• 제목/요약/키워드: Bone morphogenetic protein

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Protein transduction domain을 이용한 recombinant human bone morphogenetic protein-2의 골재생효과 (Bone regenerative effects of recombinant human bone morphogenetic protein-2 employed protein transduction domain)

  • 정성원;김남희;육종인;김창성;김형준;조규성
    • Journal of Periodontal and Implant Science
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    • 제37권3호
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    • pp.497-509
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    • 2007
  • Bone morphogenetic proteins(BMPs) are regarded as members of the transforming growth $factor-{\beta}$ superfamily with characteristic features in their amino acid sequences. A number of studies have demonstrated the biologic activities of BMPs, which include the induction of cartilage and bone formation. Recently there was a attempt to overcome a limitation of mass production, and economical efficieny of rh-BMPs. The method producing PTD by using bacteria have advantages of acquiry a mass of proteins. Hences, a new treatment which deliver protein employed by protein transduction domain(PTD) has been tried. The purpose of this study was to evaluate the bone regenerative effect of TATBMP-2 and TAT-HA2-BMP-2 employed by PTD from HlV-1 TAT protein for protein translocation in the rat calvarial model. An 8mm calvarial, critical size osteotomy defect was created in each of 32 male Spraque-Dawley rats(weight $250{\sim}300g$). The animals were divided into 4 groups of 32 animals each (4 animals/group/healing interval). The defect was treated with TATBMP-2/ACS(Absorbable collagen sponge) (TATBMP-2 0.1mg/ml), TAT-HA2-BMP-2/ACS(TAT-HA2-BMP-2 0.1mg/ml), ACS alone or left untreated for surgical control(negative control). The rats were sacrificed at 2 or 8 weeks postsurgery, and the results were evaluated histologically. The results were as follows: New bone formation were not significantly greater in the TATBMP-2/ACS group relative to negative, and positive control groups. New bone was evident at the defect sites in TAT-HA2-BMP-2/ACS group relative to negative, positive control and TATBMP-2 groups. There were a little bone regeneration in TATBMP-2 groups. While, enhanced local bone formation were observed in TAT-HA2-BMP-2 group. But, The results was not the same in all rat defects. Therefore, further investigations are required to develop a method. which disperse homogenously, and adhere to target cells.

성견에서 임프란트 매식시 골형성단백 사용에 따른 골재생에 관한 연구 (A STUDY OF EFFECTS OF BONE MORPHOGENETIC PROTEIN BONE REGENERATION OF IMPLANTS IN DOGS)

  • 조진희;방몽숙;이종호
    • 대한치과보철학회지
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    • 제32권4호
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    • pp.593-607
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    • 1994
  • The purpose of this study is to evaluate the effect of the bone morphogenetic protein, bone matrix gelatin and collagen matrix on the amount and shape of generating new bone adjacent to the implant. Implants were inserted in the mandible of adult dogs at 2 months after teeth extraction. Artificial bony defects, 3mm in width and 4mm in depth were made at the mesial and distal side of implant. Experimental groups were divided into three groups ; Group 1 : Defects filled with collagen matrix and bone morphogenetic protein, Group 2 : Defects filled with bone matrix gelatin. Control group : Defects filled with only collagen matrix. After implantation, the animals were sacrificed at 1,3,5 and 10 weeks for light microscopic examination. For the fluorescent microscopic examination. each tertracycline Hcl and calcein were injected at 1, 3, 5, 8 and 10 weeks after implantation. The results obtained were as follows : 1. The molecular weight of bovine BMP was about 18,100 by hydroxyapatite chromatography. 2. Osseointegration was observed in experimental groups 1 & 2, and BMG and BMP had an excellent bone forming capability as a filling materials to the repair of the bone defects. 3. The degree of healing of bone defect area, the experimental group 1 showed more prominent bone formation than control group, and the control group showed fibrous connective tissue between the implant and the bone. 4. In the fluorescent microscopic findings, bone remodelling was observed regenerative lamellar bone at defect area in experimental group 1, and partial remodelling in experimental group 2, In the control group, fibrous connective tissue was observed between the implant and bone surface and sign of remodelling was not apperaed. Above results suggest that BMP has rapid osteoinductive property and can be used clinically as a bone substitute on bone defects around implants.

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Expression of Recombinant Human Bone morphogenetic protein 2 (hBMP2) in Insect cells

  • Kim, Seong-Wan;Kim, Seong-Ryul;Park, Seung Won;Goo, Tae-Won;Choi, Kwang-Ho
    • International Journal of Industrial Entomology and Biomaterials
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    • 제34권1호
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    • pp.1-5
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    • 2017
  • Bone morphogenetic protein 2 (BMP2) plays an important role in the development of bone and cartilage. It is involved in the hedgehog pathway, TGF beta signaling pathway, and in cytokine-cytokine receptor interaction. It is involved also in cardiac cell differentiation and epithelial to mesenchymal transition. In this study, We expressed human BMP2 (hBMP2) recombinant protein using Baculovirus Expression Vector System (BEVS) in Sf9 insect cells. The hBMP2 cDNA was cloned into baculovirus transfer vector, pBacgus-4x-1 and recombinant baculovirus was screened out through X-gal and GUS-fusions assay. Western blot analysis shown that molecular weight of hBMP2 recombinant protein was about 44.71 kDa.

Emodin stimulates the osteoblast differentiation via activating bone morphogenetic protein-2 gene expression at low concentration

  • Cheon, Myeong-Sook;Lee, Su-Ui;Kim, Ho-Kyoung;Kim, Young-Sup;Min, Yong-Ki;Kim, Seong-Hwan
    • 한국한의학연구원논문집
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    • 제13권1호통권19호
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    • pp.139-145
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    • 2007
  • Emodin is one of the main active components of a traditional Korean medicine isolated from the root and rhizomes of Rheum palmatum L. In this study, of 222 natural compounds to evaluate the anabolic activities, emodin activated bone morphogenetic protein (BMP)-2 promoter in the differentiation process of mouse osteoblastic MC3T3-E1 cells. Emodin was shown to significantly stimulate the activity and expression of alkaline phosphatase, an earlyphase marker of osteoblastic differentiation, on the differentiation day 7, and induce the osteopontin mRNA expression from the differentiation day 14. In addition, low concentration (up to 5 M) of emodin dramatically promoted the induction of mineralization in MC3T3-E1 subclone 4 cells. The stimulatory effect of emodin on the osteoblast differentiation/mineralization could be associated with its potential to stimulate the BMP-2 gene expression. Although further studies are needed to determine the precise mechanism, this study suggests that the use of herbal medicine containing natural compounds with anabolic activity such as emodin could have a beneficial effect on bone health.

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Vertical bone augmentation using collagenated or non-collagenated bone substitute materials with or without recombinant human bone morphogenetic protein-2 in a rabbit calvarial model

  • Hyun-Chang Lim;Kyeong-Won Paeng;Ui-Won Jung;Goran I. Benic
    • Journal of Periodontal and Implant Science
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    • 제53권6호
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    • pp.429-443
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    • 2023
  • Purpose: The aim of this study was to determine 1) the bone-regenerative effect of porcine bone block materials with or without collagen matrix incorporation, 2) the effect of a collagen barrier, and 3) the effect of adding recombinant human bone morphogenetic protein-2 (rhBMP-2) to the experimental groups. Methods: Four treatment modalities were applied to rabbit calvaria: 1) deproteinized bovine bone mineral blocks (DBBM), 2) porcine bone blocks with collagen matrix incorporation (PBC), 3) porcine bone blocks alone without collagen matrix incorporation (PB), and 4) PBC blocks covered by a collagen membrane (PBC+M). The experiments were repeated with the addition of rhBMP-2. The animals were sacrificed after either 2 or 12 weeks of healing. Micro-computed tomography (micro-CT), histologic, and histomorphometric analyses were performed. Results: Micro-CT indicated adequate volume stability in all block materials. Histologically, the addition of rhBMP-2 increased the amount of newly formed bone (NB) in all the blocks. At 2 weeks, minimal differences were noted among the NB of groups with or without rhBMP-2. At 12 weeks, the PBC+M group with rhBMP-2 presented the greatest NB (P<0.05 vs. the DBBM group with rhBMP-2), and the PBC and PB groups had greater NB than the DBBM group (P>0.05 without rhBMP-2, P<0.05 with rhBMP-2). Conclusions: The addition of rhBMP-2 enhanced NB formation in vertical augmentation using bone blocks, and a collagen barrier may augment the effect of rhBMP-2.

Bone Healing in Ovariectomized-rabbit Calvarial Defect with Tricalcium Phosphate Coated with Recombinant Human Bone Morphogenetic Protein-2 Genetically Engineered in Escherichia coli

  • Kim, Jung-Han;Kim, Chang-Joo;Shin, Sang-Hun
    • Maxillofacial Plastic and Reconstructive Surgery
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    • 제36권2호
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    • pp.37-49
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    • 2014
  • Purpose: This study compares the bone formation ability of tricalcium phosphate (TCP) with and without recombinant human bone morphogenetic protein-2 (rhBMP-2) and assesses TCP as a carrier of rhBMP-2. Methods: Bilateral round defects (diameter: 8.0 mm) were formed in the cranium of eight New Zealand white rabbits. The defects were grafted with TCP only (control group) or with rhBMP-2-coated TCP (experimental group). The animals were sacrificed at 1st week, 2nd week, 4th week, and 8th week postoperatively; two rabbits sacrificed each time. The skulls were harvested and subjected to radiographic and histological examination. Results: Radiologic evaluation showed faster bone remodeling in the experimental group than in the control group. Histologic evaluation (H&E, Masson's trichrome stain) showed rapid bone formation, remodeling and calcification in the 1st and 2nd week in the experimental group. Immunohistochemical evaluation showed higher expression rate of osteoprotegerin, receptor activator of nuclear factor ${\kappa}B$ ligand, and receptor activator of nuclear factor ${\kappa}B$ in the experimental group at the 1st and 2nd week than in the control group. Conclusion: rhBMP-2 coated TCP resulted in rapid bone formation, remodeling, and calcification due to rhBMP-2's osteogenic effect. TCP performed properly as a carrier for rhBMP-2. Thus, the use of an rhBMP-2 coating on TCP had a synergic effect on bone healing and, especially, bone remodeling and maturation.

MRONJ 예방과 치료를 위한 최신지견 (Contemporary Concept for Prevention and treatment of MRONJ (Medication Related Osteonecrosis of Jaw))

  • 박정현;김선종
    • 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.

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Bone Healing Properties of Autoclaved Autogenous Bone Grafts Incorporating Recombinant Human Bone Morphogenetic Protein-2 and Comparison of Two Delivery Systems in a Segmental Rabbit Radius Defect

  • Choi, Eun Joo;Kang, Sang-Hoon;Kwon, Hyun-Jin;Cho, Sung-Won;Kim, Hyung Jun
    • Maxillofacial Plastic and Reconstructive Surgery
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    • 제36권3호
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    • pp.94-102
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    • 2014
  • Purpose: This study aims to validate the effect of autoclaved autogenous bone (AAB), incorporating Escherichia coli-derived recombinant human bone morphogenetic protein-2 (ErhBMP-2), on critical-sized, segmental radius defects in rabbits. Delivery systems using absorbable collagen sponge (ACS) and fibrin glue (FG) were also evaluated. Methods: Radius defects were made in 12 New Zealand white rabbits. After autoclaving, the resected bone was reinserted and fixed. The animals were classified into three groups: only AAB reinserted (group 1, control), and AAB and ErhBMP-2 inserted using an ACS (group 2) or FG (group 3) as a carrier. Animals were sacrificed six or 12 weeks after surgery. Specimens were evaluated using radiology and histology. Results: Micro-computed tomography images showed the best bony union in group 2 at six and 12 weeks after operation. Quantitative analysis showed all indices except trabecular thickness were the highest in group 2 and the lowest in group 1 at twelve weeks. Histologic results showed the greatest bony union between AAB and radial bone at twelve weeks, indicating the highest degree of engraftment. Conclusion: ErhBMP-2 increases bony healing when applied on AAB graft sites. In addition, the ACS was reconfirmed as a useful delivery system for ErhBMP-2.

Effects of the combination of bone morphogenetic protein-2 and nano-hydroxyapatite on the osseointegration of dental implants

  • Pang, KangMi;Seo, Young-Kwon;Lee, Jong-Ho
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • 제47권6호
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    • pp.454-464
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    • 2021
  • Objectives: This study aimed to investigate the in vitro osteoinductivity of the combination of bone morphogenetic protein-2 (BMP-2) and nanohydroxyapatite (nHAp) and the in vivo effects of implants coated with nHAp/BMP-2. Materials and Methods: To evaluate the in vitro efficacy of nHAp/BMP-2 on bone formation, bone marrow-derived mesenchymal stem cells (BM-MSCs) were seeded onto titanium disks coated with collagen (Col), Col/nHAp, or Col/nHAp/BMP-2. Protein levels were determined by a biochemical assay and reverse transcriptase-polymerase chain reaction. Stem cell differentiation was analyzed by flow cytometry. For in vivo studies with mice, Col, Col/nHAp, and Col/nHAp/BMP-2 were injected in subcutaneous pockets. Titanium implants or implants coated with Col/nHAp/BMP-2 were placed bilaterally on rabbit tibias and evaluated for 4 weeks. Results: In the in vitro study, BM-MSCs on Col/nHAp/BMP-2 showed reduced levels of CD73, CD90, and CD105 and increased levels of glycosaminoglycan, osteopontin, and alkaline phosphatase activity. After 4 weeks, the Col/nHAp/BMP-2 implant showed greater bone formation than the control (P=0.07), while no differences were observed in bone implant contact and removal torque. Conclusion: These results suggest that a combination of BMP-2 and an nHAp carrier would activate osseointegration on dental implant surfaces.

Biodegradable Screws Containing Bone Morphogenetic Protein-2 in an Osteoporotic Rat Model

  • Jin, Eun-Sun;Kim, Ji Yeon;Lee, Bora;Min, JoongKee;Jeon, Sang Ryong;Choi, Kyoung Hyo;Jeong, Je Hoon
    • Journal of Korean Neurosurgical Society
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    • 제61권5호
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    • pp.559-567
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    • 2018
  • Objective : The aim of this study was to evaluate the effect for biodegradable screws containing bone morphogenetic protein-2 (BMP-2) in an osteoporotic rat model. Methods : Twenty-four female Wistar rat (250-300 g, 12 weeks of age) were randomized into four groups. Three groups underwent bilateral ovariectomy (OVX). Biodegradable screws with or without BMP-2 were inserted in the proximal tibia in two implantation groups. The extracted proximal metaphysis of the tibiae were scanned by exo-vivo micro-computed tomography. Evaluated parameters included bone mineral density (BMD), trabecular bone volume (BV/TV), trabecular number, trabecular thickness, and trabecular separation (Tb.Sp). The tibia samples were pathologically evaluated by staining with by Hematoxylin and Eosin, and trichrome. Results : Trabecular formation near screw insertion site was evident only in rats receiving BMP-2 screws. BMD and BV/TV significantly differed between controls and the OVX and OVX with screw groups. However, there were no significant differences between control and OVX with screw BMP groups. Tb.Sp significantly differed between control and OVX and OVX with screw groups (p<0.05), and between the OVX and OVX with screw BMP group (p<0.05), with no statistically significant difference between control and OVX with screw BMP groups. Over the 12 weeks after surgery, bone lamellae in direct contact with the screw developed more extensive and thicker trabecular bone around the implant in the OVX with screw BMP group compared to the OVX with screw group. Conclusion : Biodegradable screws containing BMP-2 improve nearby bone conditions and enhance ostoeintegration between the implant and the osteoporotic bone.