Publications (24)67.29 Total impact
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Article: Defect in Runx2 gene accelerates ureteral obstruction-induced kidney fibrosis via increased TGF-β signaling pathway.
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ABSTRACT: Runt-related transcription factor 2 (Runx2) plays an important role in bone formation and de novo synthesis of proteins, including type 1 collagen. Runx2 has a potent effect on signaling of transforming growth factor (TGF)-β and vice versa, implicating its significant role in fibrosis. Chronic renal failure comprises fibrosis, characterized as an increase in TGF-β signaling, and expression of α-smooth muscle actin (α-SMA), and extracellular matrix proteins. Here, we evaluated the role of Runx2 in ureteral obstruction (UO)-induced kidney fibrosis using mice whose Runx2 gene expression is genetically down-regulated. UO caused tubular atrophy and dilation, expansion of interstitium, and increased expression of collagens and α-SMA with a concomitant decrease in expression of Runx2. Deficiency of Runx2 gene (Runx2(+/-) mice) showed higher expression of collagens and α-SMA in the kidney following UO compared to wild type (Runx2(+/+)) mice. UO-induced activation of TGF-β signaling was higher in the Runx2(+/-) kidney than Runx2(+/+) kidney, suggesting an inhibitory effect of Runx2 on TGF-β signaling in kidney fibrosis. Besides, overexpression of the Runx2 gene using an adenoviral vector in kidney tubule cells resulted in attenuated TGF-β-induced Smad3 phosphorylation and expressions of α-SMA and collagen I. Furthermore, Runx2 gene deficient mouse embryonic fibroblasts induced greater activation of Smad3 and expression of α-SMA in response to TGF-β. Collectively, Runx2 plays a protective role in UO-induced kidney fibrosis by inhibition of TGF-β signaling, suggesting Runx2 as a novel target for protection against fibrosis-related diseases such as chronic renal failure.Biochimica et Biophysica Acta 04/2013; · 4.66 Impact Factor -
Article: DICAM inhibits angiogenesis via suppression of AKT and p38 MAP kinase signaling.
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ABSTRACT: AIMS: Dual Ig domain Containing Adhesion Molecule (DICAM), a protein with homology to the junctional adhesion molecule family, has been demonstrated to interact with integrin αVβ3 that plays a critical role in angiogenesis. Here, we determined the role of DICAM during angiogenesis and the molecular mechanisms involved in the inhibition of angiogenesis.Methods and ResultsDICAM was expressed on the endothelial cells of large vessels to small capillaries. In human umbilical vein endothelial cells (HUVECs), DICAM was up-regulated by vascular endothelial growth factor (VEGF) through the MEK/ERK and PI3 K/AKT pathways. Furthermore, the exogenous expression of DICAM in HUVECs suppressed angiogenesis in vitro Matrigel and in vivo plug assays, and conversely, DICAM knockdown enhanced angiogenesis. In addition, DICAM inhibited HUVEC migration and accelerated apoptosis via down-regulation of Bcl-2, but did not affect viability or proliferation of HUVEC. Mechanistically, the exogenous expression of DICAM suppressed VEGF-induced phosphorylarion of AKT and p38 MAP kinase. When integrin signaling was activated by vitronectin, a forced expression of DICAM attenuated integrin β3/FAK signaling and downstream AKT and p38 MAP kinase signaling in HUVECs. CONCLUSION: Collectively, DICAM suppressed angiogenesis by attenuating AKT and p38 MAP kinase signaling, which suggests that DICAM may be a novel negative regulator of angiogenesis.Cardiovascular research 02/2013; · 5.80 Impact Factor -
Article: 4-hexylresorcinol stimulates the differentiation of SCC-9 cells through the suppression of E2F2, E2F3 and Sp3 expression and the promotion of Sp1 expression.
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ABSTRACT: The dormancy-inducing factors of bacteria inhibit tumor cell growth. In the present study, we evaluated the antitumor effects of the dormancy-inducing factor 4-hexylresorcinol (4-HR) using real-time cell electronic sensing (RT-CES) in SCC-9 cells (tongue squamous cell carcinoma cells). Treatment with 4-HR suppressed the growth of SCC-9 cells in a dose-dependent manner. We used a DNA microarray to identify genes that showed a significant change in expression upon 4-HR administration in SCC-9 cells. Among the differentially expressed genes, the protein expression of several cell proliferation related factors, including E2F1, E2F2, E2F3, E2F4, E2F5, E2F6, Sp1 and Sp3, were determined by western blot analyses. Treatment with 4-HR strongly suppressed E2F2 and slightly suppressed E2F3 but did not change the expression of E2F1, E2F4, E2F5 and E2F6 relative to no treatment. Furthermore, 4-HR increased Sp1 expression in a dose-dependent manner and decreased Sp3 expression. Therefore, the ratio of Sp1 to Sp3, an important driving force of epithelial cell differentiation, was drastically increased. Consistent with this observation, 4-HR increased the expression of the epithelial cell differentiation markers involucrin and keratin 10. Together, our results indicate that 4-HR induces the differentiation of SCC-9 via the modulation of the E2F-mediated signaling pathway.Oncology Reports 06/2012; 28(2):677-81. · 1.84 Impact Factor -
Article: Nitrogen grafting onto polycarprolactone by a simple surface modification with atmospheric pressure glow discharge (Ar-APGD) and promoted neonatal human fibroblast growth
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ABSTRACT: Plasma surface modifications of polymer scaffolds using biomolecules such as oxygen, nitrogen, and other active grafting molecules have been studied to enhance biological responses such as cell attachment, spreading, and proliferation. According to the reports, nitrogen grafting requires corrosive or mixture gas environment, or post treatment. This study aimed to evaluate a simple atmospheric pressure plasma surface modification in order to graft nitrogen derivatives and to promote biological responses. In this study, a polycarprolactone (PCL) film was modified within 10 min by argon atmospheric pressure discharge (Ar-APGD). Excited argon atoms, nitrogen atoms, oxygen atoms, and hydroxyl functional groups were observed from the optical emission spectra of the discharge. Decreased carbonyl functional groups and ether functional groups were observed; notably, immobilized nitrogen was observed on the PCL surface after the Ar-APGD treatment. Promoted neonatal Human Dermal Fibroblast (nHDF) growth patterns were observed on the Ar-APGD-treated surface. Keywordsbiodegradable polymer–plasma–atmospheric pressure–surface modification–neonatal human dermal fibroblastMacromolecular Research 04/2012; 19(11):1134-1141. · 1.15 Impact Factor -
Article: Reactive Oxygen Species-specific Mechanisms of Drug Resistance in Paraquat-resistant Acute Myelogenous Leukemia Sublines
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ABSTRACT: Reactive oxygen species (ROS)-specific mechanisms of drug resistance were explored in paraquat (PQ)-resistant acute myelogenous leukemia cell (OCI/AML-2) sublines. For this, PQ-resistant AML sublines, AML-2/PQ100 and AML-2/PQ400, were selected in the presence of PQ concentrations of 100 μg/ml and 400 μg/ml, respectively. They showed a moderate level of cross resistance to cisplatin and doxorubicin. They were also slightly more resistant than the parental cell (AML-2/WT) to etoposide, camptothecin and daunorubicin. The resistance of PQ-resistant AML-2 sublines to cisplatin seemed to be due to increased amounts of metallothionein, which was not only supported by reversal of resistance to cisplatin by propargylglycin (an inhibitor of metallothionein synthesis) but also confirmed by Western blot analysis and reverse transcription-PCR assay. In addition, both AML-PQ100 and /PQ400 sublines showed increased activities of Cu-, Zn-containing superoxide dismutase (Cu,Zn-SOD) and Mn-containing superoxide dismutase (Mn-SOD), whereas AML-2/PQ400, but not AML-2/PQ100, showed increased glutathione S-transferase activity as compared to that of AML-2/WT. However, there was no difference in other ROS-related cellular antioxidants between AML-2/WT and its PQ-resistant sublines. Taken together, these results strongly suggest that increases in levels of metallothionein, glutathione S-transferase, Cu,Zn-SOD and Mn-SOD play important roles in protective mechanisms against toxicity of PQ or ROS in AML cells. KeywordsAcute Myelogenous Leukemia-GlutathioneMolecules and Cells 04/2012; 10(1):38-46. · 2.18 Impact Factor -
Article: DICAM inhibits osteoclast differentiation through attenuation of the integrin αVβ3 pathway.
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ABSTRACT: Dual immunoglobulin (Ig) domain-containing adhesion molecule (DICAM) is involved in cell-cell adhesion through a heterophilic interaction with αVβ3 integrin, which suggests that DICAM may participate in osteoclast differentiation. DICAM was localized in the plasma membrane of RAW264.7 and THP-1 cells, and its expression gradually increased during osteoclastogenesis in mouse bone marrow-derived macrophages (BMMs) treated with receptor activator of nuclear factor κ-B ligand (RANKL) and macrophage colony-stimulating factor (M-CSF). Forced expression of DICAM in BMMs and RAW264.7 cells blocked the generation of tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts. Conversely, knockdown of DICAM by small hairpin RNA (shRNA) increased osteoclast formation in RAW264.7 cells. DICAM-mediated suppression of osteoclast differentiation was in part due to the inhibition of the p38 mitogen-activated protein (MAP) kinase pathway, which was corroborated by a decrease in the expression of c-Fos and nuclear factor of activated T cells (NFAT)c1. Mechanistically, DICAM directly interacted with integrin β3, which inhibited heterodimerization between integrin αV and β3. Exogenous expression of integrin β3 or high-dose M-CSF rescued DICAM-mediated inhibition of osteoclastogenesis, suggesting crosstalk between the integrin β3 and c-Fms pathways. Finally, recombinant DICAM ectodomain suppressed the RANKL- and M-CSF-induced osteoclastogenesis of BMMs. Collectively, these results indicate that DICAM acts as a negative regulator of osteoclast differentiation by suppressing the integrin αVβ3 pathway.Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 04/2012; 27(9):2024-34. · 6.04 Impact Factor -
Article: Runx2 protein stabilizes hypoxia-inducible factor-1α through competition with von Hippel-Lindau protein (pVHL) and stimulates angiogenesis in growth plate hypertrophic chondrocytes.
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ABSTRACT: The regulation of hypoxia-inducible factor-1α (HIF-1α) during endochondral bone formation is not fully understood. Here, we investigated the cross-talk between HIF-1α and Runt-related transcription factor 2 (Runx2) in the growth plate. Runx2 caused the accumulation of HIF-1α protein in ATDC5 chondrocytes and HEK293 cells under normoxic conditions. Runx2 also increased the nuclear translocation of HIF-1α when coexpressed in HEK293 cells and interacted with HIF-1α at the oxygen-dependent degradation domain (ODDD). In addition, Runx2 competed with von Hippel-Lindau tumor suppressor protein by directly binding to ODDD-HIF-1α and significantly inhibited the ubiquitination of HIF-1α, even though Runx2 did not change the hydroxylation status of HIF-1α. Furthermore, overexpression of Runx2 resulted in the significant enhancement of vascular endothelial growth factor (VEGF) promoter reporter activity and protein secretion. Runx2 significantly increased angiogenic activity in human umbilical vein endothelial cells in vitro. In wild-type mice, HIF-1α and Runx2 were colocalized in hypertrophic chondrocytes in which the cluster of differentiation 31 (CD31) protein was expressed at embryonic day 15.5 (E15.5). In contrast, the expression of HIF-1α was markedly reduced in areas of CD31 expression in Runx2(-/-) mice. These results suggest that Runx2 stabilizes HIF-1α by binding to ODDD to block the interaction between von Hippel-Lindau protein and HIF-1α. In conclusion, Runx2, HIF-1α, and VEGF may regulate vascular angiogenesis spatially and temporally in the hypertrophic zone of the growth plate during endochondral bone formation.Journal of Biological Chemistry 02/2012; 287(18):14760-71. · 4.77 Impact Factor -
Article: Topically administered Risedronate shows powerful anti-osteoporosis effect in ovariectomized mouse model.
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ABSTRACT: We investigated the therapeutic effect of topical Risedronate (RIS) on a mouse model of estrogen-deficient osteoporosis. Fourteen-week-old female mice were ovariectomized and assigned to 4 groups: SHAM-operated (SHAM), OVX mice treated with vehicle (OVX-V), OVX mice treated with 0.2% RIS (OVX-0.2% RIS), and OVX-mice treated with 0.02% RIS (OVX-0.02% RIS). Topical samples containing RIS were prepared in 10% (w/w) polyethylene glycol (PEG, MW 400) and 80 μg of sample was spread on the mice's mid-backs every 3 days for 5 weeks. Micro-CT analysis of femora demonstrated that OVX-0.2% RIS exhibited a 29% greater bone mineral density and 24% greater bone volume fraction than that of OVX-V group. Investigation of the trabecular bone in OVX-0.2% RIS revealed a 24% higher bone volume (BV/TV), 51% higher trabecular number (Tb.N), and 40% lower trabecular separation (Tb.Sp) compared to OVX-V mice. Additionally, bone phenotypes of tibiae were further confirmed by histological analysis. OVX-0.2% RIS group exhibited a 494% greater BV/TV, 464% less Tb.Sp, 81% greater active osteoclast surface (Oc.S/BS) and 26% less osteoclast number (N.Oc/BS) than that of OVX-V group. Collectively, these results indicated that topical delivery of RIS has powerful pharmaceutical effects on the prevention of osteoporosis and bone turnover.Bone 01/2012; 50(1):149-55. · 4.02 Impact Factor -
Article: Histomorphometric analysis of sinus augmentation using bovine bone mineral with two different resorbable membranes.
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ABSTRACT: OBJECTIVE: The purpose of this study was to compare the effects of two different resorbable collagen membranes on new bone formation after sinus grafts with anorganic bovine bone mineral (BBM). MATERIALS AND METHODS: For 64 patients presenting with an initial residual bone height ≤4 mm at the posterior maxilla, the sinus floors were grafted with BBM (Bio-Oss(®) ). The lateral windows were covered by one of the two bio-resorbable membranes, Bio-Arm(®) or Bio-Gide(®) . The histomorphometric data were obtained 7-15 months after sinus augmentation at the time of the implant installation. RESULTS: The core biopsy specimens of Bio-Arm (n = 37 sites) and Bio-Gide group (n = 22 sites) were compared. The results showed that the BBM particles were in direct contact with the newly formed bone in all cases. In histomorphometric analysis, the Bio-Gide group showed significantly higher new bone formation (33.3 ± 12%) compared with the Bio-Arm group (26.3 ± 8.1%) (P < 0.05). All the implants survived successfully after a mean follow-up of 35.3 months (range 22-63 months) in the Bio-Arm group and 55.5 months (range 35-66 months) in the Bio-Gide group. The amount of new bone in the specimens did not significantly correlate with the residual bone height at the time of surgery or the length of the healing period. CONCLUSIONS: The type of resorbable membrane did not readily affect the long-term survival of the implants at the grafted sinus. On the other hand, Bio-Gide group showed more new bone formation than the Bio-Arm group, which implied that the function of the membrane can influence the remodeling of the grafted sinus. As the amount of residual bone substitute particle had not decreased significantly over time, the results suggest that the BBM was rarely resorbable for at least 15 months after the surgery.Clinical Oral Implants Research 11/2011; · 2.51 Impact Factor -
Article: Interrelationship of Runx2 and estrogen pathway in skeletal tissues.
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ABSTRACT: Two key molecules in skeletal tissues are bone formation master transcription factor Runx2 and the steroid hormone estrogen. It is well known that these two molecules play pivotal roles in bone homeostasis; however, the functional interaction between Runx2 and estrogen synthesis in skeletal tissues is largely unknown. Recent studies have indicated that there is a positive relationship between Runx2 and the estrogen biosynthesis pathway. In this review, a possible functional link between Runx2 and estrogen synthesis pathway in skeletal tissues will be discusses as well as the biological significance of this interaction.BMB reports 10/2011; 44(10):613-8. · 1.72 Impact Factor -
Article: 4-hexylresorcinol inhibits NF-κB phosphorylation and has a synergistic effect with cisplatin in KB cells.
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ABSTRACT: Cisplatin is a representative anti-cancer drug and 4-hexylresorcinol (4-HR) is known as an antiparasitic and antiseptic agent. The aims of this study were to evaluate the effect of 4-HR on the activation of nuclear factor-κB (NF-κB) in cell cultures, to evaluate the antitumor effect of 4-HR plus cisplatin combination therapy in a xenograft model, and to evaluate transglutaminase-2 (TG-2) and phosphorylated NF-κB (pNF-κB) expression in the xenograft model. To determine the effect of 4-HR on NF-κB phosphorylation, co-immunoprecipitation and Western blot analysis were done in KB cells. To examine the in vivo effect of the cisplatin plus 4-HR combination therapy, KB cells were grafted into nude mice. Drugs were injected into the peritoneal cavity daily. Tumor size, body weight, and duration of survival were checked daily. Specimens from main mass were used in immunohistochemical staining for the analysis of TG-2 and pNF-κB expression. In the in vitro test, as the 4-HR concentrations increased, the fraction of the bound complex NF-κB-inhibitory-κB (IκB) increased. Consequently, the level of free IκB decreased. In the xenograft model, the cisplatin plus 4-HR group exhibited a significantly decreased tumor growth rate than in the saline group (P=0.039). The mean survival time of the cisplatin plus 4-HR group was 51.20±3.96 days and was significantly prolonged compared with the other groups (P<0.05). The body weight of the cisplatin plus 4-HR group had significantly less weight loss than the cisplatin only group (P=0.045). In the immunohistochemical analysis, the cisplatin plus 4-HR group had a significantly lower expression of TG-2 and pNF-κB compared to the saline group (P<0.05). In conclusion, cisplatin plus 4-HR combination therapy had clear advantages over the cisplatin only treatment such as similar tumor growth inhibition compared to the cisplatin only treatment despite the reduced dosage of cisplatin, less body weight loss, and prolonged survival time.Oncology Reports 08/2011; 26(6):1527-32. · 1.84 Impact Factor -
Article: Combination of Runx2 and BMP2 increases conversion of human ligamentum flavum cells into osteoblastic cells.
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ABSTRACT: The conversion of fibroblasts into osteoblasts requires the activation of key signaling pathways, including the BMP pathway. Although Runx2 is known to be a component of the BMP pathway, the combination of Runx2 and BMP2 has not yet been examined with respect to the conversion of fibroblasts into osteoblasts. Here, human ligamentum flavum (LF) fibroblast- like cells from six patients were tested for their conversion into osteoblasts using adenoviruses expressing Runx2 or BMP2. The forced expression of Runx2 or BMP2 in primary cultured LF cells resulted in a variety of proliferation and differentiation behaviors. Combined treatment of BMP2 plus Runx2 resulted in better osteoblastic differentiation than treatment with either component alone. These results indicate that the Runx2 and BMP2 pathways possess both common and independent target genes. Collectively, Runx2 plus BMP2 mediated efficient conversion of fibroblast-like LF cells into osteoblast- like cells, suggesting the possible use of these components for clinical applications such as spinal fusion.BMB reports 07/2011; 44(7):446-51. · 1.72 Impact Factor -
Article: 4-Hexylresorcinol inhibits transglutaminase-2 activity and has synergistic effects along with cisplatin in KB cells.
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ABSTRACT: Resistance to chemotherapy is very important in the prognosis of tumors. Transglutaminase-2 (TG-2) mediated chemotherapy resistance has been widely reported. The objective of this study was to demonstrate the effect of 4-hexylresorcinol (4-HR) on TG-2 activity in nasopharyngeal squamous cell carcinoma cells (KB cells). Treatment with a mixture of 4-HR and cisplatin significantly decreased KB cell viability compared to treatment by cisplatin alone at 10 µg/ml (p<0.001). 4-HR inhibited TG-2 activity compared to cisplatin alone at 5, 10 and 20 µg/ml (p = 0.001, 0.001 and 0.003, respectively). Nuclear translocation of TG-2 was also inhibited by 4-HR treatment. 4-HR treatment also increased the fluorescence life-time of DAPI significantly compared to the untreated control or the cisplatin treated group (p<0.001). In conclusion, 4-HR inhibited TG-2 activity and showed a synergistic effect on tumor cell growth inhibition with cisplatin.Oncology Reports 03/2011; 25(6):1597-602. · 1.84 Impact Factor -
Article: The gene for aromatase, a rate-limiting enzyme for local estrogen biosynthesis, is a downstream target gene of Runx2 in skeletal tissues.
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ABSTRACT: The essential osteoblast-related transcription factor Runx2 and the female steroid hormone estrogen are known to play pivotal roles in bone homeostasis; however, the functional interaction between Runx2- and estrogen-mediated signaling in skeletal tissues is minimally understood. Here we provide evidence that aromatase (CYP19), a rate-limiting enzyme responsible for estrogen biosynthesis in mammals, is transcriptionally regulated by Runx2. Consistent with the presence of multiple Runx2 binding sites, the binding of Runx2 to the aromatase promoter was demonstrated in vitro and confirmed in vivo by chromatin immunoprecipitation assays. The bone-specific aromatase promoter is activated by Runx2, and endogenous aromatase gene expression is upregulated by Runx2 overexpression, establishing the aromatase gene as a target of Runx2. The biological significance of the Runx2 transcriptional control of the aromatase gene is reflected by the enhanced estrogen biosynthesis in response to Runx2 in cultured cells. Reduced in vivo expression of skeletal aromatase gene and low bone mineral density are evident in Runx2 mutant mice. Collectively, these findings uncover a novel link between Runx2-mediated osteoblastogenic processes and the osteoblast-mediated biosynthesis of estrogen as an osteoprotective steroid hormone.Molecular and cellular biology 03/2010; 30(10):2365-75. · 6.06 Impact Factor -
Article: Low molecular weight silk fibroin increases alkaline phosphatase and type I collagen expression in MG63 cells.
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ABSTRACT: Silk fibroin, produced by the silkworm Bombyx mori, has been widely studied as a scaffold in tissue engineering. Although it has been shown to be slowly biodegradable, cellular responses to degraded silk fibroin fragments are largely unknown. In this study, silk fibroin was added to MG-63 cell cultures, and changes in gene expression in the MG-63 cells were screened by DNA microarray analysis. Genes showing a significant (2-fold) change were selected and their expression changes confirmed by quantitative RT-PCR and western blotting. DNA microarray results showed that alkaline phosphatase (ALP), collagen type-I alpha-1, fibronectin, and transforming growth factor-beta1 expressions significantly increased. The effect of degraded silk fibroin on osteoblastogenic gene expression was confirmed by observing up-regulation of ALP activity in MG-63 cells. The finding that small fragments of silk fibroin are able to increase the expression of osteoblastogenic genes suggests that controlled degradation of silk fibroin might accelerate new bone formation. [BMB reports 2010; 43(1): 52-56].BMB reports 01/2010; 43(1):52-6. · 1.72 Impact Factor -
Article: Expression of Runx2 transcription factor in non-skeletal tissues, sperm and brain.
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ABSTRACT: Runx2 is a master transcription factor for chondrocyte and osteoblast differentiation and bone formation. However expression of Runx2 (by RT-PCR), has been reported in non-skeletal tissues such as breast, T cells and testis. To better define Runx2 activity in non-skeletal tissues, we examined transgenic (Tg) mice expressing LacZ gene under control of 3.0 kb (3 kb Tg) or 1.0 kb (1 kb Tg) of the Runx2 distal (P1) promoter, Runx2 LacZ knock-in (Runx2(+/LacZ)) and Runx2/P1 LacZ knock-in (Runx2/P1(+/LacZ)). In the Runx2 3 kb Tg mouse, beta-galactosidase (beta-gal) expression appeared in various non-skeletal tissues including testis, skin, adrenal gland and brain. beta-gal expression from both 3 kb and 1 kb Tg, reflecting activity of the Runx2 promoter, was readily detectable in seminiferous tubules of the testis and the epididymis. At the single cell level, beta-gal was detected in spermatids and mature sperms not in sertoli or Leydig cells. We also detected a positive signal from the Runx2(+/LacZ) and Runx2/P1(+/LacZ) mice. Indeed, Runx2 expression was observed in isolated mature sperms, which was confirmed by RT-PCR and Western blot analysis. Runx2, however, was not related to sex determination and sperm motility. Runx2 mediated beta-gal activity is also found robustly in the hippocampus and frontal lobe of the brain in Runx2(+/LacZ). Collectively, these results indicate that Runx2 is expressed in several non-skeletal tissues particularly sperms of testis and hippocampus of brain. It suggests that Runx2 may play an important role in male reproductive organ testis and brain.Journal of Cellular Physiology 11/2008; 217(2):511-7. · 3.87 Impact Factor -
Article: DICAM, a novel dual immunoglobulin domain containing cell adhesion molecule interacts with alphavbeta3 integrin.
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ABSTRACT: Immunoglobulin (Ig) superfamily members are abundant with diverse functions including cell adhesion in various tissues. Here, we identified and characterized a novel adhesion molecule that belongs to the CTX protein family and named as DICAM (Dual Ig domain containing cell adhesion molecule). DICAM is a type I transmembrane protein with two V-type Ig domains in the extracellular region and a short cytoplasmic tail of 442 amino acids. DICAM is found to be expressed ubiquitously in various organs and cell lines. Subcellular localization of DICAM was observed in the cell-cell contact region and nucleus of cultured epithelial cells. Cell-cell contact region was colocalized with tight junction protein, ZO-1. The DICAM increased MDCK cell adhesion to 60% levels of fibronectin. DICAM mediated cell adhesion was specific for the alphavbeta3 integrin; other integrins, alpha2, alpha5, beta1, alpha2beta1, alpha5beta1, were not involved in cell adhesion. In identifying the interacting domain of DICAM with alphavbeta3, the Ig domain 2 showed higher cell adhesion activity than that of Ig domain 1. Although RGD motif in Ig domain 2 was engaged in cell adhesion, it was not participated in DICAM-alphavbeta3 mediated cell adhesion. Furthermore, differentially expressing DICAM stable cells showed well correlated cell to cell adhesion capability with integrin beta3-overexpressing cells. Collectively, these results indicate that DICAM, a novel dual Ig domain containing adhesion molecule, mediates cell adhesion via alphavbeta3 integrin.Journal of Cellular Physiology 10/2008; 216(3):603-14. · 3.87 Impact Factor -
Article: DICAM, a novel dual immunoglobulin domain containing cell adhesion molecule interacts with αvβ3 integrin
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ABSTRACT: Immunoglobulin (Ig) superfamily members are abundant with diverse functions including cell adhesion in various tissues. Here, we identified and characterized a novel adhesion molecule that belongs to the CTX protein family and named as DICAM (Dual Ig domain containing cell adhesion molecule). DICAM is a type I transmembrane protein with two V-type Ig domains in the extracellular region and a short cytoplasmic tail of 442 amino acids. DICAM is found to be expressed ubiquitously in various organs and cell lines. Subcellular localization of DICAM was observed in the cell–cell contact region and nucleus of cultured epithelial cells. Cell–cell contact region was colocalized with tight junction protein, ZO-1. The DICAM increased MDCK cell adhesion to 60% levels of fibronectin. DICAM mediated cell adhesion was specific for the vβ3 integrin; other integrins, 2, 5, β1, 2β1, 5β1, were not involved in cell adhesion. In identifying the interacting domain of DICAM with vβ3, the Ig domain 2 showed higher cell adhesion activity than that of Ig domain 1. Although RGD motif in Ig domain 2 was engaged in cell adhesion, it was not participated in DICAM-vβ3 mediated cell adhesion. Furthermore, differentially expressing DICAM stable cells showed well correlated cell to cell adhesion capability with integrin β3-overexpressing cells. Collectively, these results indicate that DICAM, a novel dual Ig domain containing adhesion molecule, mediates cell adhesion via vβ3 integrin. J. Cell. Physiol. 216: 603–614, 2008, © 2008 Wiley-Liss, Inc.Journal of Cellular Physiology 08/2008; 216(3):603 - 614. · 3.87 Impact Factor -
Article: Analysis of the Runx2 promoter in osseous and non-osseous cells and identification of HIF2A as a potent transcription activator.
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ABSTRACT: Little is known about the upstream regulator of Runx2, a master regulator of osteoblast differentiation in bone tissues. To elucidate the molecular mechanism of Runx2 gene expression, we analyzed Runx2 promoter activity in osseous (MC3T3-E1, KS483, Kusa) and non-osseous (NIH3T3, C3H10T1/2, mouse embryonic fibroblasts) cells and also identified Runx2 upstream regulator using a Runx2 promoter-derived luciferase reporter system. After cloning 15 serial deletion constructs from -6832 bp/+390 bp to -37 bp/+390 bp of the Runx2-P1 promoter, we performed a transient transfection assay in osseous and non-osseous cells. A reduction in Runx2 promoter activity was observed in two regions; one was between -3 kb and -1 kb, and the other was between -155 bp and -75 bp. The step-down pattern in promoter activity between -3 kb and -1 kb was observed only in osseous cells. Interestingly, the step-down pattern between -155 bp and -75 bp was revealed in both cell types. Consistently, beta-galactosidase staining in axial skeleton of -3 kb-Runx2-P1-LacZ transgenic mice was positive, but that of all skeletal tissues of -1 kb-Runx2-P1-LacZ transgenic mice was negative. To identify upstream regulators of the Runx2-P1 promoter, we screened 100 transcription factors using Runx2-P1-luciferase reporter constructs in NIH3T3 fibroblasts and HeLa cells. Among them, HIF2A was identified as the strongest activator of Runx2-P1 promoter activity. A HIF2A-responsive site on the Runx2 promoter was identified between -106 bp and -104 bp by mutation analysis. An electrophoretic mobility shift assay and chromatin immunoprecipitation assay confirmed the binding of HIF2A to the Runx2-P1 promoter in vitro and in vivo, respectively. Knock-down using siRNA against HIF2A confirmed that HIF2A is an important regulator of Runx2 gene expression. Collectively, these results suggest that the region between -3 kb and -1 kb is required for the minimal skeletal tissue-specific expression of Runx2, and that the region between -155 bp and -75 bp is important for its basal transcription, which may be in part mediated by HIF2A in bone tissues.Gene 07/2008; 416(1-2):53-60. · 2.34 Impact Factor -
Article: Genetic characteristics of 207 microsatellite markers in the Korean population and in other Asian populations.
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ABSTRACT: Microsatellites, short tandem repeats, are useful markers for genetic analysis because of their high frequency of occurrence over the genome, high information content due to variable repeat lengths, and ease of typing. To establish a panel of microsatellite markers useful for genetic studies of the Korean population, the allele frequencies and heterozygosities of 207 microsatellite markers in 119 unrelated Korean, Indian and Pakistani individuals were compared. The average heterozygosity of the Korean population was 0.71, similar to that of the Indian and Pakistani populations. More than 80% of the markers showed heterozygosity of over 0.6 and were valuable as genetic markers for genome-wide screening for disease susceptibility loci in these populations. To identify the allelic distributions of the multilocus genetic data from these microsatellite markers, the population structures were assessed by clustering. These markers supported, with the most probability, three clustering groups corresponding to the three geographical populations. When we assumed only two hypothetical clusters (K), the Korean population was separate from the others, suggesting a relatively deep divergence of the Korean population. The present 207 microsatellite markers appear to reflect the historical and geographical origins of the different populations as well as displaying a similar degree of variation to that seen in previously published genetic data. Thus, these markers will be useful as a reference for human genetic studies on Asians.Molecules and Cells 05/2008; 25(2):301-4. · 2.18 Impact Factor
Top co-authors
Top Journals
- Journal of Cellular Physiology (3)
- Oncology Reports (3)
- BMB reports (3)
- Gene (2)
- Molecules and Cells (2)
Institutions
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2012
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Seoul National University
- Department of Chemistry
Seoul, Seoul, South Korea
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2011
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Gangneung-Wonju National University
Wŏnju, Gangwon, South Korea
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2004–2010
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Kyungpook National University
- • Department of Biochemistry and Cell Biology
- • School of Medicine
Sangju, North Gyeongsang, South Korea
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2008
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The University of Tokyo
- Center for Disease Biology and Integrative Medicine
Tokyo, Tokyo-to, Japan
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2003
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Korea University
- Department of Electrical Engineering
Seoul, Seoul, South Korea
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