Three-dimensional Maxillofacial Morphology Measurements in Japanese Adults with Normal Occlusion.

Accurate orthodontic analysis and diagnosis based on anatomical landmarks is essential to the success of orthodontic treatment. Helical computed tomography (CT) has evolved markedly, and dentists can now quickly obtain 3-dimensional (3D) reconstruction data using this imaging modality. The planning of orthodontic treatment had traditionally been based on cephalometric analysis using 2D landmarks. This study aimed to collect 3D morphological data using CT images to establish new landmarks for analysis and diagnosis in orthodontic treatment. Twenty male and 20 female adult Japanese dry skulls with of normal occlusion were selected. The skulls were scanned using a multidetector helical CT system (SIEMENS, Volume Zoom Plus 4, Germany). Models were reconstructed using 3D measurement software (Simplant, Dentsply Sirona, Tokyo, Japan) and 45 landmarks determined. Three-dimensional measurement for a total of 30 items representing these landmarks was then performed. The results provided 3D standard values for maxillofacial morphology in adult Japanese individuals with normal occlusion. These measurement items should allow the disadvantages of 2D cephalometric analysis to be overcome.

Vertical Vibration of Mouse Osteoblasts Promotes Cellular Differentiation and Cell Cycle Progression and Induces Aging In Vitro.

BACKGROUND: This study aimed to investigate the effect of the vibration of osteoblasts on the cell cycle, cell differentiation, and aging. MATERIALS AND METHODS: Primary maxilla osteoblasts harvested from eight-week-old mice were subjected to vibration at 3, 30, and 300 Hz once daily for 30 min; control group, 0 Hz. A cell proliferation assay and Cell-Clock Cell Cycle Assay were performed 24 h after vibration. Osteoblast differentiation assay, aging marker genes, SA-ß-Gal activity, and telomere length (qPCR) were assayed two weeks post- vibration once every two days. RESULTS: Cell proliferation increased significantly at 30 and 300 Hz rather than 0 Hz. Several cells were in the late G2/M stage of the cell cycle at 30 Hz. The osteoblast differentiation assay was significantly higher at 30 Hz than at 0 Hz. Runx2 mRNA was downregulated at 30 Hz compared to that at 0 Hz, while osteopontin, osteocalcin, and sclerostin mRNA were upregulated. p53/p21, p16, and c-fos were activated at 30 Hz. SA-ß-Gal activity increased significantly at 30 or 300 Hz. Telomere length was significantly lower at 30 or 300 Hz. CONCLUSIONS: The results suggest that providing optimal vibration to osteoblasts promotes cell cycle progression and differentiation and induces cell aging.

Three-Dimensional Evaluation of Pharyngeal Morphology in Bimaxillary Surgery with and without Horseshoe Osteotomy in Skeletal Class III Cases.

Repositioning of the jaw in orthognathic treatment generates changes in the soft tissues of the maxillofacial region, with consequent changes in the airway. The purpose of this study was to determine how type of orthognathic surgical procedure affected the 3-dimensional morphology of the upper airway. Forty patients were divided into the following 2 groups according to the type of surgical procedure used: a horseshoe osteotomy (HS) group (20 patients, comprising 11 men and 9 women; average age 24.3±4.5 years) who underwent bimaxillary surgery; and a LeFort I osteotomy (LF) group (20 patients, comprising 8 men and 12 women; average age 22.5±4.6 years) who also underwent bimaxillary surgery. Cephalometric measurements were taken and 3-dimensional pharyngeal morphology evaluated in each group. The amounts of maxilla rotation, posterior maxilla impaction, and mandibular setback all revealed a significantly larger value in the HS group. Evaluation of pharyngeal volume revealed a significant decrease in the upper pharyngeal segment in the LF group. A significant decrease in the lower pharyngeal segment was observed in both groups. Differences were noted in postoperative pharyngeal morphology between the two groups. The results of this study suggest that HS has less effect on the upper pharyngeal segment, regardless of the amount of posterior maxilla impaction.

The Effects of Fluvastatin on Indian Hedgehog Pathway in Endochondral Ossification.

Statins have demonstrated to be effective for treating chondrodysplasia and its effects were believed to be associated with the fibroblast growth factor receptor 3 (FGFR3). Statins promoted the degradation of FGFR3 in studies using disease-specific induced pluripotent stem cells and model mice, however, recent studies using normal chondrocytes reported that statins did not degrade FGFR3. In order to further investigate the effects of statins in endochondral ossification, this study examined the influence of statins on Indian hedgehog (Ihh), another important component of endochondral ossification, and its related pathways. The chondrocyte cell line ATDC5 was used to investigate changes in cell proliferation, mRNA, and protein expression levels. In addition, an organ culture of a mouse metatarsal bone was performed followed by hematoxylin-eosin staining and fluorescent immunostaining. Results indicated that expression level of Ihh increased with the addition of statins, which activated the Ihh pathway and altered the localization of Ihh. Changes in cholesterol modification may have affected Ihh diffusibility; however, further experiments are necessary. A reactive increase in parathyroid hormone-related protein (PTHrP) was observed in addition to changes in the Wnt pathway through secreted-related protein 2/3 and low-density lipoprotein 5/6. This led to the promotion of cell proliferation, increase of the hypertrophic chondrocyte layer, inhibition of apoptosis, and decrease in mineralization. This study demonstrated that statins had an influence on Ihh, and that the hyperfunction of Ihh may prevent premature cell death caused by FGFR3-related chondrodysplasia through an indirect increase in the expression of PTHrP.

Three-Dimensional Measurements of Pharyngeal Airway in Patients with Unilateral Cleft Lip and Palate.

The aim of this study was to investigate 3-dimensional (3D) airway volume in patients with unilateral cleft lip and palate (UCLP) using computed tomography (CT). The study population comprised 15 UCLP patients (UCLP group) scheduled to receive alveolar bone grafts and 15 with impacted teeth (control group). The clinical requirements for a CT scan were met in both groups. Measurements were recorded from 3D reconstructions of Digital Imaging and Communications in Medicine data obtained from the CT images. Airway volume, cross-sectional area, and linear and angular measurements were recorded. Airway volume and cross-sectional area showed no significant difference between the two groups. The narrowest section of the airway in the UCLP group was tighter than that in the control group, however (p=0.017). The results of this study suggest that this difference in the measurements of the narrowest section of the airway is involved in the particular maxillofacial morphology found in UCLP patients.

CAGE-seq analysis of osteoblast derived from cleidocranial dysplasia human induced pluripotent stem cells.

Non-coding RNAs (ncRNAs) comprise a major portion of transcripts and serve an essential role in biological processes. Although the importance of major transcriptomes in osteogenesis has been extensively studied, the function of ncRNAs in human osteogenesis remains unclear. Previously, we developed hiPSCs from patients with cleidocranial dysplasia (CCD) caused by runt-related transcription factor 2 (RUNX2) haploinsufficiency. To gain insight into ncRNAs in osteogenesis, we surveyed differential ncRNA expression profiling and promoter differences of RUNX2 using patient-specific iPSCs and cap analysis gene expression (CAGE) technology to define the promoter landscape. Revertant iPSCs (Rev1 iPSCs) edited by CRISPR/Cas9 system to harbor mutation-corrected RUNX2 exhibited increased proximal promoter expression of RUNX2, while CCD iPSCs did not. We identified 2271 ncRNA genes with altered expression levels before and after differentiation, 31 of which showed at least 20-fold higher expression in Rev1 iPSCs. Bioinformatic analysis also categorized AC007392.3, LINC00379, RP11-122D10.1, and RP11-90J7.2 as enhancer regulatory regions, and HOXA-AS2, MIR219-2, and RP11-834C11.3 as dyadic regulatory regions of these ncRNAs. In addition, two miRNAs, termed MIR199A2 and MIR152, were found to have high enrichment of osteogenic-related terms. Upon further examination of the role of MIR152 on osteoblast differentiation, we found that MIR152 knockdown induced upregulation of ALP and COL1A1 in Saos-2 cells. Thus, ncRNAs were found to regulate the osteogenic differentiation potentials of hiPSCs that are used for bone regeneration and repair owing to their differentiation potentials. These data allow understanding ncRNA profiles of hiPSCs during osteogenesis.

Interdental Distraction Osteogenesis in Unilateral Cleft Lip and Palate Patient with Wide Alveolar Cleft.

Alveolar bone grafting is routinely performed in repair of alveolar clefts. When the alveolar cleft is wider than 11 mm, however, the survival rate of the bone graft and prognosis are poor. Here, we describe successful orthodontic treatment using interdental distraction osteogenesis (IDO) with a tooth-tooth type distractor to reduce the width of the alveolar cleft in a patient with unilateral cleft lip and palate. The patient was a 12-year-old girl with unilateral cleft lip and palate, maxillary dentition midline deviation, congenitally missing maxillary lateral incisors, a palatally-displaced right upper first premolar, a wide alveolar cleft (20 mm), and mandibular prognathism due to maxillary hypoplasia. Treatment comprised a combination of orthodontic treatment and IDO. After treatment, appropriate occlusion, space closure in the maxillary arch, coincidence of the maxillary and facial midlines, and incorporation of the right maxillary first premolar into the arch were obtained. These results suggest that IDO is effective in treating cleft lip and palate patients with a wide alveolar cleft.

Survey on Condition and Orthodontic Treatment of Maxillary Lateral Incisors in Patients with Cleft Lip and Palate.

The aim of this study was to investigate the condition of the maxillary lateral incisors and evaluate the methods used for cleft closure in patients with cleft lip and palate, including the treatment of the maxillary lateral incisors. A total of 214 patients (260 clefts) with alveolar clefts who had started Phase II treatment and entered the maintenance period at the Department of Orthodontics at Tokyo Dental College, Chiba Hospital, between 1975 and 2014 were included. Panoramic, intraoral, and occlusal radiographs, as well as intraoral photographs and medical records, were used to investigate cleft classification, the presence or absence and location of maxillary lateral incisors, and frequency and treatment method for peg lateral incisors in the cleft region. There were more unilateral cleft cases (78.5%) than bilateral cleft cases. The prevalence of congenital absence of the maxillary lateral incisors was similar between unilateral (53.0%) and bilateral cases (53.3%). Peg laterals occurred frequently, with 89.9% occurring in unilateral cases. The maxillary lateral incisors were more commonly found in the secondary than in the primary palate. The number of non-extraction cases was larger than that of extraction cases, regardless of cleft type or the location of the peg laterals. In many cases, the peg laterals were treated with non-extraction and space closure or crown modification. These results suggest that, depending on their condition, the peg laterals should be preserved as much as possible in devising a treatment plan.

Three-Dimensional Evaluation of Change in Maxillary Alveolar Arch after Expansion in Unilateral Cleft Lip and Palate Patients.

Narrowing of the maxillary dental arch is a major cause of occlusal abnormalities in cleft lip and palate patients. Although the dental arch may be expanded in such cases, relapse will often occur during the subsequent retention period. In this study, the stability of expansion of the maxillary arch was investigated by examining 3-dimensional change in the maxillary arch during the treatment and post-retention periods. Three-dimensional measurements was performed on maxillary plaster models obtained from 8 unilateral cleft lip and palate patients (mean age, 12.5 years) who had undergone maxillary arch expansion using an edgewise appliance and quad helix (CLP group). The controls consisted of 8 unilateral cleft lip and alveolus patients (mean age, 12.9 years). Measurements were made during the pretreatment, post-treatment, and post-retention periods. In the CLP group, horizontal relapse was observed in the alveolar and dental arches between the second premolars, together with vertical relapse on the cleft side of the central incisor, lateral incisor, and canine. The sites where relapse occurred demonstrated decreased growth before orthodontic treatment. A correlation was observed between the extents of expansion and relapse. These findings suggest that excessive horizontal or vertical tooth movement in areas showing developmental failure should be avoided in order to increase stability after orthodontic treatment.

Three-dimensional Coordinate System for Hemifacial Microsomia.

BACKGROUND: Hemifacial microsomia (HFM) is a congenital disorder characterized by facial asymmetry, but no midline reference has been established for evaluating facial morphology in patients with HFM. The purpose of this study was to develop a 3-dimensional coordinate system unaffected by the deformity of the external acoustic aperture or orbital circumference and to quantitatively evaluate craniofacial morphology in such patients. METHODS: We quantitatively evaluated craniofacial morphology using 3-dimensional measurements with the skull base as a reference. Using computed tomography data from 15 patients with HFM and 15 controls, a coordinate system was created for each patient, and left-right differences between measurement points were compared. RESULTS: When mandibular deformity was severe, the deformity of the posterior part of the palatine bone and lateral part of the orbit increased, but this trend was not evident for other measurement points. Thus, craniofacial deformity in HFM was not always related to mandibular deformity. Moreover, no difference was evident in the position of the hypoglossal canal between controls and patients with HFM. CONCLUSIONS: Quantitative assessments are possible using the coordinate system devised in this study, irrespective of the severity of HFM. The degree of mandibular deformity detailed in the Pruzansky classification was associated with the superoinferior deformity of the posterior part of the palatine bone and anteroposterior deformity of the lateral part of the orbit.

Demographics of Postgraduate Training Course at Tokyo Dental College Department of Orthodontics and Alumni Working Trends.

The postgraduate training course at the Department of Orthodontics of Tokyo Dental College, which started in April 1975, comprises a 3-year curriculum aimed at fostering orthodontic specialists. A system of Accreditation for Orthodontists was introduced by the Japan Orthodontic Society in 1990, since which time, this postgraduate training course has also sought to provide the basic training required to obtain such certification. The purpose of this study was to investigate the demographics of the students on this course and the current work status of its graduates by means of a questionnaire-based survey. The results revealed that, when the fortieth intake of students graduated in March 2017, the total number completing the course had reached 326. The annual mean number of students on this course was 8.2, and recent years have seen a marked increase in the number of women enrolling. In total, 37.5% of the questionnaire respondents had opened orthodontic clinics; 14.8% had opened general dentistry clinics; and 42.6% were working as employees. In addition, 46.2% had an additional place of employment other than their principal place of employment, mainly at a general dentistry clinic. Regarding the field of treatment, 82.4% provided solely orthodontic treatment. We believe that this may because all the responders had completed the postgraduate orthodontics course. The rate of earning accreditation as an orthodontist was high (82.4%), with no difference in the rate of acquisition between men and women. The rate of qualification as a Board-certified orthodontist was 17.9%, with the rate of acquisition by women approximately half of that by men. The number of female orthodontists is rising, and no difference was observed between sexes in the rate of acquiring accreditation as an orthodontist. Women were found to be lagging behind men, however, in regard to the rate of advancement to masters/PHD programs; qualifying as a Board-certified orthodontist; opening an orthodontic practice; and number of days worked. These findings suggest that there are differences in regard to the actual working conditions among the alumni of our postgraduate orthodontic training course, and that these differences are sex-based.

Change in Anterior Crowding over 20 Years from Third Decade of Life in Untreated Angle Class I Crowding.

Many studies have investigated age-related change in normal occlusion and during the post-retention phase of orthodontic treatment. None, however, have investigated such change in malocclusion. The purpose of this study was to compare age-related change in Angle Class I crowding with that in normal occlusion. Dental casts obtained from 10 men and 2 women in their 20s and then again in their 40s were digitized with a 3-dimensional laser scanner to measure anterior crowding, angulation, inclination, andarch width and length. A paired t -test was used to evaluate change in these values betweenthe two sets of casts. A student's t -test was used to compare values between the crowdingand normal groups. The casts obtained from individuals with untreated Angle Class Icrowding revealed that anterior crowding increased with age due to a decrease in thelength of the maxillary arch. Clear lingual inclination of the maxillary incisors and mesiolingual inclination of the maxillary canines were also observed. A decrease was observedin the anterior arch width and an increase in crowding due to lingual inclination of themandibular canines in the mandible. The space between the mandibular central incisors and between the mandibular lateral incisors and canines was particularly associated withan increase in crowding, suggesting that this was age-related. A comparison betweenpatients in their 40s with Angle Class I crowding and those with normal occlusion revealedthat the increase in maxillary anterior crowding was greater in the former. Mandibularanterior crowding increased at around the same rate, however.

Effect of Different Bracket Prescriptions on Orthodontic Treatment Outcomes Measured by Three-dimensional Scanning.

Various types of bracket are currently available, and different prescriptions are provided for the same type of tooth. There are no definite criteria, however, on which to base bracket selection. The purpose of this study was to investigate differences in the angulation and inclination of orthodontically aligned teeth when using different prescription brackets. Thirty patients undergoing orthodontic treatment for maxillary protrusion and crowding were enrolled. After orthodontic treatment with a pre-adjusted appliance, angulation and inclination were measured on dental casts obtained from these patients (10 each with 0.022 MBT, 0.022 Roth, or 0.018 Roth brackets). The dental casts were scanned and digitized using a 3-dimensional (3-D) scanner and measured with 3-D model measurement software. A significant difference was observed in the mean angulation of the mandibular canine between the 0.022 MBT (5.81°) and 0.018 Roth groups (9.07°). Greater mesial inclination was observed in the 0.018 Roth group. No significant difference was observed in any of the other regions measured. Differences in bracket prescription showed no clinical influence on treatment outcomes. A significant difference was observed in the mandibular canine (p<0.05), suggesting that consideration is required when selecting brackets.

Surgical Orthodontic Treatment Involving Mandibular Premolar Extraction in Patient with Mandibular Retrusion Associated with Temporomandibular Joint Osteoarthritis.

Here, we report retention following surgical orthodontic treatment in a patient with vertical maxillary excess associated with temporomandibular joint osteoarthritis (TMJOA) and marked mandibular retrusion. The patient was a man aged 20 years 10 months who presented with the chief complaint of maxillary protrusion. The facial profile was of the convex type due to marked mandibular retrusion. In addition, the patient had a gummy smile. Intraoral findings revealed a Class II molar relation, +11 mm overjet, and 0 mm overbite. Mandibular dentition arch length discrepancy showed crowding of -2 mm, and the maxillary dentition showed a spaced arch of +5 mm. Panoramic radiographs confirmed flattening of the condylar head and proliferation of the bone margin. Cephalometric analysis of the skeletal pattern revealed that, horizontally, the maxilla was anterior and the mandible posterior; vertically, a dolichofacial pattern was noted. The anterior maxillary tooth axis was standard, but the anterior mandibular tooth axis showed labial inclination. Based on these findings, skeletal maxillary protrusion associated with TMJOA was diagnosed. Surgical orthodontic treatment comprised bilateral mandibular first premolar extraction with two-jaw surgery and genioplasty. Orthodontic treatment was performed with a multibracket system using a 0.22-slot pre-adjusted edgewise appliance. At 2 years and 11 months after initiation of treatment, the maxilla was transposed 6 mm upwards by orthognathic surgery and the mandible 17 mm anteriorly and 5 mm upwards by counterclockwise rotation. At 3 years and 10 months, the Pogonion was moved 6 mm anteriorly by genioplasty. At 4 years, orthodontic treatment was concluded on confirming satisfactory occlusion and improvement in facial features. At 2 years after completion of treatment, occlusion and the maxillofacial morphology remain stable, with almost no relapse. In addition, no temporomandibular joint disorder symptoms have occurred. Careful comprehensive follow-up observation will be continued.

Finite Element Analysis of Stress in Maxillary Dentition during En-masse Retraction with Implant Anchorage.

The goal of this study was to investigate how the height of the archwire hook and implant anchor affect tooth movement, stress in the teeth and alveolar bone, and the center of resistance during retraction of the entire maxillary dentition using a multibracket system. Computed tomography was used to scan a dried adult human skull with normal occlusion. Three-dimensional models of the maxillary bone, teeth, brackets, archwire, hook, and implant anchor were created and used for finite element analysis. The heights of the hook and the implant anchor were set at 0, 5, or 10 mm from the archwire. Orthodontic force of 4.9 N was systematically applied between the hook and the implant anchor and differential stress distributions and tooth movements observed for each traction condition. With horizontal traction, the archwire showed deformation in the superior direction anterior to the hook and in the inferior direction posterior to the hook. Differences in traction height and direction resulted in different degrees of deformation, with biphasic movement clearly evident both in front of and behind the hook. With horizontal traction of the hook at a height of 0 mm, all the teeth moved distally, but not with any other type of traction. At a height of 5 mm or 10 mm, deformation showed an increase. The central incisor showed extrusion under all traction conditions, with the amount showing a reduction as the height of horizontal or posterosuperior traction increased. The center of resistance was located at the root of the 6 anterior teeth and entire maxillary dentition. The present results suggest that it is necessary to consider deformation of the wire and the center of resistance during en-masse retraction with implant anchorage.

Difference in Bilateral Timing of Eruption of Permanent Teeth.

The aim of this study was to obtain basic data that might serve as criteria in the diagnosis of delayed eruption of the permanent teeth. The synchronicity of the eruption of corresponding contralateral teeth was determined. Data were obtained on both the deciduous and permanent dentition based on records made every 2 months at the Department of Pediatric Dentistry of Tokyo Dental College. These data were then used to investigate bilateral differences in the timing of eruption of the permanent teeth. Over 80% of incisors, first molars, mandibular canines, and maxillary first premolars erupted within 4 months of their contralateral counterparts, while this occurred in 75% of maxillary canines, mandibular first premolars, and mandibular second molars, 70% of maxillary and mandibular second premolars, and 65% of maxillary second molars. Bilateral differences in the timing of permanent tooth eruption varied depending on type of tooth, and these differences tended to be smaller for teeth erupting at an earlier point in the order of eruption, and greater for those erupting at a later point. These results suggest that the failure of a contralateral tooth to erupt within 4 months of its counterpart might serve as a criterion in a diagnosis of suspected delayed eruption of a permanent tooth.

Growth of Palate in Unilateral Cleft Lip and Palate Patients Undergoing Two-stage Palatoplasty and Orthodontic Treatment.

The purpose of this study was to investigate the long-term effects of two-stage palatoplasty on the morphology of the maxillary alveolar arch and occlusion using plaster models of the maxilla and mandible obtained from patients with unilateral complete cleft lip and palate who also underwent orthodontic treatment. A total of 20 patients undergoing two-stage palatoplasty by Perko's method (Group T) were enrolled. Plaster models of the maxilla and mandible were obtained from each patient at Time 1, on commencement of orthodontic treatment in the mixed dentition period; at Time 2, on that of orthodontic treatment in the permanent dentition period; and at Time 3, on completion of active orthodontic treatment. Analysis of occlusion and morphological analysis were performed using a 3-dimensional measuring system. The results were compared with 15 patients who underwent one-stage palatoplasty by the push-back method using a mucoperiosteal flap (Group P). Alveolar morphology and the relationship between the maxilla and mandible were satisfactory in Group T. The palates in Group T were deeper and larger than those in Group P. Alveolar collapse in Group T was milder, and impairment of the alveolar morphology less notable than in Group P, as surgical invasion to the anterior alveolar region was avoided during the palatal growth period. These results suggest that two-stage palatoplasty is advantageous for jaw development.

OC-STAMP promotes osteoclast fusion for pathogenic bone resorption in periodontitis via up-regulation of permissive fusogen CD9.

Cell fusion-mediated formation of multinuclear osteoclasts (OCs) plays a key role in bone resorption. It is reported that 2 unique OC-specific fusogens [ i.e., OC-stimulatory transmembrane protein (OC-STAMP) and dendritic cell-specific transmembrane protein (DC-STAMP)], and permissive fusogen CD9, are involved in OC fusion. In contrast to DC-STAMP-knockout (KO) mice, which show the osteopetrotic phenotype, OC-STAMP-KO mice show no difference in systemic bone mineral density. Nonetheless, according to the ligature-induced periodontitis model, significantly lower level of bone resorption was found in OC-STAMP-KO mice compared to WT mice. Anti-OC-STAMP-neutralizing mAb down-modulated in vitro: 1) the emergence of large multinuclear tartrate-resistant acid phosphatase-positive cells, 2) pit formation, and 3) mRNA and protein expression of CD9, but not DC-STAMP, in receptor activator of NF-κB ligand (RANKL)-stimulated OC precursor cells (OCps). While anti-DC-STAMP-mAb also down-regulated RANKL-induced osteoclastogenesis in vitro, it had no effect on CD9 expression. In our mouse model, systemic administration of anti-OC-STAMP-mAb suppressed the expression of CD9 mRNA, but not DC-STAMP mRNA, in periodontal tissue, along with diminished alveolar bone loss and reduced emergence of CD9+ OCps and tartrate-resistant acid phosphatase-positive multinuclear OCs. The present study demonstrated that OC-STAMP partners CD9 to promote periodontal bone destruction by up-regulation of fusion during osteoclastogenesis, suggesting that anti-OC-STAMP-mAb may lead to the development of a novel therapeutic regimen for periodontitis.-Ishii, T., Ruiz-Torruella, M., Ikeda, A., Shindo, S., Movila, A., Mawardi, H., Albassam, A., Kayal, R. A., Al-Dharrab, A. A., Egashira, K., Wisitrasameewong, W., Yamamoto, K., Mira, A. I., Sueishi, K., Han, X., Taubman, M. A., Miyamoto, T., Kawai, T. OC-STAMP promotes osteoclast fusion for pathogenic bone resorption in periodontitis via up-regulation of permissive fusogen CD9.

Condition-specific Quality of Life Assessment at Each Stage of Class III Surgical Orthodontic Treatment -A Prospective Study.

Surgical orthodontic treatment has been reported to improve oral health-related quality of life (OHRQL). Such treatment comprises three stages: pre-surgical orthodontic treatment; orthognathic surgery; and post-surgical orthodontic treatment. Most studies have focused on change in OHRQL between before and after surgery. However, it is also necessary to evaluate OHRQL at the pre-surgical orthodontic treatment stage, as it may be negatively affected by dental decompensation compared with at pre-treatment. The purpose of this prospective study was to investigate the influence of surgical orthodontic treatment on QOL by assessing change in condition-specific QOL at each stage of treatment in skeletal class III cases. Twenty skeletal class III patients requiring surgical orthodontic treatment were enrolled in the study. Each patient completed the Orthognathic Quality of Life Questionnaire (OQLQ), which was developed for patients with dentofacial deformity. Its items are grouped into 4 domains: "social aspects of dentofacial deformity"; "facial esthetics"; "oral function"; and "awareness of dentofacial esthetics". The questionnaire was completed at the pre-treatment, pre-surgical orthodontic treatment, and post-surgical orthodontic treatment stages. The results revealed a significant worsening in scores between at pre-treatment and pre-surgical orthodontic treatment in the domains of facial esthetics and oral function (p<0.01), and between at pre-surgical orthodontic and post-surgical orthodontic treatment in all domains except awareness of dentofacial esthetics (p<0.05, p<0.01). A significant correlation was observed between a negative change in overjet and worsening OQLQ scores at the pre-surgical orthodontic treatment stage. Significant correlations were also observed between improvement in upper and lower lip difference, soft tissue pogonion protrusion, and ANB angle and improvement in OQLQ scores at the post-surgical orthodontic treatment stage. These results indicate that morphologic change influences OHRQL in patients undergoing surgical orthodontic treatment not only after surgery, but also during pre-surgical orthodontic treatment.

Targeted reversion of induced pluripotent stem cells from patients with human cleidocranial dysplasia improves bone regeneration in a rat calvarial bone defect model.

BACKGROUND: Runt-related transcription factor 2 (RUNX2) haploinsufficiency causes cleidocranial dysplasia (CCD) which is characterized by supernumerary teeth, short stature, clavicular dysplasia, and osteoporosis. At present, as a therapeutic strategy for osteoporosis, mesenchymal stem cell (MSC) transplantation therapy is performed in addition to drug therapy. However, MSC-based therapy for osteoporosis in CCD patients is difficult due to a reduction in the ability of MSCs to differentiate into osteoblasts resulting from impaired RUNX2 function. Here, we investigated whether induced pluripotent stem cells (iPSCs) properly differentiate into osteoblasts after repairing the RUNX2 mutation in iPSCs derived from CCD patients to establish normal iPSCs, and whether engraftment of osteoblasts derived from properly reverted iPSCs results in better regeneration in immunodeficient rat calvarial bone defect models. METHODS: Two cases of CCD patient-derived induced pluripotent stem cells (CCD-iPSCs) were generated using retroviral vectors (OCT3/4, SOX2, KLF4, and c-MYC) or a Sendai virus SeVdp vector (KOSM302L). Reverted iPSCs were established using programmable nucleases, clustered regularly interspaced short palindromic repeats (CRISPR)/Cas-derived RNA-guided endonucleases, to correct mutations in CCD-iPSCs. The mRNA expressions of osteoblast-specific markers were analyzed using quantitative reverse-transcriptase polymerase chain reaction. iPSCs-derived osteoblasts were transplanted into rat calvarial bone defects, and bone regeneration was evaluated using microcomputed tomography analysis and histological analysis. RESULTS: Mutation analysis showed that both contained nonsense mutations: one at the very beginning of exon 1 and the other at the initial position of the nuclear matrix-targeting signal. The osteoblasts derived from CCD-iPSCs (CCD-OBs) expressed low levels of several osteoblast differentiation markers, and transplantation of these osteoblasts into calvarial bone defects created in rats with severe combined immunodeficiency showed poor regeneration. However, reverted iPSCs improved the abnormal osteoblast differentiation which resulted in much better engraftment into the rat calvarial bone defect. CONCLUSIONS: Taken together, these results demonstrate that patient-specific iPSC technology can not only provide a useful disease model to elucidate the role of RUNX2 in osteoblastic differentiation but also raises the tantalizing prospect that reverted iPSCs might provide a practical medical treatment for CCD.