Young-Sool Hah

Gyeongsang National University, Shinshū, South Gyeongsang, South Korea

Are you Young-Sool Hah?

Claim your profile

Publications (40)109.59 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Obesity-induced fatty liver disease is associated with increased hypothalamic inflammation. Previous reports have demonstrated that the deletion of SIRT1 in hepatocytes increases hepatic steatosis and inflammation. Using myeloid cell-specific SIRT1 knockout (KO) mice, we investigated whether ablation of SIRT1 in macrophages plays a role in regulating hepatic steatosis and hypothalamic inflammation. When challenged with a high-fat diet (HFD) for 24 weeks, hyperleptinemia, hyperinsulinemia, hepatic steatosis and macrophage infiltrations in HFD-fed KO mice were increased compared with HFD-fed WT mice. Hypothalamic expression levels of iba1 were increased in HFD-fed KO mice compared with HFD-fed WT mice. In particular, the expression levels of choline acetyltransferase were decreased in the hypothalamus of HFD-fed KO mice compared with HFD-fed WT mice. Thus, our findings suggest that SIRT1 plays a key role for hepatic steatosis and hypothalamic inflammation and that anti-inflammatory effect of SIRT1 may be important for the prevention of obesity-induced metabolic syndromes.
    Metabolic Brain Disease 04/2014; · 2.33 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Intravenous lipid emulsions (LEs) are effective in the treatment of toxicity associated with various drugs such as local anesthetics and other lipid soluble agents. The goals of this study were to examine the effect of LE on left ventricular hemodynamic variables and systemic blood pressure in an in vivo rat model, and to determine the associated cellular mechanism with a particular focus on nitric oxide. Two LEs (Intralipid(®) 20% and Lipofundin(®) MCT/LCT 20%) or normal saline were administered intravenously in an in vivo rat model following induction of anesthesia by intramuscular injection of tiletamine/zolazepam and xylazine. Left ventricular systolic pressure (LVSP), blood pressure, heart rate, maximum rate of intraventricular pressure increase, and maximum rate of intraventricular pressure decrease were measured before and after intravenous administration of various doses of LEs or normal saline to an in vivo rat with or without pretreatment with the non-specific nitric oxide synthase inhibitor N (ω)-nitro-L-arginine-methyl ester (L-NAME). Administration of Intralipid(®) (3 and 10 ml/kg) increased LVSP and decreased heart rate. Pretreatment with L-NAME (10 mg/kg) increased LSVP and decreased heart rate, whereas subsequent treatment with Intralipid(®) did not significantly alter LVSP. Intralipid(®) (10 ml/kg) increased mean blood pressure and decreased heart rate. The increase in LVSP induced by Lipofundin(®) MCT/LCT was greater than that induced by Intralipid(®). Intralipid(®) (1%) did not significantly alter nitric oxide donor sodium nitroprusside-induced relaxation in endothelium-denuded rat aorta. Taken together, systemic blockage of nitric oxide synthase by L-NAME increases LVSP, which is not augmented further by intralipid(®).
    International journal of biological sciences 01/2014; 10(4):367-76. · 3.17 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: SIRT1 modulates the acetylation of the p65 subunit of nuclear factor-κB (NF-κB) and plays a pivotal role in the inflammatory response. This study sought to assess the role of SIRT1 in rheumatoid arthritis (RA) using a myeloid cell-specific SIRT1 knockout (mSIRT1 KO) mouse. mSIRT1 KO mice were generated using the loxP/Cre recombinase system. K/BxN serum transfer arthritis was induced in mSIRT1 KO mice and age-matched littermate loxP control mice. Arthritis severity was assessed by clinical and pathological scoring. The levels of inflammatory cytokines in the serum and joints were measured by ELISA. Migration, M1 polarization, cytokine production, osteoclastogenesis, and p65 acetylation were assessed in bone marrow-derived monocytes/macrophages (BMMs). mSIRT1 KO mice showed more severe inflammatory arthritis and aggravated pathological findings than control mice. These effects were paralleled by increases in IL-1, TNF-α, TRAP-positive osteoclasts, and F4/80(+) macrophages in the ankles of mSIRT1 KO mice. In addition, BMMs from mSIRT1 KO mice displayed hyperacetylated p65 and increased NF-κB binding activity when compared to control mice, which resulted in increased M1 polarization, migration, pro-inflammatory cytokine production, and osteoclastogenesis. Our study provides in vivo evidence that myeloid cell-specific deletion of SIRT1 exacerbates inflammatory arthritis via the hyperactivation of NF-κB signaling, which suggests that SIRT1 activation may be beneficial in the treatment of inflammatory arthritis.
    PLoS ONE 01/2014; 9(2):e87733. · 3.73 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The aim of this study was to examine the effects of human umbilical cord blood-derived CD34 positive endothelial progenitor cells (CD34+ EPCs) on osteoblastic differentiation of cultured human periosteal-derived osteoblasts (POs). CD34+ cells from human umbilical cord blood were sorted to purify more EPCs in characterization. These sorted cells showed CD31, VE-cadherin and KDR expression as well as CD34 expression, and formed typical tubes in Matrigel. These sorted cells were referred to as human cord blood-derived CD34+ EPCs. In in vivo bone formation using a miniature pig model, the newly formed bone was clearly examined in defects filled with polydioxanone/pluronic F127 (PDO/Pluronic F127) scaffolds containing either human umbilical cord blood-derived CD34+ EPCs and POs, or HUVEC and POs, however, the new bone had the greatest density in the defect treated with CD34+ EPCs and POs. Osteoblastic phenotypes of cultured human POs using ALP activity and von Kossa staining were also more clearly found in CD34+ EPC-conditioned medium than CD34 negative (CD34-) cell-conditioned medium, whereas HUVEC-conditioned medium had an intermediate effect. PCR array for common cytokines and growth factors showed that secretion of IL-1β was significantly higher in CD34+ EPCs than in HUVEC, followed by level in CD34- cells. In addition, IL-1β also potently and dose-dependently increased ALP activity and mineralization of POs in culture. These results suggest that human umbilical cord blood-derived CD34+ EPCs stimulates osteoblastic differentiation of cultured human POs. The functional role of human umbilical cord blood-derived CD34+ EPCs in increasing the osteogenic phenotypes of cultured human POs may depend on IL-1β secreted from human umbilical cord blood-derived CD34+ EPCs.
    Tissue Engineering Part A 10/2013; · 4.64 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Cisplatin (CDDP) is a chemotherapeutic agent that is widely used to treat many cancers. However, initial resistance to CDDP is a serious problem in treating cancers. In this study, in order to develop an approach to overcome resistance to CDDP, we investigated the difference in apoptotic processes between CDDP-sensitive cells and CDDP-resistant cells. By screening with CDDP sensitivity tests, we chose SNU-16 cells which are relatively resistant to CDDP, and SNU-1 cells which are sensitive to CDDP. We compared the difference between the two cell lines focusing on apoptosis. CDDP-induced reactive oxygen species (ROS) generation significantly induced loss of mitochondrial membrane potential (MMP, ∆Ψm) in SNU-1 cells, but not in SNU-16 cells. In addition, the ratio of Bax to Bcl-2 was increased by CDDP treatment in SNU-1 cells, but not in SNU-16 cells. To augment the loss of MMP, ∆Ψm in SNU-16, we inhibited Akt activity of SNU-16 cells to suppress their anti-apoptotic activity. The inhibition of Akt activity led to suppression of the anti-apoptotic protein XIAP. Akt inhibition slightly enhanced CDDP-induced apoptosis in SNU-16 cells. In addition, we enhanced pro-apoptotic activity by transfecting the cells with the wild-type p53 gene. The induction of wild-type p53 can enhance CDDP-induced apoptosis not only by inducing Bax protein but also by suppressing anti-apoptotic proteins through inhibition of Akt. In conclusion, this study suggests that the primary contributor to resistance to CDDP in SNU-16 cells may well be a failure of induction of apoptosis due to a lack of induction of pro-apoptotic proteins rather than suppression of anti-apoptotic proteins, and that restoration of p53 function can overcome the resistance to CDDP not only by augmenting the pro-apoptotic drive through p53-mediated transcriptional activation but also by inhibiting the anti-apoptotic drive through inhibition of Akt activity.
    International Journal of Oncology 08/2013; · 2.66 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Angiogenesis plays a critical role in synovial inflammation and joint destruction in rheumatoid arthritis (RA). The vascular endothelial growth factor (VEGF)-A and angiopoietins are two important mediators of synovial angiogenesis. We have previously developed a novel chimeric decoy receptor, namely double anti-angiogenic protein (DAAP), which can bind both VEGF-A and angiopoietins, blocking their actions. This study was performed to evaluate the anti-arthritic effect of DAAP and combination effect with the TNF- inhibitor in collagen-induced arthritis (CIA). Recombinant DAAP, VEGF-Trap, Tie2-Fc, and dimeric-Fc proteins were produced and purified from CHO cells in large-scale bioreactors. CIA was induced in DBA/1 mice with type II collagen. The preventive effect of DAAP was determined and compared with other decoy receptors such as VEGF-Trap or Tie2-Fc, which block VEGF-A or angiopoietins, respectively. The clinical, radiographic, pathologic, and immunohistochemical analyses were performed in CIA mice. The levels of matrix metalloprotease-3 (MMP-3) and interleukin-1 (IL-1) were quantified by ELISA, and receptor activator of nuclear factor-kappa B ligand (RANKL) mRNA levels were measured with polymerase chain reaction (PCR). Finally, we investigated the combination effects of DAAP with low dose of TNF-alpha decoy receptor (etanercept, 10 mg/kg). DAAP had a much greater inhibitory effect on arthritis severity and bone destruction than VEGF-Trap or Tie2-Fc on clinical and radiographic evaluation. These inhibitory effects were accompanied by significantly diminishing pathologic abnormalities, CD31-positive vasculature, and synovial infiltration by F4/80-positive macrophages. The levels of MMP-3, IL-1, and RANKL were much lower in DAAP-injected group than those of control. Furthermore, DAAP showed therapeutic effect and a combination effect with etanercept when injected after arthritis onset in established CIA. DAAP has not only potent prophylactic effects on both inflammation and bone destruction, but also therapeutic effects, alone and combination effects with a TNF- inhibitor in CIA mice. These results suggest that DAAP could be used as an effective new therapeutic agent for RA.
    Arthritis research & therapy 08/2013; 15(4):R85. · 4.27 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The formation of dendrites by melanocytes is highly analogous to that process in neural cells. We previously reported that a C2 domain-containing protein, copine-1, is involved in the extension of dendrites by neural cells. However, the effect of C2 domain-containing proteins in dendrite formation by melanocytes has not yet been elucidated. The aim of this study was to screen novel C2 domain-containing proteins related to dendrite outgrowth in melanocytes and to investigate their precise roles in melanocyte dendrite formation during differentiation. We transduced mouse melan-a melanocytes with a recombinant adenovirus expressing a C2 domain library. Dendrite elongation, melanin content, tyrosinase activity and Western blot analyses were conducted to elucidate the possible underlying mechanisms of action in melanocytes. Sixteen sets of C2 domain-containing proteins were identified whose over-expression resulted in dendrite lengthening. Among those, we focused on the C2 domain of SYT14L (truncated mutant of SYT14L) in this study. Forced expression of full length SYT14L or the C2 domain of SYT14L induced a significant elongation of dendrite length accompanied by the induction of melanocyte differentiation-related markers, including melanin synthesis, tyrosinase catalytic activity and the expression of tyrosinase (TYR), tyrosinase related protein-1 (TRP-1) and TRP-2. In addition, over-expression of either the C2 domain or the full length form of SYT14L significantly increased the phosphorylation of ERK and CREB. These results suggest that SYT14L, especially its C2 domain, may play an important role in regulating melanocyte differentiation through the modulation of ERK and (or) CREB signaling.
    Journal of dermatological science 08/2013; · 3.71 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The purpose of this study was to examine the effects of TNF-α and IL-1β on in vitro osteoblastic differentiation of cultured human periosteal-derived cells. To examine the effects of TNF-α and IL-1β on in vitro osteoblastic differentiation of cultured human periosteal-derived cells, the cells cultured in the osteogenic induction medium were treated with 0.1-10 ng/ml TNF-α and 0.01-1 ng/ml IL-1β. TNF-α and IL-1β enhanced the alkaline phosphatase (ALP) activity and alizarin red S staining in cultured human periosteal-derived cells. However, these cytokines did not stimulate the Runt-related transcription factor (Runx) 2 activity and osteocalcin secretion. The ALP activity was decreased in the periosteal-derived cells pretreated with mitogen activated protein kinase (MAPK) inhibitors and then treated with TNF-α or IL-1β. Among the periosteal-derived cells pretreated with MAPK inhibitors, the ALP activity was markedly decreased in the cells pretreated with SP 600125, the specific inhibitor of C-Jun N-terminal kinase (JNK). The periosteal-derived cells treated with TNF-α and IL-1β showed an increase in extracellular signal-regulated kinase (ERK) and JNK phosphorylation. Among the ERK and JNK phosphorylation, JNK phosphorylation was strongly observed in the cells. These results suggest that TNF-α and IL-1β increased the in vitro osteoblastic differentiation of cultured human periosteal-derived cells by enhancing the ALP activity and mineralization process, but not by Runx2 activation. The functional role of TNF-α and IL-1β in increasing the ALP activity and mineralization of periosteal-derived cells primarily depends on the JNK signaling among the MAPK pathways.
    Molecular Biology Reports 05/2013; · 2.51 Impact Factor
  • Source
    Ho Cheol Kim, Hee-Young Cho, Young-Sool Hah
    [Show abstract] [Hide abstract]
    ABSTRACT: Muscle wasting in sepsis is associated with increased proteolysis. Interleukin-15 (IL-15) has been characterized as an anabolic factor for skeletal muscles. Our study aims to investigate the role of IL-15 in sepsis-induced muscle atrophy and proteolysis. Mice were rendered septic either by cecal ligation and puncture or by intraperitoneal injection of lipopolysaccharide (LPS, 10 mg/kg i.p.). Expression of IL-15 mRNA and protein was determined by reverse transcriptase polymerase chain reaction and Western blot analysis in the control and septic limb muscles. C2C12 skeletal muscle cells were stimulated in vitro with either LPS or dexamethasone in the presence and absence of IL-15 and sampled at different time intervals (24, 48, or 72 hours). IL-15 (10µg/kg) was intraperitoneally administered 6 hours before sepsis induction and limb muscles were sampled after 24 hours of sepsis. Cathepsin L activity was determined to measure muscle proteolysis. Atrogin-1 and muscle-specific ring finger protein 1 (MuRF1) expressions in limb muscle protein lysates was analyzed. IL-15 mRNA expression was significantly lower in the limb muscles of septic mice compared to that of controls. Cathepsin L activity in C2C12 cells was significantly lower in presence of IL-15, when compared to that observed with individual treatments of LPS or dexamethasone or tumor necrosis factor α. Further, the limb muscles of mice pre-treated with IL-15 prior to sepsis induction showed a lower expression of atrogin-1 and MuRF1 than those not pre-treated. IL-15 may play a role in protection against sepsis-induced muscle wasting; thereby, serving as a potential therapeutic target for sepsis-induced skeletal muscle wasting and proteolysis.
    Tuberculosis and Respiratory Diseases 12/2012; 73(6):312-9.
  • [Show abstract] [Hide abstract]
    ABSTRACT: The purpose of this study was to generate tissue-engineered bone using human periosteal-derived osteoblasts (PO) and polydioxanone/pluronic F127 (PDO/pluronic F127) scaffold with preseeded human periosteal-derived CD146 positive endothelial-like cells (PE). PE were purified from the periosteal cell population by cell sorting. One of the important factors to consider in generating tissue-engineered bone using osteoprecursor and endothelial cells and a specific scaffold is whether the function of osteoprecursor and endothelial cells can be maintained in originally different culture medium conditions. After human PE were preseeded into PDO/pluronic F127 scaffold and cultured in endothelial cell basal medium-2 for 7 days, human PO were seeded into the PDO/pluronic F127 scaffold with PE, and then, this cell-scaffold construct was cultured in endothelial cell basal medium-2 with osteogenic induction factors, including ascorbic acid, dexamethasone, and β-glycerophosphate, for a further 7 days. Then, this 2-week cultured construct was grafted into the mandibular defect of miniature pig. Twelve weeks after implantation, the animal was sacrificed. Clinical examination revealed that newly formed bone was seen more clearly in the defect with human PO and PDO/pluronic F127 scaffold with preseeded human PE. The experimental results suggest that tissue-engineered bone formation using human PO and PDO/pluronic F127 scaffold with preseeded human PE can be used to restore skeletal integrity to various bony defects when used in clinics. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2012.
    Journal of Biomedical Materials Research Part A 09/2012; · 2.83 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Melanogenesis is one of the characteristic parameters of differentiation in melanocytes and melanoma cells. Specific inhibitors of phosphatidylinositol 3-kinase (PI3K), such as wortmannin and LY294002, stimulate melanin production in mouse and in human melanoma cells, suggesting that PI3K and mammalian target of rapamycin (mTOR) might be involved in the regulation of melanogenesis. The involvement of the mTOR pathway in regulating melanogenesis was examined using human MNT-1 melanoma cells, and the effects of the potent inhibitor of mTOR, rapamycin, in the presence or absence of α-melanocyte-stimulating hormone (α-MSH) were evaluated. In cells treated with rapamycin, cell viability, melanin content, and tyrosinase (TYR) activity were measured and compared with untreated controls. Protein levels of TYR, tyrosinase-related protein (TYRP)-1, TYRP-2, and microphthalmia-associated transcription factor (MITF) were also analyzed by Western blot. In rapamycin-treated cells, the melanin content increased concomitantly with an elevation in TYR activity, which plays a major role in melanogenesis. There was also an up-regulation of TYR, TYRP-1, and MITF proteins. Combined treatment with rapamycin or wortmannin and α-MSH increased melanogenesis more strongly than α-MSH alone. Rapamycin-induced melanin formation may be mediated through the up-regulation of TYR protein and activity. Furthermore, rapamycin and wortmannin, inhibitors of mTOR and PI3K, respectively, have co-stimulatory effects with α-MSH in enhancing melanogenesis in melanocyte cells.
    Annals of Dermatology 05/2012; 24(2):151-7. · 0.61 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Lonicera japonica Thunb. (L. japonica T.) has been used in Korean traditional medicine for long time because of its anti-cancer and hepatic protective effect. In this study, we investigated polyphenolic extract in L. japonica T. using high-performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS) and its anti-cancer effect on hepatocarcinoma cells. Human HepG2 cell line was treated with various concentrations of polyphenolic extract. Apoptosis was detective by cell morphology, cell cycle analysis and immunoblot analysis. Polyphenolic extract inhibited cell proliferation at 48h in a dose-dependent manner. Polyphenolic extract affected HepG2 cell viability by inhibiting cell cycle progression at the G2/M transition and inducing apoptosis. Polyphenolic extract also decreased the expression of CDK1, CDC25C, cyclin B1, pro-caspases-3 and -9 and poly ADP ribose polymerase, and affected the levels of mitochondrial apoptotic-related proteins. The phosphorylation of extracellular signal-related kinase ½ (ERK 1/2), c-Jun N-terminal kinase (JNK), and p-38 mitogen-activated protein kinases (MAPKs) were increased in HepG2 cells treated with polyphenolic extract, whereas Akt was dephosphorylated. These results indicate that inhibition of PI3K/Akt and activation of MAPKs are pivotal in G2/M cell cycle arrest and apoptosis of human hepatocarcinoma cells mediated by polyphenolic extract.
    Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association 04/2012; 50(7):2407-16. · 2.99 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Cathepsin D (CatD), a lysosomal aspartic protease, plays an essential role in tumor progression and apoptosis. However, the function of CatD in cell death is not yet fully understood. In this study, we identified CatD as one of up-regulated proteins in human malignant glioblastoma M059J cells that lack the catalytic subunit of DNA-PK compared with its isogenic M059K cells with normal DNA-PK activity. M059J cells were relatively more resistant to genotoxic stress than M059K cells. Overexpression of wild-type CatD but not catalytically inactive mutant CatD (D295N) inhibited H(2)O(2)-induced cell death in HeLa cells. Furthermore, knockdown of CatD expression abolished anti-apoptotic effect by CatD in the presence of H(2)O(2). Interestingly, high expression of CatD in HeLa cells significantly activated autophagy: increase of acidic autophagic vacuoles, LC3-II formation, and GFP-LC3 puncta. These results suggest that CatD can function as an anti-apoptotic mediator by inducing autophagy under cellular stress. In conclusion, inhibition of autophagy could be a novel strategy for the adjuvant chemotherapy of CatD-expressing cancers.
    Cancer letters 04/2012; 323(2):208-14. · 4.86 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The present study evaluated the human mesenchymal stem cells (hMSCs) isolated from skin (hSMSC), bone marrow (hBMSC) and dental follicle (hDFMSC) tissues on their in vitro and in vivo osteogenic potential using demineralized bone matrix (DBM) and fibrin glue scaffold. Cells originated from three distinct tissues showed positive expressions of CD44, CD73, CD90, CD105 and vimentin, and differentiation ability into osteocytes, adipocytes and chondrocytes. hMSCs from all tissues co-cultured with a mixed DBM and fibrin glue scaffold in non-osteogenic induction media were positively stained by von Kossa and expressed osteoblast-related genes, such as osteocalcin (OC), osteonectin (ON), runt-related transcription factor 2 (Runx2) and osterix. For in vivo osteogenic evaluation, PKH26 labeled hMSCs were implanted into the subcutaneous spaces of athymic mice with a mixed scaffold. At 4 weeks of implantation, PKH26 labeled cells were detected in all hMSC-implanted groups. Bone formation with OC expression and radio-opacity intensity were observed around DBM scaffold in all hMSC-implanted groups. Interestingly, hDFMSCs-implanted group showed the highest OC expression and calcium content. These findings demonstrated that hDFMSCs could be a potential alternative autologous cell source for bone tissue engineering.
    Differentiation 03/2012; 83(5):249-59. · 2.86 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Aim of the Study. Citrus species is used in traditional medicine as medicinal herb in several Asian countries including Korea. Flavonioids became known as various properties, such as anti-oxidants, anti-inflammation and anti-cancer, and so forth. The present study, the anti-cancer effect of flavonioids isolated from Citrus aurantium L. in human gastric cancer AGS cells has been investigated. Materials and Methods. The anti-proliferative activity was assayed using MTT assay. Cell cycle analysis was done using flow cytometry and apoptosis detection was done using by hoechst fluorescent staining and Annexin V-propidium iodide double staining. Western blot was used to detect the expression of protein related with cell cycle and apoptosis. Results. Flavonoids isolated from Citrus aurantium L. have the effect of anti proliferation on AGS cells with IC50 value of 99 μg/mL. Flavonoids inhibited cell cycle progression in the G2/M phase and decrease expression level of cyclin B1, cdc 2, cdc 25c. Flavonoids induced apoptosis through activate caspase and inactivate PARP. Conclusions. Flavonoids isolated from Citrus aurantium L. induced G2/M phase arrest through the modulation of cell cycle related proteins and apoptosis through activation caspase. These finding suggest flavonoids isolated from Citrus aurantium L. were useful agent for the chemoprevention of gastric cancer.
    Evidence-based Complementary and Alternative Medicine 01/2012; 2012:515901. · 1.72 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: We investigated the effects of sodium meta-arsenite (NaAsO(2)) on human cancer cells (MDA-MB-231, MCF-7 and U-87 MG), dental papilla tissue stem cells (DPSCs) and somatic cells [MRC-5 fetal fibroblasts and adult muscle cells (MCs)] by examining telomeric properties, endogenous reverse transcriptase (RT) activity and the expression of tumorigenesis-linked genes. Half maximal inhibitory concentration (IC(50)) values were higher in DPSCs and MCs, possessing longer telomere lengths when compared to cancer cells. Levels of telomerase and RT activity, and the expression of protein 53 (p53), B-cell lymphoma 2 (BCL2), nuclear factor kappa-light-chain-enhancer of activated B-cells (NFκB), transforming growth factor beta (TGFβ) and vascular endothelial growth factor (VEGF) were significantly lower in cancer cells following sodium meta-arsenite treatment, whereas the effect was absent or marginally detected in DPSCs and somatic cells. Collectively, sodium meta-arsenite effectively induced cellular cytotoxicity by inhibiting telomerase and RT activity, and down-regulating transcript levels in cancer cells with shorter telomere lengths, whereas more tolerance was evident in DPSCs and somatic cells possessing longer telomere lengths.
    Anticancer research 12/2011; 31(12):4315-28. · 1.71 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The aim of this study was to examine the localizations and expressions of melatonin 1a (MT1a) and 1b (MT1b) receptors in rat vestibular nuclei by immunohistochemical staining and reverse transcriptase-polymerase chain reaction. Twenty male Sprague-Dawley rats were used in this study. Antibodies for the MT1a and MT1b receptors were used in 10 rats, respectively. A further 10 animals were sacrificed for RT-PCR. Tissues containing medial vestibular nuclei were selectively isolated from brain stem slices for RT-PCR. MT1a and MT1b receptor immunopositive neurons were found to be distributed throughout the four major vestibular nuclei. Both receptors were primarily detected in neuronal somata and their proximal dendrites. The presences of the mRNAs of the MT1a and MT1b receptors were confirmed by RT-PCR in medial vestibular nuclei and trigeminal ganglia. The present study demonstrates, for the first time, that MT1a and MT1b receptors are localized and expressed in rat vestibular nuclei. This study provides additional insight into the role of melatonin receptors during vestibular signal processing.
    Auris, nasus, larynx 11/2011; 39(5):479-83. · 0.58 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The aim of this study was to generate tissue-engineered bone formation using periosteal-derived cells seeded into a polydioxanone/pluronic F127 (PDO/Pluronic F127) scaffold with adipose tissue-derived CD146 positive endothelial-like cells. Considering the hematopoietic and mesenchymal phenotypes of adipose tissue-derived cells cultured in EBM-2 medium, CD146 positive adipose tissue-derived cells was sorted to purify more endothelial cells in characterization. These sorted cells were referred to as adipose tissue-derived CD146 positive endothelial-like cells. Periosteum is a good source of osteogenic cells for tissue-engineered bone formation. Periosteal-derived cells were found to have good osteogenic capacity in a PDO/Pluronic F127 scaffold, which could provide a suitable environment for the osteoblastic differentiation of these cells. Through the investigation of capillary-like tube formation on matrigel and the cellular proliferation of adipose tissue-derived CD146 positive endothelial-like cells cultured in different media conditions, we examined these cells could be cultured in EBM-2 with osteogenic induction factors. We also observed that the osteogenic activity of periosteal-derived cells could be good in EBM-2 with osteogenic induction factors, in the early period of culture. The experimental results obtained in the miniature pig model suggest that tissue-engineered bone formation using periosteal-derived cells and PDO/Pluronic F127 scaffold with pre-seeded adipose tissue-derived CD146 positive endothelial-like cells can be used to restore the bony defects of the maxillofacial region when used in clinics.
    Biomaterials 08/2011; 32(22):5033-45. · 7.60 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: This study examined the osteogenic differentiation of cultured human periosteal-derived cells grown in a three dimensional collagen-based scaffold. Periosteal explants with the appropriate dimensions were harvested from the mandible during surgical extraction of lower impacted third molar. Periosteal-derived cells were introduced into cell culture. After passage 3, the cells were divided into two groups and cultured for 28 days. In one group, the cells were cultured in two-dimensional culture dishes with osteogenic inductive medium containing dexamethasone, ascorbic acid, and β-glycerophosphate. In the other group, the cells were seeded onto a three-dimensional collagen scaffold and cultured under the same conditions. We examined the bioactivity of alkaline phosphatase (ALP), the RT-PCR analysis for ALP and osteocalcin, and measurements of the calcium content in the periosteal-derived cells of two groups. Periosteal-derived cells were successfully differentiated into osteoblasts in the collagen-based scaffold. The ALP activity in the periosteal-derived cells was appreciably higher in the three-dimensional collagen scaffolds than in the two-dimensional culture dishes. The levels of ALP and osteocalcin mRNA in the periosteal-derived cells was also higher in the three-dimensional collagen scaffolds than in the two-dimensional culture dishes. The calcium level in the periosteal-derived cells seeded onto three-dimensional collagen scaffolds showed a 5.92-fold increase on day 7, 3.28-fold increase on day 14, 4.15-fold increase on day 21, and 2.91-fold increase on day 28, respectively, compared with that observed in two-dimensional culture dishes. These results suggest that periosteal-derived cells have good osteogenic capacity in a three-dimensional collagen scaffold, which provides a suitable environment for the osteoblastic differentiation of these cells.
    Molecular Biology Reports 06/2011; 38(5):2887-94. · 2.51 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Angiogenesis plays an important role in bone development and postnatal bone fracture repair. Vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptors (VEGFRs) are primarily involved in angiogenesis. This study investigated the expression of VEGF isoforms, VEGFR-1, and VEGFR-2 during the osteoblastic differentiation of cultured human periosteal-derived cells. In addition, the effect of exogenous VEGF on the osteoblastic differentiation of cultured human periosteal-derived cells was also examined. The expression of the VEGF isoforms (VEGF(121), VEGF(165), VEGF(189), and VEGF(206)), VEGFR-1, and VEGFR-2 was observed in the periosteal-derived cells. Administration of KRN633, a VEGFR-1 and VEGFR-2 inhibitor, decreased the alkaline phosphatase (ALP) activity during the osteoblastic differentiation of cultured human periosteal-derived cells. However, the administration of VEGFR2 Kinase Inhibitor IV, a VEGFR-2 inhibitor, did not affect the ALP activity. The addition of recombinant human VEGF(165) elevated the ALP activity and increased the calcium content in the periosteal-derived cells. Treating the periosteal-derived cells with recombinant human VEGF(165) resulted in an increase in Runx2 transactivation in the periosteal-derived cells. These results suggest that exogenous VEGF stimulates the osteoblastic differentiation of cultured human periosteal-derived cells and VEGF might act as an autocrine growth factor for the osteoblastic differentiation of cultured human periosteal-derived cells.
    Molecular Biology Reports 02/2011; 38(2):1443-50. · 2.51 Impact Factor

Publication Stats

238 Citations
109.59 Total Impact Points

Institutions

  • 2007–2013
    • Gyeongsang National University
      • College of Veterinary Medicine
      Shinshū, South Gyeongsang, South Korea
    • Seegene Institute of Life Sciences
      Sŏul, Seoul, South Korea
  • 2011–2012
    • Hannam University
      • Department of Advanced Materials
      Daiden, Daejeon, South Korea
  • 2010
    • Jinju National University
      Gyeongju, North Gyeongsang, South Korea