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Background: Palatogenesis requires a precise spatiotemporal regulation of gene expression. Recent studies indicate that microRNAs (miRNAs) are key factors in normal palatogenesis. The present study aimed to explain the regulatory mechanisms of miRNAs during palate development. Methods: Pregnant ICR mice were choose at embryonic day 10.5 (E10.5). Hemotoxylin and eosin (H&E) staining was used to observe the morphological changes during the development of palatal process at embryonic day (E)13.5, E14.0, E14.5, E15.0 and E15.5. The fetal palatal tissues were collected at E13.5, E14.0, E14.5 and E15.0 to explore miRNA expression and function by high throughput sequencing and bioinformatic analysis. Mfuzz cluster analysis was used to look for miRNAs related to the fetal mice palate formation. The target genes of miRNAs were predicted by miRWalk. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was performed base on target genes. The mesenchymal cell proliferation and apoptosis related miRNAs‐genes networks were predicted and constructed using miRWalk and Cytoscape software. The expression of mesenchymal cell proliferation and apoptosis related miRNAs at the E13.5, E14.0, E14.5, and E15.0 was detected by a quantitative real‐time PCR (RT‐qPCR) assay. Results: H&E staining found that the palatal process grows vertically along the sides of the tongue at E13.5, the position of the tongue begins to descend and the bilateral palatal processes rise above the tongue at E14.0, the palatal process grows horizontally at E14.5, there is palatal contact fusion at E15.0, and the palatal suture disappeared at E15.5. Nine clusters of miRNA expression changes were identified in the fetal mice palate formation progression, including two reducing trends, two rising trends and five disordered trends. Next, the heatmap showed the miRNA expression from Clusters 4, 6, 9, 12 in the E13.5, E14.0, E14.5 and E15.0 groups. GO functional and KEGG pathway enrichment analysis found target genes of miRNAs in clusters involved in regulation of mesenchymal phenotype and the mitogen‐activated protein kinase (MAPK) signaling pathway. Next, mesenchymal phenotype related miRNA‐genes networks were constructed. The heatmap showing that the mesenchymal phenotype related miRNA expression of Clusters 4, 6, 9 and 12 at E13.5, E14.0, E14.5 and E15.0. Furthermore, the mesenchymal cell proliferation and apoptosis related miRNA‐gene networks were identified in Clusters 6 and 12, including mmu‐miR‐504‐3p‐Hnf1b, etc. The expression level of mesenchymal cell proliferation and apoptosis related miRNAs at the E13.5, E14.0, E14.5, and E15.0 was verified by a RT‐qPCR assay. Conclusions: For the first time, we identified that clear dynamic miRNA expression during palate development. Furthermore, we demonstrated that mesenchymal cell proliferation and apoptosis related miRNAs, genes and the MAPK signaling pathway are important during fetal mice palate development. [ABSTRACT FROM AUTHOR]

Objective To investigate the efficacy of block iliac bone grafting in patients with unilateral alveolar cleft in mixed dentition. Methods A retrospective study was conducted on patients with unilateral alveolar clefts in mixed dentition who were treated in the Department of Oral and Maxillofacial Surgery, Fujian Medical University Union Hospital. All patients underwent unilateral alveolar cleft bone graft repair with autogenous block iliac bone blocks. The healing of bone blocks was analyzed at 1 week and 6-12 months after surgery. Mimics software was used for the three-dimensional reconstruction and volumetric measurement of the iliac bone blocks on the follow-up imaging data of 15 patients aged 9-12 years without the eruption of canines before surgery, and the bone resorption rate of the iliac bone blocks was comparatively analyzed. Results In the 37 patients, bone grafting was successful in 32 and failed in five. The success rate of bone grafting was 86.5%. In 15 patients aged 9-12 years without the eruption of canines before surgery, eruption through the bone graft area was observed in two patients 6-12 months after the operation. Cone beam computer tomography showed that the grafted bone block exhibited good bony connections, and its resorption mainly occurred on the crests and palatal sides of the alveolar ridge. Bone resorption rates varied considerably between patients with a mean bone resorption rate of 39.0%±13.8% at 6-12 months after surgery. Conclusion For patients in mixed dentition, bone grafting with block iliac bone can achieve better osteogenesis effect. [ABSTRACT FROM AUTHOR]

Background: Tooth regeneration depends on the longevity of the dental epithelial lamina. However, the exact mechanism of dental lamina regression has not yet been clarified. To explore the role of the Sonic hedgehog (Shh) signaling pathway in regression process of the rudimentary successional dental lamina (RSDL) in mice, we orally administered a single dose of a Shh signaling pathway inhibitor to pregnant mice between embryonic day 13.0 (E13.0) and E17.0. Results: We observed that the Shh signaling pathway inhibitor effectively inhibited the expression of Shh signaling pathway components and revitalized RSDL during E15.0–E17.0 by promoting cell proliferation. In addition, mRNA‐seq, reverse transcription plus polymerase chain reaction (RT‐qPCR), and immunohistochemical analyses indicated that diphyodontic dentition formation might be related to FGF signal up‐regulation and the Sostdc1‐Wnt negative feedback loop. Conclusions: Overall, our results indicated that the Shh signaling pathway may play an initial role in preventing further development of mouse RSDL in a time‐dependent manner. Key Findings: RSDL, Shh signal, tooth regeneration, Wnt/β‐catenin, mouse molar. [ABSTRACT FROM AUTHOR]

Hard palate consists anteriorly of the palatal process of the maxilla (ppmx) and posteriorly of the palatal process of the palatine (ppp). Currently, palatal osteogenesis is receiving increasing attention. This is the first study to provide an overview of the osteogenesis process of the mouse hard palate. We found that the period in which avascular mesenchymal condensation becomes a vascularized bone structure corresponds to embryonic day (E) 14.5 to E16.5 in the hard palate. The ppmx and ppp differ remarkably in morphology and molecular respects during osteogenesis. Osteoclasts in the ppmx and ppp are heterogeneous. There was a multinucleated giant osteoclast on the bone surface at the lateral‐nasal side of the ppmx, while osteoclasts in the ppp were more abundant and adjacent to blood vessels but were smaller and had fewer nuclei. In addition, bone remodeling in the hard palate was asymmetric and exclusively occurred on the nasal side of the hard palate at E18.5. During angiogenesis, CD31‐positive endothelial cells were initially localized in the surrounding of palatal mesenchymal condensation and then invaded the condensation in a sprouting fashion. At the transcriptome level, we found 78 differentially expressed genes related to osteogenesis and angiogenesis between the ppmx and ppp. Fifty‐five related genes were up/downregulated from E14.5 to E16.5. Here, we described the morphogenesis and the heterogeneity in the osteogenic and angiogenic genes profiles of the ppmx and ppp, which are significant for subsequent studies of normal and abnormal subjects. [ABSTRACT FROM AUTHOR]

Background: The hedgehog signaling pathway is critical for developmental patterning of the limb, craniofacial and axial skeleton. Disruption of this pathway in mice leads to a series of structural malformations, but the exact role and critical period of the Hh pathway in the early development of the cranial base have been rarely described. Results: Embryos exposed to vismodegib from E7.5, E9.5, and E10.5 had a higher percentage of cranial base fenestra. The peak incidence of hypoplasia in sphenoid winglets and severe craniosynostosis in cranial base synchondroses was observed when vismodegib was administered between E9.5 and E10.5. Cranial base craniosynostosis results from accelerating terminal differentiation of chondrocytes and premature osteogenesis. Conclusions: We define the critical periods for the induction of cranial base deformity by vismodegib administration at a meticulous temporal resolution. Our findings suggest that the Hh pathway may play a vital role in the early development of the cranial base. This research also establishes a novel and easy‐to‐establish mouse model of synostosis in the cranial base using a commercially available pathway‐selective inhibitor. Key Findings: Embryos exposed to vismodegib to E7.5,E9.5 and E10.5 caused diverged cranial base phenotype.Treatment of vismodegib at E9.5 and E10.5 can lead to hypoplasia in sphenoid winglets, cranial base fenestra and severe craniosynostosis in cranial base.The cranial base craniosynostosis result from premature differentiation and osteogenesis of synchondrosis. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to investigate the clinical effect and bone resorption of iliac crest cortical-cancellous bone block grafts combined with concentrated growth factor (CGF) compared with iliac crest cortical-cancellous bone block grafts only in secondary alveolar bone grafting., Materials and Methods: Eighty-six patients (43 in the CGF group and 43 in the non-CGF group) with unilateral alveolar clefts were examined. Patients (17 in the CGF group and 17 in the non-CGF group) were randomly chosen for radiologic evaluation. Quantitative evaluation of the bone resorption rate was made with cone-beam computed tomography and Mimics 19.0 software at 1 week and 12 months after surgery., Results: The success rate of bone grafting was 95.3% and 79.1% in the CGF and non-CGF groups, respectively ( P =0.025). The mean bone resorption rate at 12 months postoperatively was 35.66±15.80% and 41.39±19.57% in the CGF and non-CGF groups, respectively ( P =0.355). The bone resorption patterns of the 2 groups were similar on the labial, alveolar process, and palatal sides, and there was no obvious bone resorption on the labial side in either group. Nasal side bone resorption in the CGF group was significantly less than that in the non-CGF group ( P =0.047)., Conclusions: Cortical-cancellous bone block grafts reduce labial bone resorption, while CGF reduces nasal bone resorption and improves the success rate. The combination of bone block and CGF in secondary alveolar bone grafting is worthy of further clinical application., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 by Mutaz B. Habal, MD.)

Objectives: To investigate the efficacy of block iliac bone grafting in patients with unilateral alveolar cleft in mixed dentition., Methods: A retrospective study was conducted on patients with unilateral alveolar clefts in mixed dentition who were treated in the Department of Oral and Maxillofacial Surgery, Fujian Medical University Union Hospital. All patients underwent unilateral alveolar cleft bone graft repair with autogenous block iliac bone blocks. The healing of bone blocks was analyzed at 1 week and 6-12 months after surgery. Mimics software was used for the three-dimensional reconstruction and volumetric measurement of the iliac bone blocks on the follow-up imaging data of 15 patients aged 9-12 years without the eruption of canines before surgery, and the bone resorption rate of the iliac bone blocks was comparatively analyzed., Results: In the 37 patients, bone grafting was successful in 32 and failed in five. The success rate of bone grafting was 86.5%. In 15 patients aged 9-12 years without the eruption of canines before surgery, eruption through the bone graft area was observed in two patients 6-12 months after the operation. Cone beam computer tomography showed that the grafted bone block exhibited good bony connections, and its resorption mainly occurred on the crests and palatal sides of the alveolar ridge. Bone resorption rates varied considerably between patients with a mean bone resorption rate of 39.0%±13.8% at 6-12 months after surgery., Conclusions: For patients in mixed dentition, bone grafting with block iliac bone can achieve better osteogenesis effect.