• Title/Summary/Keyword: BMPs

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Overview of Transforming Growth Factor β Superfamily Involvement in Glioblastoma Initiation and Progression

  • Nana, Andre Wendindonde;Yang, Pei-Ming;Lin, Hung-Yun
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.16
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    • pp.6813-6823
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    • 2015
  • Glioblastoma, also known as glioblastoma multiforme (GBM), is the most aggressive of human brain tumors and has a stunning progression with a mean survival of one year from the date of diagnosis. High cell proliferation, angiogenesis and/or necrosis are histopathological features of this cancer, which has no efficient curative therapy. This aggressiveness is associated with particular heterogeneity of the tumor featuring multiple genetic and epigenetic alterations, but also with implications of aberrant signaling driven by growth factors. The transforming growth factor ${\beta}$ ($TGF{\beta}$) superfamily is a large group of structurally related proteins including $TGF{\beta}$ subfamily members Nodal, Activin, Lefty, bone morphogenetic proteins (BMPs) and growth and differentiation factor (GDF). It is involved in important biological functions including morphogenesis, embryonic development, adult stem cell differentiation, immune regulation, wound healing and inflammation. This superfamily is also considered to impact on cancer biology including that of GBM, with various effects depending on the member. The $TGF{\beta}$ subfamily, in particular, is overexpressed in some GBM types which exhibit aggressive phenotypes. This subfamily impairs anti-cancer immune responses in several ways, including immune cells inhibition and major histocompatibility (MHC) class I and II abolishment. It promotes GBM angiogenesis by inducing angiogenic factors such as vascular endothelial growth factor (VEGF), plasminogen activator inhibitor (PAI-I) and insulinlike growth factor-binding protein 7 (IGFBP7), contributes to GBM progression by inducing metalloproteinases (MMPs), "pro-neoplastic" integrins (${\alpha}v{\beta}3$, ${\alpha}5{\beta}1$) and GBM initiating cells (GICs) as well as inducing a GBM mesenchymal phenotype. Equally, Nodal promotes GICs, induces cancer metabolic switch and supports GBM cell proliferation, but is negatively regulated by Lefty. Activin promotes GBM cell proliferation while GDF yields immune-escape function. On the other hand, BMPs target GICS and induce differentiation and sensitivity to chemotherapy. This multifaceted involvement of this superfamily in GBM necessitates different strategies in anti-cancer therapy. While suppressing the $TGF{\beta}$ subfamily yields advantageous results, enhancing BMPs production is also beneficial.

Bone regenerative effects of recombinant human bone morphogenetic protein-2 employed protein transduction domain (Protein transduction domain을 이용한 recombinant human bone morphogenetic protein-2의 골재생효과)

  • Jung, Sung-Won;Kim, Nam-Hee;Yook, Jong-In;Kim, Chang-Sung;Kim, Hyung-Jun;Cho, Kyoo-Sung
    • Journal of Periodontal and Implant Science
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    • v.37 no.3
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    • pp.497-509
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    • 2007
  • Bone morphogenetic proteins(BMPs) are regarded as members of the transforming growth $factor-{\beta}$ superfamily with characteristic features in their amino acid sequences. A number of studies have demonstrated the biologic activities of BMPs, which include the induction of cartilage and bone formation. Recently there was a attempt to overcome a limitation of mass production, and economical efficieny of rh-BMPs. The method producing PTD by using bacteria have advantages of acquiry a mass of proteins. Hences, a new treatment which deliver protein employed by protein transduction domain(PTD) has been tried. The purpose of this study was to evaluate the bone regenerative effect of TATBMP-2 and TAT-HA2-BMP-2 employed by PTD from HlV-1 TAT protein for protein translocation in the rat calvarial model. An 8mm calvarial, critical size osteotomy defect was created in each of 32 male Spraque-Dawley rats(weight $250{\sim}300g$). The animals were divided into 4 groups of 32 animals each (4 animals/group/healing interval). The defect was treated with TATBMP-2/ACS(Absorbable collagen sponge) (TATBMP-2 0.1mg/ml), TAT-HA2-BMP-2/ACS(TAT-HA2-BMP-2 0.1mg/ml), ACS alone or left untreated for surgical control(negative control). The rats were sacrificed at 2 or 8 weeks postsurgery, and the results were evaluated histologically. The results were as follows: New bone formation were not significantly greater in the TATBMP-2/ACS group relative to negative, and positive control groups. New bone was evident at the defect sites in TAT-HA2-BMP-2/ACS group relative to negative, positive control and TATBMP-2 groups. There were a little bone regeneration in TATBMP-2 groups. While, enhanced local bone formation were observed in TAT-HA2-BMP-2 group. But, The results was not the same in all rat defects. Therefore, further investigations are required to develop a method. which disperse homogenously, and adhere to target cells.

Reduction of Agricultural Non-point Pollution Source by Scenarios of Best Management Practices on Cropping System Alternatives of Main Upland Crop in Saemangeum Watershed (새만금 유역 주요 밭작물 작부체계 최적관리기법 시나리오별 농업비점오염원 저감)

  • Son, Jae Gwon;Lee, Gyeong Ae;Yoo, Dong Su;Cho, JaeYoung
    • Journal of Applied Biological Chemistry
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    • v.57 no.1
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    • pp.95-101
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    • 2014
  • Nonpoint pollution sources from agricultural activities are a major cause of water quality impairment. A nutrient management program utilizes farm practices that maintain efficient crop production systems and control agricultural nonpoint pollution sources. The objectives of present study were to identify appropriate best management practices (BMPs) according to changes of cropping system of main upland crop for reducing AGNPs loadings and to simulate the effects of the application of the several BMPs scenarios in Saemangeum watershed. The selected BMP scenarios were: 1) to convert naked barley and hulled barley to hairy vetch or chinese milk vetch, 2) to convert red pepper to soybean crop, and 3) to combine two scenarios, converting naked barley and hulled barley to hairy vetch or chinese milk vetch + converting red pepper to soybean crop. As a result of BMPs application, the crop requirement of nitrogen and phosphorus for upland crop reduced nitrogen by 41% and phosphorus by 47% in scenario 1, whereas scenario 2 reduced nitrogen by 30% and phosphorus by 23%. Overall, scenario 3 reduced nitrogen by 72% and phosphorus by 70% in agricultural non-point pollution sources associated with chemical fertilizer and livestock manure in Saemangeum watershed.

Minimizing Nutrient Loading from SCB Treated Paddy Rice Fields through Water Management (SCB 액비 시용 논에서 물관리를 통한 양분의 수계 부하 최소화 방안)

  • Kim, Min-Kyeong;Kwon, Soon-Ik;Kang, Seong-Soo;Jung, Goo-Bok;Hong, Seung-Chang;Chae, Mi-Jin;So, Kyu-Ho
    • Korean Journal of Soil Science and Fertilizer
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    • v.45 no.5
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    • pp.671-675
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    • 2012
  • This study was conducted to establish the BMPs (Best Management Practices) for preventing pollutant loadings from paddy rice field applied livestock liquid manure from 2008 through 2011. Cultivated paddy rice fields (Gyeonggi province, Korea) were treated with SCB (Slurry composting and bio-filtration process) liquid fertilizer. The BMPs for paddy rice field developed in this study includes: 1) the controlling a drainage water gate in paddy rice field from right after SCB liquid fertilizer application to 3 weeks after rice transplanting; 2) livestock liquid fertilizer application to paddy rice soils in 20 days before rice transplanting to encourage the utilization of liquid fertilizer; 3) preservation of surface water depth to 5 cm in a paddy field right after SCB liquid fertilizer applied to minimize a water pollution and enhance the utilization of liquid fertilizer; and 4) blocking a water gate at least for 2 days to inactivate E. coli survival. The findings of this study will provide useful and practical guideline to applicators of agricultural soil in deciding appropriate handling and time frames for preventing pollution of water quality for sustainable agriculture.

Circadian Clock Gene Per1 Mediates BMP2-induced Osteoblast Differentiation in MC3T3-E1 Cells (MC3T3-E1 세포에서 BMP2에 의한 조골세포의 분화에 일주기 유전자 Per1이 미치는 영향)

  • Min, Hyeon-Young;Jang, Won-Gu
    • Journal of Life Science
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    • v.27 no.5
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    • pp.501-508
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    • 2017
  • Bone morphogenetic proteins (BMPs) are multifunctional cytokines that play important roles in a variety of cellular functions. Among BMP family members, BMP2 efficiently promotes osteoblast differentiation through Smad-mediated runt-related transcription factor 2 (Runx2) expression. Several recent studies suggest that BMPs are associated with clock genes, in particular Bmal1. Bmal1 protein heterodimerizes with Clock protein and then induces period 1 (Per1) expression. However, the role of Per1 on osteoblast differentiation remains unclear. In this study, we investigated whether Per1 is involved in osteoblast differentiation. MC3T3-E1 cells were treated with BMP2 for induction of osteoblastic differentiation. Osteogenic maker gene and Per1 mRNA expression were measured using real-time PCR. Interestingly, BMP2 treatment induced Per1 mRNA expression in MC3T3-E1 cells. To further investigate the function of Per1 on osteoblast differentiation, MC3T3-E1 cells were transiently transfected with pCMV-Per1. Per1 overexpression increased Runx2 mRNA and protein levels. Also, mRNA expression and promoter activity of osteocalcin were upregulated by Per1 overexpression. To investigate the effect of interaction between Per1 and osteogenic condition, MC3T3-E1 cells were cultured in osteogenic medium containing ascorbic acid and ${\beta}$-glycerophosphate. Osteogenic medium-induced ALP staining level and mineralization were synergistically increased by overexpression of Per1. Taken together, these results demonstrate that Per1 is a positive regulator of osteoblast differentiation.

Effects of Substrate to Inoculum Ratio on the Biochemical Methane Potential of Piggery Slaughterhouse Wastes

  • Yoon, Young-Man;Kim, Seung-Hwan;Shin, Kook-Sik;Kim, Chang-Hyun
    • Asian-Australasian Journal of Animal Sciences
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    • v.27 no.4
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    • pp.600-607
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    • 2014
  • The aim of this study was to assess the effect of substrate to inoculum ratio (S/I ratio) on the biochemical methane potential (BMP) and anaerobic biodegradability ($D_{deg}$) of different piggery slaughterhouse wastes, such as piggery blood, intestine residue, and digestive tract content. These wastes were sampled from a piggery slaughterhouse located in Kimje, South Korea. Cumulative methane production curves for the wastes were obtained from the anaerobic batch fermentation having different S/I ratios of 0.1, 0.5, 1.0, and 1.5. BMP and anaerobic biodegradabilities ($D_{deg}$) of the wastes were calculated from cumulative methane production data for the tested conditions. At the lowest S/I ration of 0.1, BMPs of piggery blood, intestine residue, and digestive tract content were determined to be 0.799, 0.848, and $1.076Nm^3kg^{-1}-VS_{added}$, respectively, which were above the theoretical methane potentials of 0.539, 0.644, and $0.517Nm^3kg^{-1}-VS_{added}$ for blood, intestine residue, and digestive tract content, respectively. However, BMPs obtained from the higher S/I ratios of 0.5, 1.0, and 1.5 were within the theoretical range for all three types of waste and were not significantly different for the different S/I ratios tested. Anaerobic biodegradabilities calculated from BMP data showed a similar tendency. These results imply that, for BMP assay in an anaerobic reactor, the S/I ratio of anaerobic reactor should be above 0.1 and the inoculum should be sufficiently stabilized to avoid further degradation during the assay.

THE ROLE OF BONE MORPHOGENETIC PROTEIN IN THE TOOTH CULTURE (치아 기관배양시 골형성단백의 역할에 관한 연구)

  • Chung, Il-Hyuk;Chung, Jong-Hoon;Choung, Pill-Hoon
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • v.30 no.5
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    • pp.438-443
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    • 2004
  • Objectives : The proper development of the facial structures relies upon a sequence of tightly regulated signaling interactions between the ectoderm and mesoderm involving the participation of several families of signaling molecules. Among these, bone morphogenetic proteins (BMPs) have been suggested to be a key signal that regulates the development of the mandible and the initiation and morphogenesis of the teeth. The aim of this study was to examine the artificial development of the mandibular structures and to examine the role of BMPs on tooth morphogenesis and differentiation using an organ culture system. Materials and Methods : The tooth germs from Ed 11.5, 13.5 mice were dissected, and transplanted into the diastema of the mandible primordia. The mandibles containing the transplanted tooth germs were cultured in vitro. During this period, beads soaked with BMP4 were implanted around the transplanted tooth germs. In addition, a diastema block containing the transplanted tooth germ was dissected, then transferred to an adult mouse kidney. After the organ culture, the developing mandibular explant was removed from the kidney and prepared for the tissue specimens. Odontogeneis of the transplanted tooth germs was examined after Hematoxylin-eosin, Masson-trichrome staining. Results : Proliferation and differentiation of the tooth germs cultured in the diastema was observed. In the BMP4-treated tooth germs, the formation of the first and second molars was noted. The crown of the developing tooth showed the formation of a mature cusp with the deposition of enamel and dentin matrix. In conclusion, it was confirmed that BMP4 is involved in the formation of a dental crown and the differentiation of ameloblasts and odontoblasts of the molar tooth during the development of the transplanted tooth germs.

Surface Cover Application for Reduction of Runoff and Sediment Discharge from Sloping Fields (경사지 밭에서 발생하는 토양유실 저감을 위한 피복재 적용)

  • Shin, Min-Hwan;Won, Chul-Hee;Park, Woon-Ji;Choi, Young-Hun;Shin, Jae-Young;Lim, Kyoung-Jae;Choi, Joong-Dae
    • Journal of The Korean Society of Agricultural Engineers
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    • v.53 no.6
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    • pp.129-136
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    • 2011
  • To measure effects of surface cover on runoff and sediment discharge reduction using rainfall simulator, four(5 m${\times}$30 m scale) plot experiments were conducted in this study. Surface covers made with straw mat, Polyacrylamide (PAM), chaff, and sawdust were simulated 4 times under 31.1~44.4 mm/hr rainfall intensities. Compared with results from control plot, the time of runoff generation is delayed and outflow volume decreased with surface cover. Effects on runoff reduction of straw mat, PAM, sawdust and chaff ranged 4.7~81.5 % and runoff rate reduced by 6.5~76.1 % respectively, when compared with those from control plot. The percentage of decrease in sediment discharge were 99.7~99.8 % from straw mat+sawdust+PAM plots, 85.9~95.6 % from straw mat+PAM plots, and 98.5~99.4 % from straw mat+chaff+PAM plots. The runoff, sediment discharge, and SS concentration reduction efficiencies of the cover materials were outstanding when compared to control plot. It was analyzed that reduction of runoff and sediment discharge were mainly contributed by decrease in rainfall energy impact and flow velocity and increase of infiltration due to the surface cover materials. The results could be used as a base for the development of best management practices (BMPs) to reduce runoff, sediment discharge from sloping field.

Carthamus tinctorius L. Increases BMP-2 Gene Expression during Bone Fracture Healing in Rats

  • Lee, Kwang-Hee;Sohn, Oog-Jin;Ahn, Jong-Chul;Kim, Yong-Woon;Park, So-Young;Kim, Jong-Yeon
    • The Korean Journal of Physiology and Pharmacology
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    • v.10 no.3
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    • pp.143-147
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    • 2006
  • Carthamus tinctorius L.is known to improve fracture healing, and bone morphogenetic proteins (BMPs) are associated with the formation and healing process of bone. BMP-2 and BMP-7 are two of the most important BMPs during the bone healing process. Human osteosarcoma MG63 cells and rats were used to determine the effects of Carthamus tinctorius L. extract (CTE) on BMP-2 gene expression. BMP-2 gene expression by CTE treatment in human osteosarcoma MG63 cells was not different from the control group until 8 hours of incubation, but was significantly higher, by 31%, than that of the control group at 16 hr of incubation. Microscopic findings of the 9th rib 3 weeks after fracture showed typical rimming of the osteoblast and immature bone formation in control and CTE groups. BMP-2 gene expression by in situ hybridization was remarkably increased by a CTE-supplemented diet in the fracture group compared to the control group. In conclusion, Carthamus tinctorius L. increased BMP-2 gene expression in human osteosarcoma cells and fractured bone. But further studies would be needed to elucidate the effect of CTE on fracture healing in vivo because our results did not show any evidence of healing improvement histologically $3^{rd}$ week after fracture.

Application Evaluation of Best Management Practices for Agricultural Non-Point Source Pollution using Delphi Survey Method (전문가 델파이 방법을 이용한 농업 비점오염 저감 기술의 현장 적용성 조사)

  • Kim, Min-Kyeong;Jung, Goo-Bok;Kim, Min-Young;Kim, Myung-Hyun;Cho, Kwang-Jin;Choi, Soon-Kun;Hong, Seong-Chang;So, Kyu-Ho
    • Korean Journal of Environmental Agriculture
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    • v.33 no.2
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    • pp.144-147
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    • 2014
  • BACKGROUND: It is essential to prioritize the exact and clear understanding of agricultural nonpoint source pollution (NPS) controls. The realistic policies and systems should also be developed based on this understanding. Therefore, this study aimed to present agricultural Best Management Practices (BMPs) applicable for the fields based on the Delphi survey result. METHODS AND RESULTS: This study deduced the evaluation items to assess each BMP for agricultural NPS control and conducted the surveying using the Delphi method based on agricultural BMP experts. In addition, its on-the-spot application were evaluated. Considering its importance, technical, social and economic proprieties showed that political support was ranked first and followed by cost investment, labor investment, reduction effect and resident participation. The survey findings by agricultural BMP experts showed the good performance of on-the-spot application can be achieved from fertilization by soil testing, residue and green manure application and contour plowing which are applicable within a field. Agricultural BMPs, highly applicable for the fields, were the countermeasures that farmers who are the principal bodies of agricultural NPS control could be participated directly. CONCLUSION: The active participation of farmers is essential for effective control of agricultural NPS. It is necessary to establish various incentive systems.