• Journal of Periodontal and Implant Science
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• v.41 no.5
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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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• 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.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.31 no.6
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• pp.461-468
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• 2009

Purpose: Platelet derived growth factor(PDGF)-BB and bone morphogenetic protein(BMP)-2 are well-known representative growth factors. The purposes of this study were to investigate the effect of rhPDGFBB and rhBMP-2 on osseointegration of titanium implants at periimplant bone defects grafted with hydroxyapatite and to evaluate the feasibility of imaging bone structures around screw-type titanium implant with micro-CT. Materials and Methods: The first molar and all premolars in the mandible region of four beagle dogs were extracted. Following a healing period of 4 months, three $8{\times}8{\times}6mm$-sized bony defects were formed and screw-type titanium implants were placed with hydroxyapatite(HA) block and growth factors; Control group, PDGF group and BMP group. Two months post-implantation, the mandible was harvested. Bone volume(BV), bone-to-implant contact(BIC) and bone mineral density(BMD) were analyzed with micro-CT and histology. Results: According to micro-CT analysis, BV and BMD measures of PDGF and BMP group were significantly higher than control group(BV; PDGF group: $p{\fallingdotseq}0.011$, BMP group: $p{\fallingdotseq}0.006$/BMD; PDGF group: $p{\fallingdotseq}0.020$, BMP group: $p{\fallingdotseq}0.011$) and BIC measures of BMP group were significantly higher than PDGF group($p{\fallingdotseq}0.015$). In histologic evaluation, BIC measures of BMP group was significantly higher than PDGF group($p{\fallingdotseq}0.048$). The values of BV in histologic sections were higher than in micro-CT images and the values of BIC in micro-CT images were higher than in histologic sections. Conclusion: The findings of this experimental study indicates that the use of rhPDGF-BB and rhBMP-2 can increase new bone formation in a large bony defect around titanium implant, and rhBMP-2 is more effective than rhPDGF-BB. Micro-CT can be considered useful for assessment as a rapid and nondestructive method for 3-dimensional measurement of bone healing around implants. Further study is necessary, however, to remove metal artifacts around titanium implant and to standardize the method.

• Journal of Periodontal and Implant Science
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• v.38 no.2
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• pp.125-134
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• 2008

Purpose: Bone morphogenetic protein (BMP) is a potent differentiating agent for cells of the osteoblastic lineage. It has been used in the oral cavity under a variety of indications and with different carriers. However, the optimal carrier for each indication is not known. This study evaluated the bone regenerative effect of rhBMP-2 delivered with different carrier systems. Materials and Methods: 8 mm critical-sized rat calvarial defects were used in 60 male Sprague-Dawley rats. The animals were divided into 6 groups containing 10 animals each. Two groups were controls that had no treatment and absorbable collagen membrane only. 4 groups were experimentals that contained rhBMP-2 only and applied with absorbable collagen sponge($Collatape^{(R)}$), $MBCP^{(R)}$, Bio-$Oss^{(R)}$ each. The histological and histometric parameters were used to evaluate the defects after 2- or 8-week healing period. The shape and total augmented area were stable in all groups over the healing time. Results: New bone formation was significantly greater in the rhBMP-2 with carrier group than control group. rhBMP-2/ACS was the highest in bone density but gained less new bone area than rhBMP-2/$MBCP^{(R)}$ and rhBMP-2/Bio-$Oss^{(R)}$. The bone density after 8 weeks was greater than that after 2 weeks in all groups. However, rhBMP-2 alone failed to show the statistically significant difference in new bone area and bone density compared to control group. Also $MBCP^{(R)}$ and Bio-$Oss^{(R)}$ particles remained after 8 weeks healing period. Conclusion: These results suggest that rhBMP-2 with carrier system is an excellent inductive agent for bone formation and we can use it as the predictable bone tissue engieering technique. Future study will likely focus on the kinetics of BMP release and development of carriers that is ideal for it.

• Journal of Environmental Science International
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• v.33 no.2
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• pp.121-129
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• 2024

The study investigated the effect of thermo-alkaline pretreatment on the solubilization of polyhydroxybutyrate (PHB) and its potential to enhance of thermophilic anaerobic digestion, focusing on biochemical methane potential (BMP) and methane production rate, using two different particle sizes of PHB (1500 ㎛ and 400 ㎛). Thermo-alkaline pretreatment tests were conducted at 90 ℃ for 24 hours with varying NaOH dosages from 0-80% (w/w). BMP tests with untreated PHB exhibited methane production ranging from 150.4~225.4 mL CH₄/g COD and 21.5~24.2 mL CH₄/g VSS/d, indicating higher methane production for smaller particle sizes of PHB, 400 ㎛. Thermo-alkaline pretreatment tests achieved a 95.3% PHB solubilization efficiency when 400 ㎛ PHB particles were treated with 80% NaOH dosage at 90 ℃ for 24 hours. BMP tests with pretreated PHB showed substantial improvement in thermophilic anaerobic digestion, with an increase of up to 112% in BMP and up to 168% in methane production rate. The results suggest that a combined pretreatment process, including physical (400 ㎛ PHB particles) and thermo-alkaline (90 ℃, 40-80% NaOH dosage, and 24 hours reaction time), is required for high-rate thermophilic anaerobic digestion of PHB with enhanced methane production.

• Journal of Korean Neurosurgical Society
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• v.61 no.6
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• pp.669-679
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• 2018

Objective : To compare the spinal bone fusion properties of activin A/BMP2 chimera (AB204) with recombinant human bone morphogenetic protein (rhBMP2) using a rat posterolateral spinal fusion model. Methods : The study was designed to compare the effects and property at different dosages of AB204 and rhBMP2 on spinal bone fusion. Sixty-one male Sprague-Dawley rats underwent posterolateral lumbar spinal fusion using one of nine treatments during the study, that is, sham; osteon only; $3.0{\mu}g$, $6.0{\mu}g$, or $10.0{\mu}g$ of rhBMP2 with osteon; and $1.0{\mu}g$, $3.0{\mu}g$, $6.0{\mu}g$, or $10.0{\mu}g$ of AB204 with osteon. The effects and property on spinal bone fusion was calculated at 4 and 8 weeks after treatment using the scores of physical palpation, simple radiograph, micro-computed tomography, and immunohistochemistry. Results : Bone fusion scores were significantly higher for $10.0{\mu}g$ AB204 and $10.0{\mu}g$ rhBMP2 than for osteon only or $1.0{\mu}g$ AB204. AB204 exhibited more prolonged osteoblastic activity than rhBMP2. Bone fusion properties of AB204 were similar with the properties of rhBMP2 at doses of 6.0 and $10.0{\mu}g$, but, the properties of AB204 at doses of $3.0{\mu}g$ exhibited better than the properties of rhBMP2 at doses of $3.0{\mu}g$. Conclusion : AB204 chimeras could to be more potent for treating spinal bone fusion than rhBMP2 substitutes with increased osteoblastic activity for over a longer period.

• IMMUNE NETWORK
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• v.23 no.6
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• pp.48.1-48.21
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• 2023

Mesenchymal stromal/stem cells (MSCs) possess immunoregulatory properties and their regulatory functions represent a potential therapy for acute lung injury (ALI). However, uncertainties remain with respect to defining MSCs-derived immunomodulatory pathways. Therefore, this study aimed to investigate the mechanism underlying the enhanced effect of human recombinant bone morphogenic protein-2 (rhBMP-2) primed ES-MSCs (MSC^BMP2) in promoting Tregs in ALI mice. MSC were preconditioned with 100 ng/ml rhBMP-2 for 24 h, and then administrated to mice by intravenous injection after intratracheal injection of 1 mg/kg LPS. Treating MSCs with rhBMP-2 significantly increased cellular proliferation and migration, and cytokines array reveled that cytokines release by MSC^BMP2 were associated with migration and growth. MSC^BMP2 ameliorated LPS induced lung injury and reduced myeloperoxidase activity and permeability in mice exposed to LPS. Levels of inducible nitric oxide synthase were decreased while levels of total glutathione and superoxide dismutase activity were further increased via inhibition of phosphorylated STAT1 in ALI mice treated with MSC^BMP2. MSC^BMP2 treatment increased the protein level of IDO1, indicating an increase in Treg cells, and Foxp3⁺CD25⁺ Treg of CD4⁺ cells were further increased in ALI mice treated with MSC^BMP2. In co-culture assays with MSCs and RAW264.7 cells, the protein level of IDO1 was further induced in MSC^BMP2. Additionally, cytokine release of IL-10 was enhanced while both IL-6 and TNF-α were further inhibited. In conclusion, these findings suggest that MSC^BMP2 has therapeutic potential to reduce massive inflammation of respiratory diseases by promoting Treg cells.

• KSBB Journal
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• v.18 no.3
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• pp.207-210
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• 2003

The locus coeruleus (LC) contains about half of the total number of noradrenergic neurons in the brain and those noradrenergic neurons from the LC innervate entire brain regions. The LC is a major common target region in several neurodegenerative disorders such as Alzheimer's, Pakinson's and Huntington's diseases. The brain-derived neurotrophic factor (BDNF) regulate neuronal cell survival and differentiation of central nervous system neurons, including LC noradrenergic neurons. In this study, various small molecules and growth factors were tested as candidates to promote the production of BDNF in LC noradrenergic neuronal cells. The molecules tested include neuropeptides, cytokines, growth factors, neurotransmitters, and intracellular signaling agents. Four small molecules or growth factors, FGF8b, BMP-4, forskolin, and dibutyryl cGMP, were found to increase the release of BDNF in LC noradrenergic neurons. Especially, BMP-4 significantly enhanced BDNF production over 2.5-fold in LC noradrenergic neurons.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.46 no.3
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• pp.191-196
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• 2020

Objectives: Beyond the original application approved by the U.S. Food and Drug Administration, recombinant human bone morphogenetic protein-2 (rhBMP-2) is used for medication-related osteonecrosis of the jaw (MRONJ) treatment because of its bone remodeling enhancement properties. The purpose of the study was to investigate the bone formation effect of rhBMP-2/absorbable collagen sponge (ACS) in patients with MRONJ. Materials and Methods: In this retrospective cohort study, 26 female patients diagnosed with MRONJ and who underwent mandibular sequestrectomy at Ajou University Dental Hospital from 2010 to 2018 were included. The experimental group was composed of 18 patients who received rhBMP-2/ACS after sequestrectomy, while the control group was composed of 8 patients who did not receive rhBMP-2/ACS after sequestrectomy. A total dose of 0.5 mg of rhBMP-2 was used in the experimental group at a concentration of 0.5 mg/mL. Follow-up panoramic X-rays were taken immediately after the surgery and more than 6 months after the surgery. Using those X-rays, a radiographic index of bone defect area was calculated using the modified Ihan Hren method, which measures radiographic density of the normal bone and the defect site. Results: This study suggests that rhBMP-2 contributes to new bone formation. The mean radiographic index immediately after surgery and more than 6 months after the surgery for the experimental group was 68.4% and 79.8%, respectively. The mean radiographic index immediately after surgery and more than 6 months after the surgery for the control group was 73.4% and 76.7%, respectively (Wilcoxon signed rank test, P>0.05). The mean radiographic index increased 11.4% in the experimental group and 3.27% in the control group (Mann-Whitney U-test, P<0.05). Conclusion: Based on the results, use of rhBMP-2/ACS on bone defect sites after sequestrectomy could be a successful strategy for treatment of MRONJ patients.

• Journal of Periodontal and Implant Science
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• v.47 no.2
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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.