• Journal of Periodontal and Implant Science
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• 제32권2호
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• pp.389-402
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• 2002

BMP can induce ectopic bone formation when implanted into sites such as rat muscle and can greatly enhance healing of bony defects when applied exogenously. In addition, BMP stimulated osteoblastic differentiation in vitro in various types of cells. The aim of this study was to investigate the effect of recombinant human bone morphogenetic protein(rhBMP-2) on the proliferation and osteoblastic differentiation of human periodontal ligament cells and gingival fibroblasts. The cell number and alkaline phosphatase activity were measured in 3 experimental groups of human periodontal ligament cells and gingival fibroblasts (control group, rhBMP-2 50ng/ml group, and rhBMP-2 100ng/ml group) at 1 and 2 weeks after culture. At the same time, total RNA of cultured cells were extracted and reverse trascription polymerase chain reaction(RT-PCR) was performed to determine the expression of mRNA of bone matrix protein. RhBMP-2 had no effect on the cell proliferation of human periodontal ligament cells and gingival fibroblasts. Alkaline phosphatase activity was elevated significantly by rhBMP-2 in both cells. And periodontal ligament cells showed significantly higher alkaline phosphatase activity than gingival fibroblasts. ${\beta}$-actin, type I collagen, alkaline phosphatase, BMP-2 mRNA were expressed in all of the samples. Osteopontin, osteocalcin mRNA were expressed in all periodontal ligament cell groups, and rhBMP-2 50ng/ml group, rhBMP-2 100ng/ml group of 2 week culture period of gingival fibroblasts. Bone sialoprotein mRNA was only expressed in rhBMP-2 50ng/ml group and rhBMP-2 100ng/ml group of 2-week culture period. These results suggest that rhBMP-2 stimulates osteoblastic differentiation in human periodontal ligament cells and gingival fibroblasts in vitro.

• 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.

• 대한본초학회지
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• 제37권1호
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• pp.51-59
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• 2022

Objectives : The process through which mesenchymal cells condense and differentiate into chondrocytes to form new bone is known as endochondral bone formation. Chondrogenic differentiation and hypertrophy are essential steps in bone formation and are influenced by various factors. The stem bark and root bark of Eleutherococcus sessiliflorus (ES) have been widely used to treat growth retardation and arthritis in traditional Korean Medicine. In this study, we aimed to investigate the possible role of the stem bark of ES in the stimulation of chondrogenic differentiation in clonal murine chondrogenic ATDC5 cells. Methods : In ATDC5 cells treated with ES extract, cell viability and extracellular matrix production were determined using CCK-8 assay and Alcian blue staining, respectively, and alkaline phosphatase activity was measured. We also examined mRNA and protein expression levels of genes related to chondrogenic expression in ATDC5 cells using reverse transcription-polymerase chain reaction and western blot analyses. Results : ES extract increased the accumulation of Alcian blue-stained cartilage nodules and alkaline phosphatase activity in ATDC5 cells. It increased the mRNA expressions of chondrogenic markers including bone sialoprotein (BSP), cartilage collagens, Runt-related transcription factor-2 (RUNX-2), osteocalcin (OCN), β-catenin, and bone morphogenetic protein-2 (BMP-2), as well as the protein expressions of β-catenin, RUNX-2, BMP-2, and alkaline phosphatase (ALP). Conclusion : Taken together, these results suggest that ES extract exhibits a chondromodulating activity and therefore may be a possible agent for the treatment of bone growth disorders.

• 약학회지
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• 제53권4호
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• pp.206-216
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• 2009

3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (Statins) are potent inhibitors of cholesterol biosynthesis. Cholesterol-lowering therapy using statins significantly reduces the risk of coronary heart disease. Various discovery of statins as bone anabolic agents has spurred a great deal of interest among both basic and clinical bone researchers. In-vitro and some animal studies suggest that statins increase the bone mass by enhancing bone morphogenetic protein-2 (BMP-2)-mediated osteoblast expression. Clinical and animal test results of statins focusing on the prevention and treatment of bone fractures was collected. Three independent literature searches were performed by using from January 1, 2002 to September 2008 for clinical and animal test results. Search term included statins, HMG-CoA reductase inhibitors, pleiotropic effects, fracture, osteoporosis and clinical and animal test. No consensus has been reached whether clinical use of statins has beneficial effects on bone health, partly due to lower statin concentrations because of first-pass metabolism by the liver. Experimental use of statins as stimulators of bone formation suggests that they may have widespread applicability in the field of orthopaedics. With their combined effects on osteoblasts and osteoclasts, statins have the potential to enhance resorption of synthetic materials and improve bone ingrowth. In conclusion, The use of statins in the prevention and treatment of bone fractures requires further study. But observational studies suggest that statins for decreasing bone fractures including osteoporosis have to be considered local direct administration like transdermal or subcutaneous type over oral adminstration.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제26권2호
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• pp.179-185
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• 2000

The purpose of this study was to develop an osteogenic, biodegradable material using polymer and BMP. It was designed to have structural function and be moldable, for the reconstruction of load bearing areas and deformities of various configurations. Bone apatite was added to Poly(L-lactide)(PLLA) and made porous for osteoconductability and ease of BMP loading. The materials, with or without BMP purified from porcine bone matrix, were evaluated in cranial bone defect models in rats for biocompatibility and bone regeneration capability. The following results were obtained: The PLLA-BMP material with BMP added to the polymer showed 30% healing of cranial bone defects in rats during the 2 weeks to 3 months period of observation. The moldable PLLA agent without BMP also showed 25% bone healing capacity. Although new bone formation was incomplete in the critical size defect of rat cranium, it can be concluded that the unique moldability of those agents makes them useful for the reconstruction of various bone defects and maxillofacial deformities.

• 한국임상수의학회지
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• 제31권5호
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• pp.417-420
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• 2014

몇몇의 정형외과 질환에서 골이식은 필수적이며, 합성 골물질은 골이식물로서 널리 쓰여지고 있다. 한편, 골형성 단백질과 섬유아세포 성장 인자와 같은 골 유도 단백질은 골아세포의 분화 및 증식을 촉진시킬 수 있다. 이러한 물질들의 조합은 조기에 골형성을 촉진시킬 수 있어 수의임상에서 널리 사용되고 있다. 이번 증례보고에서는 합성 골물질과 골유도 단백질을 조합하여 대형 골결손부를 성공적으로 치료한 개의 2 증례를 보고하고자 한다.

• 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.

• International Journal of Industrial Entomology and Biomaterials
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• 제27권1호
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• pp.159-165
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• 2013

Bone morphogenetic proteins (BMPs) belong to the transforming growth factor (TGF-${\beta}$) superfamily and are involved in osteoblastic differentiation. The largest TGF-${\beta}$ superfamily subgroup shares genetic homology with human BMPs (hBMPs) and silkworm decapentaplegic (dpp). In addition, hBMPs are functionally interchangeable with Drosophila dpp. Bombyx mori dpp may induce bone formation in mammalian cells. To test this hypothesis, we synthesized the 1,285-base pairs cDNA of full-length B. mori dpp using total RNAs obtained from the fat body of 3-day-old of the $5^{th}$ instar larvae and cloned the cDNA into the pCEP4 mammalian expression vector. Next, B. mori dpp was expressed in C3H10T1/2 cells. The target cells transfected with the pCEP4-Bm dpp plasmid showed biological functions similar to those of osteogenic differentiation induction growth factors such as hBMPs. We determined the relative mRNA expression rates of Runt-related transcription factor 2 (RUNX2), osterix, osteocalcin, and alkaline phosphatase (ALP) to validate the osteoblast-specific differentiation effects of B. mori dpp by performing quantitative real-time RT-PCR. Interestingly, mRNA expression levels of the 3 marker genes except RUNX2, in cells expressing B. mori dpp were much higher than those in control cells and C3H10T1/2 cells transfected with pCEP4. These results suggested that B. mori dpp signaling regulates osterix expression during osteogenic differentiation via RUNX2-independent mechanisms.

• 한국해양바이오학회지
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• 제15권1호
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• pp.24-32
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• 2023

The Laminaria japonica Aresch (Sea tangle) belongs to the brown algae and has a long history as a food material in Asia, including Korea. Recent studies have found that the fermented Sea tangle extract (FST) inhibited the differentiation of osteoclasts and protected osteoblasts from oxidative damage. This study aims to explore the possibility that FST can induce the differentiation of osteoblasts and identify the responsible mechanism. According to our results, FST induced differentiation into osteogenic cells in the presence of osteoblastic MC3T3-E1 cells under non-toxic conditions.. This finding was confirmed by phalloidin staining, increased alkaline phosphatase activity, and calcium deposition. Additionally, it was found that this process was achieved by increasing the expression of key factors involved in osteoblast differentiation, such as runt-related transcription factor-2, osterix, β-catenin, and bone morphogenetic protein-2. Moreover, FST increased autophagy, which may contribute to the maintenance of the bone formation homeostasis, and is associated with the activation of the phosphatidylinositol 3-kinase/Akt and mitogen-activated protein kinase signaling pathways. Although further research about the bioactive substances contained in FST and the tests of their efficacy are required, the results of this study indicate that FST has incredible applicability as a functional material for maintaining the bone homeostasis.

• BMB Reports
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• 제57권7호
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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.