• Journal of Genetic Medicine
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• v.9 no.2
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• pp.89-92
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• 2012

Campomelic dysplasia (CMD) is a rare, often lethal, genetic disorder characterized by multiple congenital anomalies and abnormal development of the reproductive organs in males. Mutations in the SOX9 gene are known to cause CMD. We present a Korean CMD girl with a normal 46,XX karyotype and a female reproductive organ phenotype. She was born at 2.35 kg at 38 weeks of gestation and showed characteristic phenotypes, including cleft palate, micrognathia, hypertelorism, flat nasal bridge, congenital bowing of limbs, hypoplastic scapulae, deformed pelvis, and 11 pairs of ribs. She also had an atrioseptal defect of the heart and marked laryngotracheomalacia requiring tracheostomy and tracheopexy. SOX9 mutation analysis revealed the presence of a novel nonsense mutation, $p.Gln369^*$, and the patient was genetically confirmed to have CMD. Although she showed marked failure to thrive and neurodevelopmental delay, she is now 40 months of age and is the only surviving patient with CMD in Korea.

• Journal of Oral Medicine and Pain
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• v.26 no.1
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• pp.87-93
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• 2001

SOX9과 SRY 유전자는 척추동물에서 남성고환의 형성을 유도하는 요소로 알려졌다. SOX9 유전자는 SRY related HMG box gene중 하나로 유전질환의 XY성전환 및 성을 결정하는 데에 관여하며 성결정시기에 그 양에 따른 성전환 발생등 연구가 진행되고 있다. 그러나 이 유전자가 성별판정에 유용할 지는 확실치 않다. 반면 SRY 유전자는 포유동물에서의 배형성시기 고환형성을 결정하는 Y염색체 유전자로 남성에만 존재하고 여성에는 존재 않는다. 현재까지 이을 이용하여 법의학적 검체에서 남성판별에 유용하게 사용되고 있다. 본 실험에서는 X, Y와 같은 성염색체가 아닌 상동염색체상에 있으면서 SRY 유전자와 더불어 남성고환을 결정하는 또다른 요소로서의 기능을 가진 SOX9 유전자를 치아에서 검출하여 법의학적 성별판정에 유용할 수 있는지 알아보고자 본 연구를 수행하였다. 남녀각각 5개의 치아에서 치수와 상아질을 분리한 후 DNA를 추출하여 SOX9과 SRY 유전자의 특이적인 시발체를 제작하고 중합효소연쇄반응을 시행하여 증폭하고 전기영동을 시행하였다. 그 결과 SOX9 유전자는 남녀모두에서 유전자가 검출되었고, SOX9 유전자산물과 SRY 유전자를 혼합하여 사용시 남자에서만 유전자가 검출되었다. 이는 법의치과학적 성별판정에 있어 SOX9 유전자는 사람의 치아에서는 남녀 모두 존재하며 남녀 구별을 위한 성별판정에는 이용할 수 없으며 SRY 유전자와 함께 적용시 남성 특이적 SRY 유전자 검사중 발생할 수 있는 가성 음성 반응여부를 확인하는 데 유용할 것으로 사료된다.

• Journal of Interdisciplinary Genomics
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• v.3 no.2
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• pp.30-34
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• 2021

Campomelic dysplasia (CD) is a rare genetic disorder characterized by multiple skeletal anomalies and the abnormal development of male reproductive organs. To date, the SOX9 gene is the only known causal gene for CD, and approximately 90 causative mutations in SOX9 have been identified worldwide. CD is diagnosed based on clinical characteristics of skeletal dysplasia (e.g., short bowed long bones, kyphoscoliosis, bell-shaped thoracic cage with 11 pairs of ribs, and hypoplastic scapulars), typical facial features of Pierre Robin sequence with cleft palate, and gonadal dysgenesis in 46,XY individuals. Most patients with CD exhibit life-threatening respiratory failure owing to laryngotracheomalacia and hypoplastic thorax during the neonatal period. Although fatal complications decrease after infancy, several medical conditions continue to require proper management. A better understanding of this rare but lethal condition may lead to more appropriate treatments for patients.

• Animal cells and systems
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• v.13 no.3
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• pp.289-295
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• 2009

Cyclic AMP-mediated signaling pathways regulate a number of cellular functions. In this study, we examined the regulatory role of cAMP signaling pathways in chondrogenesis of chick limb bud mesenchymal cells in vitro. Forskolin, which increases cellular cAMP levels by the activation of adenylate cyclase, enhanced chondrogenic differentiation. Inhibition of PKA with specific inhibitors (H89 or KT5720) blocked pre-cartilage condensation stage, indicating that chondrogenesis is regulated by the increase in cellular cAMP level and subsequent activation of PKA. Downstream signaling pathway of PKA leading to gene expression was investigated by examination of several nuclear transcription factors. Forskolin treatment increased transcription level for a cartilage-specific marker gene Sox9. However, inhibition of PKA with H89 led to restore expression of Sox9, indicating PKA activity was required to regulate the expression of Sox9 in chondrogenesis. In addition, CREB was highly phosphorylated at early stage of mesenchyme culture, and followed by progressive dephosphorylation. CBP and ATF, another CRE related proteins were transiently expressed at the early stage of chondrogenesis with a pattern similar to CREB phosphorylation. Electrophoretic mobility shift assays confirmed that the binding activity of CREB to the CRE is closely correlated to the phosphorylation pattern of CREB. Therefore, cAMP-mediated signal transduction to nuclear events for the induction of genes appeared to be required at the early stage of chick limb bud chondrogenesis.

• Journal of Korean Neurosurgical Society
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• v.63 no.5
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• pp.559-565
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• 2020

Objective : Conflicting results regarding SOX17 genes and the risk of intracranial aneurysms (IA) exist in the Korean population, although significant positive correlations were noted in genome-wide association studies in European and Japanese populations. Therefore, we aimed to investigate an association between SOX17 gene variants and IA using exome sequencing data. Methods : This study included 26 age-gender matched IA patients and 26 control subjects. The SOX17 gene variants identified from whole-exome sequencing data were examined. Genetic associations to estimate odds ratio (OR) and 95% confidence interval (CI) were performed using the software EPACTS. Results : The mean age of the IA and control groups were 51.0±9.3 years and 49.4±14.3 years, respectively (p=0.623). Seven variants of SOX17, including six single nucleotide polymorphisms and one insertion and deletion, were observed. Among these variants, rs12544958 (A>G) showed the most association with IA, but the association was not statistically significant (OR, 1.97; 95% CI, 0.81-4.74; p=0.125). Minor allele frequencies of the IA patients and controls were 0.788 and 0.653, respectively. None of the remaining variants were significantly associated with IA formation. Conclusion : No significant association between SOX17 gene variants and IA were noted in the Korean population. A large-scale exome sequencing study is necessary to investigate any Korean-specific genetic susceptibility to IA.

• BMB Reports
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• v.49 no.6
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• pp.343-348
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• 2016

GATA4 has been reported to act as a negative regulator in osteoblast differentiation by inhibiting the Dlx5 transactivation of Runx2 via the attenuation of the binding ability of Dlx5 to the Runx2 promoter region. Here, we determine the role of GATA4 in the regulation of bone sialoprotein (Bsp) in osteoblasts. We observed that the overexpression of Runx2 or Sox9 induced the Bsp expression in osteoblastic cells. Silencing GATA4 further enhanced the Runx2- and Sox9-mediated Bsp promoter activity, whereas GATA4 overexpression down-regulated Bsp promoter activity mediated by Runx2 and Sox9. GATA4 also interacted with Runx2 and Sox9, by attenuating the binding ability of Runx2 and Sox9 to the Bsp promoter region. Our data suggest that GATA4 acts as a negative regulator of Bsp expression in osteoblasts.

• Animal Bioscience
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• v.36 no.8
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• pp.1180-1189
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• 2023

Objective: Discovering the mechanism of cell specification is important to manipulate cellular lineages. To obtain lineage-specific cell lines, the target lineage needs to be promoted, and counterpart lineages should be suppressed. Embryos in the early blastocyst stage possess two different cell populations, the inner cell mass (ICM) and trophectoderm. Then, cells in the ICM segregate into epiblasts (Epi) and primitive endoderm (PrE). PrE cells in embryos show specific expression of platelet-derived growth factor (PDGF) and its receptor, PDGF receptor A (PDGFRA). In this study, we suppressed PDGF signaling using two methods (CRISPR/Cas9 injection and inhibitor treatment) to provide insight into the segregation of embryonic lineages. Methods: CRISPR/Cas9 RNAs were injected into parthenogenetically activated and in vitro fertilized embryos. The PDGF receptor inhibitor AG1296 was treated at 0, 5, 10, and 20 µM concentration. The developmental competence of the embryos and the number of cells expressing marker proteins (SOX2 for ICM and SOX17 for PrE) were measured after the treatments. The expression levels of the marker genes with the inhibitor were examined during embryo development. Results: Microinjection targeting the PDGF receptor (PDGFR) A reduced the number of SOX17-positive cell populations in a subset of day 7 blastocysts (n = 9/12). However, microinjection accompanied diminution of Epi cells in the blastocyst. The PDGF receptor inhibitor AG1296 (5 µM) suppressed SOX17-positive cells without reducing SOX2-positive cells in both parthenogenetic activated and in vitro fertilized embryos. Within the transcriptional target of PDGF signaling, the inhibitor significantly upregulated the Txnip gene in embryos. Conclusion: We identified that PDGF signaling is important to sustain the PrE population in porcine blastocysts. Additionally, treatment with inhibitors was a better method to suppress PrE cells than CRISPR/Cas9 microinjection of anti-PDGF receptor α gene, because microinjection suppressed number of Epi cells. The PDGF receptor might control the number of PrE cells by repressing the proapoptotic gene Txnip. Our results can help to isolate Epi-specific cell lines from blastocysts.

• Journal of Korean Neurosurgical Society
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• v.47 no.1
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• pp.26-29
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• 2010

Objective: Recurrent lumbar disc herniation has been reported to occur in 5% to 15% of surgically treated primary lumbar disc herniation cases. We investigated the molecular biologic characteristics of primary herniated discs and recurrent discs to see whether the recurrent discs has the similar biological features with primary herniated discs. Methods: Primary hemiated disc and recurrent disc cells were obtained by discectomy of lumbar disc patients and cells were isolated and then taken through monolayer cultures. We compared chondrogenic and osteogenic mRNA gene expression, and western blot between the two groups. Results: The mRNA gene expression of recurrent disc cells were increased 1.47* times for aggrecan, 1.38 times for type I collagen, 2.04 times for type II collagen, 1.22 times for both Sox-9 and osteocalcin, and 1.31 times for alkaline phosphatase, respectively, compared with the primary herniated lumbar disc cells (*indicates p < 0.05). Westem blot results for each aggrecan, type I collagen, type II collagen, Sox-9, osteocalcin, and alkaline phosphatase were similar between the primary herniated disc cells and recurrent disc cells. Conclusion: These results indicate that the recurrent disc cells have similar chondrogenic and osteogenic gene expression compared to primary herniated disc cells. Therefore, we assumed that the regeneration of remaining discs could fill the previous discectomy space and also it could be one of the factors for disc recurrence especially in the molecular biologic field.

• Journal of Korean Medicine Rehabilitation
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• v.30 no.4
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• pp.17-30
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• 2020

Objectives The purpose of this study is to evaluate the healing effect of Yukmijihwang-tang (YM) on femur fractured mice. Methods Mice were randomly divided into 6 groups: normal, control, positive control, YM with low, medium, high dosage each. All groups were prepared with femur fracture and treated diffrently. In order to measure bone regeneration effects, we analysed the levels of cyclooxygenase-2 (COX2), bone morphogenetic protein-2 (BMP2), collagen type II alpha 1 chain (Col2a1), Sox9, runt-related transcription factor 2 (Runx2), and osterix genes expressed in bone. For morphological analysis, muscles were removed and femur was observed with naked eye. Results COX2 gene expression in bone marrow significantly decreased. BMP2 gene expression significantly increased. Col2a1 gene expression significantly increased. Sox9 gene expression increased as well. Runx2 gene expression in bone marrow increased, but there was no statistical significance. Osterix gene expression significantly increased. Union of the fracture site progressed more in YM group compared to the control group. The fracture union score was significantly decreased in YM group compared to the control group. Conclusions YM showed anti-inflammatory effect, promoted bone regeneration by stimulating the bone regeneration factor. In conclusion, YM can help fracture healing and it well be applied clinically to patients with fracture.

• Journal of Korean Neurosurgical Society
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• v.43 no.4
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• pp.190-193
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• 2008

Objective : Cancer-testis (CT) genes are considered promising candidates for immunotherapeutic approaches. The aim of this study was to investigate which CT genes should be targeted in immunotherapy for brain tumors. Methods : We investigated the expression of 6 CT genes (MAGE-E1, SOX-6, SCP-1, SSX-2, SSX-4, and HOMTES-85) using reverse-transcription polymerase chain reaction in 26 meningiomas and 32 other various brain tumor specimens, obtained from the patients during tumor surgery from 2000 to 2005. Results : The most frequently expressed CT genes of meningiomas were MAGE-E1, which were found in 22/26 (85%) meningioma samples, followed by SOX-6 (9/26 or 35%). Glioblastomas were most frequently expressed SOX-6 (6/7 or 86%), MAGE-E1 (5/7 or 71%), followed by SSX-2 (2/7 or 29%) and SCP-1 (1/7 or 14%). However, 4 astrocytomas, 3 anaplastic astrocytomas, and 3 oligodendroglial tumors only expressed MAGE-E1 and SOX-6. Schwannomas also expressed SOX-6 (5/6 or 83%), MAGE-E1 (4/6 or 67%), and SCP-1 (2/6 or 33%). Conclusion : The data presented here suggest that MAGE-E1 and SOX-6 genes are expressed in a high percentage of human central nervous system tumors, which implies the CT genes could be the potential targets of immunotherapy for human central nervous system tumors.