• BMB Reports
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• 제45권4호
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• pp.247-252
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• 2012

Although previous studies have demonstrated that BMP9 is highly capable of inducing osteogenic differentiation of mesenchymal stem cells, the molecular mechanism involved remains to be fully elucidated. In this study, we showed that BMP9 simultaneously promotes the activation of Smad1/5/8, p38 and ERK1/2 in C3H10T1/2 cells. Knockdown of Smad4 with RNA interference reduced nuclear translocation of Smad1/5/8, and disrupted BMP9-induced osteogenic differentiation. BMP9-induced osteogenic differentiation was blocked by p38 inhibitor SB203580, whereas enhanced by ERK1/2 inhibitor PD98059. SB203580 decreased BMP9-activated Smads singling, and yet PD98059 stimulated Smads singling in C3H10T1/2 cells. The effects of inhibitor were reproduced with adenovirus expressing siRNA targeted p38 and ERK1/2, respectively. Taken together, our findings revealed that Smads, p38 and ERK1/2 are involved in BMP9-induced osteogenic differentiation. Also, it is noteworthy that p38 and ERK1/2 may play opposing regulatory roles in mediating BMP9-induced osteogenic differentiation of C3H10T1/2 cells.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제43권6호
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• pp.373-387
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• 2017

Objectives: The purpose of this study was to introduce our three experiments on bone morphogenetic protein (BMP) and its carriers performed using the critical sized segmental defect (CSD) model in rat fibula and to investigate development of animal models and carriers for more effective bone regeneration. Materials and Methods: For the experiments, 14, 16, and 24 rats with CSDs on both fibulae were used in Experiments 1, 2, and 3, respectively. BMP-2 with absorbable collagen sponge (ACS) (Experiments 1 and 2), autoclaved autogenous bone (AAB) and fibrin glue (FG) (Experiment 3), and xenogenic bone (Experiment 2) were used in the experimental groups. Radiographic and histomorphological evaluations were performed during the follow-up period of each experiment. Results: Significant new bone formation was commonly observed in all experimental groups using BMP-2 compared to control and xenograft (porcine bone) groups. Although there was some difference based on BMP carrier, regenerated bone volume was typically reduced by remodeling after initially forming excessive bone. Conclusion: BMP-2 demonstrates excellent ability for bone regeneration because of its osteoinductivity, but efficacy can be significantly different depending on its delivery system. ACS and FG showed relatively good bone regeneration capacity, satisfying the essential conditions of localization and release-control when used as BMP carriers. AAB could not provide release-control as a BMP carrier, but its space-maintenance role was remarkable. Carriers and scaffolds that can provide sufficient support to the BMP/carrier complex are necessary for large bone defects, and AAB is thought to be able to act as an effective scaffold. The CSD model of rat fibula is simple and useful for initial estimate of bone regeneration by agents including BMPs.

• 한국물환경학회지
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• 제29권1호
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• pp.29-35
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• 2013

Recently, various Best Management Practices (BMPs) have been applied at a field to reduce soil erosion. Hourly Runoff and Sediment Model for Best Management Practices (HRSM4BMP) model could be used to evaluate soil erosion reduction for various agricultural BMPs at fields. Runoff and sediment yield from source areas have to be predicted with greater accuracies to evaluate sediment reduction efficiently with BMPs. To achieve this, the best parameters related with runoff and sediment modules of the HRSM4BMP model should be identified with proper calibration processes. Although manual calibration is often utilized in calibrating runoff and sediment using the HRSM4BMP, objective calibration method would be recommended. The purpose of the study was to develop an automatic calibration tool of the HRSM4BMP model with PARASOL method. This automatic calibration tool was applied to Bangdongri, Chuncheon-si to evaluate its calibration performance. The $R^2$, NSE and RMSE value for runoff estimation were 0.92, 0.92, $0.3m^3$, and for sediment yield estimation were 0.94, 0.94, 0.0027 kg. As shown in this result, automatic calibration tool of HRSM4BMP model would be used to determine the best parameters and can be used to simulate runoff and sediment yield with acceptable accuracies.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제35권3호
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• pp.137-145
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• 2009

As an efficient controlled release system for rhBMP-2, a functional nanoparticle-hydrogel complex, incorporated with matrix metalloproteinase(MMP) sensitive peptide cross-linker, was developed and used as a bone transplant. In vivo bone formation was evaluated by soft x-ray, histology, alkaline phosphatase(ALP) activity and mineral contents analysis, based on the rat calvarial critical size defect(8mm in diameter) model. Significantly, effective bone regeneration was achieved with the rhBMP-2 loaded MMP sensitive hyaluronic acid(HA) based hydrogel-Nanoparticles(NP) complex, as compared to only MMP HA, the MMP HA-NP without rhBMP-2, or even with the rhBMP-2. These improvements included the formation pattern of bone and functional marrow, the degree of calcium quantification, and the ALP activity. These results indicate that the MMP sensitive HA with nano-particle complex can be a promising candidate for a new bone defect replacement matrix, and an enhanced rhBMP-2 scaffold.

• 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.

• Macromolecular Research
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• 제14권5호
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• pp.565-572
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• 2006

Recombinant human bone morphogenic protein-2 (rhBMP-2), which is known as one of the major local stimuli for osteogenic differentiation, was immobilized on the surface of hyaluronic acid (HA)-modified poly$(\varepsilon-caprolactone)$ (PCL) (HA-PCL) scaffolds to improve the attachment, proliferation, and differentiation of human bone marrow stem cells (hBMSCs) for bone tissue engineering. The rhBMP-2 proteins were directly immobilized onto the HA-modified PCL scaffolds by the chemical grafting the amine groups of proteins to carboxylic acid groups of HA. The amount of covalently bounded rhBMP-2 was measured to 1.6 pg/mg (rhBMP/HA-PCL scaffold) by using a sandwich enzyme-linked immunosorbant assay. The rhBMP-2 immobilized HA-modified-PCL scaffold exhibited the good colonization, by the newly differentiated osteoblasts, with a statistically significant increase of the rhBMP-2 release and alkaline phosphatase activity as compared with the control groups both PCL and HA-PCL scaffolds. We also found enhanced mineralization and elevated osteocalcin detection for the rhBMP-2 immobilized HA-PCL scaffolds, in vitro.

• 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.

• 한국물환경학회지
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• 제34권6호
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• pp.591-601
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• 2018

Optimized BMP plans for controlling water quality using the Pareto trade-off surface curve in upper basin of Namgang Dam is proposed. The proposed alternatives consist of BMP installation scenarios in which the reduction efficiency of non-point pollutants is maximized in a given budget. The multi-objective optimization process for determining the optimal alternatives was performed without direct implementation of a watershed model such as SWAT analysis, thereby reducing the time taken. The shortening of the calculation time further enhances the applicability of the multi-objective optimization technique in preparing regional water quality management alternatives. In this study, different types of BMP are applied depending on the land use conditions. Fertilizer input control and vegetative filter strip are considered as alternatives to applying BMP to the field but only control of fertilizer input can be applied to rice paddies. Fertilizer input control and vegetative filter strip can be installed separately or simultaneously in a hydrologic response unit. Finally, 175 BMP application alternatives were developed for the water quality management of the upper river basin of Namgang dam. The proposed application alternative can be displayed on the map, which has the advantage of clearly defining the BMP installation location.

• 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.

• International Journal of Oral Biology
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• 제49권2호
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• pp.48-52
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• 2024

This study explores the histological features and Bmp4 expression patterns in the replaced tooth germ of Xenopus laevis. Tooth germ formation starts from the dental placode through epithelial-mesenchymal interactions, involving various signaling pathways such as Fgf, Shh, Bmp, and Wnt. In mice, Bmp4 expression in the dental placode inhibits Pax9 expression in the dental mesenchyme. Although absent in the presumptive dental lamina of birds and toothless mammals, Bmp4 remains conserved in reptiles and fish owing to gene duplication. However, its expression in amphibian tooth germs is poorly understood. Three-month-old X. laevis were employed in this study. Initially, samples underwent paraffin embedding and were sectioned into 5 or 12 ㎛ ribbons for H&E staining and in situ hybridization, respectively. Results revealed teeth appearing in two maxillary rows: the labial side, with prefunctional and functional teeth, and the lingual side, with replaced tooth germs behind functional teeth. Enameloid was observed between the inner dental epithelium and dental mesenchyme at the cap or early bell stages, whereas enamel and dentin formed during the late bell or mineralization stages from the replaced tooth germ. Bmp4 expression was evident in the inner dental epithelium (ameloblasts), dental papilla (odontoblasts), stellate reticulum, and Hertwig's epithelial root sheath. Overall, these findings highlight the conservation of Bmp4 expression in X. laevis tooth development.