Osteoclast-Driven Osteogenesis, Bone Remodeling and Biomaterial Resorption: A New Profile of BMP2-CPC-Induced Alveolar Bone Regeneration.

This bedside-to-bench study aimed to systematically investigate the value of applying BMP2-loaded calcium phosphate cement (BMP2-CPC) in the restoration of large-scale alveolar bone defects. Compared to deproteinized bovine bone (DBB), BMP2-CPC was shown to be capable of inducing a favorable pattern of bone regeneration and bone remodeling accompanied by active osteoclastogenesis and optimized biomaterial resorption when applied in reconstructive periodontally accelerated osteogenic orthodontics (PAOO) surgery. To verify the regulatory role of osteoclasts in the BMP2-CPC-induced pattern of bone regeneration, in vitro and in vivo studies were designed to elucidate the underlying mechanism. Our results revealed that osteoclasts played a multifaceted role (facilitating osteogenesis, bone remodeling and biomaterial resorption) in the BMP2-CPC-induced bone regeneration. Osteoclasts contributed to the osteogenic differentiation of mesenchymal stem cells (MSCs) by secreting calcium ions, CTHRC1 and PDGF-B. Moreover, the increased osteoclasts promoted the remodeling of new bone and BMP2-CPC resorption, leading to a harmonized replacement of biomaterials with mature bone. In conclusion, the in vitro and in vivo experimental results corresponded with the clinical results and showed the optimized properties of BMP2-CPC in activating osteoclast-driven bone regeneration and remodeling, thus indicating the highly promising prospects of BMP2-CPC as an ideal therapeutic for alveolar bone defects.

Satb2 expression in Foxc1-promoted osteogenic differentiation of MC3T3-E1 cells is negatively regulated by microRNA-103-3p.

The forkhead transcription factor C1 (Foxc1) is a cell-fate-determining factor that controls cranial bone development and osteogenic differentiation. Previously, it was demonstrated that various microRNAs (miRNAs) play important roles in osteogenesis and regulate the complex process of osteogenic differentiation. However, it remains unclear how miRNA expression changes during Foxc1-promoted osteogenic differentiation. In this study, we successfully overexpressed the Foxc1 gene in MC3T3-E1 cells and investigated the alterations in the miRNA expression profile on day 3 after osteogenic induction by using a miRNA microarray. Nine downregulated miRNAs and eight upregulated miRNAs were found to be differentially expressed. Among these miRNAs, miR-103-3p was consistently downregulated in the Foxc1-overexpressing MC3T3-E1 cells and was identified as a negative regulator of osteogenic differentiation by using a gain- and lose-of-function assay. The special AT-rich sequence-binding protein 2 (Satb2), a pivotal osteogenic transcription factor, was identified as the miR-103-3p targeting gene and was verified by real-time polymerase chain reaction, western blot analysis, and luciferase assay. Overexpression of miR-103-3p markedly inhibited the expression of Satb2 and attenuated Foxc1-promoted osteogenic differentiation. Taken together, our results elucidated the miRNA expression profiles of MC3T3-E1 cells in the early stage of Foxc1-promoted osteogenic differentiation and suggested that miR-103-3p acts as a negative regulator of the osteogenic differentiation of MC3T3-E1 cells by directly targeting Satb2.

Amniotic fluid-derived stem cells mixed with platelet rich plasma for restoration of rat alveolar bone defect.

Stem cells isolated from the amniotic fluid have been shown as a promising candidate for cell therapy and tissue engineering. However, the experimental and preclinical applications of amniotic fluid-derived stem cells (AFSCs) in the very field of maxillofacial bone tissue engineering are still limited. In this study, rat AFSCs were successfully harvested and characterized in vitro. The rat AFSCs showed typical fibroblastoid morphology, stable proliferation activity and multi-differentiation potential. Flow-cytometry analysis demonstrated that these cells were positive for CD29, CD44, and CD90, while negative for hematopoietic markers such as CD34 and CD45. The regenerative performance of AFSCs-premixed with platelet rich plasma (PRP) gel in restoration of alveolar bone defect was further investigated using a modified rat maxillary alveolar defect model. Micro-computer tomography and histological examination showed a superior regenerative capacity of AFSCs-premixed with PRP gel at both 4 and 8 weeks after operation comparing with control groups. Moreover, the implanted AFSCs can survive in the defect site and directly participate in the bone tissue regeneration. Taken together, these results indicated the feasibility of an AFSCs-based alveolar bone tissue engineering strategy for alveolar defect restoration.

Tcof1-Related Molecular Networks in Treacher Collins Syndrome.

Treacher Collins syndrome (TCS) is a rare, autosomal-dominant disorder characterized by craniofacial deformities, and is primarily caused by mutations in the Tcof1 gene. This article was aimed to perform a comprehensive literature review and systematic bioinformatic analysis of Tcof1-related molecular networks in TCS. First, the up- and down-regulated genes in Tcof1 heterozygous haploinsufficient mutant mice embryos and Tcof1 knockdown and Tcof1 over-expressed neuroblastoma N1E-115 cells were obtained from the Gene Expression Omnibus database. The GeneDecks database was used to calculate the 500 genes most closely related to Tcof1. Then, the relationships between 4 gene sets (a predicted set and sets comparing the wildtype with the 3 Gene Expression Omnibus datasets) were analyzed using the DAVID, GeneMANIA and STRING databases. The analysis results showed that the Tcof1-related genes were enriched in various biological processes, including cell proliferation, apoptosis, cell cycle, differentiation, and migration. They were also enriched in several signaling pathways, such as the ribosome, p53, cell cycle, and WNT signaling pathways. Additionally, these genes clearly had direct or indirect interactions with Tcof1 and between each other. Literature review and bioinformatic analysis finds imply that special attention should be given to these pathways, as they may offer target points for TCS therapies.

A correlational study of serum alkaline phosphatase level and developmental mandibular laterognathism.

The abnormal cartilage/bone metabolism in unilateral condyle may be a direct factor that contributes to developmental mandibular laterognathism. However, although many molecules have been demonstrated to play crucial roles in the development of temporomandibular joints, the exact molecular mechanisms that lead to the disrupted condylar cartilage/bone development were greatly unknown. In this retrospective study, our findings revealed that serum alkaline phosphatase (ALP) level in adult patients with developmental mandibular laterognathism was lower than that in control subjects, and the serum ALP levels continue to reduce in adult patients (>20 years old). Although the exact relationship between the lower serum ALP level and developmental mandibular laterognathism is unclear, the findings further support the opinion that the condylar growth may sustain for a long time in the affected condyle in patients with developmental mandibular laterognathism and offer an alternative choice to use total serum ALP activity as a possible biomarker to assess condylar growth activity in patients with developmental mandibular laterognathism.

Irf6-Related Gene Regulatory Network Involved in Palate and Lip Development.

Numerous genes including Irf6 have been revealed to contribute to cleft lip with or without cleft palate (CL/P). In this study, we performed a systematic bioinformatics analysis of Irf6-related gene regulatory network involved in palate and lip development by using GeneDecks, DAVID, STRING, and GeneMANIA database. Our results showed that many CL/P candidate genes have relation with Irf6, and 9 of these genes, including Msx1, Pvrl1, Pax9, Jag2, Irf6, Tgfb3, Rara, Gli2, and Tgfb2, were enriched into the CL/P gene group. Some of these 9 genes also were commonly involved in different signaling pathways and different biological processes, and they also have protein-protein interactions with Irf6. These findings make us analyze the intricate function of Irf6 in a CL/P gene regulatory network, followed by guiding us to perform further functional studies on these genes in the future. This method also offers us a simple, cheap, but useful method to analyze the relationship with a gene regulatory network of a certain disease such as CL/P.

Characterization of a micro-roughened TiO2/ZrO2 coating: mechanical properties and HBMSC responses in vitro.

Previous studies have shown that using ZrO2 as a second phase to bioceramics can significantly increase the bonding strength of plasma-sprayed composite material. In the present study, micro-roughened titanium dioxide/zirconia (TiO2/ZrO2) (30 wt% ZrO2) coating and TiO2 coating were plasma-sprayed onto Ti plates. The micro-structural characteristics and mechanical properties of both coatings were investigated. Furthermore, the biological behavior and osteogenic differentiation of human bone marrow mesenchymal stem cells (HBMSCs) on both TiO2/ZrO2 and TiO2 coatings were compared. The results indicated that the shear bond strength and microhardness of TiO2/ZrO2 coating were statistically higher than those of TiO2 coating. Scanning electron microscope observation revealed that more irregularly shaped protuberances and denser pores were formed on the surface of TiO2/ZrO2 coating compared with those of TiO2 coating. Further comparative analysis of HBMSC proliferation and osteogenic differentiation on both coatings showed that significantly higher cellular alkaline phosphatase activity and expression levels of Runx2 and Osterix at day 10 after osteogenic culture were found on TiO2/ZrO2 coating compared with TiO2 coating, while no statistically significant difference in cell proliferation and extracellular calcium deposition was observed. The present study suggests that TiO2/ZrO2 coating may be favorable for dental implant applications.

Accurate movement of jaw segment in virtual 3D orthognathic surgery.

In traditional virtual 3D orthognathic surgery, after repositioning the maxillary segment to the desired position, surgeons usually roughly rotate or adjust the mandibular segment to obtain a relatively good relationship with maxillary dentition to calculate the virtual terminal occlusion splint. However, surgeons are not easy to avoid penetrability, overlap, or an overly large space existing between the maxillary and mandibular dentitions during this process. The present report offered a new method to obtain a suitable virtual terminal occlusal splint that could avoid penetrability, overlap, or an overly large space between the maxillary and mandibular dentitions, and simultaneously accurately moving the maxillary or mandibular segment to the desired position utilizing the planned terminal occlusion plaster models in virtual orthognathic surgery. For double jaw surgery, after aligning the planned plaster models to the 3D maxilla and mandible, we could simultaneously move the maxillary and mandibular segment as a whole that maintain the planned terminal occlusion to the desired position. This present method may enhance the accuracy of 3D virtual orthognathic surgery and save plenty of time spend on virtual surgery simulation, which also offers a useful educational method for training junior surgeons and students.

Evaluation of optimal single-photon emission computed tomography reference value and three-dimensional mandibular growth pattern in 54 Chinese unilateral condylar hyperplasia patients.

BACKGROUND: The research aimed to evaluate the optimal Single-Photon Emission Computed Tomography (SPECT) cut-off value in differentiating condylar growth activeness, to observe 3-dimensional (3D) mandibular growth pattern, and to explore the potential correlation between 3D measurement parameters and SPECT uptake ratios in Chinese unilateral condylar hyperplasia (UCH) patients. METHODS:  Data of fifty-four Chinese UCH patients were analyzed retrospectively. All patients underwent SPECT within 1 month before or after the first CT examination (CT1); and received a second CT examination at least 12 months later (CT2). Data from CT scans were analyzed by comparing bilateral differences between CT1 and CT2. The sensitivity and specificity of SPECT were calculated by the receiver operating characteristic (ROC) curve. Pearson's correlation analysis was performed to investigate whether the mandibular growth was correlated with SPECT value. RESULTS: SPECT had a sensitivity of 68.00% and a specificity of 72.41%, with an area under the ROC curve being 0.709. The optimal SPECT cut-off value for evaluating condylar activity has been determined to be 13%. In patients with an active growing condyle, there was a significant increase in Co-Gn and Co-Go, but not in Go-Gn, Go-MF, or MF-Gn. Pearson's correlation analysis revealed no correlation between 3D measurement parameters and differences in relative condylar uptake ratios. CONCLUSION: SPECT showed good diagnostic performance in UCH with the cut-off value of 13%. For those with an active growing condyle, the mandible grows diagonally and vertically, while the relative condylar uptake ratio was not directly related to mandibular growth.

Intraoral Condylectomy with 3D-Printed Cutting Guide versus with Surgical Navigation: An Accuracy and Effectiveness Comparison.

This study compares the accuracy and effectiveness of our novel 3D-printed titanium cutting guides with intraoperative surgical navigation for performing intraoral condylectomy in patients with mandibular condylar osteochondroma (OC). A total of 21 patients with mandibular condylar OC underwent intraoral condylectomy with either 3D-printed cutting guides (cutting guide group) or with surgical navigation (navigation group). The condylectomy accuracy in the cutting guide group and navigation group was determined by analyzing the three-dimensional (3D) discrepancies between the postoperative computed tomography (CT) images and the preoperative virtual surgical plan (VSP). Moreover, the improvement of the mandibular symmetry in both groups was determined by evaluating the chin deviation, chin rotation and mandibular asymmetry index (AI). The superimposition of the condylar osteotomy area showed that the postoperative results were very close to the VSP in both groups. The mean 3D deviation and maximum 3D deviation between the planned condylectomy and the actual result were 1.20 ± 0.60 mm and 2.36 ± 0.51 mm in the cutting guide group, and 1.33 ± 0.76 mm and 4.27 ± 1.99 mm in the navigation group. Moreover, the facial symmetry was greatly improved in both groups, indicated by significantly decreased chin deviation, chin rotation and AI. In conclusion, our results show that both 3D-printed cutting-guide-assisted and surgical-navigation-assisted methods of intraoral condylectomy have high accuracy and efficiency, while using a cutting guide can generate a relatively higher surgical accuracy. Moreover, our cutting guides exhibit user-friendly features and simplicity, which represents a promising prospect in everyday clinical practice.