• Journal of Periodontal and Implant Science
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• 제37권4호
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• pp.733-742
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• 2007

Bone morphogenetic proteins have been shown to possess significant osteoinSductive potential, but in order to take advantage of this effect for tissue engineering, carrier systems are essential. Successful carrier systems must enable vascular and cellular invasion, allowing BMP to act as a differentiation factor. The carrier should be reproducible, non-immunogenic, moldable, and space-providing, to define the contours of the resulting bone. The purpose of this study was to review available literature, in comparing various carriers of BMP on rat calvarial defect model. The following conclusions were deduced. 1. Bone regeneration of ACS/BMP, ${\beta}-TCP/BMP$, FFSS/BMP, $FFSS/{\beta}-TCP/BMP$, MBCP/BMP group were significantly greater than the control groups. 2. Bone density in the ACS/BMP group was greater than that in ${\beta}-TCP$, FFSS, $FFSS/{\beta}-TCP$ carrier group. 3. Bone regeneration in FFSS/BMP group was less than in ACS/BMP, ${\beta}-TCP/BMP$, MBCP/BMP group. However, New bone area of $FFSS/{\beta}-TCP/BMP$ carrier group were more greater than that of FFSS/BMP group. ACS, ${\beta}-TCP$, FFSS, $FFSS/{\beta}-TCP$, MBCP were used for carrier of BMP. However, an ideal carrier which was reproducible, non-immunogenic, moldable, and space-providing did not exist. Therefore, further investigation are required in developing a new carrier system.

• Asian Pacific Journal of Cancer Prevention
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• 제13권4호
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• pp.1183-1186
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• 2012

Objective: To observe the effect of insulin-like growth factor-1 (IGF-1) on bone morphogenetic protein (BMP)-2 expression in hepatocellular carcinoma SMMC7721 cells. Methods: Cells were divided into blank control, IGF-1, IGF-1 + SB203580, and SB203580 groups. SB203580 was used to block the p38 MAPK signaling pathway. Changes in the expression of BMP-2, p38 MAPK, and phosphorylated p38, MERK, ERK and JNK were determined using reverse transcription polymerase chain reactions (RT-PCR) and Western blot analysis. Results: Protein expression of phosphorylated BMP-2, MERK, ERK, and JNK was significantly up-regulated by IGF-1 compared with the control group ($1.138{\pm}0.065$ vs. $0.606{\pm}0.013$, $0.292{\pm}0.005$ vs. $0.150{\pm}0.081$, $0.378{\pm}0.006$ vs. $0.606{\pm}0.013$, and $0.299{\pm}0.015$ vs. $0.196{\pm}0.017$, respectively; P<0.05). Levels of BMP-2 and phosphorylated MERK and JNK were significantly reduced after blocking of the p38MAPK signaling pathway ($0.494{\pm}0.052$ vs. $0.165{\pm}0.017$, $0.073{\pm}0.07$ vs. $0.150{\pm}0.081$, and $0.018{\pm}0.008$ vs. $0.196{\pm}0.017$, respectively; P<0.05), but such a significant difference was not observed for phosphorylated ERK protein expression ($0.173{\pm}0.07$ vs. $0.150{\pm}0.081$, P>0.05). Conclusion: IGF-1 can up-regulate BMP-2 expression, and p38 MAPK signaling pathway blockage can noticeably reduce the up-regulated expression. We can conclude that the up-regulatory effect of IGF-1 on BMP-2 expression is realized through the p38 MAPK signaling pathway.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제34권1호
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• pp.49-58
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• 2008

Objective: The Purpose of the study was to investigate the bone morphogenic protein expression of rhBMP-2(recombinant human bone morphogenic protein-2) as singnaling molecule and ${\beta}-TCP$(Tricalcium phosphate) as a bone substitute and carrier medium of rhBMP-2. Materials and Methods: 16 rabbits divided into 2 group of each 8 rabbit. Two standardized bone defect, round bilateral defect was made in the cranium of the 8 rabbit of first group, and was grafted with $150{\sim}500{\mu}m$ diameter ${\beta}-TCP$ 0.25g in one side, which was soaked with rhBMP-2, and autogenous bone was grafted on another side as a positive control. Second group of 8 rabbit, only ${\beta}-TCP$ was grafted with same size and same manner. After 2, 4, 8, and 12 weeks, specimen was taken for microscopic immunohiostochemical and histomorphometric analysis. Result: Grafting ${\beta}-TCP$ with rhBMP show the early formation of the bone regenerative factor (BMP-4) and more quantity of new bone formation than only use of ${\beta}-TCP$ (8,12 week), even show less new bone formation than autogenous bone. Conclusion : The experimental study result that ${\beta}-TCP$ graft combination with rhBMP-2 as a delivery system is an effective with osteoinductive capacity and biodegradable properties, so that provide clinical availibility of composite use in reconstruction of bony defect.

• Maxillofacial Plastic and Reconstructive Surgery
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• 제29권6호
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• pp.467-473
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• 2007

이 실험은 이식재로 Deproteinated Bovine Bone Powder (DBBP)를 사용하였을 때와 골 이식재를 사용하지 않고 단순히 Absorbable Gelatin Sponge(AGS)만을 사용하였을 때의 BMP4와 BMP6의 상대적인 발현량을 real-time RT-PCR을 이용하여 비교해 보기 위한 것으로 다음과 같은 결과를 얻었다. 1. BMP4의 경우 처음 1일째와 3일째의 경우 DBBP군과 AGS군 모두 일정하게 증가하였으나 5일째 AGS군에서 감소하다가 7일째 다시 증가하였으며 9일째 다시 감소하였다. DBBP군에서는 7일까지 계속하여 증가하다가 9일째 감소하였다. DBBP군이 AGS군에 비해 발현의 양이 많은 경우가 많았지만 유의성은 없었다 (p>0.05). 2 BMP6의 경우 처음 1일째와 3일째의 경우 DBBP군과 AGS군 모두 일정하게 증가하였으나 5일째 AGS군에서 감소하다가 7일째 다시 증가하였으며 9일째 다시 감소하였다. DBBP군에서는 7일까지 계속하여 증가하다가 9일째 감소하였다. AGS군이 DBBP군에 비해 발현의 양이 많은 경우가 많았지만 유의성은 없었다 (p>0.05). 3. 두 군간에 동일시기에 BMP발현이 유의할 만한 차이를 보이지 않는 것은 DBBP와 AGS 모두 space retainer로서 작용을 하여 혈병중의 BMP발현의 양상이 비슷하기 때문으로 여겨진다. 4. 따라서 DBBP가 AGS에 비해 초기 골재생에 크게 유리한 점은 없는 것으로 여겨지며 초기 골 형성에서 BMP의 발현은 이식재의 종류가 아니라 물리적인 carrier로서의 작용이 더 중요한 것으로 여겨진다.

• BMB Reports
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• 제42권2호
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• pp.86-90
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• 2009

Deletion of smpd3 induces osteogenesis and dentinogenesis imperfecta in mice. smpd3 is highly elevated in the parietal bones of developing mouse calvaria, but not in sutural mesenchymes. Here, we examine the mechanism of smpd3 regulation, which involves BMP2 stimulation of Runx2. smpd3 mRNA expression increased in response to BMP2 treatment and Runx2 transfection in C2C12 cells. The Runx2-responsive element (RRE) encoded within the -562 to -557 region is important for activation of the smpd3 promoter by Runx2. Electrophoretic mobility shift assays revealed that Runx2 binds strongly to the -355 to -350 RRE and less strongly to the -562 to -557 site. Thus, the smpd3 promoter is activated by BMP2 and is directly regulated by the Runx2 transcription factor. This novel description of smpd3 regulation will aid further studies of bone development and osteogenesis.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제30권4호
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• pp.282-291
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• 2004

Pure-phase beta-tricalcium phosphate(${\beta}$-TCP) proved to be a bone regeneration material, providing the patient with vital bone at the defect site in a reasonable time, making a second surgical procedure for bone harvesting unnecessary. This study compares bone healing and BMP 2/4 expression in cranial defects in rabbits grafted with autogenous bone and ${\beta}$-TCP. Thirty New Zealand White rabbits was divided into 3 group of 10 animals each. Bilateral calvarial defects were made in the parietal bones of each animal. ${\beta}$-TCP placed in one defect and the other defects was filled with autogenous bone. The animal were sacrificed at 4, 8 and 12 weeks. Immunohistochemical analysis was used to investigate the expression of BMP 2/4. 1. The new bone formation around autogenous bone from 4 weeks and ${\beta}$-TCP from 8 weeks. 2. In autogenous bone graft, BMP 2/4 expression was decreased from 4 to 12 weeks. 3. In ${\beta}$-TCP graft, BMP 4 expression was increased from 8 to 12 weeks. But, BMP 2 was observed from 12 weeks. This study showed that bone healing, regeneration and, BMP 2/4 expression are delayed in grafted ${\beta}$-TCP than autogenous bone.

• 대한치과의사협회지
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• 제53권1호
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• pp.28-35
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• 2015

To overcome shortcoming of autogeneous, allogenic, xenogenic and alloplastic bone grafts, various growth factors related to bone regeneration have been identified and developed. Among them, rhBMP-2 is regarded as the most potent osteoinductive growth factor and it can trigger the differentiation of mesenchymal stem cells to osteogenic cells for accelerated new bone formation And several commercial products of rhBMP-2 are available in Korea. It is applied to maxillary sinus augmentation, guided bone regeneration and preservation of extraction socket. In this review, the development, action mechanism and clinical applications of rhBMP-2 will be described.

• Journal of Periodontal and Implant Science
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• 제41권5호
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• pp.227-233
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• 2011

Purpose: The aim of this study was to compare osteoblast behavior on zirconia and titanium under conditions cultured with bone morphogenetic protein-2. Methods: MC3T3-E1 cells were cultured on sandblasted zirconia and sandblasted/etched titanium discs. At 24 hours after seeding MC3T3-E1, the demineralized bone matrix (DBM) gel alone and the DBM gel with bone morphogenetic protein-2 (BMP-2) were added to the culture medium. The surface topography was examined by confocal laser scanning microscopy. Cellular proliferation was measured at 1, 4, and 7 days after gel loading. Alkaline phosphatase activity was measured at 7 days after gel loading. The mRNA expression of ALPase, bone sialoprotein, type I collagen, runt-related transcription factor 2 (Runx-2), osteocalcin, and osterix were evaluated by real-time polymerase chain reaction at 4 days and 7 days. Results: At 1, 4, and 7 days after loading the DBM gel alone and the DBM gel with BMP-2, cellular proliferation on the zirconia and titanium discs was similar and that of the groups cultured with the DBM gel alone and the DBM gel with BMP-2 was not significantly different, except for titanium with BMP-2 gel. ALPase activity was higher in the cells cultured with BMP-2 than in the other groups, but there was no difference between the zirconia and titanium. In ALPase, bone sialoprotein, osteocalcin, Runx-2 and osterix gene expression, that of cells on zirconia or titanium with BMP-2 gel was much more highly increased than titanium without gel at day 7. The gene expression level of cells cultured on zirconia with BMP-2 was higher than that on titanium with BMP-2 at day 7. Conclusions: The data in this study demonstrate that the osteoblastic cell attachment and proliferation of zirconia were comparable to those of titanium. With the stimulation of BMP-2, zirconia has a more pronounced effect on the proliferation and differentiation of the osteoblastic cells compared with titanium.

• Journal of Korean Neurosurgical Society
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• 제65권6호
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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.

• BMB Reports
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• 제46권2호
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• pp.107-112
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• 2013

Although BMP6 is highly capable of inducing osteogenic differentiation of mesenchymal progenitor cells (MPCs), the molecular mechanism involved remains to be fully elucidated. Using dominant negative (dn) mutant form of type I and type II $TGF{\beta}$ receptors, we demonstrated that three dn-type I receptors (dnALK2, dnALK3, dnALK6), and three dn-type II receptors (dnBMPRII, dnActRII, dnActRIIB), effectively diminished BMP6-induced osteogenic differentiation of MPCs. These findings suggested that ALK2, ALK3, ALK6, BMPRII, ActRII and ActRIIB are essential for BMP6-induced osteogenic differentiation of MPCs. However, MPCs in this study do not express ActRIIB. Moreover, RNA interference of ALK2, ALK3, ALK6, BMPRII and ActRII inhibited BMP6-induced osteogenic differentiation in MPCs. Our results strongly suggested that BMP6-induced osteogenic differentiation of MPCs is mediated by its functional $TGF{\beta}$ receptors including ALK2, ALK3, ALK6, BMPRII, and ActRII.