• Journal of Periodontal and Implant Science
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• v.37 no.4
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• pp.733-742
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• 2007

Bone morphogenetic proteins have been shown to possess significant osteoinSductive potential, but in order to take advantage of this effect for tissue engineering, carrier systems are essential. Successful carrier systems must enable vascular and cellular invasion, allowing BMP to act as a differentiation factor. The carrier should be reproducible, non-immunogenic, moldable, and space-providing, to define the contours of the resulting bone. The purpose of this study was to review available literature, in comparing various carriers of BMP on rat calvarial defect model. The following conclusions were deduced. 1. Bone regeneration of ACS/BMP, ${\beta}-TCP/BMP$, FFSS/BMP, $FFSS/{\beta}-TCP/BMP$, MBCP/BMP group were significantly greater than the control groups. 2. Bone density in the ACS/BMP group was greater than that in ${\beta}-TCP$, FFSS, $FFSS/{\beta}-TCP$ carrier group. 3. Bone regeneration in FFSS/BMP group was less than in ACS/BMP, ${\beta}-TCP/BMP$, MBCP/BMP group. However, New bone area of $FFSS/{\beta}-TCP/BMP$ carrier group were more greater than that of FFSS/BMP group. ACS, ${\beta}-TCP$, FFSS, $FFSS/{\beta}-TCP$, MBCP were used for carrier of BMP. However, an ideal carrier which was reproducible, non-immunogenic, moldable, and space-providing did not exist. Therefore, further investigation are required in developing a new carrier system.

• Macromolecular Research
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• v.14 no.5
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• pp.565-572
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• 2006

Recombinant human bone morphogenic protein-2 (rhBMP-2), which is known as one of the major local stimuli for osteogenic differentiation, was immobilized on the surface of hyaluronic acid (HA)-modified poly$(\varepsilon-caprolactone)$ (PCL) (HA-PCL) scaffolds to improve the attachment, proliferation, and differentiation of human bone marrow stem cells (hBMSCs) for bone tissue engineering. The rhBMP-2 proteins were directly immobilized onto the HA-modified PCL scaffolds by the chemical grafting the amine groups of proteins to carboxylic acid groups of HA. The amount of covalently bounded rhBMP-2 was measured to 1.6 pg/mg (rhBMP/HA-PCL scaffold) by using a sandwich enzyme-linked immunosorbant assay. The rhBMP-2 immobilized HA-modified-PCL scaffold exhibited the good colonization, by the newly differentiated osteoblasts, with a statistically significant increase of the rhBMP-2 release and alkaline phosphatase activity as compared with the control groups both PCL and HA-PCL scaffolds. We also found enhanced mineralization and elevated osteocalcin detection for the rhBMP-2 immobilized HA-PCL scaffolds, in vitro.

• Journal of Periodontal and Implant Science
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• v.45 no.6
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• pp.238-246
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• 2015

Purpose: The purpose of this study was to evaluate bone formation around recombinant human bone morphogenetic protein (rhBMP-2)-coated implants placed with or without absorbable collagen sponge (ACS) in rabbit maxillary sinuses. Methods: The Schneiderian membrane was elevated and an implant was placed in 24 sinuses in 12 rabbits. The space created beneath the elevated membrane was filled with either blood (n=6) or ACS (n=6). In the rabbits in which this space was filled with blood, rhBMP-2-coated and non-coated implants were alternately placed on different sides. The resulting groups were referred to as the BC and BN groups, respectively. The AC and AN groups were produced in ACS-grafted rabbits in the same manner. Radiographic and histomorphometric analyses were performed after eight weeks of healing. Results: In micro-computed tomography analysis, the total augmented volume and new bone volume were significantly greater in the ACS-grafted sinuses than in the blood-filled sinuses (P<0.05). The histometric analysis showed that the areas of new bone and bone-to-implant contact were significantly larger in the AC group than in the AN group (P<0.05). In contrast, none of the parameters differed significantly between the BC and BN groups. Conclusions: The results of this pilot study indicate that the insertion of ACS after elevating the Schneiderian membrane, simultaneously with implant placement, can significantly increase the volume of the augmentation. However, in the present study, the rhBMP-2 coating exhibited limited effectiveness in enhancing the quantity and quality of regenerated bone.

• BMB Reports
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• v.49 no.3
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• pp.179-184
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• 2016

Bone morphogenetic protein 9 (BMP9) is a potent inducer of osteogenic differentiation of mesenchymal stem cells. The Wnt antagonist Dickkopf-1 (Dkk1) is involved in skeletal development and bone remodeling. Here, we investigated the role of Dkk1 in BMP9-induced osteogenic differentiation of MSCs. We found that overexpression of BMP9 induced Dkk1 expression in a dose-dependent manner, which was reduced by the P38 inhibitor SB203580 but not the ERK inhibitor PD98059. Moreover, Dkk1 dramatically decreased not only BMP9-induced alkaline phosphatase (ALP) activity but also the expression of osteocalcin (OCN) and osteopontin (OPN) and matrix mineralization of C3H10T1/2 cells. Furthermore, exogenous Dkk1 expression inhibited Wnt/β-catenin signaling induced by BMP9. Our findings indicate that Dkk1 negatively regulates BMP9-induced osteogenic differentiation through inhibition of the Wnt/β-catenin pathway and it could be used to optimize the therapeutic use of BMP9 and for bone tissue engineering.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.9
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• pp.5293-5299
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• 2013

Purpose: High levels of bone morphogenetic protein (BMPs) have been reported in patients with lung cancer. This study was conducted to assess correlations between serum BMP-2 levels and prognostic outcome in patients with non-small-cell lung cancer (NSCLC). Methods: Blood samples from 84 patients with advanced NSCLC and 42 healthy controls were analyzed and quantitated for serum BMP-2 levels before and after two cycles of chemotherapy using a commercially available ELISA kit. Results: The median level of BMP-2 was 146.9 pg/ml in patients with NSCLC vs. 87.7 pg/ml in healthy controls (P<0.01). A significant correlation was observed between pretreatment serum BMP-2 level and ECOG PS, disease stage and number of organs with metastases (P<0.05). Serum BMP-2 level decreased significantly in patients who achieved objective response after two cycles of chemotherapy. Multivariate analysis showed that increased BMP-2 level and advanced clinical stage were significantly correlated with poor prognosis. Conclusion: Thes erum BMP-2 level is positively correlated with clinical stage, ECOG PS and metastatic burden and may serve as an independent negative predictor for prognosis. Decreased BMP-2 after chemotherapy could be a reliable marker for efficacy of treatment.

• Journal of Periodontal and Implant Science
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• v.35 no.2
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• pp.289-298
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• 2005

Bone morphogenetic protein-7(BMP-7), a member of the transforming growth factor superfamily, stimulates osteoblast differentiation and bone formation. There are lots of evidences supporting a direct participation of periodontal ligament(PDL) cells on periodontal tissue regeneration. The purpose of this study was to evaluate the effect of recombinant human(rh) BMP-7 on primary rat PDL cells in vitro, with special focus on the ability of bone formation. The PDL cells were cultured with rhBMP-7 at the concentration of 0, 10, 25, 50, 100 and 200ng/ml for MTT assay. We evaluated the alkaline phosphatase activity at 3 and 5 days of incubation and the ability to produce mineralized nodules of rat PDL cells at 14 days of cell culture in concentration of 0, 10, 25, 50 and 100ng/ml. The cell activity was not reduced in cells treated with BMP-7 at $10{\sim}100ng/ml$, whereas the cell activity was reduced in the concentration of 200ng/ml than the control at day 1 and 3(p<0.01). At 3 and 5 day, alkaline phosphatase activity was significantly increased in cells treated with BMP-7 at 50ng/ml and 100ng/ml(p<0.05). The area of mineralized bone nodule was greater in cells treated with BMP-7 at 50 and 100 ng/ml than the control(p<0.01). These results suggest that rhBMP-7 stimulate rat PDL cells to differentiate toward osteoblast phenotype and secretion of the extracellular matrix of rat PDL cells.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.26 no.1
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• pp.24-39
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• 2000

Various methods and graft materials have been used to fill in the defect adjacent to the implants and considered as clinically acceptable. But it is not clear whether the regenerated bone increases the implant-bone contact and supports the implant. The purpose of this study is to evaluate regenerated bone surrounding implants using bone morphogenetic protein(BMP) and demineralized freeze-dried bone(DFDB), and the interfaces between implants and regenerated bone. bBMP was extracted and partially purified from the bovine bone matrix using heparine chromatography. Demineralized freeze-dried bone was made from the dog. Inactive insoluble collagenous bone matrix(IBM) of dog was used as carrier of bBMP. Interfaces of titanium coated epoxy resin implants were processed for demineralized section for transmission electron microscopy(TEM) and those of screw type implants were for nondemineralized section for light and fluoromicroscopic examination. Implants were inserted in the inferior border of mandible of adult dogs and artificial bony defects($3{\times}3{\times}4mm$) were made at the mesial and distal side of implants. Defects were filled with BMP(BMP group) and DFDB(DFDB group). For the fluoromicroscopic examination, the fluorescent dyes(oxytetracycline, calcein green, alizarin red) were injected 2, 4, 6, 8, 12 weeks after implantation. The experimental animals were sacrificed at the 6th and the 12th week and their mandible were extirpated and processed for examination with light microscopy, fluoromicroscopy and TEM. The obtained results were as follows : 1. By the light microscopic findings, the defects were filled with woven bone at the 6th week and compact bone at the 12th week, and the osseointegrations were seen in both groups. There was no histological difference between them. 2. On the basis of the histomorphometric analysis, BMP group(6th week: 40.25%, 12th week: 56.04%) had higher bony contact ratio than DFDB group(38.37%, 42.63%). There was significant difference between two groups at the 12th week(p<0.05). 3. The amount of bone formation in BMP group was more prominent than in DFDB group. Significant difference was noted among two groups at the 6th and the 8th week(p<0.05). 4. By the transmission electron microscopic findings, $0.4-2{\mu}m$ soft tissue layer was found in adjacent to the interfaces and over the collagen fibrils of bone at the 6th week. However, about 100nm amorphous layer was noted at the interface or collagen fibrils directly extended to the titanium surface at the 12th week. There was no significant difference between two groups. 5. These results suggest that BMP and DFDB can be used as good graft materials in the regeneration of bone adjacent to implant, and BMP is more valuable as a bone inducer than DFDB.

• Journal of Veterinary Clinics
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• v.39 no.6
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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.

• IMMUNE NETWORK
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• v.23 no.6
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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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• v.26 no.2
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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.