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THE ROLE OF TRANSCRIPTION FACTOR MSX2 AND DLX5 IN CALVARIAL BONE AND SUTURE DEVELOPMENT (두개골 및 두개봉합부 초기발육과정에서의 전사조절인자인 Msx2와 Dlx5의 역할)

  • Song, Min-Ho;Park, Mi-Hyun;Nam, Soon-Hyeun;Kim, Young-Jin;Ryoo, Hyun-Mo;Kim, Hyun-Jung
    • 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.

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CT Scan Findings of Rabbit Brain Infection Model and Changes in Hounsfield Unit of Arterial Blood after Injecting Contrast Medium (토끼 뇌감염 모델의 CT 소견과 조영제 주입 후 동맥혈의 Hounsfield Unit의 변화)

  • Ha, Bon-Chul;Kwak, Byung-Kook;Jung, Ji-Sung
    • The Journal of the Korea Contents Association
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    • v.12 no.9
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    • pp.270-279
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    • 2012
  • This paper explores CT findings of a rabbit brain infection model injected with Escherichia coli and investigates the changes in Hounsfield unit (HU) of arterial blood over time. The brain infection model was produced by injecting E. coli $1{\times}10^7$ CFU/ml, 0.1 ml through the burr hole in the calvarium; 2~3 mm in depth from the dura mater, and contrast-enhanced CT, dynamic CT and arterial blood CT images were gained. It was found that various brain infections such as brain abscess, ventriculitis and meningitis. The CT image of brain abscess showed a typical pattern which the peripheral area was strongly contrast-enhanced while the center was weakly contrast-enhanced. The CT image of ventriculitis showed a strong contrast-enhancement along the lateral ventricle wall, and the CT image of meningitis showed a strong contrast-enhancement in the area between the telencephalon and the diencephalon. In dynamic CT images, the HU value of the infection core before injecting contrast medium was $31.01{\pm}3.55$. By 10 minutes after the injection, the value increased gradually to $40.36{\pm}3.76$. The HU value in the areas of the marginal rim where was hyper-enhanced showed $47.23{\pm}3.12$ before contrast injection, and it increased to $63.59{\pm}3.31$ about 45 seconds after the injection. In addition, the HU value of the normal brain tissue opposite to the E. coli. injected brain was $39.01{\pm}3.24$ before the injection, but after the contrast injection, the value increased to $49.01{\pm}4.29$ in about 30 seconds, and then it showed a gradual decline. In the arterial blood CT, the HU value before the contrast injection was $87.78{\pm}6.88$, and it increased dramatically between 10 to 30 seconds until it reached a maximum value of $749.13{\pm}98.48$. Then it fell sharply to $467.85{\pm}62.98$ between 30 seconds to 45 seconds and reached a plateau by 60 seconds. Later, the value showed a steady decrease and indicated $188.28{\pm}25.03$ at 20 minutes. Through this experiment, it was demonstrated that the brain infection model can be produced by injecting E. coli., and the characteristic of the infection model can be well observed with contrast-enhanced CT scan. The dynamic CT scan showed that the center of the infection was gradually contrast-enhanced, whereases the peripheral area was rapidly contrast-enhanced and then slowly decreased. As for arterial blood, it increased significantly between 10 seconds to 30 seconds after the contrast medium injection and decreased gradually after reaching a plateau.