• Asian Pacific Journal of Cancer Prevention
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• v.17 no.7
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• pp.3527-3531
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• 2016

Recombinant human bone morphogenetic protein-2 (rhBMP-2 ), a member of the TGF-${\beta}$ family, has been used widely in recent years to regenerate defects of the maxillary and mandible bones. Such defects are sometimes caused by resection of oral squamous cell carcinoma (OSCC) yet the biologic effects of rhBMP-2 on these carcinomas are not fully clear. The objective of this study was to determine histologically whether rhBMP-2 produces adverse effects on angiogenesis during induction of OSCC, a biologic process critical for tumor formation in an experimental model in the buccal pouch of golden Syrian hamsters. Buccal cavities were exposed to painting with 0.5% DMBA in liquid paraffin three times a week for 14 weeks, then biopsies were taken. Division was into 2 groups: a study group of 10 hamsters receiving $0.25{\mu}g/ml$ of rhBMP-2 in the $3^{rd}$ and $6^{th}$ weeks; and a control group of 10 hamsters which did not receive any additional treatment. VEGF expression and microvessel density were measured but no differences were noted between the two groups. According to this study, rh-BMP-2 does not stimulate angiogenesis during induction of OCSSs.

• Journal of Periodontal and Implant Science
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• v.25 no.3
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• pp.623-634
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• 1995

Periodontitis is characterized by gingival inflammation and results in periodontal pocket formation with loss of the supporting alveolar bone and connective tissue around the teeth. Therapeutic modalities should therefore aim not only at eliminating the gingival inflammatory process and preventing the progression of periodontal disease but also at reestablishing and regenerating the periodontal tissue previously lost to the disease. To achieve periodontal regeneration, progenitor cells must migrate to the denuded root surface, attach to it, proliferate and mature into an organized and functional fibrous attachment apparatus. Likewise, progenitor bone cells must also migrate, proliferate, and mature in conjunction with the regenerating periodontal ligament. Significant advances have been made during the last decade in understanding the factors controlling the migration, attachment and proliferation of cells. A group of naturally occuring molecules known as polypeptide growth factors in conjunction with certain matrix proteins are key regulators of these biological events. Of these, the fibroblast growth factor(FGF), platelet-derived growth factor(PDGF) , insulin like growth factor(CIGFs), transforming growth factor(TGFs), epidermal growth factor(EGF) and bone morphogenetic growth factor(BMPs) apper to have an important role in periodontal wound healing. The purpose of this study was to determine the effects of BMP on periodontal ligament cells. Human periodontal ligament cells were cultured from extracted tooth for non-periodontal reason. Cultured periodontal ligament cells were treated with BMP. Cellular activities were determined by MTT(3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide) assay and ALP(alkaline phosphatase) activity. The results were as follows ; Regardless of cultured time, cellular activities were stimulated by BMP. Also, BMP greatly increased alkaline phosphatase(ALP) in periodontal ligament cells. These results suggest that BMP not only have no cytotoxic effect on periodontal ligament cells, but also have osteogenic stimulatory effect on periodontal ligament cells.

• 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.

• Korean Journal of Oriental Medicine
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• v.13 no.1 s.19
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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 Periodontal and Implant Science
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• v.38 no.2
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• pp.125-134
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• 2008

Purpose: Bone morphogenetic protein (BMP) is a potent differentiating agent for cells of the osteoblastic lineage. It has been used in the oral cavity under a variety of indications and with different carriers. However, the optimal carrier for each indication is not known. This study evaluated the bone regenerative effect of rhBMP-2 delivered with different carrier systems. Materials and Methods: 8 mm critical-sized rat calvarial defects were used in 60 male Sprague-Dawley rats. The animals were divided into 6 groups containing 10 animals each. Two groups were controls that had no treatment and absorbable collagen membrane only. 4 groups were experimentals that contained rhBMP-2 only and applied with absorbable collagen sponge($Collatape^{(R)}$), $MBCP^{(R)}$, Bio-$Oss^{(R)}$ each. The histological and histometric parameters were used to evaluate the defects after 2- or 8-week healing period. The shape and total augmented area were stable in all groups over the healing time. Results: New bone formation was significantly greater in the rhBMP-2 with carrier group than control group. rhBMP-2/ACS was the highest in bone density but gained less new bone area than rhBMP-2/$MBCP^{(R)}$ and rhBMP-2/Bio-$Oss^{(R)}$. The bone density after 8 weeks was greater than that after 2 weeks in all groups. However, rhBMP-2 alone failed to show the statistically significant difference in new bone area and bone density compared to control group. Also $MBCP^{(R)}$ and Bio-$Oss^{(R)}$ particles remained after 8 weeks healing period. Conclusion: These results suggest that rhBMP-2 with carrier system is an excellent inductive agent for bone formation and we can use it as the predictable bone tissue engieering technique. Future study will likely focus on the kinetics of BMP release and development of carriers that is ideal for it.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.12
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• pp.5243-5245
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• 2016

Background and Objective : Bone morphogenic protein-2 (BMP-2) plays an essential role in mesenchymal cell differentiation into osteoblasts، through many intracellular pathways which may also be active in tumors. Invasive oral squamous cell carcinomas account for more than 90% of head and neck malignancies in many cancer registries. They are classified into three types according to epithelial cell differentiation. The present study aimed to identify any relation between BMP-2 expression and tumor histology. Materials and methods: BMP-2 expression was compared immunohistochemically among 30 cases (19 male and 11 female, mean age 48 years) of oral squamous cell carcinoma, Division was into 3 groups (each containing 10 cases) according to the histological grade. Results: No significant correlation between BMP-2 expression and histological grade was observed. Changes in localization and cytoplasmic staining were also not apparent. Conclusion: From the results of this study BMP-2 does not appear to have any application as a prognostic marker for oral squamous cell carcinomas.

• Journal of Korean Neurosurgical Society
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• v.61 no.6
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• pp.669-679
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• 2018

Objective : To compare the spinal bone fusion properties of activin A/BMP2 chimera (AB204) with recombinant human bone morphogenetic protein (rhBMP2) using a rat posterolateral spinal fusion model. Methods : The study was designed to compare the effects and property at different dosages of AB204 and rhBMP2 on spinal bone fusion. Sixty-one male Sprague-Dawley rats underwent posterolateral lumbar spinal fusion using one of nine treatments during the study, that is, sham; osteon only; $3.0{\mu}g$, $6.0{\mu}g$, or $10.0{\mu}g$ of rhBMP2 with osteon; and $1.0{\mu}g$, $3.0{\mu}g$, $6.0{\mu}g$, or $10.0{\mu}g$ of AB204 with osteon. The effects and property on spinal bone fusion was calculated at 4 and 8 weeks after treatment using the scores of physical palpation, simple radiograph, micro-computed tomography, and immunohistochemistry. Results : Bone fusion scores were significantly higher for $10.0{\mu}g$ AB204 and $10.0{\mu}g$ rhBMP2 than for osteon only or $1.0{\mu}g$ AB204. AB204 exhibited more prolonged osteoblastic activity than rhBMP2. Bone fusion properties of AB204 were similar with the properties of rhBMP2 at doses of 6.0 and $10.0{\mu}g$, but, the properties of AB204 at doses of $3.0{\mu}g$ exhibited better than the properties of rhBMP2 at doses of $3.0{\mu}g$. Conclusion : AB204 chimeras could to be more potent for treating spinal bone fusion than rhBMP2 substitutes with increased osteoblastic activity for over a longer period.

• Journal of Periodontal and Implant Science
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• v.32 no.2
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• pp.389-402
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• 2002

BMP can induce ectopic bone formation when implanted into sites such as rat muscle and can greatly enhance healing of bony defects when applied exogenously. In addition, BMP stimulated osteoblastic differentiation in vitro in various types of cells. The aim of this study was to investigate the effect of recombinant human bone morphogenetic protein(rhBMP-2) on the proliferation and osteoblastic differentiation of human periodontal ligament cells and gingival fibroblasts. The cell number and alkaline phosphatase activity were measured in 3 experimental groups of human periodontal ligament cells and gingival fibroblasts (control group, rhBMP-2 50ng/ml group, and rhBMP-2 100ng/ml group) at 1 and 2 weeks after culture. At the same time, total RNA of cultured cells were extracted and reverse trascription polymerase chain reaction(RT-PCR) was performed to determine the expression of mRNA of bone matrix protein. RhBMP-2 had no effect on the cell proliferation of human periodontal ligament cells and gingival fibroblasts. Alkaline phosphatase activity was elevated significantly by rhBMP-2 in both cells. And periodontal ligament cells showed significantly higher alkaline phosphatase activity than gingival fibroblasts. ${\beta}$-actin, type I collagen, alkaline phosphatase, BMP-2 mRNA were expressed in all of the samples. Osteopontin, osteocalcin mRNA were expressed in all periodontal ligament cell groups, and rhBMP-2 50ng/ml group, rhBMP-2 100ng/ml group of 2 week culture period of gingival fibroblasts. Bone sialoprotein mRNA was only expressed in rhBMP-2 50ng/ml group and rhBMP-2 100ng/ml group of 2-week culture period. These results suggest that rhBMP-2 stimulates osteoblastic differentiation in human periodontal ligament cells and gingival fibroblasts in vitro.

• International Journal of Oral Biology
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• v.32 no.3
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• pp.103-107
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• 2007

We hypothesized that plaque-associated bacteria may have a role in maintenance of alveolar bone. To test it, immortalized gingival epithelial HOK-16B cells were co-cultured with live or lysed eight plaque bacterial species and the expression levels of bone morphogenetic protein (BMP)-2 and -4 were examined by real time reverse transcription-polymerase chain reaction. Un-stimulated HOK-16B cells expressed both BMP-2 and -4. Co-culture with plaque bacterial lysates had significant effects on the level of BMP-2 but not on that of BMP-4. Five species including Streptococcus sanguinis, S. gordonii, Veillonella atypica, Porphyromonas gingivalis, and Treponema denticola substantially up-regulated the level of BMP-2. In contrary to the upregulatory effect of lysate, live T. denticola suppressed the expression of BMP-2. In addition, in vitro osteoblastic differentiation assay using C2C12 cells and the conditioned medium of HOK-16B cells confirmed the production of BMPs by gingival epithelial cells and the modulation of BMP expression by the lysates of S. sanguinis and T. denticola. In conclusion, we have shown that plaque bacteria can regulate the expression of BMP-2 by gingival epithelial cells, the physiologic meaning of which needs further investigation.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.4
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• pp.1183-1186
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• 2012

Objective: To observe the effect of insulin-like growth factor-1 (IGF-1) on bone morphogenetic protein (BMP)-2 expression in hepatocellular carcinoma SMMC7721 cells. Methods: Cells were divided into blank control, IGF-1, IGF-1 + SB203580, and SB203580 groups. SB203580 was used to block the p38 MAPK signaling pathway. Changes in the expression of BMP-2, p38 MAPK, and phosphorylated p38, MERK, ERK and JNK were determined using reverse transcription polymerase chain reactions (RT-PCR) and Western blot analysis. Results: Protein expression of phosphorylated BMP-2, MERK, ERK, and JNK was significantly up-regulated by IGF-1 compared with the control group ($1.138{\pm}0.065$ vs. $0.606{\pm}0.013$, $0.292{\pm}0.005$ vs. $0.150{\pm}0.081$, $0.378{\pm}0.006$ vs. $0.606{\pm}0.013$, and $0.299{\pm}0.015$ vs. $0.196{\pm}0.017$, respectively; P<0.05). Levels of BMP-2 and phosphorylated MERK and JNK were significantly reduced after blocking of the p38MAPK signaling pathway ($0.494{\pm}0.052$ vs. $0.165{\pm}0.017$, $0.073{\pm}0.07$ vs. $0.150{\pm}0.081$, and $0.018{\pm}0.008$ vs. $0.196{\pm}0.017$, respectively; P<0.05), but such a significant difference was not observed for phosphorylated ERK protein expression ($0.173{\pm}0.07$ vs. $0.150{\pm}0.081$, P>0.05). Conclusion: IGF-1 can up-regulate BMP-2 expression, and p38 MAPK signaling pathway blockage can noticeably reduce the up-regulated expression. We can conclude that the up-regulatory effect of IGF-1 on BMP-2 expression is realized through the p38 MAPK signaling pathway.