II anterior open bite using miniscrew anchorage

ABSTRACT Introduction: Anterior open bite is one of the most difficult malocclusions to correct in orthodontic treatment. Molar intrusion using miniscrew anchorage has been developed as a new strategy for open bite correction; however, this procedure still has an important concern about prolonged treatment duration in the patient with anteroposterior discrepancy due to the separate step-by-step movement of anterior and posterior teeth. Objective: This article illustrates a comprehensive orthodontic approach for dentoalveolar open bite correction of an adult patient, by using miniscrew. Case report: A woman 19 years and 5 months of age had chief complaints of difficulty chewing with the anterior teeth and maxillary incisor protrusion. An open bite of -2.0 mm caused by slight elongation of the maxillary molars was found. The patient was diagnosed with Angle Class II malocclusion with anterior open bite due to the vertical elongation of maxillary molars. After extraction of the maxillary first premolars, concurrent movements of molar intrusion and canine retraction were initiated with the combined use of sectional archwires, elastic chains and miniscrews. Results: At 4 months after the procedure, positive overbite was achieved subsequent to the intrusion of maxillary molars by 1.5 mm and without undesirable side effects. Class I canine relation was also achieved at the same time. The total active treatment period was 21 months. The resultant occlusion and satisfactory facial profile were maintained after 54 months of retention. Conclusion: The presented treatment shows the potential to shorten the treatment duration and to contribute to the long-term stability for open bite correction.

RESUMO Introdução: A mordida aberta anterior é um dos tipos de má oclusão mais difíceis de se corrigir no tratamento ortodôntico. A intrusão de molares usando ancoragem em mini-implantes foi desenvolvida como uma nova estratégia para a correção da mordida aberta. Entretanto, ainda há preocupações quanto à longa duração desse tratamento em pacientes com discrepâncias anteroposteriores, já que os dentes anteriores são movimentados em etapa distinta dos posteriores. Objetivo: Este artigo descreve uma abordagem ampla para a correção da mordida aberta dentoalveolar em uma paciente adulta, usando mini-implantes. Relato de caso: Uma paciente de 19 anos e 5 meses de idade procurou tratamento apresentando como queixas principais a dificuldade de mastigar com os dentes anteriores e a protrusão dos incisivos superiores. Verificou-se, ainda, mordida aberta de -2,0 mm, causada por um comprimento levemente maior dos molares superiores. A paciente foi diagnosticada com má oclusão de Classe II de Angle com mordida aberta anterior devido à dimensão vertical aumentada dos molares superiores. Após a extração dos primeiros pré-molares superiores, iniciou-se movimentos simultâneos de intrusão dos molares e retração dos caninos, com o uso combinado de arcos seccionados, elásticos em cadeia e mini-implantes. Resultados: Após quatro meses em tratamento, alcançou-se uma sobremordida positiva, devido à intrusão de 1,5 mm dos molares superiores, sem qualquer efeito colateral indesejável. Ao mesmo tempo, também alcançou-se relação de Classe I nos caninos. O tempo total de tratamento ativo foi de 21 meses. A oclusão e o perfil facial satisfatório alcançados ao fim do tratamento mantiveram-se após 54 meses em contenção. Conclusão: A abordagem aqui apresentada tem o potencial de encurtar a duração do tratamento e contribuir para a estabilidade em longo prazo da correção da mordida aberta.

Orthodontic management of a non-syndromic patient with concomitant bimaxillary hypohyperdontia: a case report.

INTRODUCTION: Tooth agenesis is one of the most common dental anomalies; however, the concomitant occurrence of opposite dental numerical variation of hypohyperdontia is extremely rare. OBJECTIVE: To report the successful orthodontic management of a patient with non-syndromic concomitant bilateral agenesis of mandibular canines and two midline inverted supernumerary maxillary teeth. CASE REPORT: 21-year-old female patient with a chief complaint of protrusive right maxillary central incisor. The patient was diagnosed with a mild Class II skeletal base, Angle Class III molar relationship and increased overjet associated with hypohyperdontia. Anterior open bite accompanied with tongue-thrusting habit were also observed. Two temporary anchorage devices (TADs) were implanted at the buccal side of the maxillary molar region to control vertical height. Anterior teeth retraction was done after extraction of the maxillary first premolars, to improve the excessive overjet. The treatment mechanics involved lingual brackets system for the maxillary arch and transpalatal arch for anchorage control. RESULTS: The total active treatment period was 35 months. Acceptable occlusion with increased bite force and contact area as well as functional excursion were established without interference, following complex orthodontic treatment with premolar substitution. The resultant occlusion and a satisfactory facial profile were maintained after 29 months of retention. CONCLUSION: The present case report provides implications regarding the orthodontic treatment of hypohyperdontia-associated substitution for missing teeth as an effective option for improving aesthetic and functional aspects.

Orthodontic management of a non-syndromic patient with concomitant bimaxillary hypohyperdontia: a case report

ABSTRACT Introduction: Tooth agenesis is one of the most common dental anomalies; however, the concomitant occurrence of opposite dental numerical variation of hypohyperdontia is extremely rare. Objective: To report the successful orthodontic management of a patient with non-syndromic concomitant bilateral agenesis of mandibular canines and two midline inverted supernumerary maxillary teeth. Case report: 21-year-old female patient with a chief complaint of protrusive right maxillary central incisor. The patient was diagnosed with a mild Class II skeletal base, Angle Class III molar relationship and increased overjet associated with hypohyperdontia. Anterior open bite accompanied with tongue-thrusting habit were also observed. Two temporary anchorage devices (TADs) were implanted at the buccal side of the maxillary molar region to control vertical height. Anterior teeth retraction was done after extraction of the maxillary first premolars, to improve the excessive overjet. The treatment mechanics involved lingual brackets system for the maxillary arch and transpalatal arch for anchorage control. Results: The total active treatment period was 35 months. Acceptable occlusion with increased bite force and contact area as well as functional excursion were established without interference, following complex orthodontic treatment with premolar substitution. The resultant occlusion and a satisfactory facial profile were maintained after 29 months of retention. Conclusion: The present case report provides implications regarding the orthodontic treatment of hypohyperdontia-associated substitution for missing teeth as an effective option for improving aesthetic and functional aspects.

RESUMO Introdução: A agenesia é uma das anomalias dentárias mais comuns; porém, a ocorrência concomitante de variações numéricas do tipo hipo-hiperdontia em ambas as arcadas é extremamente rara. Objetivo: Descrever o tratamento ortodôntico bem-sucedido de uma paciente não sindrômica que apresentava agenesia bilateral dos caninos inferiores e dois dentes supranumerários na região de linha média superior. Descrição: Paciente do sexo feminino com 21 anos de idade, apresentando queixa principal de protrusão dos incisivos centrais superiores. Foi diagnosticada com leve Classe II esquelética, relação de molares em Classe III de Angle, sobressaliência aumentada e hipo-hiperdontia. Além disso, a paciente apresentava mordida aberta anterior associada ao hábito de interposição lingual. Dois dispositivos de ancoragem temporária (DATs) foram instalados por vestibular na região dos molares superiores, para controle vertical. A retração dos dentes anteriores foi feita após a extração dos primeiros pré-molares superiores, para reduzir a sobressaliência acentuada. A mecânica adotada envolveu o uso de braquetes linguais na arcada superior e barra transpalatina para controle da ancoragem. Resultados: Após 35 meses de fase ativa desse tratamento complexo, com substituição dos pré-molares, obteve-se oclusão aceitável, com aumento da força oclusal e da área de contatos oclusais, bem como movimentos excursivos funcionais bem estabelecidos e sem interferências. Após 29 meses de contenção, verificou-se estabilidade da oclusão e do perfil facial. Conclusão: Esse relato de caso clínico mostra que o tratamento ortodôntico com substituição de dentes ausentes associados à hipo-hiperdontia é uma opção efetiva para a melhora dos aspectos estéticos e funcionais.

Role of intracellular Ca2+-based mechanotransduction of human periodontal ligament fibroblasts.

Human periodontal ligament (hPDL) fibroblasts are thought to receive mechanical stress (MS) produced by orthodontic tooth movement, thereby regulating alveolar bone remodeling. However, the role of intracellular calcium ([Ca2+]i)-based mechanotransduction is not fully understood. We explored the MS-induced [Ca2+]i responses both in isolated hPDL fibroblasts and in intact hPDL tissue and investigated its possible role in alveolar bone remodeling. hPDL fibroblasts were obtained from healthy donors' premolars that had been extracted for orthodontic reasons. The oscillatory [Ca2+]i activity induced by static compressive force was measured by a live-cell Ca2+ imaging system and evaluated by several feature extraction method. The spatial pattern of cell-cell communication was investigated by Moran's I, an index of spatial autocorrelation and the gap junction (GJ) inhibitor. The Ca2+-transporting ionophore A23187 was used to further investigate the role of [Ca2+]i up-regulation in hPDL cell behavior. hPDL fibroblasts displayed autonomous [Ca2+]i responses. Compressive MS activated this autonomous responsive behavior with an increased percentage of responsive cells both in vitro and ex vivo. The integration, variance, maximum amplitude, waveform length, and index J in the [Ca2+]i responses were also significantly increased, whereas the mean power frequency was attenuated in response to MS. The increased Moran's I after MS indicated that MS might affect the pattern of cell-cell communication via GJs. Similar to the findings of MS-mediated regulation, the A23187-mediated [Ca2+]i uptake resulted in the up-regulation of receptor activator of NF-κB ligand (Rankl) and Sost along with increased sclerostin immunoreactivity, suggesting that [Ca2+]i signaling networks may be involved in bone remodeling. In addition, A23187-treated hPDL fibroblasts also showed the suppression of osteogenic differentiation and mineralization. Our findings suggest that augmented MS-mediated [Ca2+]i oscillations in hPDL fibroblasts enhance the production and release of bone regulatory signals via Rankl/Osteoprotegerin and the canonical Wnt/ß-catenin pathway as an early process in tooth movement-initiated alveolar bone remodeling.-Ei Hsu Hlaing, E., Ishihara, Y., Wang, Z., Odagaki, N., Kamioka, H. Role of intracellular Ca2+-based mechanotransduction of human periodontal ligament fibroblasts.

Cathepsin K-deficient osteocytes prevent lactation-induced bone loss and parathyroid hormone suppression.

Lactation induces bone loss to provide sufficient calcium in the milk, a process that involves osteoclastic bone resorption but also osteocytes and perilacunar resorption. The exact mechanisms by which osteocytes contribute to bone loss remain elusive. Osteocytes express genes required in osteoclasts for bone resorption, including cathepsin K (Ctsk), and lactation elevates their expression. We show that Ctsk deletion in osteocytes prevented the increase in osteocyte lacunar area seen during lactation, as well as the effects of lactation to increase osteoclast numbers and decrease trabecular bone volume, cortical thickness and mechanical properties. In addition, Ctsk deletion in osteocytes increased bone Parathyroid Hormone related Peptide (PTHrP), prevented the decrease in serum Parathyroid Hormone (PTH) induced by lactation, but amplified the increase in serum 1,25(OH)2D. The net result of these changes is to maintain serum and milk calcium levels in the normal range, ensuring normal offspring skeletal development. Our studies confirm the fundamental role of osteocytic perilacunar remodeling in physiological states of lactation and provides genetic evidence that osteocyte-derived Ctsk contributes not only to osteocyte perilacunar remodeling, but also to the regulation of PTH, PTHrP, 1,25-Dyhydroxyvitamin D (1,25(OH)2D), osteoclastogenesis and bone loss in response to the high calcium demand associated with lactation.

Association between Prevertebral Soft Tissue Thickening and Dysphagia in Cases of Traumatic Cervical Spinal Cord Injury.

OBJECTIVE: The objectives of this study were to clarify whether prevertebral soft tissue (PVST) thickening increases the risk of dysphagia, to identify at which vertebral level determining PVST thickness is useful, and to determine cutoff values. METHODS: A total of 80 patients with traumatic cervical spinal cord injury (TCSCI) treated over a 43-month period at a single regional institution specializing in cervical spinal cord injuries participated in the study. The exclusion criteria were having undergone anterior cervical spine surgery; a history of complicated traumatic brain injury, complicated vertebral artery injury, or brain injury; endotracheal intubation at day 30 after onset; the disappearance of neurological symptoms within 24 hours after onset; and the use of a halo vest. The associations between PVST thicknesses at C1, C2, C3, C6, and C7 measured by CT on the day of onset and the presence of dysphagia (Food Intake LEVEL Scale score <8) at 30 and 60 days after onset of TCSCI were analyzed using ROC curves to calculate the maximum area under the curve and the PVST cutoff values for these vertebrae. Associations between various risk factors, including PVST thickness, and dysphagia at days 30 and 60 after onset were examined using univariate and multivariate analyses. RESULTS: Independent associations with dysphagia were found with the C3 PVST thickness (day 30: ≥8.3 mm, day 60: ≥9.4 mm) and tracheostomy. CONCLUSION: PVST thickness or injury seems to be an independent risk factor for dysphagia. By measuring PVST, it is possible to estimate the severity of dysphagia even in acute conditions.

Screening of key candidate genes and pathways for osteocytes involved in the differential response to different types of mechanical stimulation using a bioinformatics analysis.

This study aimed to predict the key genes and pathways that are activated when different types of mechanical loading are applied to osteocytes. mRNA expression datasets (series number of GSE62128 and GSE42874) were obtained from Gene Expression Omnibus database (GEO). High gravity-treated osteocytic MLO-Y4 cell-line samples from GSE62128 (Set1), and fluid flow-treated MLO-Y4 samples from GSE42874 (Set2) were employed. After identifying the differentially expressed genes (DEGs), functional enrichment was performed. The common DEGs between Set1 and Set2 were considered as key DEGs, then a protein-protein interaction (PPI) network was constructed using the minimal nodes from all of the DEGs in Set1 and Set2, which linked most of the key DEGs. Several open source software programs were employed to process and analyze the original data. The bioinformatic results and the biological meaning were validated by in vitro experiments. High gravity and fluid flow induced opposite expression trends in the key DEGs. The hypoxia-related biological process and signaling pathway were the common functional enrichment terms among the DEGs from Set1, Set2 and the PPI network. The expression of almost all the key DEGs (Pdk1, Ccng2, Eno2, Egln1, Higd1a, Slc5a3 and Mxi1) were mechano-sensitive. Eno2 was identified as the hub gene in the PPI network. Eno2 knockdown results in expression changes of some other key DEGs (Pdk1, Mxi1 and Higd1a). Our findings indicated that the hypoxia response might have an important role in the differential responses of osteocytes to the different types of mechanical force.

Orthodontic correction of severe Class II malocclusion in a patient with Prader-Willi syndrome.

Prader-Willi syndrome (PWS) is a complex disorder that affects multiple systems and may cause craniofacial and dentofacial abnormalities. However, there is still a lack of evidence in the literature regarding the progress of orthodontic treatment in patients with PWS. This case report describes the successful orthodontic treatment of a patient with PWS. A girl, 9 years 0 months of age, who had been diagnosed with PWS had protruding maxillary incisors and a convex profile. Her malocclusion was due to the posteriorly positioned mandible. Screening tests for sleep apnea syndrome showed that she had sleep-disordered breathing, including obstructive sleep apnea and bruxism. We also observed an excessive overjet of 10.0 mm, a deep overbite of 6.8 mm, and the congenital absence of the mandibular second premolars. The patient was diagnosed with an Angle Class II malocclusion and a skeletal Class II jaw-base relationship with a deep overbite. Functional appliance therapy with mandibular advancement, which can enlarge the upper airway and increase the upper airspace, was performed to prevent further deterioration of the patient's obstructive sleep apnea. An acceptable occlusion with a proper facial profile and functional excursion were achieved without interference after comprehensive 2-stage treatment that incorporated orthodontic therapy for the patient's excessive overjet and deep overbite. The resulting occlusion was stable, and the occlusal force and the contact area gradually increased over a 2-year retention period. These results suggest that orthodontic treatment offers the opportunity to greatly improve the health and quality of life of people with PWS.

Modification of Dentofacial Growth Associated with Goldenhar Syndrome.

The rare developmental defect, Goldenhar syndrome is characterized by complex craniofacial and dentofacial anomalies. Here we describe the successful orthodontic treatment of a 5-year-old Japanese Goldenhar syndrome patient with mild facial asymmetry, right microtia, right-side hearing loss, and tongue-thrusting by a modification of dentofacial growth using a non-surgical orthopedic treatment approach. Improvement of the vertical discrepancies on the affected side and canted occlusal plane as well as mandibular deviation were achieved with a functional orthopaedic approach. Stable and acceptable occlusion were obtained over the 32-month post-retention period. A non-surgical orthodontic treatment approach offers satisfactory facial aesthetic outcomes in Goldenhar syndrome.

Alternation in the gap-junctional intercellular communication capacity during the maturation of osteocytes in the embryonic chick calvaria.

INTRODUCTION: The intercellular network of cell-cell communication among osteocytes is mediated by gap junctions. Gap junctional intercellular communication (GJIC) is thought to play an important role in the integration and synchronization of bone remodeling. To further understand the mechanism of bone development it is important to quantify the difference in the GJIC capacity of young and developmentally mature osteocytes. MATERIALS AND METHODS: We first established an embryonic chick calvaria growth model to show the growth of the calvaria in embryos at 13 to 21days of age. We then applied a fluorescence recovery after photobleaching (FRAP) technique to compare the difference in the GJIC capacity of young osteocytes with that of developmentally mature osteocytes. Finally, we quantified the dye (Calcein) diffusion from the FRAP data using a mathematic model of simple diffusion which was also used to identify simple diffusion GJIC pattern cells (fitted model) and accelerated diffusion GJIC pattern cells (non-fitted model). RESULTS: The relationship between the longest medial-lateral length of the calvaria (frontal bone) and the embryonic age fit a logarithmic growth model: length=5.144×ln(day)-11.340. The morphometric data during osteocyte differentiation showed that the cellular body becomes more spindle-shaped and that the cell body volume decreased by approximately 22% with an increase in the length of the processes between the cells. However, there were no significant differences in the cellular body surface area or in the distance between the mass centres of the cells. The dye-displacement rate in young osteocytes was significantly higher than that in developmentally mature osteocytes: dye displacement only occurred in 26.88% of the developmentally mature osteocytes, while it occurred in 64.38% of the young osteocytes. Additionally, in all recovered osteocytes, 36% of the developmentally mature osteocytes comprised non-fitted model cells while 53.19% of the young osteocytes were the non-fitted model, which indicates the active transduction of dye molecules. However, there were no statistically significant differences between the young and developmentally mature osteocytes with regard to the diffusion coefficient, permeability coefficient, or permeance of the osteocyte processes, which were 3.93±3.77 (×10(-8)cm(2)/s), 5.12±4.56 (×10(-5)cm(2)/s) and 2.99±2.47 (×10(-13)cm(2)/s) (mean±SD), respectively. CONCLUSIONS: These experiments comprehensively quantified the GJIC capacity in the embryonic chick calvaria and indicated that the cell-cell communication capacity of the osteocytes in the embryonic chick calvaria was related to their development.

[Indirect usage of miniscrew anchorage to intrude overerupted mandibular incisors in a Class II patient with a deep overbite]. / Intérêts de l'utilisation des mini-vis orthodontiques en tant qu'ancrage indirect dans la correction de l'égression d'incisives mandibulaires pour un patient présentant une classe II hypodivergente∗.

Vertical dentoalveolar discrepancies are a common problem in orthodontic patients but are often difficult to treat with traditional mechanics. This case report illustrates the successful treatment of overerupted mandibular incisors via the indirect use of miniscrew anchorage. A woman (age, 22 years 9 months) had chief complaints of maxillary incisor protrusion and crooked teeth. An excessive curve of Spee caused by elongation of the mandibular incisors was also found. The patient was diagnosed with a severe Class II Division 1 malocclusion and a deep overbite. After extraction of the mandibular first premolars and the subsequent leveling phase, the elongated incisors were intruded with a novel method, which involved the combined use of sectional archwires and miniscrews placed in the premolar areas. After the procedure, the mandibular incisors had been intruded by 6.5 mm with no undesirable side effects. The total active treatment period was 42 months. The resultant occlusion and satisfactory facial profile were maintained after 30 months of retention. Our novel intrusion approach shows potential for correcting a deep overbite.