Circular RNA CircSATB2 facilitates osteosarcoma progression through regulating the miR-661/FUS-mediated mRNA of ZNFX1.

Circular RNAs (circRNAs) are a class of non-coding RNAs which take part in the regulation of the initiation and development of different types of cancer. Numerous studies have demonstrated that circRNAs are involved in the progression of osteosarcoma (OS) as well. Thus, we put our emphasis on the exploration of crucial circRNAs in the process of OS initiation and progression. Using RNA sequencing, we found that circSATB2 was highly expressed in OS tissues compared with adjacent normal tissues. Then, we confirmed the high expression of circSATB2 in OS cell lines and OS tissues and its high expression was related to poor prognosis of OS patients. Functional experiments exhibited that circSATB2 promoted OS proliferation and migration in vitro, primary OS model and OS lung metastasis model showed that circSATB2 aggravated OS progression in vivo. Mechanistically, circSATB2 was found to promote OS progression through sponging miR-661 and FUS regulating the mRNA of ZNFX1. Therefore, circSATB2 could act as a prognostic marker and a therapeutic target for osteosarcoma in the future.

In vivo self-assembly and delivery of VEGFR2 siRNA-encapsulated small extracellular vesicles for lung metastatic osteosarcoma therapy.

The prognosis of lung metastatic osteosarcoma (OS) remains disappointing. siRNA-based gene silencing of VEGFR2 is a promising treatment strategy for lung metastatic OS, but there is a lack of safe and efficient delivery systems to encapsulate siRNAs for in vivo administration. This study presented a synthetic biological strategy that remolds the host liver with synthesized genetic circuits for efficient in vivo VEGFR2 siRNA delivery. After being taken-up by hepatocytes, the genetic circuit (in the form of a DNA plasmid) reprogrammed the liver to drive the autonomous intrahepatic assembly and encapsulation of VEGFR2 siRNAs into secretory small extracellular vesicles (sEVs), thus allowing for the transport of self-assembled VEGFR2 siRNAs towards the lung. The results showed that our strategy was superior to the positive medicine (Apatinib) for OS lung metastasis in terms of therapeutic efficacy and toxic adverse effects and may provide a feasible and viable therapeutic solution for lung metastatic OS.

Volumetric cone-beam computed tomography evaluation and risk factor analysis of external apical root resorption with clear aligner therapy.

OBJECTIVES: To investigate the prevalence and severity of external apical root resorption (EARR) volumetrically with clear aligner therapy using cone-beam computed tomography (CBCT) as well as determine the possible risk factors and develop a prediction model for EARR. MATERIALS AND METHODS: In this retrospective study, 320 incisors from 40 Class II patients treated with aligners (Invisalign) were included in this study. CBCT images were obtained at pretreatment (T0) and posttreatment (T1). Root volume was calculated by three-dimensional reconstruction of CBCT images, and apical tooth movement was measured from superimposed CBCT images. Changes in root volume were compared using paired t-tests, and the relationship between root volume loss and potential risk factors was analyzed by multiple linear regression. RESULTS: All of the measured incisors showed root volume loss, with an average of 11.48 ± 6.70 mm3, and the prevalence of severe resorption was 0.625%. The prediction model for EARR included variables of posttreatment sagittal root position (SRP), extraction, tooth type, and apical intrusion and extrusion displacements, with an R2 of 0.51. Age, sex, duration, pretreatment SRP, attachment, advancement, and retraction movements were excluded from the model. CONCLUSIONS: Most incisors showed mild to moderate resorption during aligner treatment; only a minimal percentage showed severe resorption. Posttreatment SRP (which showed the highest association with EARR), extraction, tooth type, and apical intrusion and extrusion displacements were risk factors for EARR.

Predicted and actual outcome of anterior intrusion with Invisalign assessed with cone-beam computed tomography.

INTRODUCTION: The purpose of this study was to compare predicted anterior teeth intrusion measurements with the actual clinical intrusion measurements using cone-beam computed tomography. Understanding the precision of the software in anticipating changes may help practitioners predict the need for overcorrection. METHODS: Twenty-two patients, with a mean age of 23.74 years, who underwent Invisalign (Align Technology, Santa Clara, Calif) clear aligners treatment for both arches only after having completed treatment with an initial series of aligners were included in this study. The pretreatment and posttreatment cone-beam computed tomography scans after the initial series were acquired by a single orthodontist practitioner. ClinCheck measurements were recorded with Align Technology. The long axis of the anterior tooth intrusion movement was measured in 142 teeth. A comparison between the predicted and actual measurements of anterior intrusion of the teeth was performed, and the intraclass correlation coefficients showed an almost perfect agreement in the linear measurements. RESULTS: A statistically notable difference between the predicted and actual measurements of anterior intrusion. The predicted intrusion movement of the maxillary canines (P = 0.001), maxillary lateral incisors (P <0.0001), and maxillary central incisors (P <0.0001) significantly differed from the actual values. Similarly, the intrusion movement in the mandibular teeth seemed to be inaccurate, with significant differences in the mandibular canines (P <0.0001) and mandibular lateral and central incisors (P <0.0001). CONCLUSIONS: The mean precision of true anterior intrusion with Invisalign clear aligners was 51.19%, and the mean amount of correction was 48.81%. The use of other supplementary methods of anterior teeth intrusion may be helpful to reduce the rate of midcourse corrections and refinements.

The expression of extracellular matrix metalloproteinase inducer (EMMPRIN) in the compression area during orthodontic relapse.

OBJECTIVE: This study investigated the expression of extracellular matrix metalloproteinase inducer (EMMPRIN) in the compression area during orthodontic relapse in rat molars. MATERIALS AND METHODS: Thirty Wistar rats (6 weeks old) underwent orthodontic tooth movement (OTM) of the left first maxillary molar for 21 days, followed by removal of the force device. The contralateral maxillary molar served as a control with no mechanical force stimuli. Animals were sacrificed at 0, 1, 3, 7, and 14 days of relapse after force withdrawal. Tooth relapse and alveolar bone parameters were measured using microcomputed tomography (micro-CT). Maxilla sections were obtained for haematoxylin and eosin (HE), immunohistochemical staining [EMMPRIN, nuclear factor kappa B ligand (RANKL) and vascular endothelial growth factor (VEGF)] and tartrate-resistant acid phosphatase (TRAP). Correlation analyses were then performed. RESULTS: After force removal, nearly 79.88% of the total relapse occurred within the initial 3 days. The number of osteoclasts clearly increased while the alveolar bone density decreased on the pressure side on Day 3 of relapse. Moreover, the EMMPRIN expression level significantly increased on Day 1, peaked up on Day 3 and decreased on Days 7 and 14. Statistically, a strong positive correlation was found between EMMRPIN expression and the osteoclast number and RANKL and VEGF expression. CONCLUSION: EMMPRIN was highly expressed on the pressure side during the orthodontic tooth relapse, which could be involved in osteoclastogenesis and alveolar bone resorption in association with RANKL and VEGF expression.

Effects of Twin Inclined Plane Device on Adaptation and Ultrastructure Variations in Condyle of Growing Rats.

OBJECTIVE: This study investigates the effects of using a twin inclined plane device (TIPD) on the remolding and ultrastructure variation of mandibular condyle in growing rats. MATERIALS AND METHODS: Forty-eight male Wistar rats (six weeks old, body weight of approximately 190-210 g) were divided into experimental group (wearing appliance, n = 32) and control group (no appliance, n = 16). Samples were collected on days 3, 14, 30, and 60. The immunohistochemical analysis for vascular endothelial growth factor (VEGF) and type II collagen was carried out. Tartrate-resistant acid phosphatase (TRAP) reaction was performed to evaluate the osteoclastic activity. Three-dimensional morphometric images were reconstructed for morphometric analysis by microcomputed tomography (micro-CT). The ultrastructure of the condylar surface was observed by scanning electron microscopy (SEM). RESULTS: The expression of VEGF significantly increased, while the expression of type II collagen decreased in the experimental group at days 30 and 60. Furthermore, the enhanced osteoclast activity was observed under the subchondral bone, which was highest at day 30, and decreased to the lowest at day 60 in the experimental group. In addition, adaptive subchondral bone remolding in the posterior part of the condyle was observed at day 60 in the experimental group, and the SEM revealed the ultrastructure variations after installation of the TIPD. However, these changes began to reverse after 30 days. CONCLUSION: Condylar tissue changes point to the osteoclastic activity in the posterior region of the condyle. These adaptive changes point to bone resorption in the posterior condyle. Type II collagen and VEGF contribute to the MCC remolding induced by the TIPD. The ultrastructural changes in the posterior condylar area in response to mechanical stresses are recoverable at the initial stage.

Innovation of Invisalign technology and its efficacy for tooth movement / 口腔疾病防治

@#The Invisalign system has been used in the clinic for nearly two decades and its invisible, comfortable and beautiful features are increasingly favored by doctors and patients. In recent years, Invisalign technology is constantly innovating from mild crowding (G1), relatively complicated tooth movement (G2), anterior tooth torque control (G3), anterior open bite (G4), deep overbite (G5), first four premolar extraction (G6), and posterior open bite (G7) to the correction of skeletal class Ⅱmalocclusion in adolescents. Its indications has covered almost all areas of traditional fixed orthodontics. However, as this technology is in the developmental stage, there is a discontinuity between the computer-designed positioning and the clinical results. Although Invisalign has manifested excellent performance in correcting tooth intrusion, tipping movement and distal movement, its ability to correct tooth rotation and extrusion still needs improvement. This paper reviews the characteristics of Invisalign G1-G7 and Invisalign MA and the efficacy of these systems in correcting different types of tooth movement.

Correction of a dental arch-width asymmetric discrepancy with a slow maxillary contraction appliance.

A boy, aged 12 years 3 months, sought treatment for a complete unilateral Brodie bite. His maxillary dental arch was asymmetric, and his dentition was 10 mm wider than normal values for his age. The transverse discrepancy was his chief complaint because it caused a chewing dysfunction. We used a special slow maxillary contraction appliance, which contains a screw, connectors, and retainers, to contract the maxillary transverse asymmetric dental arch. This was followed by preadjusted fixed appliances to level the teeth and adjust the occlusion. A symmetric and functional Class I occlusion was achieved.

The effects of gradually induced backward movement of the mandible by a Twin Inclined Plane Device in rats.

OBJECTIVE: To develop a model of gradually induced backward movement of the mandible under normal masticatory action and to examine morphological changes in the mandible and condylar cartilage in rats. MATERIALS AND METHODS: The newly developed Twin Inclined Plane Device (TIPD) was composed of upper and lower posterior metal crowns with a long inclined plane on both sides separately and was applied in experimental groups of 6-week-old male Wister rats. After 3, 14, 30, and 60 days, the rats were euthanatized and samples were collected. Various measurements and hematoxylin-and-eosin stains were performed. RESULTS: From day 30 on, the length of the condylar process was shorter in the TIPD groups than in the control groups (P < .05). The angulation of the condylar process axis to the mandibular plane was greater in the TIPD groups (P < .01). The thickness of the condylar cartilage in the posterior part of the posterior region was thinner in the TIPD groups (P < .05) on day 30 and even thinner (P < .01) on day 60; from day 30 on, the thickness in the anterior part of the posterior region was thicker in the TIPD groups (P < .01). CONCLUSION: TIPD can successfully induce backward movement of the mandible under normal masticatory action. TIPD can cause region-specific changes in condylar cartilage and leads to a continuous remodeling.

[Expression of cathepsin K and IL-6 mRNA in root-resorbing tissue during tooth movement in rats].

OBJECTIVE: To investigate the expression and the localization of Cathepsin K and IL-6 mRNA in root-resorbing tissue and to elucidate the molecular changes and mechanism of root resorption induced by tooth movement. METHODS: Rats were subject to experimental tooth movement to induce root resorption. In situ hybridization was performed to identify the cells in root-resorbing tissue that produced Cathepsin K or IL-6 the difference of CK mRNA or IL-6 mRNA expression between root resorption group and control group was calculated by t-test. RESULTS: Cathepsin K mRNA was highly and selectively expressed in multinuclear odontoclast and IL-6 mRNA expressed in fibroblast, osteoblast, osteocyte and cementoblast. The expression of Cathepsin K mRNA and IL-6 mRNA in root-resorbing tissue increased evidently compared with the normal periodontium. CONCLUSIONS: Odontoclast in the root-resorbing tissue expresses Cathepsin K mRNA that participates in proteolysis during root resorption. IL-6 plays a very important role in the root resorption as a multifunctional cytokine.