• Title/Summary/Keyword: Bone Morphogenetic Protein 4

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DEVELOPMENT OF BONE REGENERATING MATERIAL USING BONE MORPHOGENETIC PROTEIN(rhBMP-2) AND BIORESORBABLE POLYMER (유전자재조합 인간 골형성단백2 및 생흡수성고분자를 이용한 골형성유도체의 개발)

  • Lee, Jong-Ho;Kim, Jong-Won;Ahn, Kang-Min;Kim, Kack-Kyun;Lee, Zang-Hee
    • Maxillofacial Plastic and Reconstructive Surgery
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    • v.21 no.4
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    • pp.325-331
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    • 1999
  • We tested the bone regenerating capacity and histologic response of bioresorbable matrix-type implant, which was made with Poly(lactide-co-glycolide)(PLGA) and bone apatite for the carrier of bone morphogenetic protein(BMP). The critical size defect of 8mm in diameter was created at the calvaria of SD rats(n=18), and repaired with polymer implant with $15{\mu}g$ of rhBMP-2(n=9) or without it(n=9). At 2 weeks, 1 months after implantation, the animals were sacrificed(3 animals at every interval and group) and histologically evaluated. The calvarial defect which was repaired with polymer with BMP healed with newly formed bone about 70% of total defect. But that without BMP showed only 0 to under 30% bony healing. Inflammatory response was absent in both group through the experimental period, but there's marked foreign body giant response though it was a little less significant in polymer with BMP group. As the polymer was resorbed, the space was infiltrated and replaced by fibrovascular tissue, not by bone. In conclusion, our formulation of bioresorbable matrix implant loaded with bone morphogenetic protein works good as a bone regenerating material. However, it is mandatory to devise our system to have better osteoinductive and osteoconductive property, and less multinucleated giant cell response.

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Evaluation the Effectiveness of Fibrinogen to Overcome Bone Radiation Damage (방사성골괴사 극복을 위한 피브린지지체의 효용성 평가)

  • Jung, Hong-Moon
    • Journal of the Korean Society of Radiology
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    • v.15 no.4
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    • pp.539-545
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    • 2021
  • Radiation therapy is accompanied by adverse radiation effective. In particular, it is accompanied by disorders of the vascular system. Therefore, oxygen and nutrient deficiency occurs in the regeneration area. Eventually, osteoradionecrosis is formed in this cellular environment. According to a precedent study, bone morphogenetic protein-2 is used to overcome osteoradionecrosis. The purpose of this study was to investigate the regeneration ability of osteoradionecrosis by treating bone-forming protein-2 on a fibrinogen scaffold which is a biomaterial that is frequently used for bone regeneration after irradiation of the rat head. In addition, the purpose of this study was to verify the bone regeneration effect from the eight weeks. According to the experimental results, in the calvarial defected model of the irradiated mouse, making bone-formation was obtained after 8 weeks rather than bone-formation period in the early 4 weeks. moreover, it was found that the regenerated bone formation of the fibrinogen scaffold is formed from the inside of the bone of the defect area.

Comparative analysis of carrier systems for delivering bone morphogenetic proteins

  • Jung, Im-Hee;Lim, Hyun-Chang;Lee, Eun-Ung;Lee, Jung-Seok;Jung, Ui-Won;Choi, Seong-Ho
    • Journal of Periodontal and Implant Science
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    • v.45 no.4
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    • pp.136-144
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    • 2015
  • Purpose: The objective of this study was to comparatively assess the bone regenerative capacity of absorbable collagen sponge (ACS), biphasic calcium phosphate block (BCP) and collagenated biphasic calcium phosphate (CBCP) loaded with a low dose of recombinant human bone morphogenetic protein-2 (rhBMP-2). Methods: The CBCP was characterized by X-ray diffraction and scanning electron microscopy. In rabbit calvaria, four circular 8-mm-diameter defects were created and assigned to one of four groups: (1) blood-filled group (control), (2) rhBMP-2-soaked absorbable collagen sponge (0.05 mg/mL, 0.1 mL; CS group), (3) rhBMP-2-loaded BCP (BCP group), or (4) rhBMP-2-loaded CBCP (CBCP group). The animals were sacrificed either 2 weeks or 8 weeks postoperatively. Histological and histomorphometric analyses were performed. Results: The CBCP showed web-like collagen fibrils on and between particles. Greater dimensional stability was observed in the BCP and CBCP groups than in the control and the CS groups at 2 and 8 weeks. The new bone formation was significantly greater in the BCP and CBCP groups than in the control and CS groups at 2 weeks, but did not significantly differ among the four groups at 8 week. The CBCP group exhibited more new bone formation in the intergranular space and in the center of the defect compared to the BCP group at 2 weeks, but a similar histologic appearance was observed in both groups at 8 weeks. Conclusions: The dose of rhBMP-2 in the present study enhanced bone regeneration in the early healing period when loaded on BCP and CBCP in rabbit calvarial defects.

Effect of the combined use of bone morphogenetic protein and platelet-derived growth factor on bone formation in nude mouse (누드마우스에서 골 형성에 대한 BMP와 PDGF 복합사용의 효과)

  • Lee, Seoung-Ho;Choi, Byung-Ho;Zhu, Shi-Jiang;Huh, Jin-Young;Jung, Jae-Hyung;Kim, Byung-Yong
    • Journal of Periodontal and Implant Science
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    • v.35 no.2
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    • pp.263-269
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    • 2005
  • Bone morphogenetic protein(BMP) and platelet-derived growth factor(PDGF) have been demonstrated tostimulate bone formation when applied locally in vivo. To explore whether or not the combined use of BMP and PDGF could have promotive effect and synergic interaction on bone formation in vivo, bone marrow mesenchymal stem cells were treated with BMP-2, PDGF-BB, or BMP-2 plus PDGF-BB, and then these cells were injected into the subcutaneous space on the dorsum of nude mice. The bone formation was evaluated after 12 weeks. Histomorphometric analysis demonstrated that the subcutaneous nodules formed in nude mice contained 25.3% newly formed bone in the BMP-2 treated cells, 14.4% newly formed bone in the PDGF-BB treated cells, and 8.9% newly formed bone in the RMP-2 plus PDGF-BB treated cells. The results showed that the combination of BMP-2 and PDGF-BB had neither a promotive effect nor synergic interact on bone formation in vivo.

Response of osteoblast-like cells cultured on zirconia to bone morphogenetic protein-2

  • Han, Seung-Hee;Kim, Kyoung-Hwa;Han, Jung-Seok;Koo, Ki-Tae;Kim, Tae-Il;Seol, Yang-Jo;Lee, Yong-Moo;Ku, Young;Rhyu, In-Chul
    • Journal of Periodontal and Implant Science
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    • v.41 no.5
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    • pp.227-233
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    • 2011
  • Purpose: The aim of this study was to compare osteoblast behavior on zirconia and titanium under conditions cultured with bone morphogenetic protein-2. Methods: MC3T3-E1 cells were cultured on sandblasted zirconia and sandblasted/etched titanium discs. At 24 hours after seeding MC3T3-E1, the demineralized bone matrix (DBM) gel alone and the DBM gel with bone morphogenetic protein-2 (BMP-2) were added to the culture medium. The surface topography was examined by confocal laser scanning microscopy. Cellular proliferation was measured at 1, 4, and 7 days after gel loading. Alkaline phosphatase activity was measured at 7 days after gel loading. The mRNA expression of ALPase, bone sialoprotein, type I collagen, runt-related transcription factor 2 (Runx-2), osteocalcin, and osterix were evaluated by real-time polymerase chain reaction at 4 days and 7 days. Results: At 1, 4, and 7 days after loading the DBM gel alone and the DBM gel with BMP-2, cellular proliferation on the zirconia and titanium discs was similar and that of the groups cultured with the DBM gel alone and the DBM gel with BMP-2 was not significantly different, except for titanium with BMP-2 gel. ALPase activity was higher in the cells cultured with BMP-2 than in the other groups, but there was no difference between the zirconia and titanium. In ALPase, bone sialoprotein, osteocalcin, Runx-2 and osterix gene expression, that of cells on zirconia or titanium with BMP-2 gel was much more highly increased than titanium without gel at day 7. The gene expression level of cells cultured on zirconia with BMP-2 was higher than that on titanium with BMP-2 at day 7. Conclusions: The data in this study demonstrate that the osteoblastic cell attachment and proliferation of zirconia were comparable to those of titanium. With the stimulation of BMP-2, zirconia has a more pronounced effect on the proliferation and differentiation of the osteoblastic cells compared with titanium.

Increased osteoinductivity and mineralization by minimal concentration of bone morphogenetic protein-2 loaded onto biphasic calcium phosphate in a rabbit sinus

  • Kim, Jae-Shin;Cha, Jae-Kook;Lee, Jung-Seok;Choi, Seong-Ho;Cho, Kyoo-Sung
    • Journal of Periodontal and Implant Science
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    • v.46 no.5
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    • pp.350-359
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    • 2016
  • Purpose: The purpose of the present study was to evaluate the effectiveness of a minimal concentration of bone morphogenetic protein-2 (BMP-2) in terms of quantitative and qualitative analyses of newly formed bone in a rabbit maxillary sinus model. Methods: In 7 rabbits, sinus windows were prepared bilaterally. Biphasic calcium phosphate (BCP) loaded with 0.05 mg/mL BMP-2 was grafted into one sinus (the BMP group) and saline-soaked BCP was placed into the other (the control group) in each animal. The animals were allowed an 8-week healing period before being sacrificed. Specimens including the augmented area and surrounding tissues were then removed and evaluated both radiographically and histologically. Results: There was a difference in the mineralization of new bone between the groups. In the BMP group, the greater part of the new bone consisted of mature lamellar bone with an evident trabecular pattern, whereas the control group showed mostly woven bone, consisting only partially of lamellar bone. Histometrically, the area of new bone was significantly greater ($4.55{\pm}1.35mm^2$ vs. $2.99{\pm}0.86mm^2$) in the BMP group than in the control group (P<0.05); however, the total augmentation volumes were not significantly different between the groups. Conclusions: Within the limitations of this study, it can be suggested that a minimal concentration of BMP-2 (0.05 mg/mL) had an osteoinductive effect with accelerated mineralization in a rabbit sinus model using a BCP carrier.

Effects of Cheunggyeongsamul-tang Extract on Longitudinal Bone Growth in Adolescent Female Rats (청경사물탕(淸經四物湯) 추출물의 성장기 흰쥐 장골길이 성장에 대한 효과)

  • Lee, Jung-Hun;Lee, Se-Na;Son, Jae-Bong;Keum, So-Hyun;Leem, Kang-Hyun
    • The Korea Journal of Herbology
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    • v.24 no.4
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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.

Improvement of osteogenic potential of biphasic calcium phosphate bone substitute coated with two concentrations of expressed recombinant human bone morphogenetic protein 2

  • Choi, Hyun-Min;Park, No-Je;Jamiyandorj, Otgonbold;Choi, Kyung-Hee;Hong, Min-Ho;Oh, Seung-Han;Park, Young-Bum;Kim, Sung-Tae
    • Journal of Periodontal and Implant Science
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    • v.42 no.4
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    • pp.119-126
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    • 2012
  • Purpose: The aim of this study was to determine whether biphasic calcium phosphate (BCP) bone substitute with two different concentrations of Escherichia coli-expressed recombinant human bone morphogenetic protein 2 (ErhBMP-2) enhances new bone formation in a standardized rabbit sinus model and to evaluate the concentration-dependent effect of ErhBMP-2. Methods: Standardized, 6-mm diameter defects were made bilaterally on the maxillary sinus of 20 male New Zealand white rabbits. Following removal of the circular bony windows and reflection of the sinus membrane, BCP bone substitute without coating (control group) was applied into one defect and BCP bone substitute coated with ErhBMP-2 (experimental group) was applied into the other defect for each rabbit. The experimental group was divided into 2 subgroups according to the concentration of ErhBMP-2 (0.05 and 0.5 mg/mL). The animals were allowed to heal for either 4 or 8 weeks and sections of the augmented sinus and surrounding bone were analyzed by microcomputed tomography and histologically. Results: Histologic analysis revealed signs of new bone formation in both the control and experimental groups with a statistically significant increase in bone formation in experimental group 1 (0.05 mg/mL ErhBMP-2 coating) after a 4-week healing period. However, no statistically significant difference was found between experimental group 1 and experimental group 2 (0.5 mg/mL ErhBMP-2 coating) in osteoinductive potential (P<0.05). Conclusions: ErhBMP-2 administered using a BCP matrix significantly enhanced osteoinductive potential in a standardized rabbit sinus model. A concentration-dependent response was not found in the present study.

High-Level Expression of Recombinant Human Bone Morphogenetic Protein-4 in Chinese Hamster Ovary Cells

  • PARK JUNHO;YU SUNGRYUL;YOON JAESEUNG;BAEK KWANGHEE
    • Journal of Microbiology and Biotechnology
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    • v.15 no.6
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    • pp.1397-1401
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    • 2005
  • Bone morphogenetic protein-4 (BMP-4) is a signaling homodimeric molecule that acts as a morphogen to influence cell fate in a concentration-dependent manner. The limited supply of a pure preparation of BMP-4, due to very low level of their expression in vivo, makes it difficult not only to study the biological activities of BMPs, but also to use them as a clinical tool. For a large-scale production of BMP-4, human BMP-4 cDNA was expressed in Chinese hamster ovary (CHO) cells by a recently development vector system, which confers position-independent stable expression of the foreign genes. The CHO cell line expressing recombinant human BMP-4 (rhBMP-4) at the level of $7\;{\mu}g/ml$ could be obtained after stepwise selection with methotrexate. This level of expression is about 70 times higher than those previously reported. The partially processed form of BMP-4 as well as mature form could be detected, when the aliquots of culture media were analyzed by Western blot. The glycosylation pattern and biological activity of the rhBMP-4 were determined by glycosidase treatment and the induction rate of alkaline phosphatase in mouse osteoblastic cells.