Genetic studies have revealed a critical role of Distal-homeobox (Dlx) genes in bone formation, and our previous study showed that Dlx2 overexpressing in neural crest cells leads to profound abnormalities of the craniofacial tissues. The aim of this study was to investigate the role and the underlying molecular mechanisms of Dlx2 in osteogenic differentiation of mouse bone marrow stromal cells (BMSCs) and pre-osteoblast MC3T3-E1 cells. Initially, we observed upregulation of Dlx2 during the early osteogenesis in BMSCs and MC3T3-E1 cells. Moreover, Dlx2 overexpression enhanced alkaline phosphatase (ALP) activity and extracellular matrix mineralization in BMSCs and MC3T3-E1 cell line. In addition, micro-CT of implanted tissues in nude mice confirmed that Dlx2 overexpression in BMSCs promoted bone formation in vivo. Unexpectedly, Dlx2 overexpression had little impact on the expression level of the pivotal osteogenic transcription factors Runx2, Dlx5, Msx2, and Osterix, but led to upregulation of Alp and Osteocalcin (OCN), both of which play critical roles in promoting osteoblast maturation. Importantly, luciferase analysis showed that Dlx2 overexpression stimulated both OCN and Alp promoter activity. Through chromatin-immunoprecipitation assay and site-directed mutagenesis analysis, we provide molecular evidence that Dlx2 transactivates OCN and Alp expression by directly binding to the Dlx2-response cis-acting elements in the promoter of the two genes. Based on these findings, we demonstrate that Dlx2 overexpression enhances osteogenic differentiation in vitro and accelerates bone formation in vivo via direct upregulation of the OCN and Alp gene, suggesting that Dlx2 plays a crucial role in osteogenic differentiation and bone formation.
1 December 2015 in International Journal of Oral and Maxillofacial Surgery
The surgery-first approach (SFA), without presurgical orthodontic treatment, has become favoured in the treatment of dentomaxillofacial deformities. This approach has been applied in our institution since 2012. The purpose of this study was to report our experience with the SFA for skeletal malocclusion. Fifty patients with skeletal malocclusions were enrolled in this study (11 bimaxillary protrusion, 27 skeletal class III malocclusion, and 12 facial asymmetry). After orthognathic-orthodontic consultation, suitability for SFA was determined and a treatment plan drawn up. Patients then underwent orthognathic surgery, which included Le Fort I maxillary osteotomy, bilateral sagittal split ramus osteotomy, subapical osteotomy, and genioplasty. Postoperative orthodontic treatment was started after a healing period of 2 weeks. The mean postoperative orthodontic treatment duration was 14.9 months, which is shorter than that of traditional joint orthognathic-orthodontic treatment. In the bimaxillary protrusion group, this was about 19 months, which was longer than for the other groups. After joint orthognathic-orthodontic treatment, a good facial profile and ideal occlusion were achieved. With the advantages of earlier improvements in patient facial aesthetics and dental function, the reduction in difficulty and treatment duration of orthodontic management, and increasing patient acceptance, SFA is regarded as an ideal and valuable alternative for this potentially complicated procedure.
To evaluate the changes of alveolar dehiscence and fenestration after augmented corticotomy-assisted orthodontic treatment on cone-beam computed tomography (CBCT) compared with traditional pre-surgical orthodontics, both quantitatively and qualitatively. Two hundred and four anterior teeth from 17 skeletal class III malocclusions were divided into four groups. Groups G1 (upper teeth) and G3 (lower teeth), comprising 120 teeth, accepted traditional pre-surgical orthodontics; groups G2 (upper teeth) and G4(lower teeth), comprising 84 teeth, accepted augmented corticotomy-assisted pre-surgical orthodontics. The changes of alveolar bone dehiscence and fenestration of each tooth in all groups were evaluated with the help of CBCT. Quantitative analysis for comparing both groups: For the upper teeth, d1 − d0 was different between both groups while f1 − f0 was not statistically different. For the lower teeth, d1 − d0 was statistically different between both groups while f1 − f0 was not statistically different. Qualitative analysis: For the teeth that had no dehiscence before treatment, G2 and G4 had a better transition than did G1 and G3. For those having dehiscence before treatment, G4 had a better transition than did G3. For teeth having no fenestration before treatment, there was no statistically significant difference in transition between the control and treatment groups. For those having fenestration before treatment, G4 had a better transition than did G3. For skeletal class III patients, augmented corticotomy-assisted orthodontic treatment is a promising method of improving alveolar bone dehiscence and fenestration for lower anterior teeth, and it also has the potential to protect both lower and upper anterior teeth against dehiscence.
1 September 2011 in Journal of Craniofacial Surgery
Background: Fibrous dysplasia is a benign developmental dysplastic disorder of the bone in which abnormal fibroblastic proliferation replaces the normal bone matrix. Craniomaxillofacial fibrous dysplasia can cause severe deformity with devastating functional and aesthetic consequence. Precise surgical removal of the fibro-osseous tissue is the key to ultimately restore normal function and aesthetics. Navigational surgical tool has become a useful adjunct in the surgical management of the craniomaxillofacial skeleton. Methods: Thirteen patients with facial asymmetry and deformity caused by craniomaxillofacial fibrous dysplasia were enrolled into this study. With preoperative planning and three-dimensional simulation, normal anatomic contours of the deformed area were recreated by superimposing unaffected to the affected side. After registration, surgical facial recontouring was performed under the guidance of navigation system. Results: Good accuracy was achieved with the registration of patient's facial skeleton and preoperative three-dimensional reconstructed model in all the cases. With intraoperative navigational guidance, facial bone recontouring was performed uneventfully in all cases. Surgical accuracy was evaluated by comparing the preoperative and postoperative computed tomography scan measurement. The mean maximum discrepancy between the actual surgical reduction and preoperative planning was less than 2 mm. Symptoms associated with optical nerve compression were eliminated in affected individuals. All patients' facial symmetry and aesthetics were improved. Conclusion: Navigation-guided facial bone recontouring is a valuable treatment modality in managing craniomaxillofacial fibrous dysplasia.