• Journal of Periodontal and Implant Science
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• 제39권1호
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• pp.77-86
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• 2009

Purpose: Recombinant human bone morphogenetic protein-2(rhBMP-2) has been evaluated as potential candidates for periodontal and bone regenerative therapy. In spite of good prospects in BMP applications, there is economically unavailable for clinical use in dental area. The purpose of this study was to evaluate the osteogenic effect of rhBMP-2 produced by E.coli expression system. Materials and methods: Eight-mm critical-size calvarial defects were created in 48 male Sprague-Dawley rats. The animals were divided into 6 groups of 8 animals each. Each group received one of the following: Negative control(sham-surgery control), positive control(absorbable collagen sponge(ACS) alone) and experimental(ACS loaded with rhBMP-2). Defects were evaluated by histologic and histometric parameters following 2- and 8-week healing intervals. Results: The experimental group showed significant defect closure at 2 and 8weeks than the sham surgery and positive control groups. Moreover, the experimental group showed significantly greater new bone and augmented area than the other groups at both 2 and 8weeks. Conclusion: rhBMP-2 produced by E.coli expression system may be effective for bone regeneration.

• Maxillofacial Plastic and Reconstructive Surgery
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• 제36권3호
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• pp.94-102
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• 2014

Purpose: This study aims to validate the effect of autoclaved autogenous bone (AAB), incorporating Escherichia coli-derived recombinant human bone morphogenetic protein-2 (ErhBMP-2), on critical-sized, segmental radius defects in rabbits. Delivery systems using absorbable collagen sponge (ACS) and fibrin glue (FG) were also evaluated. Methods: Radius defects were made in 12 New Zealand white rabbits. After autoclaving, the resected bone was reinserted and fixed. The animals were classified into three groups: only AAB reinserted (group 1, control), and AAB and ErhBMP-2 inserted using an ACS (group 2) or FG (group 3) as a carrier. Animals were sacrificed six or 12 weeks after surgery. Specimens were evaluated using radiology and histology. Results: Micro-computed tomography images showed the best bony union in group 2 at six and 12 weeks after operation. Quantitative analysis showed all indices except trabecular thickness were the highest in group 2 and the lowest in group 1 at twelve weeks. Histologic results showed the greatest bony union between AAB and radial bone at twelve weeks, indicating the highest degree of engraftment. Conclusion: ErhBMP-2 increases bony healing when applied on AAB graft sites. In addition, the ACS was reconfirmed as a useful delivery system for ErhBMP-2.

• Journal of Periodontal and Implant Science
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• 제30권4호
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• pp.757-779
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• 2000

The aim of our study is to achieve complete periodontal tissue regeneration by the application of BMP and resorbable membrane. Three beagle dogs aged over one and half years and weighed 14 to 16 kg were used in this study. Mandibular 1st, 2nd premolars were extracted bilaterally. Horizontal furcation defects were induced around 3rd, 4th premolars bilaterally. BMP-4 were applied in the right side with resorbable membranes and only resorbable membranes were applied in the left side respectively. Each animal was sacrificed at 2, 4, and 8weeks, after regenerative surgery. Specimens were prepared with Hematoxylin-Eosin stain and Goldner's modified Masson Trichrome stain for light microscopic evaluation. The results were as follows: 1. At 2 weeks after regenerative surgery, downgrowth of junctional epithelium was observed both in the membraneapplied site and BMP-4-and-membrane-applied site. 2. At 4 weeks after regenerative surgery, resorbable membranes were completely resolved, therefore would not prevent downgrowth of junctional epithelium. New bone formation, new cementum formation and Sharpey's fiber were observed in BMP-4-andmembrane-applied site. 3. At 8 weeks after regenerative surgery, downgrowth of junctional epithelium was observed in the membrane-applied site. But, new cementum formation was observed in the same site. The extensive regeneration of new bone, new cementum and remarkable formation of Shapey's fiber were showed in BMP-4-and-membrane-applied site. 4. Resorbable membranes were resolved via the cell-mediated processes. 5. Periodontal tissue regeneration were better achieved in the BMP-4-andmembrane-applied site than in the membrane-applied site. Within the above results, BMP-4 may have the strong capability to form the new bone and resorbable membrane may be able to prevent the bony ankylosis. However, resolution rate of resorbable membrane may not be enough to protect rapid epithelial downgrowth for ideal periodontal regeneration. In conclusion, I suggest BMP-4 may have the strong possibility to be utilized in the clinical periodontal treat-

• The Korean Journal of Physiology and Pharmacology
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• 제17권5호
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• pp.447-453
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• 2013

Osteoblastic activity of nectandrin A was examined in C2C12 cells. Nectandrin A enhances the BMP-induced osteoblastic differentiation and mineralization, manifested by the up-regulation of differentiation markers (alkaline phosphatase and osteogenic genes) and increased calcium contents. In C2C12 cells co-transfected with expression vector encoding Smad4 and Id1-Luc reporter, nectandrin A increased Id1 luciferase activity in a concentration-dependent manner, when compared to that in BMP-2 treated cells, indicating that Smad signaling pathway is associated with nectandrin A-enhanced osteoblastic differentiation in C2C12 cells. In addition, nectandrin A activated p38 mitogen-activated protein kinase (MAPK) in time- and concentration-dependent manners, and phosphorylated form of pSmad1/5/8 and alkaline phosphatase activity were both decreased when the cells were pretreated with SB203580, a p38 MAPK inhibitor, suggesting that p38 MAPK might be an upstream kinase for Smad signaling pathway. Taken together, nectandrin A enhances the BMP-induced osteoblastic differentiation and mineralization of C2C12 cells via activation of p38 MAPK-Smad signaling pathway, and it has a therapeutic potential for osteoporosis by promoting bone formation.

• Archives of Plastic Surgery
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• 제37권3호
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• pp.207-212
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• 2010

Purpose: The object of this study is to develop a novel BMP-2 delivery system for continuous osteogenic differentiation and to induce osteogenesis of stem cells using a bi-phase alginate carrier in vitro. Methods: Alginate nanoparticle loaded BMP-2 was prepared by the reverse emulsification-diffusion technique. Physical properties and release profiles of alginate carriers were measured by Instron and ELISA kit, respectively. Cell viability and alkaline phosphate activity of hBMSCs differentiation was also evaluated by MTS and Metra BAP assays, respectively. Results: Optimal concentration for bi-phase alginate carrier was determined as 2 wt% by evaluating mechanical and biological properties, and differentiation of BMSCs for bone regeneration. The 2% bi-phase alginate carrier had the lowest initial and final release ratio. In addition, the 2% bi-phase alginate carrier had a little higher ALP activity than the homogeneous carrier. An improved controlled release profile was obtained by combining alginate hydrogel with lyophilized particles. Conclusion: Bi-phase alginate carrier has many advantages such as biocompatibility and controlled release capability. It is expected to be effective as a scaffold and carrier in bone tissue engineering.

• Asian Pacific Journal of Cancer Prevention
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• 제17권7호
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• pp.3527-3531
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• 2016

Recombinant human bone morphogenetic protein-2 (rhBMP-2 ), a member of the TGF-${\beta}$ family, has been used widely in recent years to regenerate defects of the maxillary and mandible bones. Such defects are sometimes caused by resection of oral squamous cell carcinoma (OSCC) yet the biologic effects of rhBMP-2 on these carcinomas are not fully clear. The objective of this study was to determine histologically whether rhBMP-2 produces adverse effects on angiogenesis during induction of OSCC, a biologic process critical for tumor formation in an experimental model in the buccal pouch of golden Syrian hamsters. Buccal cavities were exposed to painting with 0.5% DMBA in liquid paraffin three times a week for 14 weeks, then biopsies were taken. Division was into 2 groups: a study group of 10 hamsters receiving $0.25{\mu}g/ml$ of rhBMP-2 in the $3^{rd}$ and $6^{th}$ weeks; and a control group of 10 hamsters which did not receive any additional treatment. VEGF expression and microvessel density were measured but no differences were noted between the two groups. According to this study, rh-BMP-2 does not stimulate angiogenesis during induction of OCSSs.

• 한국콘텐츠학회논문지
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• 제10권3호
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• pp.196-203
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• 2010

본 연구는 BMP-4의 발현을 통해 골절 후 골유합에 대한 미세전류의 효과를 관찰하였다. 실험동물은 체중 2.5~3 kg내외의 6개월 령 뉴질랜드 웅성 토끼 24마리를 사용하였으며 경골 골절 후 미세전류를 적용한 실험군과 비적용군인 대조군으로 나누었고, 시간경과에 따른 변화를 관찰하기 위하여 3일, 7일, 14일 및 28일군으로 나누어 BMP-4에 대한 면역조직화학적 염색을 실행하여 다음과 같은 결론을 얻었다. BMP-4의 발현은 미세전류를 적용한 실험군과 자연치유군인 대조군 모두 시간이 경과함에 따라 증가하다가 감소되었다. 그러나 골절 7일 후 까지 동일 시점에서 실험군이 대조군에 비해 더욱 강한 면역양성 반응을 보였다. 특히 경골 골절 7일 후 대조군은 하버씨계의 동심원과 간질층판을 중심으로 중등도의 갈색의 면역양성반응을 보인데 반해 실험군의 경우 바깥층판을 포함하여 매우 강한 갈색의 면역양성반응을 보였다. 위의 결과로 보면 골절 후 미세전류를 적용할 때 치유과정 초기에 골형성단백질인 BMP-4의 발현을 증가시켜 골절 치유를 촉진시킴을 알 수 있었다.

• 대한치과보철학회지
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• 제46권3호
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• pp.307-319
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• 2008

STATEMENT OF PROBLEM: It is known that an anodic oxidation technique, one of the methods for the implant surface treatment, remarkably increased surface area, enhanced wettability and accelerated the initial bone healing. Purpose: This study was performed to evaluate the wettability of anodized titanium surface which has a nanotubular structure, to assess osseointegration after the placement of implant with nano-size tubes on tibia of rats and to analyze quantitatively transferable rhBMP-2 on each surface. MATERIAL AND METHOD: Four different kinds of surface-treated titanium discs (polished (machined surface) group, micro (blasting surface) group, nano (anodizedmachined surface) group, and nano-micro (anodized-blasting surface) group) were fabricated (n=10). Three different media were chosen to measure the surface contact angles; distilled water, plasma and rhBMP-2 solution. After a single drop (0.025 $m{\ell}$) of solution, the picture was taken with the image camera, and contact angle was measured by using image analysis system. For the test of osseointegration, 2 kinds of anodized surface (anodized-machined surface, anodized-blasting surface) implants having 2.0 mm in diameter and 5.0 mm in length inserted into the tibia of Wistar rats. After 3 weeks, tibia were harvested and the specimens were stained with hematoxylin and eosin for histological analysis. To test the possibility of drug delivery, after soaking sample groups in the concentration of 250 ng/$m{\ell}$l of rhBMP-2 for 48 hours, the excess solution of rhBMP-2 were removed. After that, they were lyophilized for 24 hours, and then the rhBMP-2 on the surface of titanium was resolved for 72 hours in PBS. All the extracted solution was analyzed by ELISA. One-way analysis of variance (ANOVA) was performed on the data. RESULTS: The wettability is improved by anodic oxidation. The best wettability was shown on the nano-micro group, and it was followed by nano group, micro group, and polished group. In the histological findings, all implants showed good healing and the new bone formation were observed along the implant surface. After 3 days, nano-micro group delivered the most amount of rhBMP-2, followed by nano group, micro group, and polished group. CONCLUSION: It indicated that anodic oxidation on blasting surface produce functionally graded nano-micro porous structure and enhance hydrophilicity of the surface and osseointegration. The findings suggest that the nano-micro porous structure could be a useful carrier of osteogenic molecules like rhBMP-2.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제34권2호
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• pp.119-130
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• 2008

Absorbable atelo-collagen sponge $TERUPLUG^{(R)}$, Termo Co. Tokyo, Japan) is inserted in the extraction wound where alveolar bone is exposed. It protects wounds and promotes the formation of granulation. This is made of atelo-collagen, to minimize antigenicity, which is cross-linked by heat treatment for biocompatibility. $TERUPLUG^{(R)}$ consists of between 85 and 95 % of collagen type I and between 5 to 15 % of collagen type III. The raw material for the collagen is derived from bovine skin. It features a sponge block design and is shaped for easy insertion in the extraction wound. This study was designed to find out the bone healing capacity of $TERUPLUG^{(R)}$. We implanted $TERUPLUG^{(R)}$ (experimental group I) and $TERUPLUG^{(R)}$ with rhBMP-2 (experimental group II) in the rabbit cranium defect and then histologically analysed the specimen. The results were as follows. 1. In the 4 weeks, a lot of the newly formed collagen fibers around material of the experimental group I implanted $TERUPLUG^{(R)}$ were observed. But, in the experimental group II implanted $TERUPLUG^{(R)}$ with rhBMP-2, a little of newly formed collagen fibers around material were observed. The cell proliferating activity and apoptosis of the experimental group I, II was positive in and around the implanted material. 2. In the 8 weeks, the amount of newly formed and matured bone in the experimental group II was more observed than the experimental group I and control group. The results of this study indicate that absorbable atelo-collagen sponge ($TERUPLUG^{(R)}$) is relatively favorable bone void filler with biocompatibility and has the better bone healing capacity in case of application with rhBMP-2.

• 한국식품저장유통학회지
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• 제23권2호
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• pp.259-266
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• 2016

본 연구에서는 기능성이 밝혀져 있는 여주 분말을 첨가하여 쌀누룩을 제조하고 이 누룩을 이용하여 막걸리를 제조하였다. 여주 분말-쌀누룩(BMP-RN)은 BMP를 0, 0.5, 1.0 및 2.0%로 쌀에 첨가하여 제조하였고, 막걸리 발효가 진행되는 동안 발효 특성, 미생물 특성 및 항산화 특성을 확인하였다. 막걸리 발효 중 pH는 담금 직후(발효 0일째) 각각 4.52(0% BMP-RN), 4.93(0.5%), 4.80(1.0%) 및 4.88(2.0%)에서 발효 7일째 4.15, 4.30, 4.57 및 4.77로 감소하였고, 이에 상응하여 총산은 0.60~0.78%에서 1.18-1.42%로 증가하였다. 가용성 고형분은 발효 초기(0일째) $2.2{\sim}4.4^{\circ}Brix$에서 발효 종기(7일째) $8.6{\sim}9.3^{\circ}Brix$로 증가하였고 알코올 함량은 발효 종기 13.0%로 증가하였다. 한편, 수용성 phenolics 함량은 발효 0일째 각각 0.92~1.41 mg/mL에서 발효 종기(7일째) 1.85~2.48 mg/mL로 증가하였고 이에 상응하여 DPPH와 ABTS 라디칼 소거활성 및 FRAP 환원력은 각각 발효 0일째 46.95~70.04%, 55.33~74.13% 및 0.629~1.243에서 발효 7일째 54.98~83.4%, 70.34~92.39% 및 0.964~1.455로 증가하였다. 여주 분말 첨가 막걸리가 여주 분말 무첨가 막걸리(일반 막걸리)보다 수용성 phenolics 및 항산화 활성이 높았다. 이 결과로 여주-쌀누룩을 이용하여 기능성 막걸리 제조가 가능할 수 있을 것으로 판단되었다.