Orodental malformations associated with human MSX1 sequence variants.

BACKGROUND: MSX1 sequence variants have been known to cause human tooth agenesis (TA) with or without orofacial clefts. However, their roles during the whole processes of tooth development are not fully understood. This study aimed to characterize a 4-membered family with TA carrying a novel MSX1 pathogenic variant and investigate the disease mechanism. METHODS: The authors conducted whole exome analysis to define the disease-causing sequence variant. They performed microcomputed tomography, morphometric analyses, transcriptome profiling, and molecular characterization to study the affected teeth and the gene variant. RESULTS: The authors identified an MSX1 pathogenic variant, p.Glu232∗, in affected family members with TA and concomitant orodental anomalies, namely, prominent maxillary labial frenum, central incisor diastema, median maxillary anterior alveolar cleft, tooth fusion, mandibular molar dysmorphology, thin dentin layer, and slender dental roots. MSX1-defective teeth were not apparently microdontic but had thin dentin layers. The mandibular molars showed a homeotic transformation to maxillary counterparts. Genes involved in extracellular matrix organization and dentinogenesis, such as DMP1 and MMP20, were downregulated in dental pulp tissues of MSX1-defective teeth. The p.Glu232∗-truncated MSX1 properly localized to the nucleus but partially lost its transactivation ability. Analyzing reported cases indicated that truncation sequence variants within the homeobox domain of MSX1 caused a more severe TA phenotype than those outside of the homeobox domain, probably due to dominant negativity compared with haploinsufficiency. CONCLUSIONS: This study provides in vivo evidence that MSX1 contributes to developmental processes of various orodental tissues in humans. PRACTICAL IMPLICATIONS: Clinically, hypertrophic labial frenum, incisor diastema, and median maxillary anterior alveolar cleft might be considered diagnostic for MSX1-associated TA.

Craniofacial and olfactory sensory changes after long-term unilateral nasal obstruction-an animal study using MMP-3-LUC transgenic rats.

Nasal obstruction exerts considerable physiological effects on the respiratory system and craniofacial morphology during the developmental stage. This study used MMP-3-LUC transgenic rats for in vivo tracking of long-term expression in the rat nasal region after unilateral nasal obstruction. Skeletal changes of the craniofacial, nasal, and sinus regions were measured through micro-computed tomography examination and analysis with 3D image processing and calculation. Matrix metalloproteinase-3 and olfactory marker protein expression were also investigated through immunohistochemistry (IHC). Unilateral nasal obstruction significantly reduced the MMP-3 signal in the nasal region of MMP-3-LUC transgenic rats, which was mainly expressed in the respiratory epithelium. Long-term obstruction also caused morphological changes of the craniofacial hard tissue, such as nasal septal deviation, longer inter-jaw distance, and increased maxillary molar dental height. It also caused compensatory growth in olfactory nerve bundles and the olfactory epithelium, as confirmed by IHC. In our study, long-term unilateral nasal obstruction caused nasal septal deviation toward the unobstructed side, hyper divergent facial development including longer molar dental height, and reduced MMP-3 production. However, further investigation is necessary to explore the mechanism in depth.

Orthodontic correction of acquired open bite with TMJ degeneration: A retrospective study of outcomes and stability.

BACKGROUND/PURPOSE: Newly developed temporary anchorage devices (TADs) serve a strong orthodontic anchorage to intrude molars for correction of anterior open bite (AOB). We measured cephalometric changes in skeletal open bite patients which developed subsequently to temporomandibular joint disorders with bilateral point contacts at terminal molars. METHODS: We retrospectively recruited 32 patients who had been treated their TMD before orthodontic correction (overbite: -3.14 ± 1.86 mm). Partial orthodontic appliances were used to intrude posterior teeth using TADs until positive OB obtained (T1). Full fixed appliances were then used to achieve proper overjet and overbite (T2). We collected lateral cephalograms before (T0), during (T1) and after (T2) treatment, and at follow-ups (T3). Using ANOVA, we analyzed the differences among these time points to determine treatment changes and stability of orthodontic results. RESULTS: In this group predominantly comprising young adult women, orthodontic treatment with TADs significantly reduced upper posterior dental heights (T2-T0:-1.84 ± 0.66 mm) and facilitated the retraction and uprighting upper incisors (T2-T0: -9.92 ± 1.72°), to achieve appropriate OJ (T2-T0: -3.21 ± 0.49 mm) and OB (T2-T0: 4.10 ± 0.28 mm) with p < 0.05. Except upper posterior dental height, most of cephalometric changes including OJ, OB, and upper incisal axis remained significant at follow-ups with retention time of 3.7 ± 2.6 years. Only three out of 30 patients experienced small amount of open bite at T3. CONCLUSION: Orthodontic correction of OJ remained relatively stable among 90 % of patients with TMJ degeneration by intrusion via TADs. This modern but conservative orthodontic approach can improve occlusal functions in skeletal open bites.

Molecular signaling and mechanisms of low-level laser-induced gene expression in cells involved in orthodontic tooth movement.

BACKGROUND: The study aimed to observe molecular signaling, including reactive oxygen species (ROS) and mitochondrial membrane potential (ΔΨm), to evaluate the alteration of gene expression by low-level laser therapy (LLLT) and the correlation between its mechanisms and the NF-kB pathway in cells involved in orthodontic tooth movement. METHODS: Osteoblast-like cells (MG63), immortalized periodontal ligament cells (iPDL), and M1 macrophage-like cells were irradiated by 980-nm LLLT with energy densities of 1 and 10 J/cm2 ΔΨm and intracellular ROS were monitored using fluorescent probes. The changes of mRNA expression were assessed using reverse transcription polymerase chain reaction (RT-PCR). NF-kB inhibitor, ROS scavenger, and ΔΨm suppressor were used to analyze signals associated with the regulation of gene expression. Finally, Western blot analysis was performed to confirm NF-kB signaling after LLLT. RESULTS: We found the increases of ΔΨm and ROS in all three cell types after LLLT, but no significant difference was observed between 1 and 10 J/cm2 LLLT. Regarding gene expression, some target genes were upregulated in MG63 6 h, 12 h, and 1 day after LLLT and in iPDL cells 12 h and 1 day after LLLT. However, no changes occurred in M1 cells. The inhibitor that significantly reduced most changes in gene expression was NF-kB inhibitor. Western blot analysis showed the increase in p-IkBα level after LLLT in iPDL and MG63, but not in M1. CONCLUSION: The 980-nm LLLT increased ΔΨm and ROS production in all three cell types. However, changes in gene regulation were found only in MG63 and iPDL cells, which related to the NF-kB pathway.

PAX9 mutations and genetic synergism in familial tooth agenesis.

Familial tooth agenesis (FTA) is one of the most common craniofacial anomalies in humans. Loss-of-function mutations in PAX9 and WNT10A have been known to cause FTA with various expressivity. In this study, we identified five FTA kindreds with novel PAX9 disease-causing mutations: p.(Glu7Lys), p.(Val83Leu), p.(Pro118Ser), p.(Ser197Argfs*23), and c.771+4A>G. Concomitant PAX9 and WNT10A pathogenic variants found in two probands with severe phenotypes suggested an effect of mutational synergism. All overexpressed PAX9s showed proper nuclear localization, excepting the p.(Pro118Ser) mutant. Various missense mutations caused differential loss of PAX9 transcriptional ability. PAX9 overexpression in dental pulp cells upregulated LEF1 and AXIN2 expression, indicating a positive regulatory role for PAX9 in canonical Wnt signaling. Analyzing 176 cases with 63 different mutations, we observed a distinct pattern of tooth agenesis for PAX9-associated FTA: Maxillary teeth are in general more frequently affected than mandibular ones. Along with all second molars, maxillary bicuspids and first molars are mostly involved, while maxillary lateral incisors and mandibular bicuspids are relatively less affected. Genotypically, missense mutations are associated with fewer missing teeth than frameshift and nonsense variants. This study significantly expands the phenotypic and genotypic spectrums of PAX9-associated disorders and reveals a molecular mechanism of genetic synergism underlying FTA variable expressivity.

Measurements of craniofacial morphology using photogrammetry in children with sleep-disordered breathing.

OBJECTIVE: To assess the craniofacial morphology in children with sleep-disordered breathing (SDB) using nonradiation and readily accessible photogrammetry technique. METHODS: Included children aged 3-18 years with SDB-related symptoms from April 2019 to February 2020 in a tertiary center. All participants underwent craniofacial photogrammetry and overnight polysomnography (PSG). Participants were stratified into 2 groups (obstructive sleep apnea [OSA] group: apnea-hypopnea index [AHI] ≥ 1 and non-OSA group: AHI <1). Craniofacial photogrammetry was performed to derive variables of craniofacial features in standardized frontal and profile views. The 2 groups were propensity score matched based on age, sex, and body mass index (BMI) percentiles. Associations between craniofacial feature variables and OSA (AHI ≥1) likelihood were examined using logistic regression test. intraclass correlation coefficient (ICC) was used to evaluate the intrarater and interrater reliability. RESULTS: In total, 58 children were enrolled for the analysis after matching. All 3 variables representing the mandibular plane angle in the profile view were increased in the OSA group (mego-tn: 34.85 ± 5.99 vs 31.65 ± 5.96°, odds ratio [OR]: 1.10, 95% CI:1.02 to 1.18, P = .01; tn-gogn: 28.65 ± 6.38 vs 25.91 ± 5.38°, OR: 1.08, 95% CI:1.02 to 1.15, P = .012; and gome-tsup: 26.71 ± 6.13 vs 22.20 ± 5.89°, OR: 1.13, 95% CI:1.04 to 1.23, P = .003). CONCLUSIONS: Craniofacial photogrammetry revealed increased mandibular inclination in children with OSA. A steep mandibular plane with craniofacial photogrammetry is considered a potential predictor of pediatric OSA. Further investigation with a large sample size is required to clarify the validity of photogrammetry in evaluating pediatric OSA.

Changes in Cone-Beam Computed Tomography Pediatric Airway Measurements After Adenotonsillectomy in Patients With OSA.

Importance: Early intervention using cone-beam computed tomography (CBCT) and adenotonsillectomy for children with obstructive sleep apnea (OSA) may prevent impaired growth, adverse cardiovascular consequences, learning deficits, and poor quality of life. Objective: To assess changes in CBCT airway measurements and polysomnography (PSG) parameters that occur after adenotonsillectomy in children with OSA and to determine whether CBCT changes are correlated with apnea-hypopnea index (AHI) reduction. Design, Setting, and Participants: This prospective cohort study was conducted at a tertiary medical center from 2013 to 2016. Children aged 7 to 13 years with PSG-confirmed OSA (ie, AHI ≥1) were recruited. Data analysis was performed from March to July 2021. Exposures: All participants underwent CBCT and PSG before and after adenotonsillectomy. Main Outcomes and Measures: Changes in PSG and CBCT parameters after adenotonsillectomy were analyzed. Results: A total of 49 children (mean [SD] age, 9.5 [1.8] years; 34 boys [69.4%]) were recruited. Eighteen participants (36.7%) had obesity. After adenotonsillectomy, AHI significantly decreased from 11.4 to 1.2 events per hour (mean difference, -10.24 events per hour; 95% CI, -13.84 to -6.64 events per hour). The following CBCT parameters significantly increased: total airway volume (from 11 265 to 15 161 mm3; mean difference, 3896.6 mm3; 95% CI, 2788.0 to 5005.2 mm3), nasopharyngeal volume (from 2366 to 3826 mm3; mean difference, 1459.7 mm3; 95% CI, 1122.9 to 1796.5 mm3), minimal nasopharyngeal airway area (from 128 to 191 mm2; mean difference, 63.1 mm2; 95% CI, 47.4 to 78.8 mm2), mean nasopharyngeal airway area (from 144 to 231 mm2; mean difference, 86.8 mm2; 95% CI, 67.0 to 106.5 mm2), oropharyngeal volume (from 8898 to 11 335 mm3; mean difference, 2436.9 mm3; 95% CI, 1477.0 to 3396.8 mm3), minimal oropharyngeal airway area (from 82 to 158 mm2; mean difference, 76.2 mm2; 95% CI, 57.0 to 95.4 mm2), and mean oropharyngeal airway area (from 182 to 234 mm2; mean difference, 52.5 mm2; 95% CI, 33.6 to 71.4 mm2). Among all parameters, only body mass index percentile showed large effect size between the group with residual OSA (postoperative AHI ≥1) and the group with resolved disease, with the residual OSA group having a higher body mass index percentile (87.8 vs 61.4; mean difference, 26.33; 95% CI, 10.00 to 42.66). A quantile regression model revealed that total airway volume and minimal oropharyngeal airway area were significantly correlated with reductions in AHI. Conclusions and Relevance: These findings suggest that in children undergoing adenotonsillectomy, improvements in total airway volume and oropharyngeal minimal airway area were correlated with reduction of AHI. Future studies are needed to assess whether CBCT has a role in the evaluation of children with OSA who are being considered for adenotonsillectomy.

Cyclic mechanical stretch regulates the AMPK/Egr1 pathway in tenocytes via Ca2+-mediated mechanosensing.

PURPOSE: Mechanical stimuli are essential for the maintenance of tendon tissue homeostasis. The study aims to elucidate the mechanobiological mechanisms underlying the maintenance of tenocyte homeostasis by cyclic mechanical stretch under high-glucose (HG) condition. MATERIALS AND METHODS: Primary tenocytes were isolated from rat Achilles tendon and 2D-cultured under HG condition. The in vitro effects of a single bout, 2-h cyclic biaxial stretch session (1 Hz, 8%) on primary rat tenocytes were explored through Flexcell system. Cell viability, tenogenic gene expression, intracellular calcium concentration, focal adhesion kinase (FAK) expression, and signaling pathway activation were analyzed in tenocytes with or without mechanical stretch. RESULTS: Mechanical stretch increased tenocyte proliferation and upregulated early growth response protein 1 (Egr1) expression. An increase in intracellular calcium was observed after 30 min of stretching. Mechanical stretch phosphorylated FAK, calmodulin-dependent protein kinase kinase 2 (CaMKK2), and 5' adenosine monophosphate-activated protein kinase (AMPK) in a time-dependent manner, and these effects were abrogated after blocking intracellular calcium. Inhibition of FAK, CaMKK2, and AMPK downregulated the expression of Egr1. In addition, mechanical stretch reinforced cytoskeletal organization via calcium (Ca2+)/FAK signaling. CONCLUSIONS: Our study demonstrated that mechanical stretch-induced calcium influx activated CaMKK2/AMPK signaling and FAK-cytoskeleton reorganization, thereby promoting the expression of Egr1, which may help maintain tendon cell characteristics and homeostasis in the context of diabetic tendinopathy.

Changes of blood-brain-barrier function and transfer of amyloid beta in rats with collagen-induced arthritis.

BACKGROUND: Rheumatoid arthritis (RA) is characterized by synovial inflammation, cartilage damage, and systemic inflammation. RA is also associated with the occurrence of neuroinflammation and neurodegenerative diseases. In this study, the impacts of RA on the function of the blood-brain barrier (BBB) and the disposition of amyloid beta (Aß), including BBB transport and peripheral clearance of Aß, were investigated in rats with collagen-induced arthritis (CIA), an animal model with similarity to clinical and pathological features of human RA. METHODS: CIA was induced in female Lewis rats. In addition to neuroinflammation, the integrity and function of the BBB were examined. The expression of Aß-transporting proteins at brain blood vessels was measured. Blood-to-brain influx and plasma clearance of Aß were determined. RESULTS: Both microgliosis and astrogliosis were significantly increased in the brain of CIA rats, compared with controls. In terms of BBB function, the BBB permeability of sodium fluorescein, a marker compound for BBB integrity, was significantly increased in CIA rats. Moreover, increased expression of matrix metalloproteinase-3 (MMP-3) and MMP-9 and decreased expression of tight junction proteins, zonula occludens-1 (ZO-1) and occludin, were observed in brain microvessels of CIA rats. In related to BBB transport of Aß, protein expression of the receptor of advanced glycation end product (RAGE) and P-glycoprotein (P-gp) was significantly increased in brain microvessels of CIA rats. Notably, much higher expression of RAGE was identified at the arterioles of the hippocampus of CIA rats. Following an intravenous injection of human Aß, significant higher brain influx of Aß was observed in the hippocampus of CIA rats. CONCLUSIONS: Neuroinflammation and the changes of BBB function were observed in CIA rats. The increased RAGE expression at cerebral blood vessels and enhanced blood-to-brain influx of Aß indicate the imbalanced BBB clearance of Aß in RA.

Evaluation of Upper Airway in Children with Obstructive Sleep Apnea Using Cone-Beam Computed Tomography.

OBJECTIVE: Cone-beam computed tomography (CBCT) offers three-dimensional structures in assessing upper airway of patients. This study aims to compare the cone-beam computerized tomography scan measurements between children with obstructive sleep apnea (OSA) and primary snoring. STUDY DESIGN: Case-control study. METHODS: This prospective study was conducted in a tertiary referral center. Thirty-six children with moderate-to-severe OSA (with apnea-hypopnea index [AHI] > 5 events/hour) and 36 age-, gender-, and obesity-matched children with primary snoring (AHI <1) were enrolled. The measurements in CBCT parameters were compared between children with moderate-to-severe OSA and primary snorers by conditional logistic regression model. RESULTS: A total of 72 children (mean age, 7.9 ± 2.8 years; 64% male) were included. Children with moderate-to-severe OSA had a significantly smaller nasopharyngeal (2900 ± 1400 vs. 3800 ± 1800 mm3 , P = .017) and oropharyngeal airway volume (5600 ± 2700 vs. 7400 ± 4000 mm3 , P = .026) than those with primary snoring. Children with moderate-to-severe OSA, as compared to primary snorers, also had a significantly smaller minimal airway area in nasopharynx (77.4 ± 37.7 vs. 107.7 ± 52.0 mm2 , P = .006) and oropharynx (66.6 ± 61.9 vs. 101.6 ± 65.8 mm2 , P = .023). Moreover, the airway length was not significantly different between children with moderate-to-severe OSA and primary snoring. CONCLUSIONS: The three-dimensional CBCT airway analysis could be used as a useful tool to evaluate upper airway in children with OSA. LEVEL OF EVIDENCE: 3 Laryngoscope, 131:680-685, 2021.

Architectural changes in alveolar bone for dental decompensation before surgery in Class III patients with differing facial divergence: a CBCT study.

This study aimed to investigate alveolar bone change around mandibular anterior teeth during orthodontic decompensation in patients with skeletal Class III malocclusion and different vertical facial patterns. The records of 29 consecutive Class III patients selected from those pending two-jaw orthognathic surgery were divided into low (≤ 28°), average (30°-37°), and high (≥ 39°) mandibular plane angle (MPA) groups. The DICOM files of CBCT scans and STL files of digital dental models, taken before (T1) and after (T2) presurgical orthodontic treatment, were imported into Dolphin imaging software to reconstruct dentoskeletal images. T1 and T2 images were superimposed and analyzed for bone thickness and height at the level of root apex on each mid-sagittal slice of six mandibular anterior teeth. Differences between T1 and T2 were analyzed by non-parametric tests and mixed-effect model analysis. The results showed that the measurements of alveolar bone height generally decreased after treatment, regardless of MPA. The facial divergence, incisor irregularity, tooth site, treatment time, and change in proclination were identified as the significant factors affecting alveolar bone thickness and height during treatment. The presurgical orthodontic treatment to decompensate mandibular anterior teeth should be very careful in all MPA groups.

Simplified orthognathic surgical treatment using non-surgical asymmetric maxillary expansion: A case report.

BACKGROUND: Transverse problems can be exacerbated by highly compensated occlusion in patients with skeletal asymmetry, which makes pre-surgical decompensation harder to achieve. OBJECTIVE: This case report describes a case of combined orthognathic surgery with facial asymmetry. We used pre-orthodontic surgical simulation to visualize the goal for presurgical orthodontics, planning for a one-jaw surgical treatment option. METHODS: The planned asymmetric expansion was performed using a maxillary skeletal expander (MSE II) with surgical corticopuncture over only the left side before MSE activation. Surgery was performed to achieve mandibular left outward yaw rotation to correct the patient's facial asymmetry after the planned amount of expansion was reached. RESULTS: The results showed substantial improvement of facial aesthetics as well as skeletal symmetry. Cooperation and communication between surgeon and orthodontist ensured that the final results were satisfactory.

Airway increase after open bite closure with temporary anchorage devices for intrusion of the upper posteriors: Evidence from 2D cephalometric measurements and 3D magnetic resonance imaging.

OBJECTIVE: The aim of this study was to analyse morphological changes in the upper airways in patients with anterior open bite treated with temporary anchorage devices for intrusion of upper posterior teeth. MATERIALS AND METHODS: Twelve nonobese (body mass index: <25) anterior open bite patients between the ages of 19 and 44 years (mean age: 22.83 ± 8.19 years) were recruited for this study. Cephalometric radiographs and magnetic resonance imaging (MRI) scans before and after anterior bite closure without bracketing on anterior teeth were used to measure the upper airway, which was divided into retropalatal and retroglossal regions. RESULTS: The mandibular plane angle and lower facial height were significantly reduced by intrusion of the upper posteriors and autorotation of the mandible. The retroglossal airway width (AW2) and retroglossal area (RG area) measured on cephalometric radiographs both increased significantly after treatment. Retroglossal volume increased and the retroglossal width/length ratio decreased significantly in MRI analysis. All other measurements were not significantly changed. However, no statistically significant correlations were observed between all measurements in 2D and 3D images, with the exception of the AW2 linear measurement in 2D images correlating with the AP length in MRI axial view images (r = 0.56, P = 0.0430). CONCLUSION: Counterclockwise rotation of the mandible after anterior open bite closed using orthodontic treatment changed the airway morphology. Retroglossal volume significantly increased and the airway shape became less elliptical after bite closure.

970 nm low-level laser affects bone metabolism in orthodontic tooth movement.

OBJECTIVE: During orthodontic tooth movement (OTM), the speed of movement depends on the rate of bone turnover. In this study, we used a rat model to investigate the effect of 970 nm low-level laser therapy (LLLT) on OTM under different dose and frequency protocols. METHODS: We first compared the OTM rates between the OTM only control and the OTM + LLLT group (1250 J/cm2) in Experiment 1 and showed that LLLT significantly increased OTM. In Experiment 2, we employed 3 different LLLT protocols: the low-dose group and the high-dose group receiving 5 doses of 750 J/cm2 and 15,000 J/cm2 of LLLT every 3 days, respectively, and the early high-dose group which received 5 daily doses at 15,000 J/cm2 at the beginning of the experiments. The OTM-only control group received no LLLT. Tooth movement rate was measured through sequential silicone impressions. MicroCT was also performed to evaluate bone de-mineralization rate. Bone histmorphometry was used to compare the bone turnover rate between LLLT group and control group. Finally, TRAP, Osteocalcin, and VEGF expression is evaluated by immunohistochemistry (IHC) in tissue sections. RESULTS: When LLLT treatment was given every three days, both the 1250 J/cm2 and 15,000 J/cm2 groups showed significantly increased OTM compared to the control group. No significant difference was observed in the 750 J/cm2 group, or in the early irradiation group, when compared with controls, although 750 J/cm2 showed the same trend of accelerating OTM. The MicroCT result of rat maxilla demonstrated that LLLT increased bone remodeling and showed decreased bone mineral density and bone volume/total volume in the furcation areas of the maxillary first molars at the end of experiment. LLLT without OTM increased bone turnover as evidenced by fluorochrome incorporation. Immunohistochemistry analyses revealed high osteocalcin expression at later stages of OTM in the LLLT group, while VEGF expression was highly induced in the LLLT + OTM group at an early stage. CONCLUSION: Our results suggest that the 970 nm LLLT increases the rate of OTM in a dose-sensitive and frequency-dependent manner. Further animal and human studies are needed to determine the optimal timing and dosage of LLLT for OTM acceleration.

Hyperglycemia Augments the Adipogenic Transdifferentiation Potential of Tenocytes and Is Alleviated by Cyclic Mechanical Stretch.

Diabetes mellitus is associated with damage to tendons, which may result from cellular dysfunction in response to a hyperglycemic environment. Tenocytes express diminished levels of tendon-associated genes under hyperglycemic conditions. In contrast, mechanical stretch enhances tenogenic differentiation. However, whether hyperglycemia increases the non-tenogenic differentiation potential of tenocytes and whether this can be mitigated by mechanical stretch remains elusive. We explored the in vitro effects of high glucose and mechanical stretch on rat primary tenocytes. Specifically, non-tenogenic gene expression, adipogenic potential, cell migration rate, filamentous actin expression, and the activation of signaling pathways were analyzed in tenocytes treated with high glucose, followed by the presence or absence of mechanical stretch. We analyzed tenocyte phenotype in vivo by immunohistochemistry using an STZ (streptozotocin)-induced long-term diabetic mouse model. High glucose-treated tenocytes expressed higher levels of the adipogenic transcription factors PPARγ and C/EBPs. PPARγ was also highly expressed in diabetic tendons. In addition, increased adipogenic differentiation and decreased cell migration induced by high glucose implicated a fibroblast-to-adipocyte phenotypic change. By applying mechanical stretch to tenocytes in high-glucose conditions, adipogenic differentiation was repressed, while cell motility was enhanced, and fibroblastic morphology and gene expression profiles were strengthened. In part, these effects resulted from a stretch-induced activation of ERK (extracellular signal-regulated kinases) and a concomitant inactivation of Akt. Our results show that mechanical stretch alleviates the augmented adipogenic transdifferentiation potential of high glucose-treated tenocytes and helps maintain their fibroblastic characteristics. The alterations induced by high glucose highlight possible pathological mechanisms for diabetic tendinopathy. Furthermore, the beneficial effects of mechanical stretch on tenocytes suggest that an appropriate physical load possesses therapeutic potential for diabetic tendinopathy.

Early Orthodontic Tooth Movement into Regenerative Bony Defects: A Case Report.

Early orthodontic tooth movement following regenerative surgery is controversial. In this case, during protraction of the maxillary right first premolar to substitute for the long-term missing maxillary right canine, Bio-Oss and Bio-Gide were used for lateral ridge augmentation at the area of the maxillary right lateral incisor and to cover the denuded surface at the buccal side of the first premolar. Orthodontic tooth movement (OTM) commenced 2 weeks after regenerative surgery. After 8 months, new bone formation was observed on the root surface of the first premolar during implant surgery. A cone beam computed tomography scan taken 1.5 years postsurgery revealed good maintenance of regenerative bone at the same site. This satisfactory outcome of early OTM following regenerative surgery suggests biomechanical stimulation may not jeopardize the regenerative effect.

Revisiting the stability of mini-implants used for orthodontic anchorage.

BACKGROUND/PURPOSE: The aim of this study is to comprehensively analyze the potential factors affecting the failure rates of three types of mini-implants used for orthodontic anchorage. METHODS: Data were collected on 727 mini-implants (miniplates, predrilled titanium miniscrews, and self-drilling stainless steel miniscrews) in 220 patients. The factors related to mini-implant failure were investigated using a Chi-square test for univariate analysis and a generalized estimating equation model for multivariate analysis. RESULTS: The failure rate for miniplates was significantly lower than for miniscrews. All types of mini-implants, especially the self-drilling stainless steel miniscrews, showed decreased stability if the previous implantation had failed. The stability of predrilled titanium miniscrews and self-drilling stainless steel miniscrews were comparable at the first implantation. However, the failure rate of stainless steel miniscrews increased at the second implantation. The univariate analysis showed that the following variables had a significant influence on the failure rates of mini-implants: age of patient, type of mini-implant, site of implantation, and characteristics of the soft tissue around the mini-implants. The generalized estimating equation analysis revealed that mini-implants with miniscrews used in patients younger than 35 years, subjected to orthodontic loading after 30 days and implanted on the alveolar bone ridge, have a significantly higher risk of failure. CONCLUSION: This study revealed that once the dental surgeon becomes familiar with the procedure, the stability of orthodontic mini-implants depends on the type of mini-implant, age of the patient, implantation site, and the healing time of the mini-implant. Miniplates are a more feasible anchorage system when miniscrews fail repeatedly.

Cloning, expression and characterization of CCL21 and CCL25 chemokines in zebrafish.

Chemokines are a large group of proteins implicated in migration, activation, and differentiation of leukocytes. They are well-surveyed in mammals, but less is known in lower vertebrates about their spatiotemporal expressions and functions. From an evolutionary point of view, comparative analyses may provide some fundamental insights into these molecules. In mammals, CCL21 and CCL25 are crucial for thymocyte homing. Herein, we identified and cloned the zebrafish orthologues of CCL21 and CCL25, and analyzed their expression in embryos and adult fish by in situ hybridization. We found that CCL21 was expressed in the craniofacial region, pharynx, and blood vessels in embryos. In adult fish, CCL21 transcripts were located in the kidney, spinal cord, and blood cells. In contrast, expression of CCL25 was only detected in the thymus primordia in embryos. In adult fish, transcripts of CCL25 were maintained in the thymus, and they were also found in the brain and oocytes. Furthermore, we performed an antisense oligonucleotide experiment to evaluate the biological function of CCL25. Results showed that the recruitment of thymocytes was impeded by morpholino-mediated knockdown of CCL25, suggesting that CCL25 is essential for colonization of T-cells in the thymus in early development. Together, our results demonstrate the basic profiles of two CCL chemokines in zebrafish. The tissue-specific expression patterns may pave the way for further genetic dissection in this model organism.

Stability of miniplates and miniscrews used for orthodontic anchorage: experience with 492 temporary anchorage devices.

OBJECTIVES: The aim of this retrospective study was to evaluate systematically the potential factors that influence failure rates of temporary anchorage devices (TADs) used for orthodontic anchorage. MATERIALS AND METHODS: Data on 492 TADs (miniplates, pre-drilling miniscrews, and self-drilling miniscrews) in 194 patients were collected. The factors related to TAD failure were evaluated using univariate analysis and multivariate forward stepwise logistic regression analysis. RESULTS: There were no significant differences in failure rates among the TADs for the following variables: gender, type of malocclusion, facial divergency, implantation site (buccal, lingual, or crestal/midpalatal), location (anterior or posterior), method of force application (power chain or Ni-Ti coil spring), arch (upper or lower), type of soft tissue (attached gingiva or removable mucosa), and most of the cephalometric measurements that reflect dento-cranio-facial characteristics. An increased failure rate was noted for the self-drilling miniscrew type of TAD, TADs used for tooth uprighting, those inserted on bone with lower density, those associated with local inflammation of the surrounding soft tissue, those loaded within 3 weeks after insertion, and those placed in patients with greater mandibular retrusion. Failure rates of the self-drilling miniscrews installed by an oral surgeon and by an orthodontist did not differ significantly. CONCLUSIONS: Inflammation of soft tissue surrounding a TAD and early loading within 3 weeks after insertion were the most significant factors predicting TAD failure. Both orthodontists and oral surgeons who install orthodontic TADs must undergo sufficient training to achieve clinical excellence.

Comparison of treatment outcomes between skeletal anchorage and extraoral anchorage in adults with maxillary dentoalveolar protrusion.

INTRODUCTION: The goal of this retrospective cephalometric study was to compare orthodontic outcomes in patients with maxillary dentoalveolar protrusion malocclusion treated with extraoral headgear or mini-implants for maximum anchorage. MATERIALS: Forty-seven subjects with Angle Class II malocclusion or Class I bimaxillary dentoalveolar protrusion were treated by retracting the maxillary dentoalveolar process by using the extraction space of the bilateral maxillary first premolars. Two anchorage systems were used. Group 1 (n = 22) received traditional anchorage preparation with a transpalatal arch and headgear; group 2 (n = 25) received mini-implants (miniplates, miniscrews, or microscrews) for bony anchorage. Pretreatment and posttreatment lateral cephalograms were superimposed to compare the following parameters between groups: (1) amount of maxillary central incisor retraction, (2) reduction in maxillary central incisor angulation, (3) anchorage loss of the maxillary first molar, (4) movements of the maxillary central incisor and first molar in the vertical direction, and (5) changes in skeletal measurements representing the anteroposterior and vertical jaw relationships. RESULTS: The skeletal anchorage group had greater anterior tooth retraction (8.17 vs 6.73 mm) and less maxillary molar mesialization (0.88 vs 2.07 mm) than did the headgear group, with a shorter treatment duration (29.81 vs 32.29 months). Translational movement of the incisors was more common than tipping movement, and intrusion of the maxillary dentition was greater, in patients receiving miniplates than in those receiving screw-type bony anchorage, resulting in counterclockwise rotation of the mandible and a statistically significant decrease in the mandibular plane angle. Cephalometric analysis of skeletal measurements in patients with low to average mandibular plane angles showed no significant difference between groups, although greater maxillary incisor retraction and less mesial movement of the first molar were noted in the mini-implant group. In patients with a high mandibular plane angle, those receiving skeletal anchorage had genuine intrusion of the maxillary first molar and reduction in the mandibular plane angle, whereas those receiving headgear anchorage had extrusion of the maxillary first molar and an increase of mandibular plane angle. In contrast to the posterior movement in the headgear group, anterior movement of Point A was noted in the mini-implant group. CONCLUSIONS: In both the anteroposterior and vertical directions, skeletal anchorage achieved better control than did the traditional headgear appliance during the treatment of maxillary dentoalveolar protrusion. Greater retraction of the maxillary incisor, less anchorage loss of the maxillary first molar, and the possibility of counterclockwise mandibular rotation all facilitated the correction of the Class II malocclusion.