Defining a critical period in calvarial development for Hedgehog pathway antagonist-induced frontal bone dysplasia in mice / 国际口腔科学杂志·英文版

The Hedgehog (Hh) signalling pathway is essential for cellular proliferation and differentiation during embryonic development. Gain and loss of function of Hh signalling are known to result in an array of craniofacial malformations. To determine the critical period for Hh pathway antagonist-induced frontal bone hypoplasia, we examined patterns of dysmorphology caused by Hh signalling inhibition. Pregnant mice received a single oral administration of Hh signalling inhibitor GDC-0449 at 100 mg•kg or 150 mg•kg body weight at preselected time points between embryonic days (E)8.5 and 12.5. The optimal teratogenic concentration of GDC-0449 was determined to be 150 mg•kg. Exposure between E9.5 and E10.5 induced frontal bone dysplasia, micrognathia and limb defects, with administration at E10.5 producing the most pronounced effects. This model showed decreased ossification of the frontal bone with downregulation of Hh signalling. The osteoid thickness of the frontal bone was significantly reduced. The amount of neural crest-derived frontal bone primordium was reduced after GDC-0449 exposure owing to a decreased rate of cell proliferation and increased cell death.

Morphological classification of mandible posterior region based on cone beam CT images / 中华口腔医学杂志

Objective@#To classify the morphology of mandible posterior region and provide reference for the planning of dental implantation.@*Methods@#Cone beam CT data of 208 patients were collected. The CT data were imported into CS 3D imaging V3 software and then the morphology of mandible posterior region were analyzed. The types of premolar and molar mandible cross-section morphology were recorded, classified and analyzed.@*Results@#The results showed that type A (vertical type) (79%-96%) was the most common in the premolars, whereas type B (inclined type) (36%-37%) and type C (lingual inverted concave) (30%-54%) were the most common types in the molars, followed type D (absorption severe type) (2%-5%). There was a statistically significant differences in tooth positions (P<0.001), tooth deficiency aspect (P<0.001) and different side (P=0.013), different age (P<0.001), and different gender (P=0.007).@*Conclusions@#Using cone beam CT to determine the morphology of mandible may be a reference for the planning of dental implantation.

Hedgehog pathway antagonist-induced oromandibular limb hypogenesis in mouse / 中华口腔医学杂志

Objective@#To analysis teratogenic effect of GDC-0449 to fetus and set up the animal model of GDC-0449 induced oromandibular limb hypogenesis in mouse for further research of its pathogenesis.@*Methods@#Twenty-seven pregnant Institute of Cancer Research (ICR) mice were randomly divided into: control group, embryonic day 8.5 (E8.5) exposed groups, E9.5 exposed groups, E10.5 exposed groups, E11.5 exposed groups, E12.5 exposed groups, E13.5 exposed groups, E14.5 exposed groups and E15.5 exposed groups. Each group had 3 mice. Exposed groups were treated with the Hedgehog pathway antagonist GDC-0449 at a single dose 150 mg/kg by oral gavage from E8.5 to E15.5. At E16.5, embryonic phenotypes were analyzed in detail by stereo microscope and histology. After establish an optimal dysmorphogenic concentration, 6 pregnant ICR mice were randomly divided into control group and the optimal group, embryonic phenotypes were analyzed by whole-mount skeletal staining and micro-computed tomography at E18.5.@*Results@#The mice were exposed to GDC-0449 on E11.5 and E12.5 had a high incidence of cleft palate. GDC-0449 exposed between E9.5 and E10.5 caused craniofacial and limb dysmorphology, including micrognathia, microglossia, ectrodactylia, partial anodontia and cleft palate. Most interestingly, these are extremely similar to oromandibular limb hypogenesis syndrome.@*Conclusions@#The results of this study indicate that GDC-0449 can be used to induce micrognathia, microglossia, ectrodactylia, partial anodontia and cleft palate. This work established a novel mouse model for oromandibular limb hypogenesis.

Occlusal stimulation regulates bone remodeling during bone defect repair using collagen substitutes：a morphological analysis / 中国组织工程研究

BACKGROUND:Occlusal stimulation is essential for mandible function and remodeling, but there is stil a lack of clear understanding about the effect of occlusal stimulation on the bone remodeling in the process of bone defect repair using bone grafts. OBJECTIVE:To analyze the possible regulative effect of occlusal stimulation on bone remodeling in the process of bone defect repair using colagen substitutes. METHODS:Standard models of bone defects were respectively established in left mandible and parietal bone area of adult Sprague-Dawley rats. Then the bone defects area were filed with colagen and bone meal. The differences of two bone defects areas were observed by X-ray, hematoxylin-eosin staining, Gomori staining, tartrate-resistant acid phosphatase staining and bone morphogenetic protein 2 immunohistochemical staining at the 12th week after operation. RESULTS AND CONCLUSION: New bone formation was visible in the bone defect regions of the mandible and parietal bone. The amount of lamelar bone formation and the degree of mineralization of the new bone were significantly increased in the parietal bone defect compared with the mandibular bone defect area, indicating the bone remodeling in the parietal bone defect area was better than that in the mandible bone defect area. The integral absorbance values of tartrate-resistant acid phosphatase and bone morphogenetic protein 2 in the parietal bone defect area were lower than those in the mandibular bone defect area, indicating that the viabilities of osteoblasts and osteoclasts in the parietal bone defect area were lower than those in the mandible bone defect area. These results demonstrate that occlusal stimulation may delay the bone remodeling during the repair of mandibular bone defects by regulating bone mineralization and maturation.

Denervation of the inferior alveolar nerve is associated with bone formation and bone mass maintenance in extraction sockets / 中国组织工程研究

BACKGROUND: There is a close relationship between innervations and bone formation and bone mass maintenance in the extraction sockets. OBJECTIVE:To study the possible effect of denervations on the regulation of new bone formation and bone mass maintenance in the extraction sockets. METHODS:The unilateral inferior nerve of dogs was sectioned to establish an animal denervation model. The normal side was used as control. After model establishment, the premolars of denervated side and normal side were extracted. Histological method was used to test new bone formation and bone mass maintenance in the extraction sockets at the 2nd, 4th, 8th and 12th weeks after tooth extraction. RESULTS AND CONCLUSION:The percentage of new bone areas in the extraction sockets was significantly lower in the experiment group than the control group at weeks 2, 4, 8 after tooth extraction (P < 0.01). The height difference between the buccal and lingual alveolar ridge was higher in the experimental group than the control group at weeks 2, 4, 8, 12 after tooth extraction (P < 0.05 or P < 0.01). These findings indicate that denervation is closely related with new bone formation and bone mass maintenance in the extraction sockets.