• Title/Summary/Keyword: bone morphogenetic protein-2

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Ginseng saponins and the treatment of osteoporosis: mini literature review

  • Siddiqi, Muhammad Hanif;Siddiqi, Muhammad Zubair;Ahn, Sungeun;Kang, Sera;Kim, Yeon-Ju;Sathishkumar, Natarajan;Yang, Dong-Uk;Yang, Deok-Chun
    • 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.

Effects of Daidzein on mRNA Expression of Bone Morphogenetic Protein Receptor Type I and II Genes in the Ovine Granulosa Cells

  • Chen, A Qin;Xu, Zi Rong;Yu, Song Dong;Yang, Zhi Gang
    • Asian-Australasian Journal of Animal Sciences
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    • v.23 no.3
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    • pp.326-332
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    • 2010
  • Daidzein, a natural isoflavonoid phytoestrogen, structurally resembles estradiol (E2) and possesses estrogenic activity. This study was designed to test the hypothesis that daidzein may mimic the effects of E2 on ovine follicle development by regulation of the mRNA expression of bone morphogenetic protein receptor genes and thereby influence the reproductive system. Granulosa cells were cultured in serum-free McCoy's 5A medium with and without supplementation of daidzein. Results showed that daidzein (10-100 ng/ml) significantly increased the proliferation of ovine granulosa cells (p<0.05), but inhibited the growth of granulosa cells at a dose of 1,000 ng/ml (p<0.01). Daidzein inhibited progesterone production in a dose dependent manner; however, it did not affect estradiol production by granulosa cells. We also investigated the effects of daidzein on BMPRII, BMPRIB and ALK-5 mRNA expression in ovine granulosa cells by quantitative real-time PCR. Treatment of granulosa cells with daidzein increased significantly expression of these genes at 10-100 ng/ml. Thus, these data suggested that a low concentration of daidzein (10-100 ng/ml) had a direct stimulatory effect on ovine granulosa cells while a high concentration was toxic.

THE EFFECT OF BONE MORPHOGENETIC PROTEIN 2(BMP2) ON THE GROWTH OF CRANIAL BONE AND EARLY MORPHOGENESIS OF THE CRANIAL SUTURE (Bone Morphogenetic Protein 2 가 두개골 성장 및 두개봉합부의 초기형태발생에 미치는 영향)

  • Jung, Hae-Kyung;Park, Mi-Hyun;Ryoo, Hyun-Mo;Nam, Soon-Hyeun;Kim, Young-Jin;Kim, Hyun-Jung
    • Journal of the korean academy of Pediatric Dentistry
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    • v.30 no.2
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    • pp.217-228
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    • 2003
  • Co-ordinate growth of the brain and skull is achieved through a series of tissue interactions between the developing brain, the growing bones of the skull and the sutures that unite the bones. Craniosynostosis, the premature fusion of cranial sutures, presumably involves disturbance of these interactions. Bmp2, one of bone morphogenetic proteins (Bmps), is involved in the regulation of the shapes of individual bones and the relative proportions of the skeleton. Mutations in the homeobox gene Msx2, known as a downstream gene of Bmp, cause Boston-type human craniosynostosis. The phenotype of Dlx5 homozygote mutant mouse presents craniofacial abnormalities including a delayed ossification of calvarial bone. These facts suggest important roles of Bmp2, Msx2 and Dlx5 genes in the cranial bone growth and suture morphogenesis. To elucidate the function of these molecules in the early morphogenesis of mouse cranial sutures, we first analyzed by in situ hybridization the expression of Bmp2(E15-18), Msx2 and Dlx5 genes in the developing sagittal suture of calvaria during the embryonic stage. Bmp2 mRNA was intensely expressed in the osteogenic fronts and also at the low level in the periosteum of parietal bones during embryonic stage, Msx2 mRNA was intensely expressed in the sutural mesenchyme and mildly expressed in the dura mater during the embryonic stage. Dlx5 mRNA was intensely expressed osteogenic fronts and parietal bones. To further examine the role of Bmp signaling in cranial suture, we did in vitro experiments in E15.5 mouse calvarial explants. Interestingly, implantation of Bmp2-soaked beads onto the osteogenic fronts after 48 hours organ culture resulted in the increase of the tissue thickness and cell number around Bmp2 beads, compared to BSA control beads. In addition Bmp2 induced etopic expressions of Msx2 and Dlx5 genes. On the other hand, overexpression of FGF2 did not induce the expression of Msx2 and Dlx5. Taken together, these data indicate that Bmp2 signaling molecule has a important role in regulating the cranial bone growth and early morphogenesis of cranial suture. We also suggest that Bmp signaling is involved in all the stages of osteogenesis of cranial bones and the maintenance of cranial suture by regulating Msx2 and Dlx5 genes, and that Msx2 and Dlx5 genes are specific transcription factors of Bmp signaling pathway.

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Characteristics of contact and distance osteogenesis around modified implant surfaces in rabbit tibiae

  • Choi, Jung-Yoo;Sim, Jae-Hyuk;Yeo, In-Sung Luke
    • Journal of Periodontal and Implant Science
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    • v.47 no.3
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    • pp.182-192
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    • 2017
  • Purpose: Contact and distance osteogenesis occur around all endosseous dental implants. However, the mechanisms underlying these processes have not been fully elucidated. We hypothesized that these processes occur independently of each other. To test this, we used titanium (Ti) tubes to physically separate contact and distance osteogenesis, thus allowing contact osteogenesis to be measured in the absence of possible triggers from distance osteogenesis. Methods: Sandblasted and acid-etched (SLA) and modified SLA (modSLA) implants were used. Both types had been sandblasted with large grit and then etched with acid. The modSLA implants then underwent additional treatment to increase hydrophilicity. The implants were implanted into rabbit tibiae, and half were implanted within Ti tubes. The bone-to-implant contact (BIC) ratio was calculated for each implant. Immunohistochemical analyses of bone morphogenetic protein (BMP)-2 expression and new bone formation (Masson trichrome stain) were performed. Results: The implants outside of Ti tubes were associated with good bone formation along the implant surface. Implantation within a Ti tube significantly reduced the BIC ratio (P<0.001). Compared with the modSLA implants, the SLA implants were associated with significantly higher BIC ratios, regardless of the presence or absence of Ti tubes (P=0.043). In the absence of Ti tubes, the bone adjacent to the implant had areas of new bone formation that expressed BMP-2 at high levels. Conclusions: This study disproved the null hypothesis and suggested that contact osteogenesis is initiated by signals from the old bone that undergoes distance osteogenesis after drilling. This signal may be BMP-2.

Activin A/BMP2 Chimera (AB204) Exhibits Better Spinal Bone Fusion Properties than rhBMP2

  • Ryu, Dalsung;Yoon, Byung-Hak;Oh, Chang-Hyun;Kim, Moon-Hang;Kim, Ji-Yong;Yoon, Seung Hwan;Choe, Senyon
    • 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.

Molecular weight-associated cellular response to silk fibroin fragments demonstrated in MG63 cells

  • Jo, You-Young;Kweon, HaeYong;Kim, Seong-Gon
    • International Journal of Industrial Entomology and Biomaterials
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    • v.35 no.1
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    • pp.7-13
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    • 2017
  • In this study, changes in gene expression after administration of silk fibroin fragments ($size{\approx}30kDa$) were evaluated in MG63 cells using a cDNA microarray assay. In addition, the level of alkaline phosphatase (ALP) activity and cellular proliferation in the group administered moderately sized silk fibroin fragments ($size{\approx}30kDa$) (MSF) were compared to those in the group administered smaller silk fibroin fragments (size < 1 kDa) (SSF). The results of the cDNA microarray assay show increased expression of genes that are related to the cell cycle and inflammation. ALP, bone morphogenetic protein-7, bone morphogenetic protein receptor type IA, and runt-related transcription factor 2 exhibited significantly lower expression compared to control cells (fold ratio < 0.5). Relative ALP activity of the $100{\mu}g/mL$ MSF group was significantly lower than that of the SSF group (P < 0.05). Thus, the MSF group showed increased expression of genes associated with cellular proliferation and inflammation but decreased expression of genes associated with osteogenesis.

Effect of Insulin-like Growth Factor-1 on Bone Morphogenetic Protein-2 Expression in Hepatic Carcinoma SMMC7721 Cells through the p38 MAPK Signaling Pathway

  • Xu, Guan-Jun;Cai, Sheng;Wu, Jian-Bing
    • 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.

The Analysis of Bone regenerative effect with carriers of bone morphogenetic protein in rat calvarial defects (백서두개골 결손부에서 BMP전달체의 골재생효과분석)

  • Jung, Sung-Won;Jung, Jee-Hee;Chae, Gyung-Joon;Jung, Ui-Won;Kim, Chang-Sung;Cho, Kyoo-Sung;Chai, Jung-Kiu;Kim, Chong-Kwan;Choi, Seong-Ho
    • 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.