Effects of Vitamin K₂ on Adipogenic and Osteogenic Differentiation in Mesenchymal Stem Cells from Human Umbilical Cord Blood

Yeum, Chung Eun,Park, Seung Yeon,Kang, Tae Jin,Han, Hoon,Chae, Gue Tae Trans Tech Publications, Ltd. 2007 Key engineering materials Vol.342 No.-

<P>Mesenchymal stem cells(MSCs) have the potential to self-replicate, proliferate and differentiate into chondrocytes, adipocytes, osteocytes and myocytes. Recent studies indicate that vitamin K2 plays a role in bone metabolism. But the mechanism is still unclear. We evaluated effect of vitamin K2 on osteogenesis and adipogenesis of MSCs from umbilical cord blood(UCB). By exposing MSCs to osteogenic and adipogenic medium with and without vitamin K2, the effects of vitamin K2 were analyzed. The results showed that vitamin K2 inhibits adipogenesis while at the same time it stimulates osteoblastic differentiation. These data are expected to provide novel information needed for successful therapeutic development for various types of osteoporosis and similar diseases related to bone formation.</P>

Different Effects of Leukotriene B4 Receptors on the Proliferation of Mesenchymal Stem Cells

( Seung Yeon Park ),( Chung Eun Yeum ),( Seong Beom Lee ),( Heung Jae Chun ),( Gue Tae Chae ) 한국조직공학·재생의학회 2009 조직공학과 재생의학 Vol.6 No.1

We investigated whether leukotriene B4(LTB4) and its receptor play important roles in the proliferation of umbilical cord blood derived mesenchymal stem cells(UMSCs). Although it was previously reported that LTB4 induced tumor and stem cell proliferation, LTB4 did not enhance proliferation of the UMSCs. However, the two LTB4 receptors appeared to play opposite roles in the proliferation of UMSCs. The blocking of BLT1 by U-75302 enhanced proliferation of the UMSCs. By contrast, blocking of BLT2 by LY255283 inhibited proliferation of the UMSCs. Also, U-75302 up regulated and LY255283 down regulated the p38 and p44/42 MAPK activation. In conclusion, LTB4 receptors oppositely regulate proliferation of the UMSCs through the p38 and p44/42 MAPK pathways. The LTB4 receptor antagonists were identified to be factor having an effect on the proliferation of UMSCs. The results of this study suggest that the LTB4 receptor signaling pathway might be a novel target for proliferation of the UMSCs.

Rifampicin Inhibits the LPS-induced Expression of Toll-like Receptor 2 via the Suppression of NF-ՊB DNA-binding Activity in RAW 264.7 Cells

Seong Keun Kim,Young Mi Kim,Chung Eun Yeum,Song-Hyo Jin,Gue Tae Chae,Seong-Beom Lee 대한생리학회-대한약리학회 2009 The Korean Journal of Physiology & Pharmacology Vol.13 No.6

Rifampicin is a macrocyclic antibiotic which is used extensively for treatment against Mycobacterium tuberculosis and other mycobacterial infections. Recently, a number of studies have focused on the immune-regulatory effects of rifampicin. Therefore, we hypothesized that rifampicin may influence the TLR2 expression in LPS-activated RAW 264.7 cells. In this study, we determined that rifampicin suppresses LPS-induced TLR2 mRNA expression. The down-regulation of TLR2 expression coincided with decreased production of TNF-Ձ. Since NF-ՊB is a major transcription factor that regulates genes for TLR2 and TNF-Ձ, we examined the effect of rifampicin on the LPS-induced NF-ՊB activation. Rifampicin inhibited NF-ՊB DNA-binding activity in LPS-activated RAW 264.7 cells, while it did not affect IKKՁ/Ղ activity. However, rifampicin slightly inhibited the nuclear translocation of NF-ՊB p65. In addition, rifampicin increased physical interaction between pregnane X receptor, a receptor for rifampicin, and NF-ՊB p65, suggesting pregnane X receptor interferes with NF-ՊB binding to DNA. Taken together, our results demonstrate that rifampicin inhibits LPS-induced TLR2 expression, at least in part, via the suppression of NF-ՊB DNA-binding activity in RAW 264.7 cells. Thus, the present results suggest that the rifampicin-mediated inhibition of TLR2 via the suppression of NF-ՊB DNA- binding activity may be a novel mechanism of the immune-suppressive effects of rifampicin.

Intravitreal Delivery of Mesenchymal Stem Cells Loaded onto Hydrogel Affects the Regulatory Expression of Endogenous NGF and BDNF in Ischemic Rat Retina

( Ji Yeon Lee ),( Ji Man Shin ),( Chung Eun Yeum ),( Gue Tae Chae ),( Myung Hoon Chun ),( Su Ja Oh ) 한국조직공학·재생의학회 2012 조직공학과 재생의학 Vol.9 No.5

The utility of a biodegradable hyaluronic acid (HyA)-based hydrogel as a tissue scaffold for intravitreal carriage of mesenchymal stem cells (MSCs) into the retina was tested. A rat model of retinal ischemia-reperfusion (IR) injury was used. DiI-labeled MSCs from three passages were loaded onto hydrogel and injected into the vitreous body of experimental and control eyeballs 1 week after IR. The neutral hydrogel was also modified to a basic pH. A control carrier, 0.01 M phosphate-buffered saline (pH 7.2; PBS) was compared. Retinal tissues were prepared 1 week and 2 weeks after MSCs application. MSCs localization and effects were evaluated on immunostained retinal preparations with confocal microscopy. MSCs localization was apparent in the retinas loaded onto hydrogels, adhering tightly to the inner limiting membrane, whereas those in PBS floated in the vitreous body. Nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) were expressed in the end feet of M?ller cells in the normal retina. NGF expression was slightly reduced 2 weeks IR, had expanded into the proximal processes 3 weeks IR, but it appeared reversely 1 week and 2 weeks after MSCs application, respectively. BDNF expression was higher in the ischemic and MSCs-treated ischemic retinas than in the normal and MSCs-treated control retinas, respectively. These findings demonstrate that HyA-based hydrogel is an efficient vehicle for intravitreal MSC transplantation into the retina, and that MSCs thus transplanted induce M?ller glial cells to produce growth factors concerned with the survival of retinal ganglion cells.

Moisture Wound Healing Characteristics of Alginate Sponge and Hydrogel

Ga Young Park(박가영),Jeong Hyun Yeum(염정현),Dong Joon Yang(양동준),Guen Oh Park(박근오),Yun Hee Kim(김윤희),Saewha Jeon(전세화),Tae Jung Kim(김태정),Eun Jung Oh(오은정),Ho Yun Chung(정호윤),Jin Hyun Choi(최진현) 한국고분자학회 2018 폴리머 Vol.42 No.1

건조/가교법으로 제조한 알지네이트 스폰지 및 하이드로젤의 물리적, 생물학적 특성 및 창상치유 특성을 고찰하였다. 하이드로젤은 스폰지 대비 높은 평형 함수율을 보유하였고, 자체적으로 수분을 함유하고 있기 때문에 상대적으로 우수한 습윤 창상치유 환경을 제공할 수 있었다. 알지네이트 스폰지 및 하이드로젤의 사이토카인 결속효과에 기인하여 대식세포로부터 분비되는 전염증성 사이토카인의 함량이 감소됨을 확인하였으며, 특히 하이드로젤의 사이토카인 억제효과가 더욱 두드러지게 나타났는데, 이는 보다 팽윤된 상태에서 알지네이트 분자의 사이토카인에 대한 결속력이 증가함을 의미한다. 창상형성 초기 하이드로젤에 의한 창상치유 및 수축 효과가 스폰지에 비해 우수한 것으로 나타났으나, 상피화는 스폰지를 적용했을 때 보다 우세하게 진행되었다. 조직학적 평가와 RNA 발현 분석으로부터 알지네이트 스폰지 및 하이드로젤은 혈관 및 콜라겐 섬유의 형성, 상피조직의 재생 및 단백질의 생성 등을 촉진함을 확인하였다. Alginate sponge and hydrogel were prepared by a drying/crosslinking method and their wound healing characteristics were investigated comparatively. The alginate hydrogel had a higher equilibrium water content than the sponge, providing a moist wound healing condition without absorbing exudate from a wound. The amounts of proinflammatory cytokines released by macrophages were lowered due to the cytokine-binding effects of the alginate sponge and hydrogel. The hydrogel lowered the cytokine level more dominantly than the sponge, suggesting that the affinity of alginate molecules to cytokines increases at a more swollen state. The hydrogel allowed superior wound healing and contraction at the early stage of application. However, epithelialization was conspicuous when the sponge was applied. It was confirmed through histological examination and RNA expression analysis that angiogenesis, formation of collagen fibers, regeneration of epithelium, and production of protein were promoted using the alginate sponge and hydrogel as wound dressing materials.

Rifampicin Inhibits the LPS-induced Expression of Toll-like Receptor 2 via the Suppression of NF-${\kappa}B$ DNA-binding Activity in RAW 264.7 Cells

Kim, Seong-Keun,Kim, Young-Mi,Yeum, Chung-Eun,Jin, Song-Hyo,Chae, Gue-Tae,Lee, Seong-Beom The Korean Society of Pharmacology 2009 The Korean Journal of Physiology & Pharmacology Vol.13 No.6

Rifampicin is a macrocyclic antibiotic which is used extensively for treatment against Mycobacterium tuberculosis and other mycobacterial infections. Recently, a number of studies have focused on the immune-regulatory effects of rifampicin. Therefore, we hypothesized that rifampicin may influence the TLR2 expression in LPS-activated RAW 264.7 cells. In this study, we determined that rifampicin suppresses LPS-induced TLR2 mRNA expression. The down-regulation of TLR2 expression coincided with decreased production of TNF-$\alpha$ Since NF-${\kappa}B$ is a major transcription factor that regulates genes for TLR2 and TNF-$\alpha$, we examined the effect of rifampicin on the LPS-induced NF-${\kappa}B$ activation. Rifampicin inhibited NF-${\kappa}B$ DNA-binding activity in LPS-activated RAW 264.7 cells, while it did not affect IKK$\alpha/\beta$ activity. However, rifampicin slightly inhibited the nuclear translocation of NF-${\kappa}B$ p65. In addition, rifampicin increased physical interaction between pregnane X receptor, a receptor for rifampicin, and NF-${\kappa}B$ p65, suggesting pregnane X receptor interferes with NF-${\kappa}B$ binding to DNA. Taken together, our results demonstrate that rifampicin inhibits LPS-induced TLR2 expression, at least in part, via the suppression of NF-${\kappa}B$ DNA-binding activity in RAW 264.7 cells. Thus, the present results suggest that the rifampicin-mediated inhibition of TLR2 via the suppression of NF-${\kappa}B$ DNA-binding activity may be a novel mechanism of the immune-suppressive effects of rifampicin.

Vitamin D Receptor Gene TaqI, BsmI and FokI Polymorphisms in Korean Patients with Tuberculosis

Kang, Tae-Jin,Jin, Song-Hou,Yeum, Chung-Eun,Lee, Seong-Beom,Kim, Chi-Hong,Lee, Sang-Haak,Kim, Kwan-Hyoung,Shin, Eun-Soon,Chae, Gue-Tae The Korean Association of Immunobiologists 2011 Immune Network Vol.11 No.5

Background: The active metabolite (1, 25- dihydroxycholecalciferol) of vitamin D (25-hydroxycholecalciferol) leads to activation of macrophages and deficiency of vitamin D seems to be involved in the risk of tuberculosis. The effects of vitamin D are exerted by interaction with the vitamin D receptor (VDR) and may be influenced by polymorphism in the VDR gene. In this study, variation in the VDR gene was investigated in Korean population with tuberculosis. Methods: We typed three VDR polymorphisms of restriction endonuclease sites for TaqI, BsmI and FokI in 155 patients with tuberculosis and 105 healthy volunteers. Results: The frequencies of FokI genotypes determined from TB patients were 29.13% for FF, 56.31% for Ff, and 14.56% for ff. We observed 1.4-fold increased prevalence of the Ff genotype in TB patients compared with normal healthy groups (p=0.0857). However, there was no significant association between the genotype groups, TB patient and normal control, for FokI polymorphism. There was also no significant association between VDR gene and tuberculosis in another polymorphism (BsmI and TaqI). Conclusion: Three polymorphisms (TaqI, BsmI and FokI) in the VDR gene do not appear to be responsible for host susceptibility to human tuberculosis in Korean population.

허혈손상망막에 이식된 성체줄기세포의 소재 및 운명

권복실 ( Fu Shi Quan ),신지만 ( Ji Man Shin ),김인범 ( In Beom Kim ),염정은 ( Chung Eun Yeum ),채규태 ( Gue Tae Chae ),천명훈 ( Myung Hoon Chun ),오수자 ( Su Ja Oh ) 한국조직공학·재생의학회 2009 조직공학과 재생의학 Vol.6 No.4

To investigate the differentiation potency of be engraft mesenchymal stem cells to the retinal cell population through the retina ischemia-reperfusion injury model of rat. Ischemic injury model was made by an elevation of intra-ocular pressure in young adult Sprague-Dawely rats. Adult stem cells of third passages labeled with DiI were applied by an intravitreous injection at 3, 5, and 7 days after the ischemia-reperfusion injury(PI), respectively, cared for 2 weeks, and in case of 7 days PI group were also cared for 4 and 6 weeks. For specification of engraft stem cells, immunofluorescent staining by antibodies against retinal neuronal marker molecules was done. Retinal ischemia led to reduce in both thickness and cell number, principally in the inner retina and to a lesser extent in the outer retina. DiI labeled stem cells were migrated and well associated with host retina tissue by 7 days PI. The retinas of stem cell engraft group were thicker than those of the ischemia group, however, and edematous caused maybe by cell suspension solution volume compared to those of normal control group. Stem cells were located mainly in the ganglion cell layer of 7 days PI engraft group, even though there was no co-localization of DiI and neuronal markers. These results suggest that stem cells influence endogenous neuroprotective mechanisms rather than differentiation into any retinal cell population against neuronal degeneration followed by ischemia injury. It has also been suggested that tissue-specific carriers are necessary for successful transplantation of stem cells into degenerated neral retinas.

Bis deficiency results in early lethality with metabolic deterioration and involution of spleen and thymus.

Youn, Dong-Ye,Lee, Dong-Hyoung,Lim, Mi-Hyun,Yoon, Jung-Sook,Lim, Ji Hee,Jung, Seung Eun,Yeum, Chung Eun,Park, Cheol Whee,Youn, Ho-Joong,Lee, Jae-Seon,Lee, Seong-Beom,Ikawa, Masahito,Okabe, Masaru,Tsuj American Physiological Society 2008 AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND M Vol.295 No.6

<P>Bcl-2 interacting cell death suppressor (Bis), also known as Bag3 or CAIR-1, is involved in antistress and antiapoptotic pathways. In addition to Bcl-2, Bis binds to several proteins, suggesting it has diverse functions in normal and pathological conditions. To better define the physiological function of Bis in vivo, we developed bis-deficient mice with a cre-loxP system. Targeted disruption of exon 4 of the bis gene was demonstrated by Southern blotting and PCR, and Western blotting showed that no intact or truncated Bis protein was synthesized in bis(-/-) mice. While heterozygotes were fertile and appeared normal, Bis-deficient mice showed growth retardation and died by 3 wk after birth. The relative weight of the thymus and spleen was reduced and the total numbers of white blood cells, splenocytes, and thymocytes were significantly reduced compared with wild-type littermates. Serum profiles indicated significant hypoglycemia as well as decrease in triglyceride and cholesterol levels. Expression profiles of metabolic genes indicated that gluconeogenesis and beta-oxidation are activated in the liver of bis(-/-) mice. This activation, as well as a decrease in peripheral fat and an induction of fatty liver, appears to be an adaptive response to hypoglycemia. Our study reveals that the absence of Bis has considerable influences on postnatal growth and survival, possibly due to a nutritional impairment.</P>