Chung-Chen Jane Yao

DAP-kinase induces apoptosis by suppressing integrin activity and disrupting matrix survival signals.

Death-associated protein kinase (DAP-kinase) is a calcium/calmodulin-dependent serine/threonine kinase, and participates in various apoptosis systems. However, its apoptosis-promoting mechanism is poorly understood. Here, we demonstrate that DAP-kinase suppresses integrin-mediated cell adhesion and signal transduction, whereas dominant-negative interference of this kinase promotes adhesion. This effect of DAP-kinase is neither a consequence of apoptosis nor a result of decreased expression of integrins. Rather, DAP-kinase downregulates integrin activity through an inside-out mechanism. We present evidence indicating that this adhesion-inhibitory effect accounts for a major mechanism of the apoptosis induced by DAP-kinase. First, in growth-arrested fibroblasts, DAP-kinase triggers apoptosis in cells plated on fibronectin, but does not affect the death of cells on poly-l-lysine. Second, in epithelial cells, DAP-kinase induces apoptosis in the anoikis-sensitive MCF10A cells, but not in the anoikis-resistant BT474 cells. Most importantly, the apoptosis-promoting effect of DAP-kinase is completely abolished by enforced activation of integrin-mediated signaling pathways from either integrin itself or its downstream effector, FAK. Finally, we show that integrin or FAK activation blocks the ability of DAP-kinase to upregulate p53. Our results indicate that DAP-kinase exerts apoptotic effects by suppressing integrin functions and integrin-mediated survival signals, thereby activating a p53-dependent apoptotic pathway.

Maxillary Molar Intrusion with Fixed Appliances and Mini-implant Anchorage Studied in Three Dimensions

The intrusion of an overerupted maxillary molar using traditional orthodontic treatment is a real challenge. The aim of this study was to investigate the envelope of intrusive movements of a maxillary molar in cases using mini-implants as anchorage with partial or full-mouth fixed edgewise appliances. The cusp tips of the pretreatment and postintrusion dental casts were recorded by a three-dimensional (3D) digitizer. The 3D data of the serial dental casts were analyzed to distinguish the direction and magnitude of individual tooth movement. The mean intrusive movement of the maxillary first molars was three to four mm, with a maximum of over eight mm. For the adjacent maxillary second molars and second premolars, the amount of intrusion was two mm and 1-2 mm, respectively. This study demonstrated that significant true intrusion of maxillary molars could be obtained in a well-controlled manner by using fixed appliances with titanium mini-implants as bony anchorage.

The tumor suppressor DAPK inhibits cell motility by blocking the integrin-mediated polarity pathway

Death-associated protein kinase (DAPK) is a calmodulin-regulated serine/threonine kinase and possesses apoptotic and tumor-suppressive functions. However, it is unclear whether DAPK elicits apoptosis-independent activity to suppress tumor progression. We show that DAPK inhibits random migration by reducing directional persistence and directed migration by blocking cell polarization. These effects are mainly mediated by an inhibitory role of DAPK in talin head domain association with integrin, thereby suppressing the integrin–Cdc42 polarity pathway. We present evidence indicating that the antimigratory effect of DAPK represents a mechanism through which DAPK suppresses tumors. First, DAPK can block migration and invasion in certain tumor cells that are resistant to DAPK-induced apoptosis. Second, using an adenocarcinoma cell line and its highly invasive derivative, we demonstrate DAPK level as a determining factor in tumor invasiveness. Collectively, our study identifies a novel function of DAPK in regulating cell polarity during migration, which may act together with its apoptotic function to suppress tumor progression.

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.

Intrusion of the overerupted upper left first and second molars by mini-implants with partial-fixed orthodontic appliances: a case report.

Overeruption of maxillary molar(s) because of loss of the opposing teeth creates occlusal interference and functional disturbances. To restore proper occlusion, intrusion of the overerupted molars becomes essential before reconstruction can be initiated. A plausible procedure is orthodontic intrusion, which demands calibrated anchorage support from intraoral multiunit teeth and from headgear wear. In this report, we present a simplified and localized version of the orthodontic appliances in conjunction with mini-implants to intrude the overerupted molars. The purpose of using implants as skeletal anchorage was to eliminate the need for patient compliance for headgear wear and to overcome the difficulty resulting from the shortage of anchor teeth. The results showed that the biological responses of the teeth and the surrounding bony structures to the intrusion appeared normal and acceptable. Furthermore, the periodontal health and vitality of the teeth were well maintained even after a one-year follow-up.

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.

Three-dimensional dental model analysis of treatment outcomes for protrusive maxillary dentition: Comparison of headgear, miniscrew, and miniplate skeletal anchorage

INTRODUCTION The aim of this retrospective study on dental models was to compare the orthodontic outcomes of maxillary dentoalveolar protrusion treated with headgear, miniscrews, or miniplates for maximum anchorage. METHODS The 40 subjects were diagnosed as having either Angle Class II malocclusion or Class I bimaxillary dentoalveolar protrusion. All patients were treated to retract the maxillary dentoalveolar process by using the extraction space of the bilateral maxillary first premolars. They were divided into 3 groups according to the type of anchorage used. Group 1 (n = 16) received traditional anchorage preparation with a transpalatal arch and headgear, group 2 (n = 15) received miniscrews, and group 3 (n = 9) received miniplates for skeletal anchorage. To investigate the movement of the maxillary teeth during dentoalveolar retraction, we used a 3-dimensional (3D) digitizer to assess the positional changes of the maxillary teeth relative to the stable palatal rugose structures on the serial dental models. The 3D coordinates representing pretreatment and posttreatment maxillary dental casts were superimposed to determine the movement of individual teeth from the positional changes of 18 landmarks of the central incisor, canine, second premolar, and first molar. RESULTS Three-dimensional analysis of the maxillary dental models in the buccopalatal, anteroposterior, and vertical directions showed significant differences in tooth movements between the headgear and the mini-implant (miniscrew or miniplate) groups. Both skeletal anchorage groups had greater incisor retraction (6.9 mm for the miniscrew, 7.3 mm for the miniplate) than did the headgear group (5.5 mm). Mesialization of occlusal centroid of the maxillary molar in the skeletal anchorage groups was less than that in the headgear group (1.3 mm for the miniscrew, 1.4 mm for the miniplate, 2.5 mm for the headgear). Tooth movements in the anteroposterior and buccopalatal directions did not reach a statistically significant difference between the miniscrew and miniplate groups, but the maxillary posterior teeth of the subjects receiving miniplates showed greater intrusion than those receiving miniscrews anchorage. CONCLUSIONS This 3D analysis of serial dental models demonstrated that, compared with headgear, skeletal anchorage achieved better results in the treatment of maxillary dentoalveolar protrusion. Significant intrusion of the maxillary posterior teeth was noted in the miniplate group but not in the miniscrew and headgear groups. Greater retraction of the maxillary anterior teeth, less anchorage loss of the maxillary posterior teeth, and the possibility of maxillary molar intrusion all facilitated correction of the Class II malocclusion, especially for patients with a hyperdivergent face.

Radiographic Assessment of Skeletal Maturation Stages for Orthodontic Patients: Hand-wrist Bones or Cervical Vertebrae?

BACKGROUND/PURPOSE The skeletal maturation status of a growing patient can influence the selection of orthodontic treatment procedures. Either lateral cephalometric or hand-wrist radiography can be used to assess skeletal development. In this study, we examined the correlation between the maturation stages of cervical vertebrae and hand-wrist bones in Taiwanese individuals. METHODS The study group consisted of 330 male and 379 female subjects ranging in age from 8 to 18 years. A total of 709 hand-wrist and 709 lateral cephalometric radiographs were analyzed. Hand-wrist maturation stages were assessed using National Taiwan University Hospital Skeletal Maturation Index (NTUH-SMI). Cervical vertebral maturation stages were determined by the latest Cervical Vertebral Maturation Stage (CVMS) Index. Spearmans rank correlation was used to correlate the respective maturation stages assessed from the hand-wrist bones and the cervical vertebrae. RESULTS The values of Spearmans rank correlation were 0.910 for males and 0.937 for females, respectively. These data confirmed a strong and significant correlation between CVMS and NTUH-SMI systems (p less than 0.001). After comparison of the mean ages of subjects in different stages of CVMS and NTU-SMI systems, we found that CVMS I corresponded to NTUH-SMI stages 1 and 2, CVMS II to NTUH-SMI stage 3, CVMS III to NTUHSMI stage 4, CVMS IV to NTUH-SMI stage 5, CVMS V to NTUH-SMI stages 6, 7 and 8, and CVMS VI to NTUH-SMI stage 9. CONCLUSION Our results indicate that cervical vertebral maturation stages can be used to replace hand-wrist bone maturation stages for evaluation of skeletal maturity in Taiwanese individuals.

MMP-3 Response to Compressive Forces in vitro and in vivo

During orthodontic tooth movement, bone resorption occurs at the compression site. However, the mechanism underlying resorption remains unclear. Applying compressive force to human osteoblast-like cells grown in a 3D collagen gel, we examined gene induction by using microarray and RT-PCR analysis. Among 43 genes exhibiting significant changes, cyclo-oxygenase-2, ornithine decarboxylase, and matrix metalloproteinase-3 (MMP-3) were up-regulated, whereas membrane-bound interleukin-1 receptor accessory protein was down-regulated. The MMP-3 protein increases were further confirmed by Western blot. To ascertain whether MMP-3 is up-regulated in vivo by orthodontic force, we examined human bone samples at the compressive site by realigning the angulated molars. Immunohistochemical staining revealed MMP-3 distributed along the compressive site of the bony region within 3 days of compression. Since MMP-3 participates in degradation of a wide range of extracellular matrix molecules, we propose that MMP-3 plays an important role in bone resorption during orthodontic tooth movement.

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.