• 한국가금학회:학술대회논문집
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• 한국가금학회 2002년도 가을 학술발표논문집
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• pp.96-97
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• 2002

Primordial germ cells (PGCs) are the progenitors of the sperms or eggs of adult. Evidence suggests that the specification of primordial germ cells (PGCs) in the mammalian embryo does not depend on maternal determinants. Recent previous studies in the mouse has shown that several bone morphogenetic proteins (BMPs) are required for the formation of PGCs. However, there is no study about the effect of BMPs on avian PGCs. Here, we studied the effects of recombinant human BMP-2 (rhBMP-2) and recombinant human BMP-4 (rhBMP-4) on chicken blastodermal cells in culture. As a results, the addition of rhBMP-2 and rhBMP-4 increased the number of SSEA-1 positive cells in dose-dependent manner. However, there is no synergic effect by using both rhBMP-2 and rhBMP-4.

• Maxillofacial Plastic and Reconstructive Surgery
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• 제27권4호
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• pp.307-314
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• 2005

After dental implant are planted into their bony site among the various growth factors associated with bone formation. BMP is expressed in the bone surrounding the implant fixture. By taking a close look at BMP2, BMP4 which are growth factors that take put in bone formation, its histologic features and radiographic bone healing patterns we would like to examine the mechanism of osseointegration. We randomly used 8 male and female house rabbit amd used diameter 5 mm height spiral shaped implants(Ostem, Korea) for animal use handled as a resorbable blast machined(RBM) surface and machined surface. 2group were formed and each group had RBM surface and machined surface implant or a simple bone cavity. After 3, 7, 14 and 28 days post surgery 2 objects were sacrificed from each group and histologic specimens were acquired. RT-PCR analysis was conducted and after H&E staining the extent of osseointegration was measured applying a histologic feature and histomorphometric analysis program. Quanitity one -4.41(Bio-Rad, USA) was used after scanning the PCR product image of the growth factors manifested in each group. According to the histomorphometric features the RBM, Machined surface group showed increased contact between bone and implant surface at 3, 7, 14 and 28 days after surgery. The BMP2 level increased in both experiment groups but remained unchanged in the contrast group. BMP4 levels stayed steady after the early post implantation period for RBM but showed decreased in the machined surface group and contrast group. The amount of contact between bone and implant surface increased with the passage of time. BMP2, BMP4 were expressed in both experimental group and contrast group. These growth factors play a role in osseointegration of implant.

• 대한소아치과학회지
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• 제29권3호
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• pp.345-353
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• 2002

Bone morphogenetic proteins(BMPs)는 형태형성 및 세포 분화동안 다양한 조절 역할을 담당하는 신호전달 인자이다. 시상두개봉합부 발생시 BMPs와 그 수용체의 역할을 분석하기 위해, in situ hybridization방법을 이용하여 태생 15일에서 18일 시상두개봉합부에서 그 발현 양상을 분석하였다. BMP-2와 BMP-3은 태생 15일부터 osteogenic front와 두정골에서 발현을 보였으며 태생 16일부터 모낭에서 발현이 시작되었다. BMP-4는 osteogenic front에서 강하게 발현되었으며, 간엽조직 및 두정골에서 약하게 발현되었다. BMP-5는 모낭에서 발현되었다. 이전 연구에서 BMP-6는 비후된 연골세포에서 발현된다고 보고되었으나 본 연구에서는 발현되지 않았다. BMP-7은 태생기에 두정골에서 발현되었다. BMPR-IB는 osteogenic front의 외측 가장자리에서 발현되었으나, BMPR-IA는 발현되지 않았다. 이런 결과를 종합해 볼 때, 두개봉합부 초기 형태발생시 BMP-4는 미분화 간엽세포로부터 골아세포로 commit되는 초기단계에 중요한 역할을 하며, BMP-2와 BMP-3는 전구 골아세포에서 골아세포로의 분화과정에, BMP-7은 좀 더 분화가 진행된 골아세포 및 골의 분화 유지에 중요하며, type I 수용체 중 BMPR-IB가 BMP들의 신호전달에 중요한 역할을 함을 예측 할 수 있다. 결론적으로 BMP 신호전달은 다양한 BMP 리간드들과 그 수용체들에 의해 골아세포 분화 전반에 걸쳐 관여하고 있음을 시사한다.

• 대한한의학회지
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• 제23권2호
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• pp.190-197
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• 2002

Objectives : This study was performed to examine the effect of Yukmigiwhang-tang kamibang, a mixture of oriental herbal extracts, on the transcription of bone fonnation genes, BMP4 (bone morphogenetic protein 4) and TG2 (transglutaminase-2). Methods : Bone-related cells, MG-63 (human male osteosarcoma), HOS-TE85 (human female osteosarcoma), and KG-l (bone marrow) were cultured with portions of Yukmigiwhang-tang kamibang and the transcription activities of bone-related genes, BMP4 (bone morphogenetic protein 4) and TG2 (transglutaminase-2), were determined by Reverse-Transcription Polymerase Chain Reaction (RT-PCR). Results : Transcription of BMP4 gene in HOS-TE85 cell increased up to 40% at 0.3% (v/v) of Yukmigiwhang- tang kamibang extract and that of TG2 gene in MG-63 cells also increased up to 40% at 0.3-0.4% of the same extract. Although it was less significant when compared to those in other cells, the transcription of BMP4 gene in KG-l cells also increased up to 10 to 25%. Conclusions : These results clearly demonstrated that Yukmigiwhang-tang kamibang have an effect on transcription activity of bone-related genes, TG2 and BMP4, suggesting that it may play an important role in bone formation.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제30권3호
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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.

• 대한치과보철학회지
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• 제51권4호
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• pp.307-314
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• 2013

연구 목적: 본 연구는 골형성단백질의 서방출을 위해 헤파린과 골형성단백질 (rhBMP-2)을 화학적으로 고정시킨 양극산화 티타늄 임플란트가 골 결손부에서 임플란트 주변의 수직적 골증대에 미치는 효과를 방사선학적으로 평가하고자 시행되었다. 연구 재료 및 방법: Pure-Titanium을 사용하여 길이 7.0 mm, 직경 3.5 mm의 실험용 임플란트 18개를 제작하였다. 모든 임플란트를 양극산화처리 하였고, 플랫폼 하방 2.5 mm에 식립 기준선을 표시하였다. rhBMP-2가 코팅되지 않은 임플란트 집단을 대조군으로, dip and dry 방법으로 rhBMP-2를 물리적 흡착시킨 집단을 BMP군, 3,4-dihydroxyphenylalanine(DOPA)-heparin을 이식하고 rhBMP-2를 화학적으로 고정시킨 집단을 Hep-BMP군으로 설정하였다. 각군별6개씩의 임플란트를 3마리의 비글견 양측 하악에 한쪽에 3개씩 총 18개를 치조정 상방으로 2.5 mm 노출시켜 식립하였다. 식립 직후와 4주, 8주에 식립부위의 방사선학적 검사가 시행되었고, 각 시기별, 각 군별 임플란트의 근원심 변연골의 수직적 재생량에 대한 평균값과 표준편차를 얻었다. Kruskal-Wallis test와 Mann-Whitney U test를 이용하여 4주, 8주에서 대조군과 실험군들의 차이를 비교 분석하고, 유의 수준5%에서 통계적으로 검정하였다. 결과:방사선학적 관찰 결과 임플란트 근원심 변연골 재생량(평균값 ${\pm}$ 표준편차)은 4주에 대조군은 $0.09{\pm}0.22mm$, BMP군은 $1.02{\pm}0.72mm$, Hep-BMP군은 $1.29{\pm}0.51mm$ 였으며, 8주에서는 각각 $0.11{\pm}1.26mm$, $1.11{\pm}0.58mm$, $1.59{\pm}0.79mm$였다. 두 실험군 모두 4주와 8주에서 대조군과 비교 시 유의한 수직적 골증대를 나타냈으나(P<.05), Hep-BMP군과BMP군의 비교에서는 유의한 변연골 재생량 차이를 보이지 않았다(P>.05). 결론: 골형성단백질을 물리적으로 흡착시키거나 서방출 위해 헤파린을 이용하여 화학적으로 고정시킨 양극산화 임플란트 표면은 모두 골 결손부에서 임플란트 주변골의 수직적 증대에 효과적이었다. 그러나 방사선학적 관찰의 한계 내에서 골형성단백질의 이 두가지 적용방법간에는 수직적 골증대량에 유의한 차이가 없었다.

• 대한치과의사협회지
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• 제46권8호
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• pp.494-504
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• 2008

Osseointegration is a result of bone formation and bone regeneration process, which take place at the interface between bone and implant and biologic determinants such as cytokine, growth factors, bone matrix proteins play an important role in osseointegration. The purpose of this study is to compare the expressoin of TGF-$\beta$, IGF-I, BMP2, BMP4 during osseointegration. We designed an experimental group which was inserted with a RBM surface titanium implants and machined surface, and compared with a control group which had a simple bone cavity and normal bone. Titanium implants were placed into tibia of 8 rabbits. We compared the expression of TGF-$\beta$, IGF-I, BMP2, BMP4 using RT_PCR (reverse transcriptase chain reaction)analysis in day 3,7,14 and 28 of implant insertion. According to the results, growth factors of experimental groups were more expressed than control groups. Among experimental groups, expression of TGF-$\beta$, IGF-I, BMP4 of BMP group had tedency to increase more at 14th, 28th days than Machined surface group. Therefore, our results suggest that TGF-$\beta$, IGF-I, BMP4 are expressed within the bone around the implant and more increased around rough surface implants while osseointegration occurs after dental implant insertion.

• 생명과학회지
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• 제22권4호
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• pp.456-465
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• 2012

유전자 재조합 이형이합체 인간 뼈 형성촉진인자(rhBMP)들은 뼈 재생을 위한 조직공학연구에 중요한 요소들이다. 그러나 실제 뼈 재생에 관한 연구를 수행함에 이들을 이용하는 것은 뼈 형성 촉진인자들이 짧은 반감기를 가지며 비교적 고농도의 단백질을 사용해야 하기 때문에 그만큼 많은 비용이 소요된다는 문제점을 가지고 있다. 이러한 한계를 뛰어넘기 위하여, 본 연구에서는 단백질 전달 서열(PTD)이 융합된 인간 뼈 형성촉진인자 2와 7이 이형이합체 유전자 재조합 단백질(rhBMP2/7-PTD)을 발현하는 세포주를 확립하였다. 이형이합체의 형성은 BMP 2와 BMP 7 단백질 및 PTD 영역의 사이에 각각 4개의 glycine 아미노산 염기서열이 첨가될 수 있도록 하여 각 단백질의 folding이 자유롭도록 디자인하였다. 이렇게 개발된 세포주는 고농도의 rhBMP2/7-PTD을 지속적으로 발현하여 배양액 내로 분비함으로 조직공학용 연구 및 개발에 효율적으로 이용 할 수 있다. 이상의 세포주에서 발현된 rhBMP2/7-PTD 단백질은 뼈 세포분화 유도를 확인 할 수 있는 ALP 활성을 나타냄으로써 뼈 성장촉진 단백질로서 생물학적인 활성을 가지고 있음을 보였다. 본 연구의 결과로 개발된 rhBMP2/7-PTD 형질전환 세포주는 향후 뼈 조직 재생과 같은 연구에 중요하고 효과적인 도구로 이용될 수 있을 것으로 사료된다.

• 한국양식학회지
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• 제8권4호
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• pp.343-354
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• 1995

순환여과식 사육수조에서 잉어(Cyprinus carpio) 치어를 사육하면서, 사료 단백질원인 혈분의 첨가 함량에 따라 총 5개 실험군을 3 반복으로 무작위 배치하고 6 주 동안 사육실험을 하였다. 실험사료의 단백질원은 동물성 $20\%$, 식물성 약 $75\%$를 사용하였고, 조단백질 $40\%$, 3,640 kcal/kg을 기준으로 실험실에서 제조하였다 : 사료 1 (100 FMP, control), $100\%$ fish meal protein : 사료 2 (25 BMP), $75\%$ fish meal $protein+25\%$ blood meal protein : 사료 3 (50 BMP), $50\%$ fish meal $protein+50\%$ blood meal protein ; 사료 4 (75 BMP), $25\%$ fish meal $protein+75\%$ blood meal protein ;사료 5 (100 BMP), $100\%$ blood meal protein. 6 주간의 주사육실험 결과, 혈분 첨가량이 증가할수록 증체량과 사료효율이 증가하였다. 대조군(100 FMP)에 비해 75 BMP와 100 BMP실험군의 증체량과 사료효율이 유의하게 높았다(P<0.05). 3주간의 교차확인실험에서도 100 FMP 대조군보다 100 BMP 실험군에서 높은 증체량과 사료효율을 나타내었다. (P<0.05). 사료의 유인성평가실험은 100 FMP와 100 BMP사료의 유인성을 측정하기 위해 수행되었다. 유인성평가 결과, 초기에는 100 BMP 실험군의 유인성이 100 FMP 대조군보다 낮았으나 2 주만에 큰 차이가 없게 되었다. 본 실험결과, 성장기 잉어 사료의 단백질원으로서 어분단백질을 혈분단백질로 $100\%$까지 대체 가능함을 알 수 있었다.

• Journal of Periodontal and Implant Science
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• 제30권3호
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• pp.505-527
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• 2000

The 3 beagle dogs aged over one and half years and weighed 14 to 16 Kg were utilized in this study. Horizontal furcation defects were induced around 3rd, and 4th premolars bilaterally. BMP-4 in conjunction with EGF and BMP-4 only were applied in the right and left premolars respectively. 1 animal was sacrificed at 2nd week, 4th week, and 8th week, after regenerative surgery respectively. Semi-thin sections using glass-knife were stained with hematoxylin- eosin and trichrome for light microscopic study. The results were as follows : 1 . The long junctional epithelial downgrowth was observed in both area applied with BMP-4 and with BMP-4 and EGF at 2nd week after the surgery. 2 . The extensive regeneration of new bone and cementum was appeared at 4th week and the maturation of bone was observed at 8th week in both area applied with BMP-4 and with BMP-4 and EGF. 3 . The root ankylosis and resorption was presented along the exposed root surface at the coronal 1/3 of defect in the BMP-4 applied site, but it was not shown in the site applied with BMP-4 in conjunction with EGF at the 4th week. At 8th week, the root ankylosis was apparently appeared in the BMP-4 and EGF applied site as well as in the BMP-4 applied site. 4 . The periodontal ligament tissue including Sharpey's fiber inserted into cementum and alveolar bone, was formed along the exposed root surface in the area applied with BMP-4 only, but in the site applied with BMP-4 and EGF, the collagen fiber running parallel to the root surface without Sharpey's fiber, was observed in the periodontal ligament space at 4th and 8th week. Within the above results, BMP-4 had the remarkable capability to regenerate the periodontal tissue and EGF had possibility to prevent from the root ankylosis. Therefore, growth factors including BMP-4 and EGF may have the strong possibility to be utilized in the clinical periodontal treatments.