• 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.

• 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.

• 생명과학회지
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• 제10권2호
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• pp.218-227
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• 2000

Bone morphogenetic protein 1 (BMP-1) is part of a complex capable of inducing ectopic bone formation in mammals. Studies on TGF-β1 processing and Drosophila dorsal-ventral patterning have focused attention on BMP-1 as important in mediating the biological activity of this bone inducing complex. Herein, the bacterial expression, refolding, purification, and initial characterization of the BMP-1 proteolytic domain (BPD) are described. A semi-quantitative fluorescence-based thin layer chromatography assay was developed to assist in rapidly screening for optimal renaturation conditions. According to a preliminary screen for optimal conditions for the refolding of BPD , a detectable proteolytic activity against a high turnover substrate for astacin, a homologous protease from crayfish was observed. The conditions identified have allowed the expression of sufficient amounts of BPD for the characterization of the protein. Its proteolytic activity exhibits the same cleavage specificity as astacin against seven substrates that were previously synthesized for studying astacin. Furthermore, this activity is inhibited by the metal chelator 1,10-phenanthroline but not by its analogue 1,7-phenanthroline. The collagenase inhibitor Pro-Leu-Gly hydroxamate was found to inhibit both astacin and BPD activity. The results presented in this paper argue that BMP-1 does in fact possess an intrinsic proteolytic activity.

• 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.

• 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.

• 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.

• 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.

• Maxillofacial Plastic and Reconstructive Surgery
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• 제37권
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• pp.16.1-16.7
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• 2015

Background: This study aimed to investigate new bone formation using recombinant human bone morphogenetic protein 2 (rhBMP-2) and locally applied bisphosphonate in rat calvarial defects. Methods: Thirty-six rats were studied. Two circular 5 mm diameter bony defect were formed in the calvaria using a trephine bur. The bony defect were grafted with $Bio-Oss^{(R)}$ only (group 1, n = 9), $Bio-Oss^{(R)}$ wetted with rhBMP-2 (group 2, n = 9), $Bio-Oss^{(R)}$ wetted with rhBMP-2 and 1 mM alendronate (group 3, n = 9) and $Bio-Oss^{(R)}$ wetted with rhBMP-2 and 10 mM alendronate (group 4, n = 9). In each group, three animals were euthanized at 2, 4 and 8 weeks after surgery, respectively. The specimens were then analyzed by histology, histomorphometry and immunohistochemistry analysis. Results: There were significant decrease of bone formation area (p < 0.05) between group 4 and group 2, 3. Group 3 showed increase of new bone formation compared to group 2. In immunohistochemistry, collagen type I and osteoprotegerin (OPG) didn't show any difference. However, receptor activator of nuclear factor ${\kappa}B$ ligand (RANKL) decreased with time dependent except group 4. Conclusion: Low concentration bisphosphonate and rhBMP-2 have synergic effect on bone regeneration and this is result from the decreased activity of RANKL of osteoblast.

• 한국임상수의학회지
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• 제40권2호
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• pp.85-92
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• 2023

Fractures in the horse industry are challenging and a common cause of death in racehorses. To accelerate fracture healing, tissue engineering (TE) provides promising ways to regenerate bone tissues. This study aimed to evaluate the osteogenic effects of biphasic calcium phosphate collagen (BCPC) graft, bone morphogenetic protein 2 (BMP2), mesenchymal stem cell (MSC), and platelet-rich plasma (PRP) treatments in horses. Four thoroughbred horses were included in the study, and, in each horse, three cortical defects with a diameter of 5 mm and depth of 10 mm were formed in the third metacarpal bones (MC) and metatarsal bones (MT). The defects were randomly assigned to one of six treatment groups (saline, BCPC, BMP2, MSC, PRP, and control). Injections of saline, BMP2, PRP, or MSCs were made at 1, 3, and 5 weeks after defect surgery. Bone regeneration effects were assessed by radiography, quantitative computed tomography (QCT), micro-computed tomography (μCT), histopathological, and histomorphometric evaluation. The new bone ratio (%) in the histomorphometric evaluation was higher in the BMP2 group than in the control and saline groups. Radiographic and QCT values were significantly higher in the BCPC groups than in the other groups. QCT values of the BMP2 group were significantly higher than in the control and saline groups. The present study demonstrated that BCPC grafts were biologically safe and showed osteoconductivity in horses and the repeated injections of BMP2 without a carrier can be simple and promising TE factors for treating horses with bone fractures.

• 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.