• Asian Pacific Journal of Cancer Prevention
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• v.14 no.9
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• pp.5293-5299
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• 2013

Purpose: High levels of bone morphogenetic protein (BMPs) have been reported in patients with lung cancer. This study was conducted to assess correlations between serum BMP-2 levels and prognostic outcome in patients with non-small-cell lung cancer (NSCLC). Methods: Blood samples from 84 patients with advanced NSCLC and 42 healthy controls were analyzed and quantitated for serum BMP-2 levels before and after two cycles of chemotherapy using a commercially available ELISA kit. Results: The median level of BMP-2 was 146.9 pg/ml in patients with NSCLC vs. 87.7 pg/ml in healthy controls (P<0.01). A significant correlation was observed between pretreatment serum BMP-2 level and ECOG PS, disease stage and number of organs with metastases (P<0.05). Serum BMP-2 level decreased significantly in patients who achieved objective response after two cycles of chemotherapy. Multivariate analysis showed that increased BMP-2 level and advanced clinical stage were significantly correlated with poor prognosis. Conclusion: Thes erum BMP-2 level is positively correlated with clinical stage, ECOG PS and metastatic burden and may serve as an independent negative predictor for prognosis. Decreased BMP-2 after chemotherapy could be a reliable marker for efficacy of treatment.

• 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.

• Proceedings of the Korea Water Resources Association Conference
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• 2016.05a
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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.

• Journal of Dental Rehabilitation and Applied Science
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• v.40 no.1
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• pp.13-23
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• 2024

Purpose: This aim of this study was to demonstrate growth factors that differentiate human mesenchymal stem cells into chondrocytes and to evaluate cell proliferation enhancement by needle size differences. Materials and Methods: Human mesenchymal stem cells were cultured in chondrogenic medium supplemented with BMP-2, BMP-4, BMP-6, BMP-7, BMP-13, FGF-2, FGF-18, IGF-1, TGF-β1, TGF-β2, TGF-β3 and without growth factors for 14, 21, and 28 days. Then, the expression levels of SOX-5, SOX-6, SOX-9 and FOXO1A were comparatively analyzed. Human mesenchymal stem cells were inoculated into culture dishes using 18, 21, and 26 gauge (G) needles, and cell proliferation was measured after 24, 48, and 72 hours, respectively. Results: In addition to the previously known FGF, IGF-1, and TGFβ1,the BMP family growth factors such as BMP-2, BMP-4, BMP-6, and BMP-7 increased the expression of chondrocyte differentiation genes SOX-5, SOX-6, SOX-9, and FOXO1A. At 48 hours, the 26G group, the smallest needle, showed significant cell proliferation improvement compared to the control group and the 18G group. At 72 hours, the 26G group, the smallest needle, showed significant increase in cell proliferation compared to the control group. Conclusion: Through this study, growth factors with the ability to induce chondrocyte differentiation of human mesenchymal stem cells were investigated, and cell proliferation changes by needle size differences were determined.

• International Journal of Industrial Entomology and Biomaterials
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• v.34 no.1
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• pp.1-5
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• 2017

Bone morphogenetic protein 2 (BMP2) plays an important role in the development of bone and cartilage. It is involved in the hedgehog pathway, TGF beta signaling pathway, and in cytokine-cytokine receptor interaction. It is involved also in cardiac cell differentiation and epithelial to mesenchymal transition. In this study, We expressed human BMP2 (hBMP2) recombinant protein using Baculovirus Expression Vector System (BEVS) in Sf9 insect cells. The hBMP2 cDNA was cloned into baculovirus transfer vector, pBacgus-4x-1 and recombinant baculovirus was screened out through X-gal and GUS-fusions assay. Western blot analysis shown that molecular weight of hBMP2 recombinant protein was about 44.71 kDa.

• Journal of Korean Neurosurgical Society
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• v.65 no.6
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• pp.825-833
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• 2022

Objective : ABM/P-15 (anorganic bone matrix/15-amino acid peptide fragment) is a commercially available synthetically manufactured P-15 collagen peptide fragment, that is adsorbed on ABM. This study was done to investigate the efficacy of ABM/P-15 in achieving fusion in the lumbar spine and comparing it with that of recombinant bone morphogenic protein-2 (rhBMP-2) and demineralized bone matrix (DBM). Methods : A retrospective observational study of prospectively collected data of 140 patients who underwent lumbar spinal fusion surgeries in a single specialty spine hospital between 2016 and 2020, with a minimum 6-month follow-up was conducted. Based on the material used for the augmentation of the bone graft at the fusion site, the patients were divided into three categories namely ABM/P-15, rhBMP-2, and DBM group. Results : ABM/P-15, rhBMP-2, and DBM were used in 46, 44, and 50 patients, respectively. Patient characteristics like age, gender, bone mineral density, smoking history, and presence of diabetes mellitus were comparable amongst the three groups. Average follow-up was 16.0±5.2, 17.9±9.8, and 26.2±14.9 months, respectively in ABM/P-15, rhBMP-2, and DBM groups. The fusion was achieved in 97.9%, 93.2%, and 98% patients while the average time-to-union was 4.05±2.01, 10±4.28, and 9.44±3.49 months (p<0.001), respectively for ABM/P-15, rhBMP-2, and DBM groups. The average pre-operative Visual analogue scale score was 6.93±2.42, 7.14±1.97, 7.01±2.14 (p=0.900) for ABM/P-15, rhBMP-2 and DBM groups, respectively, which reduced to 1.02±0.80, 1.21±0.96, and 0.54±0.70 (p=0.112), respectively at the last follow up. Pre-operative Oswestry disability index scores were 52.7±18.02, 55.4±16.8, and 53.56±19.6 (p=0.751) in ABM/P-15, rhBMP-2, and DBM groups, which post-operatively reduced to 33.77±15.52, 39.42±16.47, and 38.3±15.89 (p=0.412) and further to 15.74±8.3, 17.41±10.45, and 16.76±9.81 (p=0.603), respectively at the last follow-up. Conclusion : ABM/P-15 appears to achieve union significantly earlier than rhBMP-2 and DBM in lumbar spinal fusion cases while maintaining a comparable clinical and complication profile.

• International Journal of Stem Cells
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• v.15 no.2
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• pp.144-154
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• 2022

Background and Objectives: Neural stem cells (NSCs) remain in the mammalian brain throughout life and provide a novel therapeutic strategy for central nervous system (CNS) injury. Bone morphogenetic protein-6 (BMP-6) had shown a protective effect in different types of cells. However, the role of BMP-6 in NSCs is largely unclear. The present study was aimed to investigate whether BMP-6 could protect human NSCs (hNSCs) against the oxygen and glucose deprivation (OGD)-induced cell death. Methods and Results: Upon challenge with OGD treatment, cell viability was significantly decreased in a time-dependent manner, as indicated by the CCK-8 assay. BMP-6 could attenuate the OGD-induced cell injury in a dose-dependent manner and decrease the number of TUNEL-positive cells. Moreover, BMP-6 markedly weakened the OGD-induced alterations in the expression of procaspase-8/9/3 and reversed the expression of cleaved-caspase-3. Interestingly, noggin protein (the BMP-6 inhibitor) attenuated the neuroprotective effect of BMP-6 in cultured hNSCs. Furthermore, the p38 MAPK signaling pathway was activated by OGD treatment and BMP-6 markedly inhibited the phosphorylation of p38 in a concentration-dependent manner. Pretreatment with noggin abolished the effect of BMP-6 on p38 activation. SB239063, a selective p38 inhibitor, exerted similar effects with BMP-6 in protecting hNSCs against the OGD-induced apoptosis. These results indicated that blocking the phosphorylation of p38 might contribute to the neuroprotective effect of BMP-6 against the OGD-induced injury in hNSCs. Conclusions: These findings suggested that BMP-6 might be a therapeutic target in the OGD-induced cell death, which provides a novel therapeutic strategy for enhancing host and graft NSCs survival in hypoxic-ischemic brain injury.

• Journal of Periodontal and Implant Science
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• v.35 no.2
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• pp.263-269
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• 2005

Bone morphogenetic protein(BMP) and platelet-derived growth factor(PDGF) have been demonstrated tostimulate bone formation when applied locally in vivo. To explore whether or not the combined use of BMP and PDGF could have promotive effect and synergic interaction on bone formation in vivo, bone marrow mesenchymal stem cells were treated with BMP-2, PDGF-BB, or BMP-2 plus PDGF-BB, and then these cells were injected into the subcutaneous space on the dorsum of nude mice. The bone formation was evaluated after 12 weeks. Histomorphometric analysis demonstrated that the subcutaneous nodules formed in nude mice contained 25.3% newly formed bone in the BMP-2 treated cells, 14.4% newly formed bone in the PDGF-BB treated cells, and 8.9% newly formed bone in the RMP-2 plus PDGF-BB treated cells. The results showed that the combination of BMP-2 and PDGF-BB had neither a promotive effect nor synergic interact on bone formation in vivo.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.37
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• pp.16.1-16.7
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• 2015

Background: This study aimed to investigate new bone formation using recombinant human bone morphogenetic protein 2 (rhBMP-2) and locally applied bisphosphonate in rat calvarial defects. Methods: Thirty-six rats were studied. Two circular 5 mm diameter bony defect were formed in the calvaria using a trephine bur. The bony defect were grafted with $Bio-Oss^{(R)}$ only (group 1, n = 9), $Bio-Oss^{(R)}$ wetted with rhBMP-2 (group 2, n = 9), $Bio-Oss^{(R)}$ wetted with rhBMP-2 and 1 mM alendronate (group 3, n = 9) and $Bio-Oss^{(R)}$ wetted with rhBMP-2 and 10 mM alendronate (group 4, n = 9). In each group, three animals were euthanized at 2, 4 and 8 weeks after surgery, respectively. The specimens were then analyzed by histology, histomorphometry and immunohistochemistry analysis. Results: There were significant decrease of bone formation area (p < 0.05) between group 4 and group 2, 3. Group 3 showed increase of new bone formation compared to group 2. In immunohistochemistry, collagen type I and osteoprotegerin (OPG) didn't show any difference. However, receptor activator of nuclear factor ${\kappa}B$ ligand (RANKL) decreased with time dependent except group 4. Conclusion: Low concentration bisphosphonate and rhBMP-2 have synergic effect on bone regeneration and this is result from the decreased activity of RANKL of osteoblast.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.30 no.3
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• pp.193-202
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• 2004

Distraction osteogenesis(DO) is defined as a gradual mechanical process of mechanical stretching two vascularized bone surface apart with a critical rate and rhythm such that new bone forms within the expanding gap, reliably bridges the gap, and ultimately remodels to normal structure. DO has become a mainstay in bone tissue engineering and has significantly improved our armamentarium for reconstructive craniomaxillofacial procedures. But the molecular and biological mechanisms that regulate the formation of new bone during distraction osteogenesis are not completely understood. BMPs are potent osteoinductive agents. Our hypothesis was that BMPs, especially BMP-2 and BMP-4, might play an importent role in the signaling pathways that link the mechanical forces created by distraction to biological responses and in promting new bone formation. Using a rabbit's mandible, we investigated the expression of BMP-2, -4 at different time points during distraction osteogenesis. The purpose of this study is to research the pattern of expression of BMP-2, -4 in new bone formation during distraction osteogenesis of the rabbit mandible. The experimental group was applied gradual distraction (0.7mm a day by twice a day, 4.9mm in total, for 7 days) and the control group was carried out osteotomy alone. They were examined clinically, histologically, and by RT-PCR analysis. On 3 days after osteotomy, the high level of expression of BMP-2, -4 was detected. But, the expression of BMP-4 was decreased during latency period. As distraction was started, its expression was increased and maintained till postoperative 28days. In control group, the expression of BMP-4was remarkably decreased till postoperative 14 days. On the other hand, the expression of BMP-2 was no difference between experimental group and control group. The expression of BMP-4 was maintanined at high level during the entire experimental period in both group. These findings suggested that excellent bone formation during distraction osteogenesis is associated with enhanced expression of BMP-4 genes by mechanical tension stress.