• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제36권6호
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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.

• Journal of Periodontal and Implant Science
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• 제39권1호
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• pp.77-86
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• 2009

Purpose: Recombinant human bone morphogenetic protein-2(rhBMP-2) has been evaluated as potential candidates for periodontal and bone regenerative therapy. In spite of good prospects in BMP applications, there is economically unavailable for clinical use in dental area. The purpose of this study was to evaluate the osteogenic effect of rhBMP-2 produced by E.coli expression system. Materials and methods: Eight-mm critical-size calvarial defects were created in 48 male Sprague-Dawley rats. The animals were divided into 6 groups of 8 animals each. Each group received one of the following: Negative control(sham-surgery control), positive control(absorbable collagen sponge(ACS) alone) and experimental(ACS loaded with rhBMP-2). Defects were evaluated by histologic and histometric parameters following 2- and 8-week healing intervals. Results: The experimental group showed significant defect closure at 2 and 8weeks than the sham surgery and positive control groups. Moreover, the experimental group showed significantly greater new bone and augmented area than the other groups at both 2 and 8weeks. Conclusion: rhBMP-2 produced by E.coli expression system may be effective for bone regeneration.

• 한국임상수의학회지
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• 제29권5호
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• pp.412-415
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• 2012

1년령의 중성화된 수컷 요크셔테리어와 7년령의 암컷 푸들이 골절의 지연유합으로 내원하였다. 요크셔테리어의 경우 오른쪽 요골과 척골의 원위부가 골절되었고, 푸들의 경우 왼쪽 경골과 비골의 원위부가 골절되었다. 두 환자에서 신체검사 및 방사선검사를 통해 골절의 유합이 지연되고 있음을 확인하였다. 골절부는 금속판 및 나사못으로 고정시키고 자가해면질골을 골절 틈새에 이식하였다. 또한 빠른 골유합을 위해 $20{\mu}g$의 rh-BMP 2 가 포함된 matrigel을 골절부에 주입하였다. 수술 후 방사선검사를 통해 골절부의 치유 상태를 확인하였다. 장기간의 방사선검사에서 두 마리 모두 빠른 골유합을 보였다. 첫 증례에서는 방사선사진상에서 2주째에 요골과 척골 골절 틈새에 골밀도가 증가하였다. 20주째에는 골절선이 더 이상 관찰되지 않았으며, 정상 외관을 회복하였다. 두 번째 증례에서는 방사선사진상에서 11주째에 골절 치유가 진행되고 있음이 확인되었다. 이 두 증례 모두 예상한 것보다 골절의 치유가 빠르게 일어났다. 따라서 rh-BMP 2와 matrigel은 지연유합된 골절의 치유를 촉진하는데 효과가 있다고 생각된다.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제36권3호
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• pp.161-171
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• 2010

Introduction: This study was to assess the effectiveness of new bone formation and regeneration by using a rhBMP-2 and $\beta-TCP$ as a carrier in rabbits’mandible. Materials and Methods: The mandibles of 36 rabbits were exposed and cortical bone was penetrated for this study. The experimental subjects were divided into 3 groups each 12 rabbits ; control group, experimental group 1, and experimental group 2. Control group had the defect itself without any treatment, in the experimental group 1, $\beta-TCP$P only was grafted, and in the experimental group 2, rhBMP-2 soaked in $\beta-TCP$ was grafted. The rabbits were sacrificed after 1, 2, 3, 4, 6, and 8weeks, and new bone formation area was examined and measured for bone quantitative and qualitative analysis with light, fluorescent and polarized microscopy. Results: In the experimental group 1, new bone formation from the adjacent host bone was made by osteoconduction, and in the experimental group 2, direct new bone formation by osteoinduction of rhBMP-2 as well as new bone formation by osteoconduction of $\beta-TCP$ were observed. Conclusion: rhBMP-2 of experimental group 2 is very effective in the bone formation in early 2weeks and bone remodelling from 3weeks.

• 대한본초학회지
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• 제24권3호
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• pp.69-77
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• 2009

Objectives : This study was designed to investigate the effects of horse bone powder extract on the growth of longitudinal bone in adolescent male rats. Methods： Longitudinal bone growth was measured by fluorescent microscopy. To examine the effects on the growth plate metabolism, the total height of growth plate, the induction of local insulin-like growth factor-1 (IGF-1), and bone morphogenetic protein-2 (BMP-2) were measured. Results： Horse bone powder extract enhanced longitudinal bone growth and total height of the growth plate. Also, it promoted the induction of local IGF-1 and BMP-2 of the growth plate. Conclusions： This study shows that the horse bone powder extract effects longitudinal bone growth in adolescent rats and might be used for both stunted adolescents and inherent growth failure patients.

• The Korean Journal of Physiology and Pharmacology
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• 제25권3호
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• pp.197-206
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• 2021

Carnosol is a phenolic diterpene phytochemical found in rosemary and sage with reported anti-microbial, anti-oxidant, anti-inflammatory, and anti-carcinogenic activities. This study aimed to investigate the effect of carnosol on the lineage commitment of mouse bone marrow-derived mesenchymal stem cells (mBMSCs) into osteoblasts and adipocytes. Interestingly, carnosol stimulated the early commitment of mBMSCs into osteoblasts in dose-dependent manner as demonstrated by increased levels of alkaline phosphatase activity and Alizarin red staining for matrix mineralization. On the other hand, carnosol significantly suppressed adipogenesis of mBMSCs and downregulated both early and late markers of adipogenesis. Carnosol showed to induce osteogenesis in a mechanism mediated by activating BMP signaling pathway and subsequently upregulating the expression of BMPs downstream osteogenic target genes. In this context, treatment of mBMSCs with LDN-193189, BMPR1 selective inhibitor showed to abolish the stimulatory effect of carnosol on BMP2-induced osteogenesis. In conclusion, our data identified carnosol as a novel osteoanabolic phytochemical that can promote the differentiation of mBMSCs into osteoblasts versus adipocytes by activating BMP-signaling.

• Journal of Periodontal and Implant Science
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• 제37권3호
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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.

• Clinical and Experimental Reproductive Medicine
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• 제48권3호
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• pp.245-254
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• 2021

Objective: In humans, polycystic ovary syndrome (PCOS) is an androgen-dependent ovarian disorder. Aberrant gene expression in folliculogenesis can arrest the transition of preantral to antral follicles, leading to PCOS. We explored the possible role of altered gene expression in preantral follicles of estradiol valerate (EV) induced polycystic ovaries (PCO) in a mouse model. Methods: Twenty female balb/c mice (8 weeks, 20.0±1.5 g) were grouped into control and PCO groups. PCO was induced by intramuscular EV injection. After 8 weeks, the animals were killed by cervical dislocation. Blood serum (for hormonal assessments using the enzyme-linked immunosorbent assay technique) was aspirated, and ovaries (the right ovary for histological examinations and the left for quantitative real-time polymerase) were dissected. Results: Compared to the control group, the PCO group showed significantly lower values for the mean body weight, number of preantral and antral follicles, serum levels of estradiol, luteinizing hormone, testosterone, and follicle-stimulating hormone, and gene expression of TGFB1, GDF9 and BMPR2 (p<0.05). Serum progesterone levels were significantly higher in the PCO animals than in the control group (p<0.05). No significant between-group differences (p>0.05) were found in BMP6 or BMP15 expression. Conclusion: In animals with EV-induced PCO, the preantral follicles did not develop into antral follicles. In this mouse model, the gene expression of TGFB1, GDF9, and BMPR2 was lower in preantral follicles, which is probably related to the pathologic conditions of PCO. Hypoandrogenism was also detected in this EV-induced murine PCO model.

• 한국정밀공학회:학술대회논문집
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• 한국정밀공학회 2009년도 춘계학술대회 논문집
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• pp.51-52
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• 2009

• BMB Reports
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• 제44권10호
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• pp.619-634
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• 2011

Bone morphogenetic protein (BMP) signaling in diseases is the subject of an overwhelming array of studies. BMPs are excellent targets for treatment of various clinical disorders. Several BMPs have already been shown to be clinically beneficial in the treatment of a variety of conditions, including BMP-2 and BMP-7 that have been approved for clinical application in nonunion bone fractures and spinal fusions. With the use of BMPs increasingly accepted in spinal fusion surgeries, other therapeutic approaches targeting BMP signaling are emerging beyond applications to skeletal disorders. These approaches can further utilize next-generation therapeutic tools such as engineered BMPs and ex vivo-conditioned cell therapies. In this review, we focused to provide insights into such clinical potentials of BMPs in metabolic and vascular diseases, and in cancer.