• 대한본초학회지
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• 제24권4호
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• pp.149-157
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• 2009

Objectives : This study was designed to investigate the effects of Cheunggyeongsamul-tang extract on the growth of longitudinal bone in adolescent female 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), IGF-1 receptor, bone morphogenetic protein-2 (BMP-2), BMPR-1A, indian hedgehog (IHH), and parathyroid hormone-related protein (PTH-rP) were measured. Results : Cheunggyeongsamul-tang extract enhanced longitudinal bone growth and total height of the growth plate. Also, it promoted the induction of local IGF-1, BMP-2, IHH and PTH-rP of the growth plate. Conclusions : This study shows that the Cheunggyeongsamul-tang extract effects longitudinal bone growth in adolescent rats and might be used for both stunted adolescents and inherent growth failure patients.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제26권4호
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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.

• 한국임상수의학회지
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• 제39권6호
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• pp.302-310
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• 2022

Recently, in human medicine and veterinary medicine, interest in synthetic bone graft is increasing. Among them, bone morphogenic protein (BMP) is currently being actively researched and applied to clinical trials. However, BMP has the disadvantage of being expensive and easily absorbed into surrounding tissues. Therefore, BMP requires the use of small amounts and rhBMP (recombinant human bone morphogenetic protein)-2 carriers that can be released slowly. Hydrogel has the property of swelling a large amount of water inside when it is aqueous solution, and when it is, it consists of more than 90 percent water. Using these properties, hydrogels are often used as rhBMP-2 carrier. The scaffold used in this study is a hydrogel made from which keratin is extracted using human hair and based on it. In this study, we wanted to see the effect of bone formation in the calvarial defect model by using keratin-based hydrogel made with human hair as a scaffold. The experiment was conducted by dividing 3 groups a total of 12 mice. Calvarial bone defect is set to all 4 mm diameters. Bone formation was evaluated by using gross evaluation, micro-computed tomography (micro-CT), immunohistochemistry. Groups using keratin-based hydrogel were significantly observed compared to Group 1s, and the most bone formations were found when rhBMP-2 and hydrogel were used. This represents the superiority of the functions of the rhBMP-2 carrier by a new material, keratin-based hydrogel. Through gross evaluation, micro-CT, and immunohistochemistry, we can confirm that keratin-based hydrogel is a useful rhBMP-2 carrier.

• 대한치과의사협회지
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• 제52권4호
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• pp.218-233
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• 2014

Bispbosphonates are a class of pharmaceutic agents, which induce apoptosis of osteoclast as well as impair osteoclastic activity to suppress bone resorption. Thus, bisphophonates are effectively used to treat osteoporosis, multiple myeloma and to prevent bone metastases of malignant cancer. However, recently dental disease have been reported associated with Bisphosphonates. Thus, there are a number of discussions about proper prevention and treatment of bisphosphonate-related osteonecrosis of jaw(BRONJ). Marshall R. Urist in 1965 made the seminal discovery that a specific protein, BMP(bone morphogenetic protein), found in the extracellular matrix of demineralized bone could induce bone formation newly when implanted in extraosseous tissues in a host. BMPs are multi-functional growth factors which are members of the transforming growth factor-beta super family and their ability is that plays a pivotal roll in inducing bone. About 18 BMP family members have been identified and characterized. Among of them, BMP-2 and BMP-7 have significant importance in bone development. In this study, patients of BRONJ were recieved who visited Department of oral and maxillofacial surgery, school of dentistry, Wonkwang university for past 3 years from 2011 to 2013. We focused on the results of the surgical intervention. We suggest that new strategy of treatment used to rhBMP-2 and LFA(Lidocaine-Fibrinogen-Aprotinin)-collagen scaffold for patients of BRONJ. The purpose of this paper is to give a brief overview of BMPs and to critically review the clinical data currently available on rhBMP-2 and LFA collage scaffold.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제30권4호
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• pp.316-322
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• 2004

A low molecular weight component named bone morphogenetic protein(BMP) chemically isolated from the organic matrix of bone, induce postfetal connective tissue cells surrounding small blood vessels to differentiate into cartilage and bone. The end product of BMP is a spherical ossicle of lamella bone filled with red bone marrow for the functional loading. This is a important point that the graft material is embedded the defect site during the implant surgery. Because present knowledge of the relationship between BMP and bone regeneration arises mainly from studies of induced bone formation in heterotopic sites, it would be helpful to determine whether BMP plays any part in the process of bone healing. The BMPs have been shown to play crucial roles in normal skeletal development as well as bone healing and are able to activate transcription of genes involved in cellular migration, proliferation, and differentiation. The delivery of BMP on matrices has been efficacious in the treatment of defect bone in implant surgery. The purpose of the histologic study was to evaluate the effect of DLB(demineralized lyophilized bone) coated with purified human BMP(hBMP-I) in immediate implant surgery with bony defect to obtain the functional structure of implant asap. The ability of a graft of hBMP-I to accelerate bony defect repair provides a rationale for its use in immediate implant surgery that have large bone defect in edentulous area.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제36권5호
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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.

• Molecules and Cells
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• 제39권5호
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• pp.389-394
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• 2016

Dovitinib (TKI258) is a small molecule multi-kinase inhibitor currently in clinical phase I/II/III development for the treatment of various types of cancers. This drug has a safe and effective pharmacokinetic/pharmacodynamic profile. Although dovitinib can bind several kinases at nanomolar concentrations, there are no reports relating to osteoporosis or osteoblast differentiation. Herein, we investigated the effect of dovitinib on human recombinant bone morphogenetic protein (BMP)-2-induced osteoblast differentiation in a cell culture model. Dovitinib enhanced the BMP-2-induced alkaline phosphatase (ALP) induction, which is a representative marker of osteoblast differentiation. Dovitinib also stimulated the translocation of phosphorylated Smad1/5/8 into the nucleus and phosphorylation of mitogen-activated protein kinases, including ERK1/2 and p38. In addition, the mRNA expression of BMP-4, BMP-7, ALP, and OCN increased with dovitinib treatment. Our results suggest that dovitinib has a potent stimulating effect on BMP-2-induced osteoblast differentiation and this existing drug has potential for repositioning in the treatment of bone-related disorders.

• 대한치과의사협회지
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• 제54권4호
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• pp.274-283
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• 2016

Bisphosphonates are widely used mainly for the treatment of osteoporosis and bone metastasis of malignancy. Since the first report of MRONJ, there have been many studies associated, however the pathogenesis of MRONJ is not yet clear. Medication-related osteonecrosis of the jaws (MRONJ) is a serious complication associated with long-term medication therapy. It is characterized by exposed necrotic bonein the jaw, which has persisted for more than 8weeks despite continuous treatment by dentist. The mechanism of development of MRONJ is still unclear and there is no definitive standard treatment for MRONJ. The purpose of this study is to investigate the jaw bone destruction mechanism of accumulated bisphosphonates, so that we can develop therapeutic method to repair the defect and stop the destruction process. The authors performed simultaneous application of PRF(Platelet rich fibrin) and BMP-2(Bone morphogenetic protein-2) to stimulate not only soft tissue healing but also osseous regeneration. Our case series demonstrate that simultaneous application of platelet rich fibrin and bone morphogenetic protein-2 can be a treatment of choice for MRONJ.

• IMMUNE NETWORK
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• 제23권6호
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• pp.48.1-48.21
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• 2023

Mesenchymal stromal/stem cells (MSCs) possess immunoregulatory properties and their regulatory functions represent a potential therapy for acute lung injury (ALI). However, uncertainties remain with respect to defining MSCs-derived immunomodulatory pathways. Therefore, this study aimed to investigate the mechanism underlying the enhanced effect of human recombinant bone morphogenic protein-2 (rhBMP-2) primed ES-MSCs (MSC^BMP2) in promoting Tregs in ALI mice. MSC were preconditioned with 100 ng/ml rhBMP-2 for 24 h, and then administrated to mice by intravenous injection after intratracheal injection of 1 mg/kg LPS. Treating MSCs with rhBMP-2 significantly increased cellular proliferation and migration, and cytokines array reveled that cytokines release by MSC^BMP2 were associated with migration and growth. MSC^BMP2 ameliorated LPS induced lung injury and reduced myeloperoxidase activity and permeability in mice exposed to LPS. Levels of inducible nitric oxide synthase were decreased while levels of total glutathione and superoxide dismutase activity were further increased via inhibition of phosphorylated STAT1 in ALI mice treated with MSC^BMP2. MSC^BMP2 treatment increased the protein level of IDO1, indicating an increase in Treg cells, and Foxp3⁺CD25⁺ Treg of CD4⁺ cells were further increased in ALI mice treated with MSC^BMP2. In co-culture assays with MSCs and RAW264.7 cells, the protein level of IDO1 was further induced in MSC^BMP2. Additionally, cytokine release of IL-10 was enhanced while both IL-6 and TNF-α were further inhibited. In conclusion, these findings suggest that MSC^BMP2 has therapeutic potential to reduce massive inflammation of respiratory diseases by promoting Treg cells.

• 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.