• The Korea Journal of Herbology
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• v.29 no.5
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• pp.31-38
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• 2014

Objectives : Egg yolk is composed of various important chemical substances for human health. A calcium shortage causes the growth retardation on the body growth. In this study, we examined the therapeutic effects of calcium, vitamin D and egg yolk peptide (EYP) treatment on the retardation of the longitudinal bone growth induced by low-calcium diet in adolescent rats. Methods : Low calcium diets were administrated for 15 days. During the last five days, calcium and/or vitamin D and/or EYP were administrated. The body weights, longitudinal bone growth rates, the heights of growth plates, and bone morphogenetic protein (BMP)-2 and insulin-like growth factor (IGF)-1 expressions were measured using histochemical analysis. Results : Low calcium diets caused the significant reduction in body weight gains and the longitudinal bone growth. The heights of growth plates and the expressions of BMP-2 and IGF-1 showed the impairment of body growth as well. Calcium and/or vitamin D administration could not significantly increase the longitudinal bone growth. However, calcium, vitamin D, and EYP administration significantly increased the bone growth, the growth plate height, and BMP-2 and IGF-1 expressions. Conclusions : These results suggest that EYP enhances the longitudinal bone growth in the calcium and/or vitamin D deficiency and it could be a promising agent for the treatment of children suffering from malnutrition.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.36 no.1
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• pp.25-29
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• 2014

The purpose of this study is to report on five cases treated with bone graft using recombinant human bone morphogenetic protein-2 (rhBMP-2) on jaw defects after cyst enucleation. We performed bone graft with BMP (rhBMP-2+${\beta}$-tricalcium phosphate/hydroxyapatite) wrapped with a collagen sponge on jaw defects after cyst enucleation. Postoperative panoramic radiographs were taken periodically. After 1 to 12 months, bone remodeling was observed in the jaw defect area. In our cases, there were few signs or symptoms of recurrence of the cyst during the follow-up period.

• Journal of Periodontal and Implant Science
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• v.37 no.3
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• pp.511-522
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• 2007

Introduction : The purpose of this study was to evaluate the possibility of the acellular dermal matrix (ADM) as a barrier membrane for bone regeneration, and to evaluate the osteogenic effect of ADM as a carrier system for rhBMP-2 in the rat calvarial defect model. Materials and Methods: An 8-mm, calvarial, critical-size osteotomy defect was created in each of 60 male Spraque-Dawley rats(weight $250{\sim}300g$). Three groups of 20 animals, each received either rhBMP-2(0.025mg/ml) in an ADM carrier, ADM only, or negative surgical control. And each group was divided into 2- and 8-weeks healing intervals. The groups were evaluated by histologic and histomorphometric parameters(10 animals/group/healing intervals). Data were expressed as $means{\pm}standard$ deviations($m{\pm}SD$). Comparisons between experimental and control groups were made using two-way ANOVA and post hoc t-test. Comparisons between 2 weeks and 8 weeks were made using paired t-test. The level of statistical difference was defined as P< 0.05. Results : The ADM group and rhBMP-2/ADM group results in enhanced local bone formation in the rat calvarial defect at both 2 and 8 weeks. The amount of defect closure and new bone formation were significantly greater in the rhBMP-2/ADM group relative to ADM group(P<0.05). At 8 weeks, the majority of ADM in the defect was contracted, and integrated with surrounding host tissues. In addition, host cell infiltration and neovascularization of the ADM in the absence of an inflammatory response were observed, and the newly formed bone around ADM showed a continuous remodeling and consolidation. Conclusion : The results of the present study indicated that ADM may be used as a barrier membrane for bone regeneration and that may be employed as a delivery system for BMPs.

• 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.

• BMB Reports
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• v.55 no.11
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• pp.565-570
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• 2022

Pulmonary arterial hypertension (PAH) is a progressive and devastating disease whose pathogenesis is associated with a phenotypic switch of pulmonary arterial vascular smooth muscle cells (PASMCs). Bone morphogenetic protein (BMP) signaling and potassium two pore domain channel subfamily K member 3 (KCNK3) play crucial roles in PAH pathogenesis. However, the relationship between BMP signaling and KCNK3 expression in the PASMC phenotypic switching process has not been studied. In this study, we explored the effect of BMPs on KCNK3 expression and the role of KCNK3 in the BMP-mediated PASMC phenotypic switch. Expression levels of BMP receptor 2 (BMPR2) and KCNK3 were downregulated in PASMCs of rats with PAH compared to those in normal controls, implying a possible association between BMP/BMPR2 signaling and KCNK3 expression in the pulmonary vasculature. Treatment with BMP2, BMP4, and BMP7 significantly increased KCNK3 expression in primary human PASMCs (HPASMCs). BMPR2 knockdown and treatment with Smad1/5 signaling inhibitor substantially abrogated the BMP-induced increase in KCNK3 expression, suggesting that KCNK3 expression in HPASMCs is regulated by the canonical BMP-BMPR2-Smad1/5 signaling pathway. Furthermore, KCNK3 knockdown and treatment with a KCNK3 channel blocker completely blocked BMP-mediated anti-proliferation and expression of contractile marker genes in HPAMSCs, suggesting that the expression and functional activity of KCNK3 are required for BMP-mediated acquisition of the quiescent PASMC phenotype. Overall, our findings show a crosstalk between BMP signaling and KCNK3 in regulating the PASMC phenotype, wherein BMPs upregulate KCNK3 expression and KCNK3 then mediates BMP-induced phenotypic switching of PASMCs. Our results indicate that the dysfunction and/or downregulation of BMPR2 and KCNK3 observed in PAH work together to induce aberrant changes in the PASMC phenotype, providing insights into the complex molecular pathogenesis of PAH.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.36 no.5
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• pp.366-374
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• 2010

Introduction: This study evaluated the capability of silk fibroin (SF) and recombinant human bone morphogenetic protein-2 loaded SF (SF-BMP) as a bone defect replacement matrix when grafted in a calvarial bone defect of rats in vivo. Materials and Methods: A total 70 calvarial critical size defects (5.0 mm in diameter) made on 35 adult female Sprague-Dawley rats were used in this study. The defects were transplanted with (1) rhBMP-2 loaded silk fibroin graft (SF-BMP: 0.8+$10\;{\mu}g$), (2) Silk fibroin (SF: $10\;{\mu}g$), and (3) no graft material (Raw). The samples were evaluated with soft x-rays, alkaline phosphatase activity, calcium/phosphate quantification, histological and histomorphometric analysis at postoperative 4 and 8 weeks. Results: The SF-BMP group ($48.86{\pm}14.92%$) had a significantly higher mean percentage bone area than the SF group ($24.96{\pm}11.01%$) at postoperative 4 weeks.(P<0.05) In addition, the SF-BMP group ($40.01{\pm}12.43%$) had a higher % bone area at postoperative 8 weeks than the SF group ($33.26{\pm}5.15%$). The mean ratio of gray scale levels to the host bone showed that the SF-BMP group ($0.67{\pm}0.08$) had a higher mean ratio level than the SF group ($0.61{\pm}0.09$) at postoperative 8 weeks. These differences were not statistically significant.(P=0.168 and P=0.243, respectively) The ratio of the calcium and phosphate contents of the SF-BMP ($0.93{\pm}0.22$) group was lower than that of the SF ($1.90{\pm}1.42$) group at postoperative 4 weeks. However, the SF-BMP group ($0.75{\pm}0.31$) had a higher Ca/$PO_4$ ratio than the SF ($0.68{\pm}0.04$) at postoperative 8 weeks. These differences were not statistically significant.(P=0.126 and P=0.627, respectively) For the bone-specific alkaline phosphatase (ALP) activity, which is recognized as a reliable indicator of the osteoblast function, the SF-BMP ($23.71{\pm}8.60\;U/L$) groups had a significantly higher value than the SF group ($12.65{\pm}6.47\;U/L$) at postoperative 4 weeks.(P<0.05) At postoperative 8 weeks, the SF-BMP ($21.65{\pm}10.02\;U/L$) group had a lower bone-specific ALP activity than the SF group ($16.72{\pm}7.35\;U/L$). This difference was not statistically significant.(P=0.263) For the histological evaluation, the SF-BMP group revealed less inflammation, lower foreign body reactions and higher bone healing than the SF group at postoperative 4 and 8 weeks. The SF group revealed more foreign body reactions at postoperative 4 weeks. However, this immunogenic reaction decreased and the remnant of grafted material was observed at postoperative 8 weeks. For histomorphometric analysis, the SF-BMP group had a significantly longer bone length to total length ratio than those of the SF group at postoperative 4 and 8 weeks.(P<0.05) Conclusion: The rhBMP-2 loaded silk fibroin graft revealed fewer immunoreactions and inflammation as well as more new bone formation than the pure silk fibroin graft. Therefore, silk fibroin may be a candidate scaffold for tissue engineered bone regeneration.

• Journal of Korean Neurosurgical Society
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• v.64 no.4
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• pp.562-574
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• 2021

Objective : This study is to evaluate the efficacy and safety of demineralized bone matrix (DBM) gel versus DBM gel with recombinant human bone morphogenetic protein-2 (rhBMP-2) used in transforaminal lumbar interbody fusion (TLIF). Methods : This study was designed as a prospective, multi-center, double-blind method, randomized study. All randomized subjects underwent TLIF with DBM gel with rhBMP-2 group (40 patients) as an experimental group or DBM gel group (36 patients) as a control group. Post-operative observations were performed at 12, 24, and 48 weeks. The spinal fusion rate on computed tomography scans and X-rays films, Visual analog scale pain scores, Oswestry disability index and SF-36 quality of life (QOL) scores were used for the efficacy evaluation. The incidence rate of adverse device effects (ADEs) and serious adverse device effects (SADEs) were used for safety evaluation. Results : The spinal fusion rate at 12 weeks for the DBM gel with rhBMP-2 group was higher with 73.68% compared to 58.82% for the DBM gel group. The 24 and 48 weeks were 72.22% and 82.86% for the DBM gel with rhBMP-2 group and 78.79% and 78.13%, respectively, for the DBM gel group. However, there were no significant differences between two groups in the spinal fusion rate at 12, 24, and 48 weeks post-treatment (p=0.1817, p=0.5272, p=0.6247). There was no significant difference between the two groups in the incidence rate of ADEs (p=0.3836). For ADEs in the experimental group, 'Pyrexia' (5.00%) was the most common ADE, followed by 'Hypesthesia', 'Paresthesia', 'Transient peripheral paralysis', 'Spondylitis' and 'Insomnia' (2.50%, respectively). ADEs reported in control group included 'Pyrexia', 'Chest discomfort', 'Pain', 'Osteoarthritis', 'Nephropathy toxic', 'Neurogenic bladder', 'Liver function analyses' and 'Urticaria' (2.86%, respectively). There was no significant difference between the two groups in the incidence rate of SADEs (p=0.6594). For SADE in the experimental group, ''Pyrexia' and 'Spondylitis' were 2.50%. SADE reported in the control group included 'Chest discomfort', 'Osteoarthritis' and 'Neurogenic bladder'. All SADEs described above were resolved after medical treatment. Conclusion : This study demonstrated that the spinal fusion rates of DBM gel group and DBM gel with rhBMP-2 group were not significantly different. But, this study provides knowledge regarding the earlier postoperative effect of rhBMP-2 containing DBM gel and also supports the idea that the longer term follow-up results are essential to confirm the safety and effectiveness.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.38
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• pp.22.1-22.6
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• 2016

Background: The aim of this study is to quantitatively evaluate the effect of rhBMP-2 for repair of bone defects after cyst enucleation using the osteogenesis index (OI). Methods: Under general anesthesia, 10 patients (12 lesions) underwent oral or maxillofacial surgery for cyst enucleation. Postoperatively, 12 lesions were divided into two groups: group A (six lesions) was treated with absorbable collagen sponge (ACS) in combination with rhBMP-2, and group B (six lesions) was treated with ACS alone. After 3 months, cone-beam computed tomographic scans were obtained to measure changes in the volume of the lesions. We then calculated the OI of each group at two different Hounsfield units to determine any statistically significant difference between these two groups (Mann-Whitney U test). Results: As tested at the level of new bone, the mean OI was 72.37 % in group A and 55.08 % in group B -a statistically significant difference (p = 0.041). As tested at the level of mature bone, the mean OI was 27.47 % in group A and 18.88 % in group B, but the difference was not statistically significant (p = 0.394). Conclusions: The application of rhBMP-2 after maxillofacial cyst enucleation accelerated new bone formation in the bone defects. Thus, the use of rhBMP-2 in combination with ACS may be considered an alternative to conventional bone grafting in some patients with postoperative bone defects.

• Journal of Life Science
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• v.27 no.5
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• pp.501-508
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• 2017

Bone morphogenetic proteins (BMPs) are multifunctional cytokines that play important roles in a variety of cellular functions. Among BMP family members, BMP2 efficiently promotes osteoblast differentiation through Smad-mediated runt-related transcription factor 2 (Runx2) expression. Several recent studies suggest that BMPs are associated with clock genes, in particular Bmal1. Bmal1 protein heterodimerizes with Clock protein and then induces period 1 (Per1) expression. However, the role of Per1 on osteoblast differentiation remains unclear. In this study, we investigated whether Per1 is involved in osteoblast differentiation. MC3T3-E1 cells were treated with BMP2 for induction of osteoblastic differentiation. Osteogenic maker gene and Per1 mRNA expression were measured using real-time PCR. Interestingly, BMP2 treatment induced Per1 mRNA expression in MC3T3-E1 cells. To further investigate the function of Per1 on osteoblast differentiation, MC3T3-E1 cells were transiently transfected with pCMV-Per1. Per1 overexpression increased Runx2 mRNA and protein levels. Also, mRNA expression and promoter activity of osteocalcin were upregulated by Per1 overexpression. To investigate the effect of interaction between Per1 and osteogenic condition, MC3T3-E1 cells were cultured in osteogenic medium containing ascorbic acid and ${\beta}$-glycerophosphate. Osteogenic medium-induced ALP staining level and mineralization were synergistically increased by overexpression of Per1. Taken together, these results demonstrate that Per1 is a positive regulator of osteoblast differentiation.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.26 no.4
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• pp.325-336
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• 2000

Bone morphogenetic protein-2/4 are members of Transforming Growth Factor-$\beta$(TGF-$\beta$) superfamily and they may induce formation of cartilage and bone in vivo. This study was performed to investigate the cellular target and period of action of BMP-2/4 and understanding of actions of BMP-2/4 at cellular level. The appearance of BMP-2/4 during healing of mandibular and periodontal defect in rat was evaluated immunohistochemically. 40 Sprague-Dawley strain white male rats, each weighing about 300gm were used. Bony defect was performed in the mandible and they were sacrificed at the day of 3rd, 10th, 20th, 30th after operation. The specimens were harvested and examined histologically and immunohistochemically by localization of anti-BMP-2/4. The results were as follows: 1. Woven bone was observed at 10th day and perfect healing of defect with compact bone and periodontal ligment space at 30th day. 2. Osteoprogenitor cells, osteoblastic cells and periosteum were positive reaction to immunohistochemical stain at 10th day. 3. Cells of bone marrow space and surface cells of osteocytes and cementoblasts were positive reaction to immunohistochemical stain at 20th day. 4. Newly formed osteocytes and cementocytes were positive reaction to immunohistochemical stain at 30th day. From the above findings, we could conclude that BMP-2/4 acted significant roles as factors of induction, proliferation and differentiation during bone healing process.