• Journal of Periodontal and Implant Science
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• v.30 no.3
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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.

• 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.30 no.4
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• pp.757-779
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• 2000

The aim of our study is to achieve complete periodontal tissue regeneration by the application of BMP and resorbable membrane. Three beagle dogs aged over one and half years and weighed 14 to 16 kg were used in this study. Mandibular 1st, 2nd premolars were extracted bilaterally. Horizontal furcation defects were induced around 3rd, 4th premolars bilaterally. BMP-4 were applied in the right side with resorbable membranes and only resorbable membranes were applied in the left side respectively. Each animal was sacrificed at 2, 4, and 8weeks, after regenerative surgery. Specimens were prepared with Hematoxylin-Eosin stain and Goldner's modified Masson Trichrome stain for light microscopic evaluation. The results were as follows: 1. At 2 weeks after regenerative surgery, downgrowth of junctional epithelium was observed both in the membraneapplied site and BMP-4-and-membrane-applied site. 2. At 4 weeks after regenerative surgery, resorbable membranes were completely resolved, therefore would not prevent downgrowth of junctional epithelium. New bone formation, new cementum formation and Sharpey's fiber were observed in BMP-4-andmembrane-applied site. 3. At 8 weeks after regenerative surgery, downgrowth of junctional epithelium was observed in the membrane-applied site. But, new cementum formation was observed in the same site. The extensive regeneration of new bone, new cementum and remarkable formation of Shapey's fiber were showed in BMP-4-and-membrane-applied site. 4. Resorbable membranes were resolved via the cell-mediated processes. 5. Periodontal tissue regeneration were better achieved in the BMP-4-andmembrane-applied site than in the membrane-applied site. Within the above results, BMP-4 may have the strong capability to form the new bone and resorbable membrane may be able to prevent the bony ankylosis. However, resolution rate of resorbable membrane may not be enough to protect rapid epithelial downgrowth for ideal periodontal regeneration. In conclusion, I suggest BMP-4 may have the strong possibility to be utilized in the clinical periodontal treat-

• Asian-Australasian Journal of Animal Sciences
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• v.30 no.8
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• pp.1066-1073
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• 2017

Objective: Growth-related traits are important economic traits in the swine industry. However, the genetic mechanism of growth-related traits is little known. The aim of this study was to screen the candidate genes and molecular markers associated with body dimension and body weight traits in pigs. Methods: A genome-wide association study (GWAS) on body dimension and body weight traits was performed in a White $Duroc{\times}Erhualian$ $F_2$ intercross by the illumina PorcineSNP60K Beadchip. A mixed linear model was used to assess the association between single nucleotide polymorphisms (SNPs) and the phenotypes. Results: In total, 611 and 79 SNPs were identified significantly associated with body dimension traits and body weight respectively. All SNPs but 62 were located into 23 genomic regions (quantitative trait loci, QTLs) on 14 autosomal and X chromosomes in Sus scrofa Build 10.2 assembly. Out of the 23 QTLs with the suggestive significance level ($5{\times}10^{-4}$), three QTLs exceeded the genome-wide significance threshold ($1.15{\times}10^{-6}$). Except the one on Sus scrofa chromosome (SSC) 7 which was reported previously all the QTLs are novel. In addition, we identified 5 promising candidate genes, including cell division cycle 7 for abdominal circumference, pleiomorphic adenoma gene 1 and neuropeptides B/W receptor 1 for both body weight and cannon bone circumference on SSC4, phosphoenolpyruvate carboxykinase 1, and bone morphogenetic protein 7 for hip circumference on SSC17. Conclusion: The results have not only demonstrated a number of potential genes/loci associated with the growth-related traits in pigs, but also laid a foundation for studying the genes' role and further identifying causative variants underlying these loci.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.29 no.5
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• pp.293-297
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• 2003

Florid cemento-osseous dysplasia (FCOD) is a benign, non-neoplastic lesion characterized by multiple sclerosing masses only within jawbones. It is frequently confused with chronic diffuse sclerosing osteomyelitis (CDSO) in previous literatures. In our study, two cases of FCOD were examined to know the characteristics of their calcifying tissues. The first case was non-infected, while the second case was severely infected, displaying the typical features of CDSO in clinico-radiologic findings. The infected FCOD case showed a lot of bacterial colonies in the main lesion with relatively rare inflammatory reaction. The globular cementum-like materials of FCOD showed woven bone pattern and was positive for Alcian blue stain, and also positive for the antibodies of ameloblastin, bone morphogenetic protein (BMP) -2 and -4. On the other hands, in the immunostains of matrix metalloproteinase (MMP) -3, -9, -10, and $TNF-{\alpha}$, macrophage infiltrated in the FCOD lesion was rarely observed. These data suggest that the cementum-like materials of FCOD contain various matrix proteins, and that the cementum-like materials are relevant to the overgrowth of the bacterial colonies by inhibition of the regional inflammatory reactions.

• Journal of Periodontal and Implant Science
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• v.44 no.4
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• pp.178-183
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• 2014

Purpose: The aim of this study was to assess the possible paracrine effect of bone morphogeneticprotein-2 (BMP-2) at the experimental site on the adjacent control site for validating a rabbit calvarial defect model as a means of verifying the effect of BMP-2. Methods: Sixteen rabbits were divided into two groups (n=8 in each) according to whether or not BMP-2 would be used. Two circular defects (8 mm in diameter) were created side by side, 2 mm apart, in the calvarium of all of the rabbits. In each animal, one of the defects was grafted with either BMP-2-loaded carrier or carrier material alone. The control defects adjacent to these grafted defects, designated CB (the nongrafted defect adjacent BMP-2-loaded carrier-grafted defect) and CC (the nongrafted defect adjacent to carrier only-grafted defect), respectively, were the focus of this study, and were filled only with a blood clot in all of the animals. Histologic observation and histomorphometric analysis were performed at 2 and 8 weeks (n=4 animals per point in time) after surgery. Results: There was no noteworthy difference in the healing pattern, and no statistically significant differences in histomorphometric parameters such as the defect closure, new bone area, or total augmented area between the CC and CB groups. Conclusions: The results of this study suggest that rabbit calvarial defects separated by a distance of 2 mm are suitable for evaluating the effects of BMP-2 and the control defect can be regarded not to be affected by BMP-2 applied defect.

• Animal Bioscience
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• v.35 no.7
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• pp.1010-1020
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• 2022

Objective: The experiment was conducted to evaluate the effects of maternal undernutrition during late pregnancy on the expressions of genes involved in growth and development in ovine fetal perirenal brown adipose tissue (BAT). Methods: Eighteen ewes with singleton fetuses were allocated to three groups at day 90 of pregnancy: restricted group 1 (RG1, 0.33 MJ metabolisable energy [ME]/kg body weight [BW]^0.75/d, n = 6), restricted group 2 (RG2, 0.18 MJ ME/kg BW^0.75/d, n = 6), and a control group (CG, ad libitum, 0.67 MJ ME/kg BW^0.75/d, n = 6). The fetuses were removed at day 140 of pregnancy. All data were analyzed by using the analysis of variance procedure. Results: The perirenal fat weight (p = 0.0077) and perirenal fat growth rate (p = 0.0074) were reduced in RG2 compared to CG. In fetal perirenal BAT, the protein level of uncoupling protein 1 (UCP1) (p = 0.0001) was lower in RG1 and RG2 compared with CG and UCP1 mRNA expression (p = 0.0265) was decreased in RG2. The protein level of myogenic factor 5 (Myf5) was also decreased in RG2 (p = 0.0001). In addition, mRNA expressions of CyclinA (p = 0.0109), CyclinB (p = 0.0019), CyclinD (p = 0.0015), cyclin-dependent kinase 1 (CDK1) (p = 0.0001), E2F transcription factor 1 (E2F1) (p = 0.0323), E2F4 (p = 0.0101), and E2F5 (p = 0.0018) were lower in RG1 and RG2. There were decreased protein expression of peroxisome proliferator-activated receptor-γ (PPARγ) (p = 0.0043) and mRNA expression of CCAAT/enhancer-binding protein-α (C/EBPα) (p = 0.0307) in RG2 and decreased PPARγ mRNA expression (p = 0.0008) and C/EBPα protein expression (p = 0.0015) in both RG2 and RG1. Furthermore, mRNA expression of bone morphogenetic protein 4 (BMP4) (p = 0.0083) and BMP7 (p = 0.0330) decreased in RG2 and peroxisome proliferator-activated receptor co-activator-1α (PGC-1α) reduced in RG2 and RG1. Conclusion: Our observations support that repression of regulatory factors promoting differentiation and development results in the inhibition of BAT maturation in fetal perirenal fat during late pregnancy with maternal undernutrition.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.34 no.4
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• pp.419-427
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• 2008

The present study aimed to investigate the osteogenic potentials of differentiated osteoblast-like cells (DOCs) induced from bone marrow-derived mesenchymal stem cells (MSCs) on ${\beta}-tricalcium$ phosphate (${\beta}-TCP$) with recombinant human bone morphogenetic protein (rhBMP-2) in vitro. Osteoblast differentiation was induced in confluent cultures by adding 100 nM dexamethasone, 10 mM ${\beta}$-glycerophosphate, 50 mM L-ascorbic acid. The Alizarin red S staining and reverse transcriptase-polymerase chain reaction (RT-PCR) were perfomed to examine the mRNA expression of alkaline phosphatase (ALP), bone sialoprotein (BSP), osteocalcin (OCN), receptor activator for nuclear factor ${\kappa}B$ ligand (RANKL), runt-related transcription factor 2 (RUNX2), collagen-Ⅰ (COL-Ⅰ). There were no significant differences in the osteogenic potentials of DOCs induced from MSCs on ${\beta}-TCP(+/-)$. According to the incubation period, there were significant increasing of Alizadin red S staining in the induction 3 weeks. The mRNA expression of ALP, RUNX2, and RANKL were higher in DOCs/${\beta}-TCP(-)$ than DOCs/${\beta}-TCP(+)$. According to rhBMP-2 concentrations, the mRNA expression of BSP was significantly increased in DOCs/${\beta}-TCP(+)$ compared to that of DOCs/${\beta}-TCP(-)$ on rhBMP 10 ng/ml. Our study presented the ${\beta}-TCP$ will have the possibility that calcium phosphate directly affect the osteoblastic differentiation of the bone marrowderived MSCs.

• Molecules and Cells
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• v.37 no.4
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• pp.330-336
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• 2014

Thymosin beta4 (TB4) has multiple functions in cellular response in processes as diverse as embryonic organ development and the pathogeneses of disease, especially those associated with cardiac coronary vessels. However, the specific roles played by TB4 during heart valve development in vertebrates are largely unknown. Here, we identified a novel function of TB4 in endothelial-mesenchymal transformation (EMT) in cardiac valve endocardial cushions in zebrafish. The expressions of thymosin family members in developing zebrafish embryos were determined by whole mount in situ hybridization. Of the thymosin family members only zTB4 was expressed in the developing heart region. Cardiac valve development at 48 h post fertilization was defected in zebrafish TB4 (zTB4) morpholino-injected embryos (morphants). In zTB4 morphants, abnormal linear heart tube development was observed. The expressions of bone morphogenetic protein (BMP) 4, notch1b, and hyaluronic acid synthase (HAS) 2 genes were also markedly reduced in atrio-ventricular canal (AVC). Endocardial cells in the AVC region were stained with anti-Zn5 antibody reactive against Dm-grasp (an EMT marker) to observe EMT in developing cardiac valves in zTB4 morphants. EMT marker expression in valve endothelial cells was confirmed after transfection with TB4 siRNA in the presence of transforming growth factor ${\beta}$ ($TGF{\beta}$) by RT-PCR and immunofluorescent assay. Zn5-positive endocardial AVC cells were not observed in zTB4 morphants, and knockdown of TB4 suppressed TGF-${\beta}$-induced EMT in ovine valve endothelial cells. Taken together, our results demonstrate that TB4 plays a pivotal role in cardiac valve formation by increasing EMT.

• The Journal of the Korea Contents Association
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• v.10 no.3
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• pp.196-203
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• 2010

This study aimed to examine the effect of microcurrent stimulation on expression of Bone Morphogenetic Protein(BMP) 4 after tibia fracture in rabbits. The twenty four adult 6 month old New Zealand white rabbits weighting 2.5~3.5 ㎏ were used. 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 microcurrent stimulation of 20~25 ${\mu}A$ 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. 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 and the 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.