• BMB Reports
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• v.44 no.10
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• pp.619-634
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• 2011

Bone morphogenetic protein (BMP) signaling in diseases is the subject of an overwhelming array of studies. BMPs are excellent targets for treatment of various clinical disorders. Several BMPs have already been shown to be clinically beneficial in the treatment of a variety of conditions, including BMP-2 and BMP-7 that have been approved for clinical application in nonunion bone fractures and spinal fusions. With the use of BMPs increasingly accepted in spinal fusion surgeries, other therapeutic approaches targeting BMP signaling are emerging beyond applications to skeletal disorders. These approaches can further utilize next-generation therapeutic tools such as engineered BMPs and ex vivo-conditioned cell therapies. In this review, we focused to provide insights into such clinical potentials of BMPs in metabolic and vascular diseases, and in cancer.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.46 no.3
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• pp.191-196
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• 2020

Objectives: Beyond the original application approved by the U.S. Food and Drug Administration, recombinant human bone morphogenetic protein-2 (rhBMP-2) is used for medication-related osteonecrosis of the jaw (MRONJ) treatment because of its bone remodeling enhancement properties. The purpose of the study was to investigate the bone formation effect of rhBMP-2/absorbable collagen sponge (ACS) in patients with MRONJ. Materials and Methods: In this retrospective cohort study, 26 female patients diagnosed with MRONJ and who underwent mandibular sequestrectomy at Ajou University Dental Hospital from 2010 to 2018 were included. The experimental group was composed of 18 patients who received rhBMP-2/ACS after sequestrectomy, while the control group was composed of 8 patients who did not receive rhBMP-2/ACS after sequestrectomy. A total dose of 0.5 mg of rhBMP-2 was used in the experimental group at a concentration of 0.5 mg/mL. Follow-up panoramic X-rays were taken immediately after the surgery and more than 6 months after the surgery. Using those X-rays, a radiographic index of bone defect area was calculated using the modified Ihan Hren method, which measures radiographic density of the normal bone and the defect site. Results: This study suggests that rhBMP-2 contributes to new bone formation. The mean radiographic index immediately after surgery and more than 6 months after the surgery for the experimental group was 68.4% and 79.8%, respectively. The mean radiographic index immediately after surgery and more than 6 months after the surgery for the control group was 73.4% and 76.7%, respectively (Wilcoxon signed rank test, P>0.05). The mean radiographic index increased 11.4% in the experimental group and 3.27% in the control group (Mann-Whitney U-test, P<0.05). Conclusion: Based on the results, use of rhBMP-2/ACS on bone defect sites after sequestrectomy could be a successful strategy for treatment of MRONJ patients.

• Clinical and Experimental Reproductive Medicine
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• v.34 no.4
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• pp.239-252
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• 2007

Objectives: In the present study, we examined the differentiation potential of human adipose-(HAD) and human umbilical cord-derived mesenchymal like stem cells (HUC) into cardiomyocytes. Methods: Cells were initially exposed to 5-azacytidine for 24h cells and then were cultivated in the presence or absence of activin A, TGF-$\beta$1, or Wnt inhibitor with various combinations of BMP and FGF. Assessment of cardiomyogenic differentiation was made upon the expression of cardiomyocyte-specific genes using RT-PCR. Results: HAD that cultivated in control medium for 4 weeks after 5-azacytidine expose showed new expression of TnT gene and increased expression of Cmlc1 and kv4.3 genes. However, HAD cultivated in the presence of combinations of BMP-4/FGF-4 (B4/F4) and BMP-4/FGF-8 (B4/F8) showed new expression of $\beta$-MHC gene and more increased expression of Cmlc1, TnT, TnI, Kv4.3 genes. Significantly enhanced expression of Cmlc1, TnT, and Kv4.3 genes were also observed compared to that cultivated in the control medium. Treatment of HUC with either 5-azacytidine or combinations of BMP and FGF did not affect the expression profile of these genes. However, when activin A or TGF-$\beta$1 was present in addition to the BMP-2/FGF-8 (B2/F8) after 5-azacytidine exposure, HUC exhibited new expression of $\beta$-MHC gene and increased expression of $\alpha$-CA, TnT and Kv4.3 genes. When Wnt inhibitor was present in addition to BMP and FGF, HUC showed new expression of Cmlc1 gene and increased expression of $\alpha$-CA, TnT, TnI and Kv4.3 genes. Conclusions: Based on these observations, it is suggested that HAD and HUC could differentiate into cardiomyocytes which might be used as therapeutic cells for the heart diseases.

• Journal of Environmental Science International
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• v.28 no.2
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• pp.203-209
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• 2019

Organic wastewater generated from polyester manufacturing processes was selected from H company to investigate the feasibility of anaerobic digestion that produces gases including methane. Bio Methane Potential (BMP) tests were conducted to measure the gas production and methane concentration for 7 process wastewater and 2 kinds of sludges from the H company. Also, along with monitoring pH and alkalinity during the anaerobic digestion process, the concentrations of COD and 1,4-dioxane were measured with 4 different operating conditions for N Emulsion (NE) and Ethylene Glycol (EG) wastewater. The BMP tests showed that 65% of methane was produced from NE and EG wastewater. This suggests that the organic wastewater from H company can be effectively treated by an anaerobic digester by which more than 90% of COD was removed.

• The Journal of the Korean dental association
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• v.53 no.5
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• pp.348-359
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• 2015

Objective: The aim of this study was to determine the effect of multi-layer of a collagen membrane alone or loaded rhBMP-2 on the buccal plate for ridge preservation after tooth extraction. Material and methods: Following bilateral extraction of the maxillary 1st and 3rd premolars in five dogs, rhBMP-2 loaded collagen membrane was applied to the buccal plates at the 1st premolar and collagen membrane only was applied to the buccal plates at the 3rd premolar unilaterally. The collagen membranes applied in the experimental groups were piled into four layers. The corresponding sites of the contralateral side healed naturally. After 3months of healing, the animals were sacrificed. Radiographic and histologic analyses were performed. Results: There was no significant difference in the healing of extraction socket at both 1st and 3rd premolars. In microcomputed tomography, the widths of the residual ridge of the experimental groups were similar with the controls. Histologically, the experimental groups did not exhibit different pattern compared to the controls regardless of the addition of rhBMP-2. Conclusion: Layering of the collagen membrane with or without rhBMP-2 on the buccal plate failed to show the effectiveness in dimensional preservation of the extraction socket.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.27 no.1
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• pp.16-23
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• 2005

It is commonly acknowledged that bone morphogenic protein (BMP-2) functions as a potential osteogenic inducer in bone formation. Recently, several papers reported that bone marrow-derived stem cell (BMSC) from human is not responsive to BMP-2 in comparison to high capacity of BMP-2 in the osteoinduction of stromal cell derived from bone marrow of rodent animals such as rat or mouse. In this study, we characterized BMSC derived from 11 years old donor for the responsiveness to rhBMP-2, dexamethasone (Dex) and 1,25-dihydroxyvitamin D (vitamin D), in order to analyze their function in the early osteogenesis. The effect of over mentioned agents was evaluated by means of assessing alkaline phosphatase (ALP) activity/staining, RT-PCR analysis and von Kossa staining. In addition, we analyzed the meaning of expressed several osteoblastic markers such as alkaline phosphatase, collagen typeI, osteopontin, bone sialoprotein and osteocalcin with relation to either differentiation or mineralization. Only in the presence of Dex, human BMSC could commit osteoblastic differentiation and matrix mineralization, and either BMP-2 or vitamin D treatment was not able to induce. But BMP-2 or Vitamin D showed potential synergy effect with Dex. ALP and bone sialoprotein were clearly expressed in response of Dex treatment compared to weak expression of osteopontin in early osteogenesis. Therefore, we expect that this study will contribute partly to elucidiating early osteogenesis mechanism in human, but variations among bone marrow donors must be considered through further study.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.32 no.4
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• pp.317-326
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• 2006

Purpose : The aim of this study was to evaluate the effect of recombinant human bone morphogenetic protein-7 (rhBMP-7) injected on the rate of new-bone formation for distraction osteogenesis on dogs. Materials & Methods : Twelve adult dogs were randomly selected into two groups of six dogs on each. Unilateral osteotomies were performed on the body of the mandible and an intraoral distractor was mounted to the mandible on dogs. One group was treated with injection of rhBMP-7 and the other group served as the control. RhBMP-7 was administered on the day of surgery by single injection into the medullary bone at the osteotomy gap. Distraction was performed five days after osteotomy as a rate of 0.5 mm twice per day for 10 days. The animals were then sacrificed at 2, 4, and 8 weeks after completion of the distraction. Two dogs in each group, totaling four dogs, were killed at 2 weeks, 4 weeks, and 8 weeks after completion of distraction, respectively. The lengthened mandibles were harvested and processed for radiographic and histological examinations. In addition, immunohistochemical examination using osteocalcin expression was studied. Results : Radiographs showed accelerated regenerate ossification with maturation of new bone in the rhBMP-7 group comparing with the control group at the 4 weeks of the consolidation. There was no significant difference in the radiographic findings at the 2 weeks and 8 weeks of the consolidation period. Histological findings demonstrated increased bone healing pattern in the rhBMP-7-treated group during all observation period. The expression of osteocalcin immunoreactivity was hardly detected in the normal mandible of dog, but the expression was detected in all experimental rhBMP-7 treated specimens. There were also significant increasing in number of positive immunostaining cells and staining intensity of osteocalcin expression in the rhBMP-7 treated group compared with those of the control group on 2-weeks and 4-weeks. There was a significant decreasing in staining intenstiy of all both two groups on 8 weeks of consolidation period, but significant differences of immunostaining was not seen in two groups. Conclusions : A single injection of rhBMP-7 at the time of osteotomy may stimulate the rate of regenerate ossification and increase callus maturation during distraction osteogenesis. In addition, it may shorten the distraction osteogenesis procedure and decrease the prevalence of complications associated with mandibular distraction osteogenesis.

• Molecules and Cells
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• v.22 no.3
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• pp.353-359
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• 2006

The bone morphogenetic protein (BMP) family has been implicated in control of cartilage development. Here, we demonstrate that BMP-2 promotes chondrogenesis by activating p38 mitogen-activated protein kinase (MAPK), which in turn downregulates $Wnt-7a/{\beta}$-catenin signaling responsible for proteasomal degradation of Sox9. Exposure of mesenchymal cells to BMP-2 resulted in upregulation of Sox9 protein and a concomitant decrease in the level of ${\beta}$-catenin protein and Wnt-7a signaling. In agreement with this, the interaction of Sox9 with ${\beta}$-catenin was inhibited in the presence of BMP-2. Inhibition of the p38 MAPK pathway using a dominant negative mutant led to sustained Wnt-7a signaling and decreased Sox9 expression, with consequent inhibition of precartilage condensation and chondrogenic differentiation. Moreover, overexpression of ${\beta}$-catenin caused degradation of Sox9 via the ubiquitin/26S proteasome pathway. Our results collectively indicate that the increase in Sox9 protein resulting from downregulation of ${\beta}$-catenin/Wnt-7a signaling is mediated by p38 MAPK during BMP-2 induced chondrogenesis in chick wing bud mesenchymal cells.

• Journal of Periodontal and Implant Science
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• v.25 no.3
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• pp.623-634
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• 1995

Periodontitis is characterized by gingival inflammation and results in periodontal pocket formation with loss of the supporting alveolar bone and connective tissue around the teeth. Therapeutic modalities should therefore aim not only at eliminating the gingival inflammatory process and preventing the progression of periodontal disease but also at reestablishing and regenerating the periodontal tissue previously lost to the disease. To achieve periodontal regeneration, progenitor cells must migrate to the denuded root surface, attach to it, proliferate and mature into an organized and functional fibrous attachment apparatus. Likewise, progenitor bone cells must also migrate, proliferate, and mature in conjunction with the regenerating periodontal ligament. Significant advances have been made during the last decade in understanding the factors controlling the migration, attachment and proliferation of cells. A group of naturally occuring molecules known as polypeptide growth factors in conjunction with certain matrix proteins are key regulators of these biological events. Of these, the fibroblast growth factor(FGF), platelet-derived growth factor(PDGF) , insulin like growth factor(CIGFs), transforming growth factor(TGFs), epidermal growth factor(EGF) and bone morphogenetic growth factor(BMPs) apper to have an important role in periodontal wound healing. The purpose of this study was to determine the effects of BMP on periodontal ligament cells. Human periodontal ligament cells were cultured from extracted tooth for non-periodontal reason. Cultured periodontal ligament cells were treated with BMP. Cellular activities were determined by MTT(3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide) assay and ALP(alkaline phosphatase) activity. The results were as follows ; Regardless of cultured time, cellular activities were stimulated by BMP. Also, BMP greatly increased alkaline phosphatase(ALP) in periodontal ligament cells. These results suggest that BMP not only have no cytotoxic effect on periodontal ligament cells, but also have osteogenic stimulatory effect on periodontal ligament cells.

• Journal of Korean Society on Water Environment
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• v.29 no.1
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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.