• Title/Summary/Keyword: stromal cells

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MicroRNA-200a/210 Controls Proliferation and Osteogenic Differentiation of Human Adipose Tissue Stromal Cells (MicroRNA-200a/210의 인체 지방 유래 중간엽 줄기세포 골분화 및 증식 조절 기전)

  • Kim, Young Suk;Park, Hee Jeong;Shin, Keun Koo;Lee, Sun Young;Bae, Yong Chan;Jung, Jin Sup
    • Journal of Life Science
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    • v.27 no.7
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    • pp.767-782
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    • 2017
  • MicroRNAs control the differentiation and proliferation of human adipose tissue-derived stromal cells (hADSCs). However, the role of miR-200a and miR210 on the osteogenic differentiaton of hADSCs has not been determined. hADSCs were isolated from human adipose tissues. Direct binding of mircoRNA to target mRNAs was determined by luciferase assay of the constructs containing putative microRNA binding sites within 3' untranslated region of target mRNAs. Overexpression of miR-200a increased the proliferation and osteogenic differentiation of hADSCs, while causing downregulation of the levels of ZEB2. Inhibition of miR-200a with antisense RNAs inhibited the proliferation and osteogenic differentiation of hADSCs. Overexpression of miR-210 was found to inhibit the proliferation of hADSCs but increase the osteogenic differentiation, while causing downregulation of the levels of IGFBP3. Inhibition of miR-210 with antisense RNAs increased the proliferation but inhibited the osteogenic differentiation of hADSCs. Analysis of the luciferase activity of the constructs containing the miR-200a target site within the ZEB2 3' region and the miR-210 target site within the IGFBP3 3' region revealed lower activity in the miR-200a- or miR-210-transfected hADSCs than in control miRNA-transfected hADSCs. Downregulation of ZEB2 or IGFBP3 in the hADSCs showed similar effects on both their proliferation and osteogenic differentiation with that of miR-200a and miR-210 overexpression, respectively. The results of the current study indicate that miR-200a and miR-210 regulate the osteogenic differentiation and proliferation of hADSCs through the direct targeting of IGFBP3 and ZEB2, respectively.

Altered Expression of RANKL/OPG after Alendronate Administration in the Developing Teeth of Postnatal Rats

  • Kim, Min-Ju;Jun, Yun-Jeong;Yu, Hong-Il;Yang, So-Yeong;Oh, Won-Man;Kim, Sun-Hun;Kim, Min-Seok
    • International Journal of Oral Biology
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    • v.36 no.1
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    • pp.37-42
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    • 2011
  • The working mechanism of bisphosphonate on bone cells is unclear despite its powerful inhibitory activity on bone resorption. The differentiation and activation of osteoclasts are essential for bone resorption and are controlled by the stimulatory RANKL and inhibitory OPG molecules. Teeth exhibit a range of movement patterns during their eruption to establish their form and function, which inevitably accompanies peripheral bone resorption. Hence, the mandible, which contains the teeth during their eruption processes, is a good model for revealing the inhibitory mechanism of bisphosphonate upon bone resorption. In the present study, RANKL and OPG expression were examined immunohistochemically in the mandible of rats with developing teeth after alendronate administration (2.5 mg/kg). The preeruptive mandibular first molars at postnatal days 3 to 10 showed the developing stages from bell to crown. No morphological changes in tooth formation were observed after alendronate administration. The number of osteoclasts in the alveolar bone around the developing teeth decreased markedly at postnatal days 3, 7 and 10 compared with the control group. RANKL induced strong positive immunohistochemical reactions in the dental follicles and stromal cells around the mandibular first molar. In particular, many osteoclasts with strongly positive reactions to RANKL appeared above the developing mandibular first molars at postnatal days 3 and 10. Immunohistochemical reactions with RANKL after alendronate administration were weaker than the control groups. However, the immunohistochemical reactivity to OPG was stronger after alendronate administration, at postnatal days 3 and 10. These results suggest that alendronate may decrease bone resorption by regulating the RANKL/OPG pathway in the process of osteoclast formation, resulting in a delay in tooth eruption.

Effects of Unripe Black Raspberry Extracts on Prostate Cancer Cell Line and Rat Model of Benign Prostatic Hyperplasia (복분자 미숙과 추출물이 전립선암 세포주와 전립선비대 백서모델에 미치는 영향)

  • Lee, Su Jung;Choi, Hye Ran;Lee, Jung-Hyun;Kwon, Ji Wung;Lee, Hee Kwon;Jeong, Jong Tae;Lee, Tae-Bum
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.43 no.4
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    • pp.507-515
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    • 2014
  • Benign prostatic hyperplasia (BPH), which is commonly found in aging men, is characterized by hyperplasia of prostatic stromal and epithelial cells beginning in the periurethral zone of the prostate. The prevalence of BPH increases in an age-dependent manner. Here, we investigated the protective effects of unripe Rubus occidentalis extracts (UROE) on BPH development using a prostate cancer cell line and testosterone-induced BPH rat model. Experiments using an established hormone-dependent prostate cancer cell line (LNCaP) showed that UROE treatment significantly decreased expression of androgen-related genes, including androgen receptor (AR), prostate specific antigen (PSA), and 5-alpha reductase 2, but not 5-alpha reductase 1, which was also observed in flutamide-treated cells. Further, AR and PSA gene expression was reduced by UROE treatment under androgen-stimulated conditions using dihydrotestosterone (DHT). BPH animals displayed elevated prostate weights. However, UROE as well as finasteride treatment significantly reduced prostate weights and DHT levels compared to testosterone-induced BPH animals. Histopathological analysis also showed that UROE treatment suppressed testosterone-induced prostatic hyperplasia. Taken together, the results suggest that UROE may effectively inhibit the development of BPH and thus may be a useful agent in BPH treatment.

Microscopic Study of the Pig Peri-implantation Embryos (전자현미경에 의한 착상 전후 돼지수정란의 형태학적 변화에 관한 연구)

  • 김진회;백청순;이훈택;정길생
    • Korean Journal of Animal Reproduction
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    • v.18 no.2
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    • pp.141-150
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    • 1994
  • Morphological features of the interaction between the hatching blastocyst and implantation in pig were studied by electron microscopy. The observations extended from late blastocyst stage to the completion of trophoblastic erosion of the epithelium and early decidual transformation of the epithelium and early decidual transformation of the stromal cells. Between day 7 and 17 of pregnancy, blastocysts from 0.3 to 12 mm in diameter were flushed from the uterine horns of Dutch Landrace pigs. On the 7th of development in the pig blastocyst, the blastocyst shedded of the zona pellucida established the tips of microvilli and with bleb-like cytoplasmic protrusions of the epithelial cells. From day 11 on in pig embryo, the bilayered trophoblast undergoes a dramatic phase of elongation so that the initially spherical expanded blastocyst becomes tubular. In pig, close apposition to the uterine wall beg-ins at about 12 $^1$/$_2$ days and then attachment occurred during the afternoon of the 16th or 18th day post coitum. At this stage, embryonic loss compared with corpus luteum number is up to 40% of ovulated oocytes. Therefore, the implantation failture of these embryos may be mainly caused by morphological abnormality and failture of zona shedding.

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Osteogenic Differentiation of Bone Marrow Stem Cells Using Thermo-Sensitive Hydrogels (온도감응성 수화젤을 이용한 골수간엽줄기세포의 골분화 유도)

  • Kim, Sun-Kyung;Hyun, Hoon;Kim, Soon-Hee;Yoon, Sun-Jung;Kim, Moon-Suk;Rhee, John-M.;Khang, Gil-Son;Lee, Hai-Bang
    • Polymer(Korea)
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    • v.30 no.3
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    • pp.196-201
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    • 2006
  • Poly (ethylene glycol)-based diblock and triblock thermo- sensitive polyester copolymers were investigated for application on tissue engineering and injectable biomaterials in drug delivery system due to their nontoxicity, biocompatibility and biodegradability. We synthesized the diblock copolymers consisting of methoxy poly (ethylene glycol) (MPEG) (Mn=750 g/mole) and poly $(\varepsilon-caprolactone)$ (PCL) by ring opening polymerization of $\varepsilon-CL$ with MPEG as an initiator in the presence of HCl $Et_2O$. The effect of diblock copolymers on in vivo osteogenic differentiation of rat bone marrow stromal cells (BMSCS) with and without the presence of osteogenic supplements (dexamethasone) was investigated. Thin sections were cut from paraffin embedded tissues and histological sections were stained by H&E, von Kossa, and immunohistochemical staining for osteocalcin. In conclusion, dexamethasone containing thermo- sensitive hydrogel might be improved osteogenic differentiation of BMSCs. We expect the osteoinduction effect to be excellent when it uses stem cell or other osteogenic materials.

CASE REPORT OF PILOMAIRICOMA (Pilomatricoma 환아에 대한 증례 보고)

  • Seo, Hyun-Woo;Kim, Ji-Hyuck;Park, Ho-Won
    • Journal of the korean academy of Pediatric Dentistry
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    • v.31 no.1
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    • pp.79-84
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    • 2004
  • Pilomatricoma is a benign soft tissue tumor of hair follicle origin. They occur most commonly in the head and neck region and are usually found in girls during the first two decades of life. Although malignant transformation has been described, it is exceedingly rare. The clinical presentation is typically that of an asymptomatic, superfical, solitary, firm mass that is often accompanied by a reddish-blue discoloration of the overlying skin. Histopathologically pilomatricoma are seen as epithelial islands embedded in a cellular stroma. The epithelial component consist of two main cell types : basaloid cells and ghost cells. Intracellular and stromal calcification is reported in many cases. Diagnosis is usually suspected based on palpation of a superficial, rock-hard mass and confirmed by histopathologic examination. Surgical excision is both curative and the treatment of choice. Recurrence is rare. In this case, the radiographs showed a dense calcification, measuring about 1cm diameter. So simple excision was peformed intraorally, and resultantly the lesion was proved to be a pilomatricoma by histological examination.

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Anti-inflammatory Effect of the Extract of Gynostemma pentaphyllum cell from Ullengdo Island as Korean Endemic Plant (한국 고유 식물 울릉도 돌외 식물 세포 배양추출물의 항염증 효과)

  • Mok, Bo-Ram;Kim, Soo-Yun;Paek, Seung hye;Jang, Young-su;Shin, Jung U;Moh, Sang Hyun
    • Journal of the Korea Academia-Industrial cooperation Society
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    • v.22 no.2
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    • pp.745-754
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    • 2021
  • The purpose of this study was to evaluate and verify the effectiveness of sustainable cosmetic raw materials developed from Gynostemma pentaphyllum, a plant native to Ulleungdo, in improving the skin barrier function and treating atopic dermatitis. Cells were derived from adult Gynostemma pentaphyllum plants, and suitable conditions for mass culture of the cells were established in a bioreactor. DNA components and amino acids extracted from this mass culture were identified from the HPLC fraction. In the in vitro efficacy evaluation results, changes in the expression levels of skin barrier-related proteins such as filaggrin (FLG) and Zonula occludens-1 (Zo-1) were insignificant. It was confirmed that the expression levels of the proteins thymic stromal lymphopoietin (TSLP) and interleukin-33 (IL-33) were significantly reduced. These results lead to the conclusion that Gynostemma pentaphyllum cell extracts have significant anti-inflammatory effects and that these extracts can be widely used as sustainable, nature-friendly active material in cosmetics with anti-inflammatory effects and targeted at improving atopic dermatitis.They may find use in anti-aging cosmetic products as well.

Effects of Bojungikgi-Tang on the Development of Experimentally-induced Endometriosis in the Rats (보중익기탕(補中益氣湯)이 실험적으로 유발된 흰쥐의 자궁내막증(子宮內膜症) 발달에 미치는 영향)

  • Lee, Jeong-Gu;Lee, Dong-Nyung;Seo, Il-Bock;Kim, Hyung-Jun
    • The Journal of Korean Obstetrics and Gynecology
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    • v.22 no.3
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    • pp.1-24
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    • 2009
  • Purpose: This study was performed to investigate the effects of Bojungikgi-Tang on the development of experimentally-induced endometriosis in rats. Methods: Endometriosis was induced in rats by autotransplanting uterine tissue to the peritoneum and we divided the rats into three groups: (1) sham-operated group (n=8), (2) surgically induced endometriosis and untreated control group(n=8), (3) surgically induced endometriosis and Bojungikgi-Tang treated group. Bojungikgi-Tang was orally administrated for 15 days after operation. Then we measured the body weight, the volume of endometriotic implants, the weight of uterus and ovary, and analysed the concentration of cytokines(MCP-1, TNF-${\alpha}$, IL-1${\beta}$, IL-6) in peritoneal fluids. Histopathology, immunohistochemistry for COX-2 and VEGF, and histochemistry for mast cell in transplanted uterine tissue were also performed. Results: 1. The volume($mm^3$) of endometriotic implants in Bojungikgi-Tang treated group(129${\pm}$39) was significantly decreased(p<0.05) compared with control group(222${\pm}$109). 2. The concentration(pg/$m{\ell}$) of MCP-1 in peritoneal fluids in Bojungikgi-Tang treated group(1012${\pm}$248) was significantly decreased(p<0.05) compared with control group(1413${\pm}$346). 3. The concentration(pg/$m{\ell}$ of TNF-${\alpha}$ in peritoneal fluids in Bojungikgi-Tang treated group(887${\pm}$196) was significantly decreased(p<0.05) compared with control group(1126${\pm}$140). 4. Histopathologically, proliferation of endometriotic epithelia, infiltration of inflammatory cells and angiogenesis in transplanted uterine tissue of Bojungikgi-Tang treated group were weakly observed than those of control group. 5. The percentage of positive epithelial layers for COX-2 in Bojungikgi-Tang treated group(56${\pm}$17) was significantly decreased(p<0.05) compared with control group(75${\pm}$16). 6. The VEGF expression of endometriotic epithelia, neovascular endothelia and stromal cells in transplanted uterine tissue of Bojungikgi-Tang treated group were weakly observed than those of control group. Conclusion: On the basis of these results, we concluded that Bojungikgi-Tang has inhibiting effects on the development of transplanted uterine tissue. And these effects may be related with decreased production of MCP-1, TNF-${\alpha}$, and decreased expression of COX-2 and VEGF infiltration by administration of Bojungikgi-Tang.

Attenuation of Experimental Autoimmune Hepatitis in Mice with Bone Mesenchymal Stem Cell-Derived Exosomes Carrying MicroRNA-223-3p

  • Lu, Feng-Bin;Chen, Da-Zhi;Chen, Lu;Hu, En-De;Wu, Jin-Lu;Li, Hui;Gong, Yue-Wen;Lin, Zhuo;Wang, Xiao-Dong;Li, Ji;Jin, Xiao-Ya;Xu, Lan-Man;Chen, Yong-Ping
    • Molecules and Cells
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    • v.42 no.12
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    • pp.906-918
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    • 2019
  • MicroRNA-223-3p (miR-223-3p) is one of the potential microRNAs that have been shown to alleviate inflammatory responses in pre-clinical investigations and is highly encased in exosomes derived from bone mesenchymal stem cells (MSC-exosomes). MSC-exosomes are able to function as carriers to deliver microRNAs into cells. Autoimmune hepatitis is one of the challenging liver diseases with no effective treatment other than steroid hormones. Here, we examined whether MSC-exosomes can transfer miR-223-3p to treat autoimmune hepatitis in an experimental model. We found that MSC-exosomes were successfully incorporated with miR-223-3p and delivered miR-223-3p into macrophages. Moreover, there was no toxic effect of exosomes on the macrophages. Furthermore, treatments of either exosomes or exosomes with miR-223-3p successfully attenuated inflammatory responses in the liver of autoimmune hepatitis and inflammatory cytokine release in both the liver and macrophages. The mechanism may be related to the regulation of miR-223-3p level and STAT3 expression in the liver and macrophages. These results suggest that MSC-exosomes can be used to deliver miR-223-3p for the treatment of autoimmune hepatitis.

Inhibiting Effecposets of Gungguijohyeoleum on the Development of Experimentally-induced Endometriosis in the Rats (궁귀조혈음(芎歸調血飮)이 흰쥐의 자궁내막증 형성 억제에 미치는 영향)

  • Choi, Byun-Tak;Seo, Il-Bock;Lee, Dong-Nyung;Kim, Hyung-Jun
    • The Journal of Korean Obstetrics and Gynecology
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    • v.21 no.3
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    • pp.34-59
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    • 2008
  • Purpose: This study was performed to investigate the inhibiting effects of Gungguijohyeoleum on the development of experimentally-induced endometriosis in rats. Methods: Endometriosis was induced in rats by autotransplanting uterine tissue to the peritoneum and we divided them into three groups: (1) sham-operated group(n=8), (2) surgically induced endometriosis and untreated control group(n=8), (3) surgically induced endometriosis and Gungguijohyeoleum treated group(n=8), Gungguijohyeoleum was orally administrated for 15 days after operation. Then we measured the body weight, the volumes of endometriotic implants, the weight of uterus and ovary, and investigated the concentrations of cytokines(MCP-1, $TNF-{\alpha}$, $IL-1{\beta}$, IL-6) in peritoneal fluids. Histopathology, immunohistochemistry for COX-2 and VEGF, and histochemistry for mast cell in transplanted uterine tissue were performed. Results: - The volume ($mm^3$) of endometriotic implants in Gungguijohyeoleum treated group ($76.4{\pm}24.5$) was significantly decreased(p<0.05) compared with control group($222.1{\pm}109.1$). - The concentration (pg/ml) of MCP-1 in peritoneal fluids in Gungguijohyeoleum treated group ($1060.8{\pm}280.8$) was significantly decreased(p<0.05) compared with control group($1412.5{\pm}345.7$). - The concentration (pg/ml) of $TNF-{\alpha}$ in peritoneal fluids in Gungguijohyeoleum treated group ($827.5{\pm}219.9$) was significantly decreased(p<0.01) compared with control group($1126.2{\pm}139.9$). - The concentration (pg/ml) of $IL-1{\beta}$ in peritoneal fluids in Gungguijohyeoleum treated group($83.4{\pm}9.0$) was significantly decreased(p<0.01) compared with control group($105.3{\pm}17.6$). - The concentration (pg/ml) of IL-6 in peritoneal fluids in Gungguijohyeoleum treated group($108.9{\pm}15.7$) was decreased compared with control group($122.8{\pm}19.3$). - Histopathologically, proliferation of endometriotic epithelia, infiltration of inflammatory cells and angiogenesis in transplanted uterine tissue of Gungguijohyeoleum treated group were weakly observed than those of control group. - The percentage(%) of positive epithelial layers for COX-2 in Gungguijohyeoleum treated group($56.8{\pm}12.8$) was significantly decreased(p<0.01) compared with control group($75.1{\pm}16.3$). -The VEGF expression of endometriotic epithelia, neovascular endothelia and stromal cells in transplanted uterine tissue of Gungguijohyeoleum treated group was weakly observed than that of control group. - The numbers of mast cells in transplanted uterine tissue in Gungguijohyeoleum treated group($35.4{\pm}18.4$) were significantly decreased(p<0.01) compared with control group ($91.0{\pm}28.3$). Conclusion: On the basis of these results, we concluded that Gungguijohyeoleum has inhibiting effects on the development of transplanted uterine tissue. And these effects may be related with decreased production of MCP-1, $TNF-{\alpha}$, $IL-1{\beta}$, COX-2, VEGF and mast cells by administration of Gungguijohyeoleum.

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