• BMB Reports
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• v.50 no.6
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• pp.308-317
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• 2017

Bone morphogenetic protein type 2 receptor (BMPR2) is one of the transforming growth $factor-{\beta}$ ($TGF-{\beta}$) superfamily receptors, performing diverse roles during embryonic development, vasculogenesis, and osteogenesis. Human BMPR2 consists of 1,038 amino acids, and contains functionally conserved extracellular, transmembrane, kinase, and C-terminal cytoplasmic domains. Bone morphogenetic proteins (BMPs) engage the tetrameric complex, composed of BMPR2 and its corresponding type 1 receptors, which initiates SMAD proteins-mediated signal transduction leading to the expression of target genes implicated in the development or differentiation of the embryo, organs and bones. In particular, genetic alterations of BMPR2 gene are associated with several clinical disorders, including representative pulmonary arterial hypertension, cancers, and metabolic diseases, thus demonstrating the physiological importance of BMPR2. In this mini review, we summarize recent findings regarding the molecular basis of BMPR2 functions in BMP signaling, and the versatile roles of BMPR2. In addition, various aspects of experimentally validated pathogenic mutations of BMPR2 and the linked human diseases will also be discussed, which are important in clinical settings for diagnostics and treatment.

• 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.

• Journal of Periodontal and Implant Science
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• v.42 no.4
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• pp.136-143
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• 2012

Purpose: The osseointegration around titanium mini-implants installed in macroporous biphasic calcium phosphate (MBCP) blocks was evaluated after incubation with recombinant human bone morphogenetic protein-2 (rhBMP-2) in an ectopic subcutaneous rat model. Methods: Mini-implants (${\varphi}1.8{\times}12$ mm) were installed in MBCP blocks (bMBCPs, $4{\times}5{\times}15$ mm) loaded with rhBMP-2 at 0.1 mg/mL, and then implanted for 8 weeks into subcutaneous pockets of male Sprague-Dawley rats (n=10). A histomorphometric analysis was performed, and the bone-to-implant contact (BIC) and bone density were evaluated. Results: Significant osteoinductive activity was induced in the rhBMP-2/bMBCP group. The percentage of BIC was $41.23{\pm}4.13%$ (mean${\pm}$standard deviation), while bone density was $33.47{\pm}5.73%$. In contrast, no bone formation was observed in the bMBCP only group. Conclusions: This model represents a more standardized tool for analyzing osseointegration and bone healing along the implant surface and in bMBCPs that excludes various healing factors derived from selected animals and defect models.

• Proceedings of the Korean Society of Precision Engineering Conference
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• 2009.06a
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• pp.51-52
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• 2009

• The Korea Journal of Herbology
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• v.24 no.1
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• pp.121-131
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• 2009

Objectives：This study was designed to investigate the effects of herbal composition and fermented Cervi Pantotrichum Cornu on the growth of longitudinal bone in the adolescent male rats. Methods： Longitudinal bone growth was measured by fluorescence microscopy. To examine the effects on the growth plate metabolism, the total height of growth plate and the induction of local insulin-like growth factor-1 (IGF-1) and bone morphogenetic protein-2 (BMP-2) were measured. Results： The herbal composition treatment enhanced longitudinal bone growth and total heght of growth plate and promoted the induction of local IGF-1 and BMP-2 of growth plate. Conclusions： This study showed that the herbal composition have the effect of bone growth in adolescent rats and might be used for the growth delayed adolescent and inherent growth failure patient.

• Journal of Korean Neurosurgical Society
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• v.65 no.2
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• pp.204-214
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• 2022

Objective : Osteoporosis result from age-related decline in the number of osteoblast progenitors in the bone marrow. Probiotics have beneficial effects on the host, when administered in appropriate amounts. This study investigated the effects of probiotics expressing specific genes, especially the effects of genetically modified bone morphogenetic protein (BMP)-2-expressing Lactobacillus plantarum CJNU 3003 (LP) on ovariectomized rats. Methods : Twenty-eight female Wistar rats (250-300 g, 12 weeks old) were divided into four groups : the sham (control), the ovariectomy (OVX)-induced osteoporosis group (OVX), the OVX and LP (OVX/LP), OVX and genetically modified BMP-2-expressing LP (OVX/LP with BMP) groups. The three groups underwent bilateral OVX and two of these groups were administered two different types of LP via oral gavage daily. At 16 weeks post-OVX, blood was collected from the heart and the bilateral tibiae were extracted and were scanned by ex-vivo micro-computed tomography and stained with hematoxylin-and-eosin (H&E) and Masson's trichrome stain for pathological assessment. The serum levels of osteocalcin (OC), rat C-telopeptide of type I collagen (CTX-I), BMP-2, and receptor activator of nuclear factor-ĸB ligand (RANKL) were measured. Results : The 3D-micro-computed tomography images showed that the trabecular structure in the OVX/LP with BMP group was maintained compared with OVX and OVX/LP groups. No significant differences were detected in trabecular thickness (Tb.Th) between control and OVX/LP with BMP groups (p>0.05). Furthermore, a tendency toward increased BMD, trabecular bone volume, Tb.Th, and trabecular number and decreased trabecular separation was found in rats in the OVX/LP with BMP groups when compared with the OVX and OVX/LP groups (p>0.05). The H&E and Masson's trichrome stained sections showed a thicker trabecular bone in the OVX/LP with BMP group compared with the OVX and OVX/LP groups. There was no difference in serum levels of OC, CTX and RANKL control and OVX/LP with BMP groups (p>0.05). In contrast, significant differences were found in OC and CTX-1 levels between the OVX and OVX/LP with BMP groups (p<0.05). Conclusion : Our results showed that the expression of genetically modified BMP-2 showed inhibition effect for bone loss in a rat model of osteoporosis.

• The Journal of Korean Medicine
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• v.33 no.2
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• pp.1-10
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• 2012

Objectives: This study was aimed to investigate the effect of Bojungikgitang-gagambang (BJIG) on longitudinal bone growth in rats. Methods: The BJIG treated group (300 mg/kg) and the control group (vehicle) were administered orally twice daily for 4 days. To investigate the effects of BJIG we measured body weight gain. The bone growth effect was analyzed by measuring between fluorescent lines marked with tetracycline, which plays the role of fluorescent dye on the surface of the tibia. Tetracycline was intraperitoneally injected. The height of growth plates in the epiphyseal plate was measured. The expression of bone morphogenetic protein-2 (BMP-2) and insuline-like growth factor-1 (IGF-1) was investigated by immunohistochemistry. Results: BJIG caused a significant acceleration of longitudinal bone growth of $349.7{\pm}15.9{\mu}m/day$ compared to control ($319.8{\pm}21.4{\mu}m/day$). The height of overall growth plate was not significantly more compared to the control, but the size of cells in the proliferative zone and hypertrophic zone were. In the immunohistochemistry, BMP-2 and IGF-1 were expressed markedly in the proliferative or hypertrophic zone, respectively. Conclusions: BJIG stimulated the chondrocyte hypertrophy and chondrogenesis in the growth plate and directly increased the longitudinal tibia length of rats.

• Molecules and Cells
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• v.37 no.3
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• pp.270-274
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• 2014

Lymphatic vessels are essential to regulate interstitial fluid homeostasis and diverse immune responses. A number of crucial factors, such as VEGFC, SOX18, PROX1, FOX2C, and GJC2, have been implicated in differentiation and/or maintenance of lymphatic endothelial cells (LECs). In humans, dysregulation of these genes is known to cause lymphedema, a debilitating condition which adversely impacts the quality of life of affected individuals. However, there are no currently available pharmacological treatments for lymphedema, necessitating identification of additional factors modulating lymphatic development and function which can be targeted for therapy. In this report, we investigate the function of genes associated with Bone Morphogenetic Protein (BMP) signaling in lymphatic development using zebrafish embryos. The knock-down of BMP type II receptors, Bmpr2a and Bmpr2b, and type I receptors, Alk3 and Alk3b, as well as SMAD5, an essential cellular mediator of BMP signaling, led to distinct lymphatic defects in developing zebrafish. Therefore, it appears that each constituent of the BMP signaling pathway may have a unique function during lymphatic development. Taken together, our data demonstrate that BMP signaling is essential for normal lymphatic vessel development in zebrafish.

• Journal of Life Science
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• v.22 no.4
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• pp.456-465
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• 2012

Heterodimeric recombinant human bone morphogenetic proteins (rhBMPs) are powerful tools for bone tissue engineering. However, BMPs have several important limitations in their application to bone regeneration. BMPs have a short half-life and must be used in high concentrations, which may be cost-inefficient. To overcome these problems, we established a stable cell line that expressed the fusion protein comprised of recombinant human BMP2/7 heterodimer protein and PTD (rhBMP2/7-PTD). This stable cell line enabled high process yields by continuously expressing rhBMP2/7-PTD products at high levels throughout cultivation. This synthesized BMP7 was fused to a BMP2 protein with four glycine residues (to allow free bond rotation of the domains) and PTD. To demonstrate that the rhBMP2/7-PTD protein that was secreted from an rhBMP2/7-PTD-expressing stable cell line exhibited biological activity consistent with its role as an osteogenic differentiation induction growth factor, we evaluated BMP-induced ALP activity. Our results suggest that this cell line may be a powerful and efficient tool for applications such as bone tissue regeneration.

• Journal of Ginseng Research
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• v.37 no.3
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• pp.261-268
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• 2013

The ginseng plant (Panax ginseng Meyer) has a large number of active ingredients including steroidal saponins with a dammarane skeleton as well as protopanaxadiol and protopanaxatriol, commonly known as ginsenosides, which have antioxidant, anticancer, antidiabetic, anti-adipocyte, and sexual enhancing effects. Though several discoveries have demonstrated that ginseng saponins (ginsenosides) as the most important therapeutic agent for the treatment of osteoporosis, yet the molecular mechanism of its active metabolites is unknown. In this review, we summarize the evidence supporting the therapeutic properties of ginsenosides both in vivo and in vitro, with an emphasis on the different molecular agents comprising receptor activator of nuclear factor kappa-B ligand, receptor activator of nuclear factor kappa-B, and matrix metallopeptidase-9, as well as the bone morphogenetic protein-2 and Smad signaling pathways.