• Imaging Science in Dentistry
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• 제34권1호
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• pp.35-48
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• 2004

Purpose: To investigate the effect of rhBMP-2 on the healing of bone defect in the low calcium diet rat. Materials and Methods: To prepare the experimental model, control group was fed a normal diet and experimental group was fed a low calcium diet for 3 weeks. And then, 4 mm bicortical perforated bone defect was made on mandibular body of each rats. Experimental group was subdivided into two groups; experimental group 1 (rats given a low calcium diet before and after bone defect) and experimental group 2 (rats given a low calcium diet before and after bone defect with rhBMP-2 application). At 1, 3, 5 and 7 weeks after bone defect formation, the rats were terminated. The healing of bone defect was assessed by three-dimensional computerized tomography, soft x-ray radiography, and histopathological examination. Results : The wound healing of the bone defect for control group, experimental group 1, and experimental group 2 showed a increase from 3 weeks after bone defect formation. The experimental group 2 showed a more increase in healing amount than control group and experimental group 1 from 5 weeks after bone defect formation and the experimental group 2 showed a complete recovery of bone defect at 7 weeks after bone defect formation. Conclusion: The healing process of bone defect is accelerated by rhBMP-2 application in the low calcium diet rats.

• Journal of Periodontal and Implant Science
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• 제37권sup2호
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• pp.397-407
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• 2007

골형성 유도 단백질(bone morphogenetic protein, BMP)은 성장이나, 골형성과정에서 중용한 역할을 한다고 입증되었고 그것의 운반체에 대한 연구가 이뤄져 왔다. 하지만 수직압이 존재하는 곳에서 골증대술에 적용할 수 있을 만큼 강한 공간유지능력이 있는 운반체에 대한 연구는 그리 많지 않았다. Macroporous biphasic calcium phosphate block (MBCP block)은 공간유지능력이 뛰어나며 강한 수직압을 견딜수 있는 골대체물질이다. 이 연구의 목적은 MBCP block을 골형성유도 단백질(rhBMP-2)의 운반체로 사용하여 백서 두개골 결손부에 적용하였을 때, 골 형성 효과를 평가하는 것이다. 36마리의 웅성백서에서 8mm 지름을 갖는 임계크기의 두 개부 결손을 형성하였다. 20마리씩 2개의 군으로 나누어 MBCP block만 이식한 군, MBCP block을 운반체로 사용하여 농도 0.025mg/ml rhBMP-2를 이식한 군으로 나누어 술 후 2주와 8주에 치유결과를 조직학적, 조직계측학적으로 비교 관찰 하였다. 조직계측학적 관찰 결과, rhBMP-2/MBCP block 군에서 MBCP block군에서 보다 2, 8주 모두 골밀도(bone density)가 유의성있게 증가하였다 (P<0.01). 각 군에서도 8주째가 2주째보다 골밀도가 유의성있게 증가하였다(P<0.01). 총조직 형성량 (augmented area)에서는 변화가 없었다. 이 연구 결과, 백서 두개골 결손부에서 MBCP block은 rhBMP의 운반체로 사용하였을 때 신생골 형성에 유의한 효과가 있을뿐 아니라 공간유지능력이 우수해서 수직압이 존재하는 골증대술(bone augmentation)시 rhBMP의 운반체로 가능성이 있다고 사료된다.

• Journal of Periodontal and Implant Science
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• 제38권2호
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• pp.153-162
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• 2008

Purpose: Recombining bone morphogenetic protein (BMP) is usually acquiredfrom high level animals. Though this method is effective, its high cost limits its use. The purpose of this study was to evaluate the effect of bone morphogenetic protein-2 with protein transduction domain (BMP-2/PTD;TATBMP-2) on bone regeneration. Rat calvarial defect model and osteoblastic differentiation model using MC3T3 cell were used for the purpose of the study. Materials and Methods: MC3T3 cells were cultured until they reached a confluence stage. The cells were treated with 0, 0.1, 1, 10, 100, 500 ng/ml of BMP-2/PTD for 21 days and at the end of the treatment, osteoblastic differentiation was evaluated usingvon Kossa staining. An 8mm, calvarial, critical-size osteotomy defect was created in each of 48 male Spraque-Dawley rats (weight $250{\sim}300\;g$). Three groups of 16 animals each received either BMP-2/PTD (0.05mg/ml) in a collagen carrier, collagen only, or negative surgical control. And each group was divided into 2 and 8 weeks healing intervals. The groups were evaluated by histologic analysis(8 animals/group/healing intervals) Result: In osteoblastic differentiation evaluation test, a stimulatory effect of BMP-2/PTD was observed in 10ng/ml of BMP-2/PTD with no observation of dose-dependent manner. The BMP-2/PTD group showed enhanced local bone formation in the rat calvarial defect at 2 weeks. New bone was observed at the defect margin and central area of the defect. However, new bone formation was observed only in 50% of animals used for 2weeks. In addition, there was no new bone formation observed at 8 weeks. Conclusion: The results of the present study indicated that BMP-2/PTD(TATBMP-2) have an positive effect on the bone formation in vitro and in vivo. However, further study should be conducted for the reproducibility of the outcomes.

• Journal of Periodontal and Implant Science
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• 제35권2호
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• pp.289-298
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• 2005

Bone morphogenetic protein-7(BMP-7), a member of the transforming growth factor superfamily, stimulates osteoblast differentiation and bone formation. There are lots of evidences supporting a direct participation of periodontal ligament(PDL) cells on periodontal tissue regeneration. The purpose of this study was to evaluate the effect of recombinant human(rh) BMP-7 on primary rat PDL cells in vitro, with special focus on the ability of bone formation. The PDL cells were cultured with rhBMP-7 at the concentration of 0, 10, 25, 50, 100 and 200ng/ml for MTT assay. We evaluated the alkaline phosphatase activity at 3 and 5 days of incubation and the ability to produce mineralized nodules of rat PDL cells at 14 days of cell culture in concentration of 0, 10, 25, 50 and 100ng/ml. The cell activity was not reduced in cells treated with BMP-7 at $10{\sim}100ng/ml$, whereas the cell activity was reduced in the concentration of 200ng/ml than the control at day 1 and 3(p<0.01). At 3 and 5 day, alkaline phosphatase activity was significantly increased in cells treated with BMP-7 at 50ng/ml and 100ng/ml(p<0.05). The area of mineralized bone nodule was greater in cells treated with BMP-7 at 50 and 100 ng/ml than the control(p<0.01). These results suggest that rhBMP-7 stimulate rat PDL cells to differentiate toward osteoblast phenotype and secretion of the extracellular matrix of rat PDL cells.

• Journal of Periodontal and Implant Science
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• 제47권2호
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• pp.86-95
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• 2017

Purpose: The aim of this study was to determine the effect of recombinant human bone morphogenetic protein-2 (rhBMP-2)-loaded synthetic bone substitute on implants that were simultaneously placed with sinus augmentation in rabbits. Methods: In this study, a circular access window was prepared in the maxillary sinus of rabbits (n=5) for a bone graft around an implant (${\varnothing}3{\times}6mm$) that was simultaneously placed anterior to the window. Synthetic bone substitute loaded with rhBMP-2 was placed on one side of the sinus to form the experimental group, and saline-soaked synthetic bone substitute was placed on the other side of the sinus to form the control group. After 4 weeks, sections were obtained for analysis by micro-computed tomography and histology. Results: Volumetric analysis showed that the median amount of newly formed bone was significantly greater in the BMP group than in the control group ($51.6mm^3$ and $46.6mm^3$, respectively; P=0.019). In the histometric analysis, the osseointegration height was also significantly greater in the BMP group at the medial surface of the implant (5.2 mm and 4.3 mm, respectively; P=0.037). Conclusions: In conclusion, an implant simultaneously placed with sinus augmentation using rhBMP-2-loaded synthetic bone substitute can be successfully osseointegrated, even when only a limited bone height is available during the early stage of healing.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제26권4호
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• pp.325-336
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• 2000

Bone morphogenetic protein-2/4 are members of Transforming Growth Factor-$\beta$(TGF-$\beta$) superfamily and they may induce formation of cartilage and bone in vivo. This study was performed to investigate the cellular target and period of action of BMP-2/4 and understanding of actions of BMP-2/4 at cellular level. The appearance of BMP-2/4 during healing of mandibular and periodontal defect in rat was evaluated immunohistochemically. 40 Sprague-Dawley strain white male rats, each weighing about 300gm were used. Bony defect was performed in the mandible and they were sacrificed at the day of 3rd, 10th, 20th, 30th after operation. The specimens were harvested and examined histologically and immunohistochemically by localization of anti-BMP-2/4. The results were as follows: 1. Woven bone was observed at 10th day and perfect healing of defect with compact bone and periodontal ligment space at 30th day. 2. Osteoprogenitor cells, osteoblastic cells and periosteum were positive reaction to immunohistochemical stain at 10th day. 3. Cells of bone marrow space and surface cells of osteocytes and cementoblasts were positive reaction to immunohistochemical stain at 20th day. 4. Newly formed osteocytes and cementocytes were positive reaction to immunohistochemical stain at 30th day. From the above findings, we could conclude that BMP-2/4 acted significant roles as factors of induction, proliferation and differentiation during bone healing process.

• International Journal of Oral Biology
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• 제34권2호
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• pp.115-121
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• 2009

Bone morphogenetic protein (BMP) 2 is a potent osteogenic factor. Although both Smad1/5 and mitogenactivated protein kinases (MAPKs) are activated by BMP2, the hierarchical relationship between them is unclear. In this study, we examined if BMP2-stimulated MAPK activation is regulated by Smad1/5 or vice versa. When C2C12 cells were treated with BMP2, the activation of extracellular signal-regulated kinase (ERK), p38 MAPK and c-Jun-N-terminal kinase was evident within 5 min. The knockdown of both Smad1 and Smad5 by small interfering RNA did not affect the activation of these MAPKs. In addition, neither the overexpression of Smad1 nor Smad5 induced ERK activation. When ERK activation was induced by constitutively active MEK1 expression, the protein level and activation of Smad1 increased. Furthermore, the inhibition of constitutively active BMP receptor type IB-induced ERK activation significantly suppressed Smad1 activation. These results indicate that Smad1/5 activation is not necessary for BMP2-induced MAPK activation and also that ERK positively regulates Smad1 activation.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제44권6호
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• pp.259-268
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• 2018

Objectives: The purpose of this study was to evaluate the synergic effect of recombinant human bone morphogenetic protein-2 (rhBMP-2) and low-level laser therapy (LLLT) on bisphosphonate-treated osteoblasts. Materials and Methods: Human fetal osteoblast cells (hFOB 1.19) were cultured with $100{\mu}M$ alendronate. Low-level Ga-Al-As laser alone or with 100 ng/mL rhBMP-2 was then applied. Cell viability was measured with MTT assay. The expression levels of receptor activator of nuclear factor kappa-B ligand (RANKL), macrophage colony-stimulating factor (M-CSF), and osteoprotegerin (OPG) were analyzed for osteoblastic activity inducing osteoclastic activity. Collagen type and transforming growth factor beta-1 were also evaluated for bone matrix formation. Results: The results showed that rhBMP-2 and LLLT had a synergic effect on alendronate-treated osteoblasts for enhancing osteoblastic activity and bone matrix formation. Between rhBMP-2 and LLLT, rhBMP-2 exhibited a greater effect, but did not show a significant difference. Conclusion: rhBMP-2 and LLLT have synergic effects on bisphosphonate-treated osteoblasts through enhancement of osteoblastic activity and bone formation activity.

• 한국환경생태학회지
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• 제26권4호
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• pp.620-628
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• 2012

본 연구에서는 산림유역의 최상류지역에 위치한 일시하천(ephemeral stream)과 간헐천(intermittent stream)이 상존하는 수변지역을 대상으로 지하수위의 계절적인 변화 양상을 파악하였다. 3곳의 산림유역(총 12개 소유역)에서 일시하천 및 간헐천의 수변구역 보호를 위한 최적관리기법을 포함하는 4개의 처리구(BMP1, BMP2, clearcut, reference)를 적용하였다. 지하수위는 각 소유역별 25개소(총 300개소)에서 2주 간격으로 측정되었으며, 벌채 전 1년과 벌채 후 2년, 총 3년 동안 관측되었다. 전체적으로 지하수위의 반응은 강우량의 영향이 큰 것으로 관찰되었다. 또한, 산림벌채전과 비교하여, 벌채 후 2년 동안 지하수위는 유의적으로 증가하였다. 특히, 벌채 1년 후(2008) 개벌처리구에서 28.2cm, 벌채 2년 후(2009) BMP2에서 54.2cm로 가장 크게 증가하였다. 그러나, 개벌처리구와 BMP2의 지하수위 변화 특성을 비교할 때, 벌채된 목재의 재적과 지하수위의 변화는 직접적인 연관성이 없는 것으로 나타났다. 산림벌채로 인한 지하수위의 증가는 �㎱굇璲� 보다 건조기간 동안 더 크게 나타났으며, 이러한 계절적인 추이는 산림벌채 후 식생구조의 차이에서 야기되는 증발산양의 변화에 기인하는 것으로 사료된다.

• Journal of Periodontal and Implant Science
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• 제46권5호
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• pp.350-359
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• 2016

Purpose: The purpose of the present study was to evaluate the effectiveness of a minimal concentration of bone morphogenetic protein-2 (BMP-2) in terms of quantitative and qualitative analyses of newly formed bone in a rabbit maxillary sinus model. Methods: In 7 rabbits, sinus windows were prepared bilaterally. Biphasic calcium phosphate (BCP) loaded with 0.05 mg/mL BMP-2 was grafted into one sinus (the BMP group) and saline-soaked BCP was placed into the other (the control group) in each animal. The animals were allowed an 8-week healing period before being sacrificed. Specimens including the augmented area and surrounding tissues were then removed and evaluated both radiographically and histologically. Results: There was a difference in the mineralization of new bone between the groups. In the BMP group, the greater part of the new bone consisted of mature lamellar bone with an evident trabecular pattern, whereas the control group showed mostly woven bone, consisting only partially of lamellar bone. Histometrically, the area of new bone was significantly greater ($4.55{\pm}1.35mm^2$ vs. $2.99{\pm}0.86mm^2$) in the BMP group than in the control group (P<0.05); however, the total augmentation volumes were not significantly different between the groups. Conclusions: Within the limitations of this study, it can be suggested that a minimal concentration of BMP-2 (0.05 mg/mL) had an osteoinductive effect with accelerated mineralization in a rabbit sinus model using a BCP carrier.