• Molecules and Cells
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• 제39권5호
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• pp.389-394
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• 2016

Dovitinib (TKI258) is a small molecule multi-kinase inhibitor currently in clinical phase I/II/III development for the treatment of various types of cancers. This drug has a safe and effective pharmacokinetic/pharmacodynamic profile. Although dovitinib can bind several kinases at nanomolar concentrations, there are no reports relating to osteoporosis or osteoblast differentiation. Herein, we investigated the effect of dovitinib on human recombinant bone morphogenetic protein (BMP)-2-induced osteoblast differentiation in a cell culture model. Dovitinib enhanced the BMP-2-induced alkaline phosphatase (ALP) induction, which is a representative marker of osteoblast differentiation. Dovitinib also stimulated the translocation of phosphorylated Smad1/5/8 into the nucleus and phosphorylation of mitogen-activated protein kinases, including ERK1/2 and p38. In addition, the mRNA expression of BMP-4, BMP-7, ALP, and OCN increased with dovitinib treatment. Our results suggest that dovitinib has a potent stimulating effect on BMP-2-induced osteoblast differentiation and this existing drug has potential for repositioning in the treatment of bone-related disorders.

• 한국수자원학회:학술대회논문집
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• 한국수자원학회 2016년도 학술발표회
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• pp.565-565
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• 2016

농림부는 농업지역에서 발생하는 비점오염원을 관리하기 위해 다양한 최적관리기법(BMP)에 대해 연구를 수행하여 효과를 검증하였으나 이를 광역 단위로 보급하여 실제 영농지역에서 BMP의 효과를 측정한 연구는 부족한 실정이다. 따라서 본 연구에서는 논 지역을 대상으로 물관리기술(물꼬)과 시비관리기술(완효성 비료) BMP를 보급하고 광역 단위로 BMP의 효과를 측정하고자 하였다. 연구대상지구는 새만금 지역에 위치한 전라북도 부안군 용계리 일대에 위치하고 있으며, 벼농사가 활발하게 이루어지고 있는 지역을 선정하였다. 논에 보급된 BMP의 효과를 측정하기 위해 BMP 참여 농가를 선정하여 물꼬와 완효성 비료를 보급하였으며, 용수로와 배출구 3지점을 선정하여 관개량을 측정하고 유출량을 측정하였다. 또한 관개수와 대조구, 처리구별(대조구, 물꼬, 완효성, 물꼬+완효성) 수질을 분석하여 배출구 별로 단위면적당 오염부하량을 산정하고 이를 통해 대조구 대비 처리구의 저감율을 분석하였다. 분석 결과, 대조구 대비 처리구의 단위면적당 오염부하량의 저감율은 SS 63.6%, BOD 45.5%, $COD_{Mn}$ 26.5%, $COD_{Cr}$ 40.1%, T-N 16.0%, T-P 12.9%, TOC 11.4%로 나타났다. 또한 연구대상지구를 SO#1(완효성 비료 95%, 비참여 농가 5%), SO#2(완효성 비료 2%, 물꼬 8%, 완효성 비료+물꼬 40%, 비참여 농가 40%), SO#M(완효성 비료 96%, 비참여 농가 4%) 3개의 배출구로 구분하여 BMP 보급 효과를 측정한 결과, 대조구 대비 SO#1에서는 수질항목별로 10.6 ~ 85.5%, SO#2는 8.1 ~ 45.9%, SO#M은 10.7 ~ 86.2%의 범위로 저감된 것으로 분석되었으며, 특히 SS의 단위면적당 오염부하 저감율이 가장 큰 것으로 나타났다. 하지만 본 연구는 7월부터 10월까지 측정된 데이터를 활용하여 산정하였기 때문에 써레질, 이앙기간에 발생한 단위면적당 오염부하량은 포함되지 않은 결과이며, 각 배수구역별 유입량의 경우 정확한 측정에 어려움이 있어 전체 관개량 대비 관개 면적을 이용하여 단위면적당 유입량을 산정하였기 때문에 추가적인 연구를 통해 효과를 검증할 필요가 있을 것으로 판단된다.

• 구강회복응용과학지
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• 제40권1호
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• pp.13-23
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• 2024

목적: 인간간엽줄기세포를 연골세포로 분화유도하는 성장인자 규명 및 주사침 크기 차이에 따른 세포증식 증진 비교이다. 연구 재료 및 방법: 인간간엽줄기세포를 연골세포유도배지에서 14, 21, 28일 배양하여 BMP-2, BMP-4, BMP-6, BMP-7, BMP-13, FGF-2, FGF-18, IGF-1, TGF-β1. TGF-β2, TGF-β3를 투여한 군들과 대조군에서 SOX-5, SOX-6, SOX-9 및 FOXO1A의 발현량을 분석하였다. 18, 21, 26 게이지(G) 주사침을 사용하여 배양접시에 인간간엽줄기세포를 접종하고 24, 48, 72시간 후 각각 세포증식을 측정하였다. 결과: 기존에 알려진 FGF, IGF-1, TGFβ1와 함께, BMP-2, BMP-4, BMP-6, BMP-7 등 BMP family 성장인자들에 의하여 연골세포분화 전사인자 유전자들인 SOX-5, SOX-6, SOX-9, FOXO1A의 유전자발현이 증가하였다. 48시간에서는 가장 작은 주사침인 26G군이 대조군 및 18G군에 비하여 유의한 세포증식 증진을 보였으며, 72시간에서도 가장 작은 주사침인 26G군이 대조군에 비하여 유의한 세포증식 증진을 보였다. 결론: 인간간엽줄기세포의 연골세포분화 유도능을 가진 성장인자들을 고찰할 수 있었고 주사침 크기에 따른 세포증식 변화를 규명할 수 있었다.

• 대한치과의사협회지
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• 제52권4호
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• pp.218-233
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• 2014

Bispbosphonates are a class of pharmaceutic agents, which induce apoptosis of osteoclast as well as impair osteoclastic activity to suppress bone resorption. Thus, bisphophonates are effectively used to treat osteoporosis, multiple myeloma and to prevent bone metastases of malignant cancer. However, recently dental disease have been reported associated with Bisphosphonates. Thus, there are a number of discussions about proper prevention and treatment of bisphosphonate-related osteonecrosis of jaw(BRONJ). Marshall R. Urist in 1965 made the seminal discovery that a specific protein, BMP(bone morphogenetic protein), found in the extracellular matrix of demineralized bone could induce bone formation newly when implanted in extraosseous tissues in a host. BMPs are multi-functional growth factors which are members of the transforming growth factor-beta super family and their ability is that plays a pivotal roll in inducing bone. About 18 BMP family members have been identified and characterized. Among of them, BMP-2 and BMP-7 have significant importance in bone development. In this study, patients of BRONJ were recieved who visited Department of oral and maxillofacial surgery, school of dentistry, Wonkwang university for past 3 years from 2011 to 2013. We focused on the results of the surgical intervention. We suggest that new strategy of treatment used to rhBMP-2 and LFA(Lidocaine-Fibrinogen-Aprotinin)-collagen scaffold for patients of BRONJ. The purpose of this paper is to give a brief overview of BMPs and to critically review the clinical data currently available on rhBMP-2 and LFA collage scaffold.

• International Journal of Industrial Entomology and Biomaterials
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• 제45권2호
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• pp.78-83
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• 2022

There are several subspecies of Bombyx mori, whose silk sericin variants differ. Silk sericin can induce bone morphogenic protein-2 (BMP-2) in macrophages, and silk sericin from different species may have different levels of BMP-2 induction ability. In this study, silk sericin from three B. mori subspecies (Baegokjam, Yeonnokjam, and Goldensilk) was prepared. They were administered to RAW264.7 cells and BMP-2 expression level was studied. Bone regeneration was evaluated using a rat calvarial defect model. BMP-2 expression level was the highest in the Baegokjam group. The bone volume in the Baegokjam group was significantly higher than that in the Yeonnokjam group (P = 0.003). In conclusion, sericin from Baegokjam showed higher levels of BMP-2 expression and bone regeneration than those from Yeonnokjam and Goldensilk.

• Journal of Periodontal and Implant Science
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• 제38권sup2호
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• pp.355-362
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• 2008

Purpose: The carrier for the delivery of bone morphogenetic proteins(BMPs) should also serve as a scaffold for new bone growth. In addition, predictable bone formation in terms of the volume and shape should be guaranteed. This study evaluated the ectopic bone formation of recombinant human BMP-2(rhBMP-2) using a micro macroporous biphasic calcium phosphate (MBCP: mixture of ${\beta}TCP$ and HA) block as a carrier in a rat subcutaneous assay model. Materials and Methods: Subcutaneous pockets were created on the back of 40 male Sprague-Dawley rats. In the pockets, rhBMP-2/MBCP and MBCP alone were implanted. The blocks were evaluated by histological and histometric parameters after a healing interval of 2 weeks (each 10 rats; MBCP and rhBMP-2/MBCP) or 8 weeks (each 10 rats; MBCP and rhBMP-2/MBCP). Results: The shape and volume of the block was maintained stable over the healing period. No histological bone forming activity was observed in the MBCP alone sites after 2 weeks and there was minimal new bone formation at 8 weeks. In the rhBMP-2/MBCP sites, new bone formation was evident in the macropores of the block. The new bone area at 8 weeks was greater than at 2 weeks. There was a further increase in the quantity of new bone with the more advanced stage of remodeling. Conclusions: A MBCP block could serve as a carrier system for predictable bone tissue engineering using rhBMPs.

• IMMUNE NETWORK
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• 제23권6호
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• pp.48.1-48.21
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• 2023

Mesenchymal stromal/stem cells (MSCs) possess immunoregulatory properties and their regulatory functions represent a potential therapy for acute lung injury (ALI). However, uncertainties remain with respect to defining MSCs-derived immunomodulatory pathways. Therefore, this study aimed to investigate the mechanism underlying the enhanced effect of human recombinant bone morphogenic protein-2 (rhBMP-2) primed ES-MSCs (MSC^BMP2) in promoting Tregs in ALI mice. MSC were preconditioned with 100 ng/ml rhBMP-2 for 24 h, and then administrated to mice by intravenous injection after intratracheal injection of 1 mg/kg LPS. Treating MSCs with rhBMP-2 significantly increased cellular proliferation and migration, and cytokines array reveled that cytokines release by MSC^BMP2 were associated with migration and growth. MSC^BMP2 ameliorated LPS induced lung injury and reduced myeloperoxidase activity and permeability in mice exposed to LPS. Levels of inducible nitric oxide synthase were decreased while levels of total glutathione and superoxide dismutase activity were further increased via inhibition of phosphorylated STAT1 in ALI mice treated with MSC^BMP2. MSC^BMP2 treatment increased the protein level of IDO1, indicating an increase in Treg cells, and Foxp3⁺CD25⁺ Treg of CD4⁺ cells were further increased in ALI mice treated with MSC^BMP2. In co-culture assays with MSCs and RAW264.7 cells, the protein level of IDO1 was further induced in MSC^BMP2. Additionally, cytokine release of IL-10 was enhanced while both IL-6 and TNF-α were further inhibited. In conclusion, these findings suggest that MSC^BMP2 has therapeutic potential to reduce massive inflammation of respiratory diseases by promoting Treg cells.

• Molecules and Cells
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• 제37권3호
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• pp.270-274
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• 2014

Lymphatic vessels are essential to regulate interstitial fluid homeostasis and diverse immune responses. A number of crucial factors, such as VEGFC, SOX18, PROX1, FOX2C, and GJC2, have been implicated in differentiation and/or maintenance of lymphatic endothelial cells (LECs). In humans, dysregulation of these genes is known to cause lymphedema, a debilitating condition which adversely impacts the quality of life of affected individuals. However, there are no currently available pharmacological treatments for lymphedema, necessitating identification of additional factors modulating lymphatic development and function which can be targeted for therapy. In this report, we investigate the function of genes associated with Bone Morphogenetic Protein (BMP) signaling in lymphatic development using zebrafish embryos. The knock-down of BMP type II receptors, Bmpr2a and Bmpr2b, and type I receptors, Alk3 and Alk3b, as well as SMAD5, an essential cellular mediator of BMP signaling, led to distinct lymphatic defects in developing zebrafish. Therefore, it appears that each constituent of the BMP signaling pathway may have a unique function during lymphatic development. Taken together, our data demonstrate that BMP signaling is essential for normal lymphatic vessel development in zebrafish.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제40권6호
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• pp.291-296
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• 2014

Objectives: Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a side effect of bisphophonate therapy that has been reported in recent years. Osteoclastic inactivity by bisphosphonate is the known cause of BRONJ. Bone morphogenetic protein-2 (BMP-2) plays an important role in the development of bone. Recombinant human BMP-2 (rhBMP-2) is potentially useful as an activation factor for bone repair. We hypothesized that rhBMP-2 would enhance the osteoclast-osteoblast interaction related to bone remodeling. Materials and Methods: Human fetal osteoblast cells (hFOB 1.19) were treated with $100{\mu}M$ alendronate, and 100 ng/mL rhBMP-2 was added. Cells were incubated for a further 48 hours, and cell viability was measured using an MTT assay. Expression of the three cytokines from osteoblasts, receptor activator of nuclear factor-${\kappa}B$ ligand (RANKL), osteoprotegerin (OPG), and macrophage colony-stimulating factor (M-CSF), were analyzed by real-time polymerase chain reaction and enzyme-linked immunosorbent assay. Results: Cell viability was decreased to $82.75%{\pm}1.00%$ by alendronate and then increased to $110.43%{\pm}1.35%$ after treatment with rhBMP-2 (P<0.05, respectively). OPG, RANKL, and M-CSF expression were all decreased by alendronate treatment. RANKL and M-CSF expression were increased, but OPG was not significantly affected by rhBMP-2. Conclusion: rhBMP2 does not affect OPG gene expression in hFOB, but it may increase RANKL and M-CSF gene expression.

• Journal of Industrial and Engineering Chemistry
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• 제67권
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• pp.244-254
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• 2018

Surface modified poly ${\text\tiny{L}}$-lactic acid (PLLA) samples with hydroxyapatite (HA), heparin and bone morphogenetic protein-2 (BMP-2) mediated by polydopamine (pDA) coating (PLLA/pDA/HA/Hep/BMP-2) were prepared, and their effects on the enhancements of bone formation and osseointegration were evaluated in vitro and in vivo as compared to PLLA, PLLA/pDA/HA, and PLLA/pDA/Hep/BMP-2. The changes in surface chemical compositions, morphologies and wettabilities were observed by X-ray photoelectron spectroscopy (XPS), field-emission scanning electron microscopy (FE-SEM), atomic force microscopy (AFM) and water contact angle measurements. Pre-coating of HA particles with pDA provided uniform and homogeneous anchoring of particles to PLLA surface. In addition, the strong ionic interaction between heparin and pDA led PLLA surface readily heparinized for loading of BMP-2. In vitro experiments revealed that the levels of alkaline phosphatase (ALP) activity, calcium deposition, and osteocalcin (OCN) gene expression were higher in MG-63 human osteosarcoma cell lines grown on PLLA/pDA/HA/Hep/BMP-2 than on control PLLA, PLLA/pDA/HA, and PLLA/pDA/Hep/BMP-2. In vivo studies using micro-computed tomography (micro-CT) also showed that PLLA/pDA/HA/Hep/BMP-2 screw exhibited greatest value of bone volume (BV) and bone volume/tissue volume (BV/TV) among samples. Histological evaluations with H&E and Von Kossa staining demonstrated that a combination of HA and BMP-2 contributed to the strong osseointegration.