• Journal of Microbiology and Biotechnology
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• v.15 no.6
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• pp.1397-1401
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• 2005

Bone morphogenetic protein-4 (BMP-4) is a signaling homodimeric molecule that acts as a morphogen to influence cell fate in a concentration-dependent manner. The limited supply of a pure preparation of BMP-4, due to very low level of their expression in vivo, makes it difficult not only to study the biological activities of BMPs, but also to use them as a clinical tool. For a large-scale production of BMP-4, human BMP-4 cDNA was expressed in Chinese hamster ovary (CHO) cells by a recently development vector system, which confers position-independent stable expression of the foreign genes. The CHO cell line expressing recombinant human BMP-4 (rhBMP-4) at the level of $7\;{\mu}g/ml$ could be obtained after stepwise selection with methotrexate. This level of expression is about 70 times higher than those previously reported. The partially processed form of BMP-4 as well as mature form could be detected, when the aliquots of culture media were analyzed by Western blot. The glycosylation pattern and biological activity of the rhBMP-4 were determined by glycosidase treatment and the induction rate of alkaline phosphatase in mouse osteoblastic cells.

• BMB Reports
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• v.57 no.7
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• pp.330-335
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• 2024

Arginine methylation, which is catalyzed by protein arginine methyltransferases (Prmts), is known to play a key role in various biological processes. However, the function of Prmts in osteogenic differentiation of mesenchymal stem cells (MSCs) has not been clearly understood. In the current study, we attempted to elucidate a positive role of Prmt7 in osteogenic differentiation. Prmt7-depleted C3H/10T1/2 cells or bone marrow mesenchymal stem cells (BMSCs) showed the attenuated expression of osteogenic specific genes and Alizarin red staining compared to the wild-type cells. Furthermore, we found that Prmt7 deficiency reduced the activation of bone morphogenetic protein (BMP) signaling cascade, which is essential for the regulation of cell fate commitment and osteogenesis. Taken together, our data indicate that Prmt7 plays important regulatory roles in osteogenic differentiation.

• 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.

• The Journal of Korean Medicine
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• v.33 no.2
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• pp.1-10
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• 2012

Objectives: This study was aimed to investigate the effect of Bojungikgitang-gagambang (BJIG) on longitudinal bone growth in rats. Methods: The BJIG treated group (300 mg/kg) and the control group (vehicle) were administered orally twice daily for 4 days. To investigate the effects of BJIG we measured body weight gain. The bone growth effect was analyzed by measuring between fluorescent lines marked with tetracycline, which plays the role of fluorescent dye on the surface of the tibia. Tetracycline was intraperitoneally injected. The height of growth plates in the epiphyseal plate was measured. The expression of bone morphogenetic protein-2 (BMP-2) and insuline-like growth factor-1 (IGF-1) was investigated by immunohistochemistry. Results: BJIG caused a significant acceleration of longitudinal bone growth of $349.7{\pm}15.9{\mu}m/day$ compared to control ($319.8{\pm}21.4{\mu}m/day$). The height of overall growth plate was not significantly more compared to the control, but the size of cells in the proliferative zone and hypertrophic zone were. In the immunohistochemistry, BMP-2 and IGF-1 were expressed markedly in the proliferative or hypertrophic zone, respectively. Conclusions: BJIG stimulated the chondrocyte hypertrophy and chondrogenesis in the growth plate and directly increased the longitudinal tibia length of rats.

• Asian Spine Journal
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• v.12 no.6
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• pp.1010-1016
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• 2018

Study Design: Retrospective cohort study. Purpose: To report on spinal fusion assessment using computed tomography (CT) after adult spinal deformity (ASD) surgery using ultra-low dose recombinant human bone morphogenetic protein 2 (RhBMP-2). Overview of Literature: The reported dose of RhBMP-2 needed for successful spinal posterolateral fusion in ASD ranges from 10 to 20 mg per spinal level. This study reports the use of ultra-low dose of RhBMP-2 (0.07 mg per facet) to achieve spinal fusion in multilevel ASD surgery. Methods: Consecutive patients who underwent ASD surgery using ultra-low dose RhBMP-2 were recruited. Routine postoperative CT analysis for spinal fusion was performed by two spine surgeons. Inter-observer agreement was calculated for facet fusion (FF) and interbody fusion (IBF) at 6 and 12 months after the procedure. Results: Six consecutive ASD patients with a mean age of 62 years (28-72 years) were examined. Each patient received a total dose of 12 mg with an average dose of $0.69{\pm}0.2mg$ (0.42-1 mg) per single FF and $1.38{\pm}0.44mg$ (0.85-2 mg) for IBF. Total 131 FF and 15 IBF were examined in the study, with 88 FFs and nine IBFs being analyzed specifically at 6 months after the surgery. FF and IBF reported by surgeons A and B at 6 months were 97.7% vs. 91.9% FF, respectively (${\kappa}=0.95$) and 100% vs. 100% IBF, respectively (${\kappa}=1$). Two patients underwent longitudinal follow-up CT at 12 months, and the FF rates reported by surgeons A and B were 100% vs. 95.8%, respectively (${\kappa}=0.96$). Five out of nine facet (56%) non-unions were identified at the cross-links. The remaining four facet pseudarthrosis were noted at 1-2 spinal levels caudal to the cross-links. At the final clinical follow-up, there was no rod breakage, deformity progression, neurological deficit, or symptom recurrence. The Oswestry Disability Index improved by an average of $32.8{\pm}6.3$, while the mental component summary of the 36-item Short-Form Health Survey improved by an average of $4.7{\pm}2.1$, and physical component summary improved by an average of $10.5{\pm}2.1$. Conclusions: To our knowledge, this is the first study to report a CT that defined 92%-98% FF and 100% IBF using the lowest reported dose of RhBMP-2 in multilevel ASD surgery. The use of ultra-low dose RhBMP-2 reduces the RhBMP-2 related complications and healthcare costs.

• Journal of Periodontal and Implant Science
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• v.30 no.1
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• pp.51-65
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• 2000

Extracellular matrix component is degraded by enzymes of thematrix metalloproteinases(MMPs). MMPs are produced by both hemopoietic and structural cells. Increased activity of MMP-3 in periodontium is strongly associated with inflammatory periodontal disease. The purpose of the present study was to estimate the effect of BMP-7 on regeneration of periodontium. The optical density was measured by microwell plate reader at 450 nm.The difference of the optical density and the relative activity ofMMP-3 according to the concentration were statistically analyzed by one way ANOVA. The results were as follows: 1. Tetracycline-HCl showed the tendency to inhibit the activity of MMP-3 at the concentration lower than $25{\mu}g/ml$. 2. Doxycycline-HCl inhibited significantly the activity of MMP-3 at the concentration lower than $100{\mu}g/ml$. 3 . Minocycline-HCl inhibited the activity of MMP-3 at the concentration in the range of 10 to 200${\mu}g/ml$. Within the limit of the present study, the above results suggested that bone morphogenetic protein-7 may play a important role in development of periodontium.

• Proceedings of the Korea Contents Association Conference
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• 2009.05a
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• pp.1124-1129
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• 2009

This study aims to examine the effects of non-invasive constant microcurrent stimulation on expression of Bone Morphogenetic Protein(BMP) 4 after tibia fracture in rabbits. Twenty four rabbits with tibia fracture were randomly divided into control and experimental groups. Each group was divided into four subgroups, based on the duration of the experiment (3, 7, 14, 28 days). The experimental groups received a constant microcurrent stimulation of $20{\sim}25{\mu}A$ intensity with surface Ag-AgCl electrode (diameter 1cm, Biopac, U.S.A.) for 24 hours a day. Cathode of the microcurrent stimulator located on the tibia directly, anode of it did on the gastrocnemius muscle. Rabbits were sacrificed on each of the postoperative days 3, 7, 14, 28. To investigate how non- invasive constant microcurrent stimulation affects bone healing, immunohistochemical analysis of BMP-4 was performed at each point. After evaluation, the test results are as follows: Comparisons of immunohistochemical observation of BMP-4 in 7 days after tibial fracture show that there was shown to be a moderate positive reaction (++) on concentric circles of Harversian system andt he interstitial lamella in the control group, while there was a very strong positive reaction (++++) on concentric circles of Harversian system and interstitial lamellain the experimental group. These results suggest that applying non-invasive constant microcurrent stimulation on fractured bone is helpful to bone healing.

• Asian-Australasian Journal of Animal Sciences
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• v.32 no.7
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• pp.949-955
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• 2019

Objective: The present study was to investigate the association of polymorphisms in exon-9 of the bone morphogenetic protein receptor-1B (BMPR-1B) gene (C864T) with litter size in 240 Dorset, 232 Mongolian, and 124 Small Tail Han ewes. Methods: Blood samples were collected from 596 ewes and genomic DNA was extracted using the phenol: chloroform extraction method. The 304-bp amplified polymerase chain reaction product was analyzed for polymorphism by single-strand conformation polymorphism method. The genotypic frequency and allele frequency of BMPR-1B gene exon-9 were computed after sequence alignment. The ${\chi}^2$ independence test was used to analyze the association of genotypic frequency and litter size traits with in each ewe breed, where the phenotype was directly treated as category. Results: The results indicated two different banding patterns AA and AB for this fragment, with the most frequent genotype and allele of AA and A. Calculated Chi-square test for BMPR-1B gene exon-9 was found to be more than that of p value at the 5% level of significance, indicating that the population under study was in Hardy-Weinberg equilibrium for all ewes. The ${\chi}^2$ independence test analyses indicated litter size differences between genotypes was not the same for each breed. The 304-bp nucleotide sequence was subjected to BLAST analysis, and the C864T mutation significantly affected litter size in singletons, twins and multiples. The heterozygosity in exon-9 of BMPR-1B gene could increase litter size for all the studied ewes. Conclusion: Consequently, it appears that the polymorphism BMPR-1B gene exon-9 detected in this study may have potential use in marker assisted selection for litter size in Dorset, Mongolian, and Small Tail Han ewes.

• Journal of Veterinary Clinics
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• v.29 no.5
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• pp.412-415
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• 2012

A 1-year-old, castrated male Yorkshire terrier (case 1) and a 7-year-old female Poodle (case 2) presented with delayed union fractures. In case 1, the dog had a fractured right distal radius and ulna. In case 2, the dog had a fractured left distal tibia and fibula. A physical examination and radiographs performed in both dogs revealed delayed union fractures with large gaps. The fracture sites were fixed by bone plate and screws. Autogenous cancellous bone graft was applied into the fracture gap. To encourage rapid bone union, we used matrigel containing $20{\mu}g$ of recombinant human bone morphogenetic protein-2 (rhBMP-2) in the fracture site. Radiographs were taken postoperatively to monitor healing. Rapid bone union was noted in both dogs in long-term radiographs. In case 1, the radiographs revealed that the fracture gaps of the radius and ulna were bridged at 2 weeks. Fracture lines were not observed and normal appearance was restored at 20 weeks. In case 2, the radiographs showed that fracture repair had progressed at 11 weeks. The fractures healed faster than expected in these two cases. The results indicate that rhBMP-2 and matrigel may be effective and useful materials to enhance healing of delayed fractures.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.36 no.6
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• pp.466-472
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• 2010

Introduction: This study examined the effect of recombinant human bone morphogenetic protein (rhBMP)-2 and $\beta$-tricalcium phosphate ($\beta$-TCP) on new bone formation in a rabbit calvarium using a rapid prototype titanium cap (RP Ti cap). Materials and Methods: Eight New Zealand white rabbits were used in this study. Hemispherical RP Ti caps (10 mm in diameter) were implanted subperiosteally on the rabbit calvaria. $\beta$-TCP was filled in the RP Ti cap in the control group, and rhBMP-2 soaked $\beta$-TCP was used in experimental group. The rabbits were sacrificed 2 and 4 weeks after the operation. The volume and pattern of newly formed bone was analyzed by micro computed tomography (CT). Results: Macroscopically, there were no abnormal findings in any of the animals. The micro CT images revealed new bone from the calvaria that expanded gradually toward the top of the titanium cap, particularly along the inner surface of the titanium cap in the experimental group at 4 weeks after grafting. There was no significant difference in new bone volume ratio between the control and experimental groups at 2 weeks after grafting. There was a statistically significant difference in the new bone volume ratio between the experimental ($14.1{\pm}1.8\;%$) and control ($7.2{\pm}1.5\;%$) groups at 4 weeks after grafting (P<0.01). Conclusion: The RP Ti cap can effectively guide new bone formation and rhBMP-2 can induce the new bone formation.