• The korean journal of orthodontics
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• v.50 no.1
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• pp.42-51
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• 2020

Objective: The objective of this study was to evaluate the effects of cetirizine, a histamine 1 receptor antagonist, on bone remodeling after calvarial suture expansion. Methods: Sixty male Sprague-Dawley rats were divided into 4 groups; the phosphate-buffered saline (PBS)-injected no expansion group, cetirizine-injected no expansion group, PBS-injected expansion group, and cetirizine-injected expansion group, and were observed at 7, 14, and 28 days. Five rats per group were examined at each observation day. Daily injections of cetirizine or PBS were administered to the relevant groups starting 2 weeks prior to expander insertion. A rapid expander was inserted in the calvarial bone to deliver 100 cN of force to the parietal suture. The specimens were prepared for hematoxylin and eosin and tartrate-resistant acid phosphatase (TRAP) staining. Suture opening and bone regeneration were evaluated using microcomputed tomography and bone histomorphometric analysis. Serum blood levels of osteocalcin and carboxy-terminal collagen crosslinks (CTX) were also evaluated. Results: TRAP-positive cell counts and CTX levels decreased while osteocalcin levels increased in the cetirizine-injected expansion group at observation day 28. In the expansion groups, the mineralized area gradually increased throughout the observation period. At day 28, the cetirizine-injected expansion group showed greater bone volume density, greater mineralized area, and narrower average suture width than did the PBS-injected expansion group. Conclusions: Cetirizine injection facilitated bone formation after suture expansion, mostly by suppressing osteoclastic activity. Histamine 1 receptor antagonists may aid in bone formation after calvarial suture expansion in the rat model.

• Journal of the korean academy of Pediatric Dentistry
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• v.30 no.3
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• pp.391-405
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• 2003

Craniosynostosis, known as a premature fusion of cranial sutures, is a developmental disorder characterized by precocious differentiation and mineralization of osteoblasts in the calvarial sutures. Recent genetic studies have demonstrated that mutation in the homeobox gene Msx2 causes Boston-type human craniosynostosis. Additionally, the phenotype of Dlx5 homozygote mutant mouse presents craniofacial abnormalities including a delayed ossification of calvarial bone. Furthermore transcription of osteocalcin, a mature osteoblast marker, is reciprocally regulated by the homeodomain proteins Msx2 and Dlx5. These facts suggest important roles of osteocalcin, Msx2 and Dlx5 genes in the calvarial bone growth and suture morphogenesis. To elucidate the function of these molecules in the early morphogenesis of mouse cranial sutures, we have first analyzed by in situ hybridization the expression of osteocalcin, Msx2 and Dlx5 genes in the developing parietal bone and sagittal suture of mouse calvaria during the embryonic (E15-E18) stage. Osteocalcin mRNA was found in the periosteum of parietal bones from E15, and gradually more highly expressed with aging. Msx2 mRNA was intensely expressed in the sutural mesenchyme, osteogenic fronts and mildly expressed in the dura mater during the embryonic stage. Dlx5 mRNA was intensely expressed osteogenic fronts and the periostem of parietal bones. To further examine the upstream signaling molecules of transcription factor Msx2 and Dlx5, we have done in vitro experiments in E15.5 mouse calvarial explants. Interestingly, implantation of BMP2-, BMP4-soaked beads onto the osteogenic fronts after 48 hours organ culture induced etopic expressions of Msx2 and Dlx5 genes. On the other hand, overexpression of $TGF{\beta}1$, GDF-6, -7, FGF-2, -4 and Shh did not induce the expression of Msx2 and Dlx5. Taken together. these data indicate that transcription factor Msx2 and Dlx5 play critical roles in the calvarial bone and suture development, and that BMP siganling is involved in the osteogenesis of calvarial bones and the maintenance of cranial sutures through regulating these two transcriotpn factors. Furthermore, different expression patterns between Msx2 and Dlx5 suggest their specific functions in the osteoblast differentiation.

• Korean Journal of Veterinary Research
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• v.64 no.1
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• pp.6.1-6.5
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• 2024

Subgaleal hematomas are accumulation of blood between periosteum and galea aponeurosis. A 2-year-old male Chihuahua was presented with a severe head swelling after trauma. Radiography and computed tomography (CT) showed a massive swelling encircling the entire calvarial vault, extending toward the cervical neck and crossing the suture line. It was heterogeneously, mild hyperdense fluid to soft tissue attenuating with contrast enhancement on CT images. On day 4, physical and imaging examination showed resolution of the calvarial swelling. Subgaleal hematoma should be considered as a differential diagnosis when there is a massive soft tissue swelling over the skull on physical and imaging examinations.

• Journal of the korean academy of Pediatric Dentistry
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• v.30 no.1
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• pp.171-180
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• 2003

The development of calvarial bones is tighly co-ordinated with the growth of the brain and needs of harmonious interactions between different tissues within the calvarial sutures. Premature fusion of cranial sutures, known as craniosynostosis, presumably involves disturbance of these interactions. Mutations in the homeobox-containg gene Msx2 cause human craniosynostosis syndrome. Msx genes, which are consist of Msx1, Msx2 and Msx3, are homeobox-containg transcripton factors, and were originally identified as homologue of Drosophila msh(muscle segment homeobox) gene. Msx1 and Msx2 genes, expressed mostly in overlapping patterns at multiple site of tissue interactions during vertebrate development, are associated with epithelial-mesenchymal interactions during organogenesis, targets of BMP and FGF signaling. To elucidate the function of Msx genes in the early morphogenesis of mouse cranial suture, we analyzed the expression of them by in situ hybridization during embryonic(E15-E18) stage, and did vivo experiments in E15.5 mouse using rhBMP-2, rhFGF-2 protein soaked bead. In the sagittal suture, Msx1 was expressed in the mesenchyme of suture and the dura mater, Msx2 was intensely expressed in the sutural mesenchyme and the dura mater. In the coronal suture both of Msx genes were expressed intensely in the sutural mesenchyme and expressed in the periosteum also. Msx1 had a broader expression pattern than Msx2. BMP2 beads induced expression of both Msx1 and Msx2, FGF2 beads induced expression of Msx1, but not Msx2. Taken together, these data suggest that Msx1 and Msx2 genes have important role in regulating the morphogenesis and maintenance of embryonic cranial suture. Both of Msx genes are expressed similarly but because of their upstream signaling, they function dependently or cooperatively according to change of signaling molecule.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.28 no.4
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• pp.264-273
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• 2002

Pulsed electromagnetic field (PEMF) was used first to induce osteogenesis in 1974. The appliance which was consisted of the Helmholtz coil configuration have used to osteogensis. The objective of this study was to determine whether PEMF, a frequency of 100 Hz and magnetic field strength of 38 gauss applied to the calvarial defect in rabbit, could affect the induction of osteogenesis and the healing of the graft bone. This field should not produce excitation of nerve or muscle and heating the tissue. To evaluate the effect of PEMF on osteogenesis, 16 rabbit under the same condition was divided into 8 experimental groups and 8 control groups. 10 mm calvarial bone defects were formed around sagittal suture. The defect of left side was left without graft while the defect of right side was grafted by bone harvested from left side. A pulsed electromagnetic field was applied for 8 hours per day. Each group was sacrificed after 1 week, 2 weeks, 4 weeks, 8 weeks. Microscopic specimens were obtained from the calvarial bone defects and surrounding tissue using Hematoxylin-Eosin staining method. The results were as follows. 1. In the group which pulsed electromagnetic field was applied, new bone formation filled up the defect was observed after 4 and 8 weeks effectively. 2. There are no difference in the healing period for the fusion between the bone and graft bone. According to the result, the PEMF with 38 Gauss, 100 Hz was very effective in the healing of bone defect and new bone formation. So The PEMF will be useful in clinical aspect for oseteogenesis.

• Journal of the korean academy of Pediatric Dentistry
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• v.29 no.3
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• pp.345-353
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• 2002

Bone morphogenetic proteins(BMPs) are secretory signal molecules which have a variety of regulatory functions during morphogenesis and cell differentiation. To evaluate roles of BMPs and their receptors on mouse sagittal suture development, we have examined their expression patterns in serial sections of sagittal sutures by in situ hybridization during embryonic stages(E15-E18). BMP-2 and BMP-3 were expressed in the osteogenic front and parietal bone on embryonic 15day, from E16 in hair follicle. BMP-4 was strongly expressed in the osteogenic front and weakly expressed in the mesenchyme and parietal bone. BMP-S was expressed in the hair follicles. BMP-6 was not expressed in this study. BMP-7 was expressed in parietal bone during embryonic stage. BMPR-IB was expressed in the osteogenic front, but BMPR-IA was not. From these datas, we suggest that the BMP-4 regulates the early commitment of mesenchymal cells to the osteogenic lineages, the BMP-2 and BMP-3 may be involved in regulating the differentiation of osteoblast precursor cells. BMP-7 was involved in maintenance of differentiated osteoblasts. BMPs were key signaling molecules that regulate early calvarial bone morphogenesis, mediated by BMPR-IB.

• Journal of the korean academy of Pediatric Dentistry
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• v.30 no.2
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• pp.217-228
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• 2003

Co-ordinate growth of the brain and skull is achieved through a series of tissue interactions between the developing brain, the growing bones of the skull and the sutures that unite the bones. Craniosynostosis, the premature fusion of cranial sutures, presumably involves disturbance of these interactions. Bmp2, one of bone morphogenetic proteins (Bmps), is involved in the regulation of the shapes of individual bones and the relative proportions of the skeleton. Mutations in the homeobox gene Msx2, known as a downstream gene of Bmp, cause Boston-type human craniosynostosis. The phenotype of Dlx5 homozygote mutant mouse presents craniofacial abnormalities including a delayed ossification of calvarial bone. These facts suggest important roles of Bmp2, Msx2 and Dlx5 genes in the cranial bone growth and suture morphogenesis. To elucidate the function of these molecules in the early morphogenesis of mouse cranial sutures, we first analyzed by in situ hybridization the expression of Bmp2(E15-18), Msx2 and Dlx5 genes in the developing sagittal suture of calvaria during the embryonic stage. Bmp2 mRNA was intensely expressed in the osteogenic fronts and also at the low level in the periosteum of parietal bones during embryonic stage, Msx2 mRNA was intensely expressed in the sutural mesenchyme and mildly expressed in the dura mater during the embryonic stage. Dlx5 mRNA was intensely expressed osteogenic fronts and parietal bones. To further examine the role of Bmp signaling in cranial suture, we did in vitro experiments in E15.5 mouse calvarial explants. Interestingly, implantation of Bmp2-soaked beads onto the osteogenic fronts after 48 hours organ culture resulted in the increase of the tissue thickness and cell number around Bmp2 beads, compared to BSA control beads. In addition Bmp2 induced etopic expressions of Msx2 and Dlx5 genes. On the other hand, overexpression of FGF2 did not induce the expression of Msx2 and Dlx5. Taken together, these data indicate that Bmp2 signaling molecule has a important role in regulating the cranial bone growth and early morphogenesis of cranial suture. We also suggest that Bmp signaling is involved in all the stages of osteogenesis of cranial bones and the maintenance of cranial suture by regulating Msx2 and Dlx5 genes, and that Msx2 and Dlx5 genes are specific transcription factors of Bmp signaling pathway.

• Journal of Periodontal and Implant Science
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• v.35 no.4
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• pp.939-948
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• 2005

The role of the periosteum on osteointegration of $Bio-Oss^{(R)}$(Geistlich, Wolhusen/Switzerland) was studied in rabbit calvarial defect. 12 New Zealand white male rabbits between 2.8 and 4 kg were included in this randomized, blinded, prospective study. Each rabbit was anesthetized with Ketamine HCl(5 mg/kg) and Xylazine HCl(1.5 ml/kg). An incision was made to the bony cranium and the periosteum was reflected. Using a 6-mm trephine bur(3i. USA), four 8-mm defects were created with copious irrigation. The defects were classified into barrier membrane($Tefgen^{(R)}$, Lifecore Biomedical. Inc, U.S.A.) only group as a control, $Bio-Oss^{(R)}$ with barrier membrane group, $Bio-Oss^{(R)}$ with periosteum covering group, and $Bio-Oss^{(R)}$ without periosteum covering group. There were 2 rabbits in each group. The wound was closed with resorbable suture materials. Rabbits were sacrificed using phentobarbital(100 mg/kg) intravenously at 1, 2, and 4 weeks after surgery. The samples were fixed in 4% paraformaldehyde, and decalcified in hydrochloric acid decalcifying solution(Fisher Scientific, Tustin, CA) at $4^{\circ}C$ for 2-4 weeks. It was embedded in paraffin and cut into 6 ${\mu}m$ thickness. The sections were stained with H & E and observed by optical microscope. The results were as follows; 1. The periosteum played an important role in osteointegration of $Bio-Oss^{(R)}$ in bone defects. 2. When the periosteum remained intact and $Bio-Oss^{(R)}$ was placed on the defect, $Bio-Oss^{(R)}$ with periosteum covering has been incorporated into the newly formed bone from 2-week postoperatively. 3. When the periosteum was removed at the surgical procedure, invasion of connective tissue took place among the granules, and new bone formation was delayed compared to periosteum covering group. Therefore, when the bone grafting was performed with periosteal incision procedure to achieve tension-free suture, the integrity of the overlying periosteum should be maintained to avoid fibrous tissue ingrowth.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.20 no.3
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• pp.269-273
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• 1998

To clarify the clinical utility of the calvarial bone graft in the maxillofacial reconstruction, we performed on anatomical study by measuring the regional thickness of the parietal bone on 17 Korean adult dry skulls. Before the sectioning the calvarium, the anatomical landmarks were marked on each specimens. And then we measured the total thickness of the parietal bone, the thickness of the outer and inner cortical plates on various points in each sections of parietal bones using a digital caliper under the stereomicroscope. The total thickness of the parietal bone was ranged from 5.17mm to 7.50mm, and there were no statistical difference in the total thickness of the parietal bone on the same points bilaterally. But there was a tendency that the thickness of the parietal bone was thicker toward to the lambda point than the coronal suture area. At the other hand, the thickness of the outer and inner plate of the parietal bone was the thickest at the first point of the right aspect on the line 1, the first point of the left aspect on the line 5, respectively. In conclusion, this study showed that the donor site of the parietal bone for the maxillofacial reconstruction should be located at more posterior and medial area of the parietal bone than the prevalent known donor site.

• Archives of Plastic Surgery
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• v.38 no.1
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• pp.77-80
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• 2011

Purpose: We report a patient with DiGeorge syndrome who was later diagnosed as mild metopic synostosis and received anterior 2/3 calvarial remodeling. Methods: A 16-month-old boy, who underwent palatoplasty for cleft palate at Chungnam National University Hospital when he was 12 months old of age, visited St. Mary's Hospital for known DiGeorge syndrome with craniosynostosis. He had growth retardation and was also diagnosed with hydronephrosis and thymic agenesis. His chromosomal study showed microdeletion of 22q11.2. On physical examination, there were parieto-occipital protrusion and bifrontotemporal narrowing. The facial bone computed tomography showed premature closure of metopic suture, orbital harlequin sign and decreased anterior cranial volume. The interorbital distance was decreased (17 mm) and the cephalic index was 93%. Results: After the correction of metopic synostosis by anterior 2/3 calvarial remodeling, the anterior cranial volume expanded with increased interorbital distance and decreased cephalic index. Fever and pancytopenia were noted at 1 month after the operation, and he was diagnosed as hemophagocytic lymphohistiocytosis by bone marrow study. He however, recovered after pediatric treatment. There was no other complication during the 12 month follow up period. Conclusion: This case presents with a rare combination of DiGeorge syndrome and metopic synostosis. When a child is diagnosed with DiGeorge syndrome soon after the birth, clinicians should keep in mind the possibility of an accompanying craniosynostosis. Other possible comorbidities should also be evaluated before the correction of craniosynostosis in patients as DiGeorge syndrome. In addition, postoperative management requires a thorough follow up by a multidisciplinary team of plastic surgeons, neurosurgeons, ophthalmologists and pediatricians.