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  1. BMP-2 induces versican and hyaluronan that contribute to post-EMT AV cushion cell migration.

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    Kei Inai

    Full Text Available Distal outgrowth and maturation of mesenchymalized endocardial cushions are critical morphogenetic events during post-EMT atrioventricular (AV valvuloseptal morphogenesis. We explored the role of BMP-2 in the regulation of valvulogenic extracellular matrix (ECM components, versican and hyaluronan (HA, and cell migration during post-EMT AV cushion distal outgrowth/expansion. We observed intense staining of versican and HA in AV cushion mesenchyme from the early cushion expansion stage, Hamburger and Hamilton (HH stage-17 to the cushion maturation stage, HH stage-29 in the chick. Based on this expression pattern we examined the role of BMP-2 in regulating versican and HA using 3D AV cushion mesenchymal cell (CMC aggregate cultures on hydrated collagen gels. BMP-2 induced versican expression and HA deposition as well as mRNA expression of versican and Has2 by CMCs in a dose dependent manner. Noggin, an antagonist of BMP, abolished BMP-2-induced versican and HA as well as mRNA expression of versican and Has2. We further examined whether BMP-2-promoted cell migration was associated with expression of versican and HA. BMP-2- promoted cell migration was significantly impaired by treatments with versican siRNA and HA oligomer. In conclusion, we provide evidence that BMP-2 induces expression of versican and HA by AV CMCs and that these ECM components contribute to BMP-2-induced CMC migration, indicating critical roles for BMP-2 in distal outgrowth/expansion of mesenchymalized AV cushions.

  2. BMP-2 Induced Expression of Alx3 That Is a Positive Regulator of Osteoblast Differentiation.

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    Takashi Matsumoto

    Full Text Available Bone morphogenetic proteins (BMPs regulate many aspects of skeletal development, including osteoblast and chondrocyte differentiation, cartilage and bone formation, and cranial and limb development. Among them, BMP-2, one of the most potent osteogenic signaling molecules, stimulates osteoblast differentiation, while it inhibits myogenic differentiation in C2C12 cells. To evaluate genes involved in BMP-2-induced osteoblast differentiation, we performed cDNA microarray analyses to compare BMP-2-treated and -untreated C2C12 cells. We focused on Alx3 (aristaless-like homeobox 3 which was clearly induced during osteoblast differentiation. Alx3, a homeobox gene related to the Drosophilaaristaless gene, has been linked to developmental functions in craniofacial structures and limb development. However, little is known about its direct relationship with bone formation. In the present study, we focused on the mechanisms of Alx3 gene expression and function during osteoblast differentiation induced by BMP-2. In C2C12 cells, BMP-2 induced increase of Alx3 gene expression in both time- and dose-dependent manners through the BMP receptors-mediated SMAD signaling pathway. In addition, silencing of Alx3 by siRNA inhibited osteoblast differentiation induced by BMP-2, as showed by the expressions of alkaline phosphatase (Alp, Osteocalcin, and Osterix, while over-expression of Alx3 enhanced osteoblast differentiation induced by BMP-2. These results indicate that Alx3 expression is enhanced by BMP-2 via the BMP receptors mediated-Smad signaling and that Alx3 is a positive regulator of osteoblast differentiation induced by BMP-2.

  3. The p38/MK2/Hsp25 pathway is required for BMP-2-induced cell migration.

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    Cristina Gamell

    Full Text Available BACKGROUND: Bone morphogenetic proteins (BMPs have been shown to participate in the patterning and specification of several tissues and organs during development and to regulate cell growth, differentiation and migration in different cell types. BMP-mediated cell migration requires activation of the small GTPase Cdc42 and LIMK1 activities. In our earlier report we showed that activation of LIMK1 also requires the activation of PAKs through Cdc42 and PI3K. However, the requirement of additional signaling is not clearly known. METHODOLOGY/PRINCIPAL FINDINGS: Activation of p38 MAPK has been shown to be relevant for a number of BMP-2's physiological effects. We report here that BMP-2 regulation of cell migration and actin cytoskeleton remodelling are dependent on p38 activity. BMP-2 treatment of mesenchymal cells results in activation of the p38/MK2/Hsp25 signaling pathway downstream from the BMP receptors. Moreover, chemical inhibition of p38 signaling or genetic ablation of either p38α or MK2 blocks the ability to activate the downstream effectors of the pathway and abolishes BMP-2-induction of cell migration. These signaling effects on p38/MK2/Hsp25 do not require the activity of either Cdc42 or PAK, whereas p38/MK2 activities do not significantly modify the BMP-2-dependent activation of LIMK1, measured by either kinase activity or with an antibody raised against phospho-threonine 508 at its activation loop. Finally, phosphorylated Hsp25 colocalizes with the BMP receptor complexes in lamellipodia and overexpression of a phosphorylation mutant form of Hsp25 is able to abolish the migration of cells in response to BMP-2. CONCLUSIONS: These results indicate that Cdc42/PAK/LIMK1 and p38/MK2/Hsp25 pathways, acting in parallel and modulating specific actin regulatory proteins, play a critical role in integrating responses during BMP-induced actin reorganization and cell migration.

  4. Deficiency of retinaldehyde dehydrogenase 1 induces BMP2 and increases bone mass in vivo.

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    Shriram Nallamshetty

    Full Text Available The effects of retinoids, the structural derivatives of vitamin A (retinol, on post-natal peak bone density acquisition and skeletal remodeling are complex and compartment specific. Emerging data indicates that retinoids, such as all trans retinoic acid (ATRA and its precursor all trans retinaldehyde (Rald, exhibit distinct and divergent transcriptional effects in metabolism. Despite these observations, the role of enzymes that control retinoid metabolism in bone remains undefined. In this study, we examined the skeletal phenotype of mice deficient in retinaldehyde dehydrogenase 1 (Aldh1a1, the enzyme responsible for converting Rald to ATRA in adult animals. Bone densitometry and micro-computed tomography (µCT demonstrated that Aldh1a1-deficient (Aldh1a1(-/- female mice had higher trabecular and cortical bone mass compared to age and sex-matched control C57Bl/6 wild type (WT mice at multiple time points. Histomorphometry confirmed increased cortical bone thickness and demonstrated significantly higher bone marrow adiposity in Aldh1a1(-/- mice. In serum assays, Aldh1a1(-/- mice also had higher serum IGF-1 levels. In vitro, primary Aldh1a1(-/- mesenchymal stem cells (MSCs expressed significantly higher levels of bone morphogenetic protein 2 (BMP2 and demonstrated enhanced osteoblastogenesis and adipogenesis versus WT MSCs. BMP2 was also expressed at higher levels in the femurs and tibias of Aldh1a1(-/- mice with accompanying induction of BMP2-regulated responses, including expression of Runx2 and alkaline phosphatase, and Smad phosphorylation. In vitro, Rald, which accumulates in Aldh1a1(-/- mice, potently induced BMP2 in WT MSCs in a retinoic acid receptor (RAR-dependent manner, suggesting that Rald is involved in the BMP2 increases seen in Aldh1a1 deficiency in vivo. Collectively, these data implicate Aldh1a1 as a novel determinant of cortical bone density and marrow adiposity in the skeleton in vivo through modulation of BMP signaling.

  5. Sphingosine 1-phosphate receptor activation enhances BMP-2-induced osteoblast differentiation

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    Sato, Chieri [Division of Rheumatology, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501 (Japan); Iwasaki, Tsuyoshi, E-mail: tsuyo-i@huhs.ac.jp [Division of Pharmacotherapy, Department of Pharmacy, School of Pharmacy, Hyogo University of Health Sciences, 1-3-6 Minatojima, Chuo-ku, Kobe 650-8530 (Japan); Kitano, Sachie; Tsunemi, Sachi; Sano, Hajime [Division of Rheumatology, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501 (Japan)

    2012-06-22

    Highlights: Black-Right-Pointing-Pointer We investigated the role of S1P signaling for osteoblast differentiation. Black-Right-Pointing-Pointer Both S1P and FTY enhanced BMP-2-stimulated osteoblast differentiation by C2C12 cells. Black-Right-Pointing-Pointer S1P signaling enhanced BMP-2-stimulated Smad and ERK phosphorylation by C2C12 cells. Black-Right-Pointing-Pointer MEK/ERK signaling is a pathway underlying S1P signaling for osteoblast differentiation. -- Abstract: We previously demonstrated that sphingosine 1-phosphate (S1P) receptor-mediated signaling induced proliferation and prostaglandin productions by synovial cells from rheumatoid arthritis (RA) patients. In the present study we investigated the role of S1P receptor-mediated signaling for osteoblast differentiation. We investigated osteoblast differentiation using C2C12 myoblasts, a cell line derived from murine satellite cells. Osteoblast differentiation was induced by the treatment of bone morphogenic protein (BMP)-2 in the presence or absence of either S1P or FTY720 (FTY), a high-affinity agonist of S1P receptors. Osteoblast differentiation was determined by osteoblast-specific transcription factor, Runx2 mRNA expression, alkaline phosphatase (ALP) activity and osteocalcin production by the cells. Smad1/5/8 and extracellular signal-regulated kinase (ERK) 1/2 phosphorylation was examined by Western blotting. Osteocalcin production by C2C12 cells were determined by ELISA. Runx2 expression and ALP activity by BMP-2-stimulated C2C12 cells were enhanced by addition of either S1P or FTY. Both S1P and FTY enhanced BMP-2-induced ERK1/2 and Smad1/5/8 phosphorylation. The effect of FTY was stronger than that of S1P. S1P receptor-mediated signaling on osteoblast differentiation was inhibited by addition of mitogen-activated protein kinase/ERK kinase (MEK) 1/2 inhibitor, indicating that the S1P receptor-mediated MEK1/2-ERK1/2 signaling pathway enhanced BMP-2-Smad signaling. These results indicate that S1P

  6. Smurf1 plays a role in EGF inhibition of BMP2-induced osteogenic differentiation

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    Lee, Hye-Lim; Park, Hyun-Jung; Kwon, Arang [Department of Molecular Genetics, School of Dentistry and Dental Research Institute, Seoul National University, Seoul 110-749 (Korea, Republic of); Baek, Kyunghwa [Department of Pharmacology, College of Dentistry and Research Institute of Oral Science, Gangneung-Wonju National University, Gangneung 210-702, Gangwondo (Korea, Republic of); Woo, Kyung Mi; Ryoo, Hyun-Mo; Kim, Gwan-Shik [Department of Molecular Genetics, School of Dentistry and Dental Research Institute, Seoul National University, Seoul 110-749 (Korea, Republic of); Baek, Jeong-Hwa, E-mail: baekjh@snu.ac.kr [Department of Molecular Genetics, School of Dentistry and Dental Research Institute, Seoul National University, Seoul 110-749 (Korea, Republic of)

    2014-05-01

    It has been demonstrated that epidermal growth factor (EGF) plays a role in supporting the proliferation of bone marrow stromal cells in bone but inhibits their osteogenic differentiation. However, the mechanism underlying EGF inhibition of osteoblast differentiation remains unclear. Smurf1 is an E3 ubiquitin ligase that targets Smad1/5 and Runx2, which are critical transcription factors for bone morphogenetic protein 2 (BMP2)-induced osteoblast differentiation. In this study, we investigated the effect of EGF on the expression of Smurf1, and the role of Smurf1 in EGF inhibition of osteogenic differentiation using C2C12 cells, a murine myoblast cell line. EGF increased Smurf1 expression, which was blocked by inhibiting the activity of either JNK or ERK. Chromatin immunoprecipitation and Smurf1 promoter assays demonstrated that c-Jun and Runx2 play roles in the EGF induction of Smurf1 transcription. EGF suppressed BMP2-induced expression of osteogenic marker genes, which were rescued by Smurf1 knockdown. EGF downregulated the protein levels of Runx2 and Smad1 in a proteasome-dependent manner. EGF decreased the transcriptional activity of Runx2 and Smurf1, which was partially rescued by Smurf1 silencing. Taken together, these results suggest that EGF increases Smurf1 expression via the activation of JNK and ERK and the subsequent binding of c-Jun and Runx2 to the Smurf1 promoter and that Smurf1 mediates the inhibitory effect of EGF on BMP2-induced osteoblast differentiation. - Highlights: • EGF increases the expression level of Smurf1 in mesenchymal precursor cells. • EGF reduces the protein levels and transcriptional activity of Runx2 and Smad1. • EGF suppresses BMP2-induced osteogenic differentiation, which is rescued by Smurf1 knockdown.

  7. A Receptor Tyrosine Kinase Inhibitor, Dovitinib (TKI-258), Enhances BMP-2-Induced Osteoblast Differentiation In Vitro

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    Lee, Yura; Bae, Kyoung Jun; Chon, Hae Jung; Kim, Seong Hwan; Kim, Soon Ae; Kim, Jiyeon

    2016-01-01

    Dovitinib (TKI258) is a small molecule multi-kinase inhibitor currently in clinical phase I/II/III development for the treatment of various types of cancers. This drug has a safe and effective pharmacokinetic/pharmacodynamic profile. Although dovitinib can bind several kinases at nanomolar concentrations, there are no reports relating to osteoporosis or osteoblast differentiation. Herein, we investigated the effect of dovitinib on human recombinant bone morphogenetic protein (BMP)-2-induced osteoblast differentiation in a cell culture model. Dovitinib enhanced the BMP-2-induced alkaline phosphatase (ALP) induction, which is a representative marker of osteoblast differentiation. Dovitinib also stimulated the translocation of phosphorylated Smad1/5/8 into the nucleus and phosphorylation of mitogen-activated protein kinases, including ERK1/2 and p38. In addition, the mRNA expression of BMP-4, BMP-7, ALP, and OCN increased with dovitinib treatment. Our results suggest that dovitinib has a potent stimulating effect on BMP-2-induced osteoblast differentiation and this existing drug has potential for repositioning in the treatment of bone-related disorders. PMID:27025387

  8. Ectopic Bone Formation in vivo Induced by a Novel Synthetic Peptide Derived from BMP-2 Using Porous Collagen Scaffolds

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    To investigate the osteoinductive and ectopicly osteogenic effects of a novel peptide P24 derived from bone morphogenetic protein 2 (BMP2), biodegradable collagen scaffolds (CS) were used to load BMP-2-derived peptide solutions with different concentrations (0.4 mg peptide/CS, 0.1 mg peptide/CS and pure CS, respectively), and the implants were implanted into muscular pockets on the back of Wistar rats.Radiographs and histological analysis were performed to evaluate the ectopic bone effects. Active ectopic bone formation was seen in both groups containing the peptide at different concentration (0.4 mg and 0.1 mg),whereas no bone formation and only fibrous tissue was seen in the pure CS group. The new bone formation induced by the peptide P24 displayed a dose-dependent and time-dependent efficiency. The new bone formation in the 0.4 mg peptide/CS group significantly increased than that of the 0.1 mg peptide/CS group. This novel BMP-2-derived peptide had excellent osteoinductive and ectopicly osteogenic properties which were similar to those of BMP2.

  9. Simultaneous gene transfer of bone morphogenetic protein (BMP -2 and BMP-7 by in vivo electroporation induces rapid bone formation and BMP-4 expression

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    Miyazaki Jun-ichi

    2006-08-01

    Full Text Available Abstract Background Transcutaneous in vivo electroporation is expected to be an effective gene-transfer method for promoting bone regeneration using the BMP-2 plasmid vector. To promote enhanced osteoinduction using this method, we simultaneously transferred cDNAs for BMP-2 and BMP-7, as inserts in the non-viral vector pCAGGS. Methods First, an in vitro study was carried out to confirm the expression of BMP-2 and BMP-7 following the double-gene transfer. Next, the individual BMP-2 and BMP-7 plasmids or both together were injected into rat calf muscles, and transcutaneous electroporation was applied 8 times at 100 V, 50 msec. Results In the culture system, the simultaneous transfer of the BMP-2 and BMP-7 genes led to a much higher ALP activity in C2C12 cells than did the transfer of either gene alone. In vivo, ten days after the treatment, soft X-ray analysis showed that muscles that received both pCAGGS-BMP-2 and pCAGGS-BMP-7 had better-defined opacities than those receiving a single gene. Histological examination showed advanced ossification in calf muscles that received the double-gene transfer. BMP-4 mRNA was also expressed, and RT-PCR showed that its level increased for 3 days in a time-dependent manner in the double-gene transfer group. Immunohistochemistry confirmed that BMP-4-expressing cells resided in the matrix between muscle fibers. Conclusion The simultaneous transfer of BMP-2 and BMP-7 genes using in vivo electroporation induces more rapid bone formation than the transfer of either gene alone, and the increased expression of endogenous BMP-4 suggests that the rapid ossification is related to the induction of BMP-4.

  10. β3 integrin-mediated spreading induced by matrix-bound BMP-2 controls Smad signaling in a stiffness-independent manner.

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    Fourel, Laure; Valat, Anne; Faurobert, Eva; Guillot, Raphael; Bourrin-Reynard, Ingrid; Ren, Kefeng; Lafanechère, Laurence; Planus, Emmanuelle; Picart, Catherine; Albiges-Rizo, Corinne

    2016-03-14

    Understanding how cells integrate multiple signaling pathways to achieve specific cell differentiation is a challenging question in cell biology. We have explored the physiological presentation of BMP-2 by using a biomaterial that harbors tunable mechanical properties to promote localized BMP-2 signaling. We show that matrix-bound BMP-2 is sufficient to induce β3 integrin-dependent C2C12 cell spreading by overriding the soft signal of the biomaterial and impacting actin organization and adhesion site dynamics. In turn, αvβ3 integrin is required to mediate BMP-2-induced Smad signaling through a Cdc42-Src-FAK-ILK pathway. β3 integrin regulates a multistep process to control first BMP-2 receptor activity and second the inhibitory role of GSK3 on Smad signaling. Overall, our results show that BMP receptors and β3 integrin work together to control Smad signaling and tensional homeostasis, thereby coupling cell adhesion and fate commitment, two fundamental aspects of developmental biology and regenerative medicine.

  11. β3 integrin–mediated spreading induced by matrix-bound BMP-2 controls Smad signaling in a stiffness-independent manner

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    Fourel, Laure; Valat, Anne; Faurobert, Eva; Guillot, Raphael; Bourrin-Reynard, Ingrid; Ren, Kefeng; Lafanechère, Laurence; Planus, Emmanuelle; Albiges-Rizo, Corinne

    2016-01-01

    Understanding how cells integrate multiple signaling pathways to achieve specific cell differentiation is a challenging question in cell biology. We have explored the physiological presentation of BMP-2 by using a biomaterial that harbors tunable mechanical properties to promote localized BMP-2 signaling. We show that matrix-bound BMP-2 is sufficient to induce β3 integrin–dependent C2C12 cell spreading by overriding the soft signal of the biomaterial and impacting actin organization and adhesion site dynamics. In turn, αvβ3 integrin is required to mediate BMP-2induced Smad signaling through a Cdc42–Src–FAK–ILK pathway. β3 integrin regulates a multistep process to control first BMP-2 receptor activity and second the inhibitory role of GSK3 on Smad signaling. Overall, our results show that BMP receptors and β3 integrin work together to control Smad signaling and tensional homeostasis, thereby coupling cell adhesion and fate commitment, two fundamental aspects of developmental biology and regenerative medicine. PMID:26953352

  12. TGF-ß1 enhances the BMP-2-induced chondrogenesis of bovine synovial explants and arrests downstream differentiation at an early stage of hypertrophy.

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    Nahoko Shintani

    Full Text Available BACKGROUND: Synovial explants furnish an in-situ population of mesenchymal stem cells for the repair of articular cartilage. Although bone morphogenetic protein 2 (BMP-2 induces the chondrogenesis of bovine synovial explants, the cartilage formed is neither homogeneously distributed nor of an exclusively hyaline type. Furthermore, the downstream differentiation of chondrocytes proceeds to the stage of terminal hypertrophy, which is inextricably coupled with undesired matrix mineralization. With a view to optimizing BMP-2-induced chondrogenesis, the modulating influences of fibroblast growth factor 2 (FGF-2 and transforming growth factor beta 1 (TGF-ß1 were investigated. METHODOLOGY/PRINCIPAL FINDINGS: Explants of bovine calf metacarpal synovium were exposed to BMP-2 (200 ng/ml for 4 (or 6 weeks. FGF-2 (10 ng/ml or TGF-ß1 (10 ng/ml was introduced at the onset of incubation and was present either during the first week of culturing alone or throughout its entire course. FGF-2 enhanced the BMP-2-induced increase in metachromatic staining for glycosaminoglycans (GAGs only when it was present during the first week of culturing alone. TGF-ß1 enhanced not only the BMP-2-induced increase in metachromasia (to a greater degree than FGF-2, but also the biochemically-assayed accumulation of GAGs, when it was present throughout the entire culturing period; in addition, it arrested the downstream differentiation of cells at an early stage of hypertrophy. These findings were corroborated by an analysis of the gene- and protein-expression levels of key cartilaginous markers and by an estimation of individual cell volume. CONCLUSIONS/SIGNIFICANCE: TGF-ß1 enhances the BMP-2-induced chondrogenesis of bovine synovial explants, improves the hyaline-like properties of the neocartilage, and arrests the downstream differentiation of cells at an early stage of hypertrophy. With the prospect of engineering a mature, truly articular type of cartilage in the context of

  13. Surface delivery of tunable doses of BMP-2 from an adaptable polymeric scaffold induces volumetric bone regeneration.

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    Bouyer, Michael; Guillot, Raphael; Lavaud, Jonathan; Plettinx, Cedric; Olivier, Cécile; Curry, Véronique; Boutonnat, Jean; Coll, Jean-Luc; Peyrin, Françoise; Josserand, Véronique; Bettega, Georges; Picart, Catherine

    2016-10-01

    The rapid and effective bone regeneration of large non-healing defects remains challenging. Bioactive proteins, such as bone morphogenetic protein (BMP)-2, are proved their osteoinductivity, but their clinical use is currently limited to collagen as biomaterial. Being able to deliver BMP-2 from any other biomaterial would broaden its clinical use. This work presents a novel means for repairing a critical size volumetric bone femoral defect in the rat by combining a osteoinductive surface coating (2D) to a polymeric scaffold (3D hollow tube) made of commercially-available PLGA. Using a polyelectrolyte film as BMP-2 carrier, we tune the amount of BMP-2 loaded in and released from the polyelectrolyte film coating over a large extent by controlling the film crosslinking level and initial concentration of BMP-2 in solution. Using microcomputed tomography and quantitative analysis of the regenerated bone growth kinetics, we show that the amount of newly formed bone and kinetics can be modulated: an effective and fast repair was obtained in 1-2 weeks in the best conditions, including complete defect bridging, formation of vascularized and mineralized bone tissue. Histological staining and high-resolution computed tomography revealed the presence of bone regeneration inside and around the tube with spatially distinct organization for trabecular-like and cortical bones. The amount of cortical bone and its thickness increased with the BMP-2 dose. In view of the recent developments in additive manufacturing techniques, this surface-coating technology may be applied in combination with various types of polymeric or metallic scaffolds to offer new perspectives of bone regeneration in personalized medicine. PMID:27454063

  14. Betulinic acid synergically enhances BMP2-induced bone formation via stimulating Smad 1/5/8 and p38 pathways

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    Choi, Hyuck; Jeong, Byung-Chul; Kook, Min-Suk; Koh, Jeong-Tae

    2016-01-01

    Background Healing of bone defects is a dynamic and orchestrated process that relies on multiple growth factors and cell types. Bone morphogenetic protein 2 (BMP2) is a key growth factor for bone healing, which stimulates mesenchymal stem cells to differentiate into osteoblasts. Betulinic acid (BetA) is a natural pentacyclic triterpenoid from plants. This study aimed to examine combinatory effects of BetA and BMP2 on ectopic bone generation in mice. Results In MC3T3-E1 preosteoblast culture, ...

  15. Fibrin Hydrogel Based Bone Substitute Tethered with BMP-2 and BMP-2/7 Heterodimers

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    Lindsay S. Karfeld-Sulzer

    2015-03-01

    Full Text Available Current clinically used delivery methods for bone morphogenetic proteins (BMPs are collagen based and require large concentrations that can lead to dangerous side effects. Fibrin hydrogels can serve as osteoinductive bone substitute materials in non-load bearing bone defects in combination with BMPs. Two strategies to even further optimize such a fibrin based system include employing more potent BMP heterodimers and engineering growth factors that can be covalently tethered to and slowly released from a fibrin matrix. Here we present an engineered BMP-2/BMP-7 heterodimer where an N-terminal transglutaminase substrate domain in the BMP-2 portion provides covalent attachment to fibrin together with a central plasmin substrate domain, a cleavage site for local release of the attached BMP-2/BMP-7 heterodimer under the influence of cell-activated plasmin. In vitro and in vivo results revealed that the engineered BMP-2/BMP-7 heterodimer induces significantly more alkaline phosphatase activity in pluripotent cells and bone formation in a rat calvarial model than the engineered BMP-2 homodimer. Therefore, the engineered BMP-2/BMP-7 heterodimer could be used to reduce the amount of BMP needed for clinical effect.

  16. BMP-2 and titanium particles synergistically activate osteoclast formation

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    Sun, S.X. [Affiliated Hospital of Ningxia Medical University, Department of Orthopedics, Yinchuan, Ningxia Hui Autonomous Region, China, Department of Orthopedics, Affiliated Hospital of Ningxia Medical University, Yinchuan, Ningxia Hui Autonomous Region (China); Guo, H.H. [Ningxia Medical University, Yinchuan, Ningxia Hui Autonomous Region, China, Ningxia Medical University, Yinchuan, Ningxia Hui Autonomous Region (China); Zhang, J. [Institute of Pathology, Xi' an Jiaotong University, Xi' an Shaanxi, China, Institute of Pathology, Xi' an Jiaotong University, Xi' an Shaanxi (China); Yu, B. [Ningxia Medical University, Yinchuan, Ningxia Hui Autonomous Region, China, Ningxia Medical University, Yinchuan, Ningxia Hui Autonomous Region (China); Sun, K.N.; Jin, Q.H. [Affiliated Hospital of Ningxia Medical University, Department of Orthopedics, Yinchuan, Ningxia Hui Autonomous Region, China, Department of Orthopedics, Affiliated Hospital of Ningxia Medical University, Yinchuan, Ningxia Hui Autonomous Region (China)

    2014-05-09

    A previous study showed that BMP-2 (bone morphogenetic protein-2) and wear debris can separately support osteoclast formation induced by the receptor activator of NF-κB ligand (RANKL). However, the effect of BMP-2 on wear debris-induced osteoclast formation is unclear. In this study, we show that neither titanium particles nor BMP-2 can induce osteoclast formation in RAW 264.7 mouse leukemic monocyte macrophage cells but that BMP-2 synergizes with titanium particles to enhance osteoclast formation in the presence of RANKL, and that at a low concentration, BMP-2 has an optimal effect to stimulate the size and number of multinuclear osteoclasts, expression of osteoclast genes, and resorption area. Our data also clarify that the effects caused by the increase in BMP-2 on phosphorylated SMAD levels such as c-Fos expression increased throughout the early stages of osteoclastogenesis. BMP-2 and titanium particles stimulate the expression of p-JNK, p-P38, p-IkB, and P50 compared with the titanium group. These data suggested that BMP-2 may be a crucial factor in titanium particle-mediated osteoclast formation.

  17. BMP-2 Is Involved in Scleral Remodeling in Myopia Development.

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    Honghui Li

    Full Text Available The development of myopia is associated with scleral remodeling, but it is unclear which factors regulate this process. This study investigated bone morphogenetic protein-2 (BMP-2 expression in the sclera of guinea pigs with lens-induced myopia (LIM and after recovery from myopia and evaluated the effect of BMP-2 on extracellular matrix (ECM synthesis in human scleral fibroblasts (HSFs cultured in vitro. Lens-induced myopia was brought about in two groups of guinea pigs (the lens-induced myopia and myopia recovery groups by placing -4.00 D lenses on the right eye for three weeks. The left eye served as a contralateral control. In the recovery group, the lenses were removed after one week. The refractive power and axial length of the eyes were measured, and the BMP-2 expression levels in the sclera were measured. After three weeks, the lens-induced eyes acquired relative myopia in both groups of guinea pigs. Immunostaining of the eyeballs revealed significantly decreased BMP-2 expression in the posterior sclera of the myopic eyes compared to the contralateral eyes. One week after lens removal, BMP-2 expression recovered, and no differences were observed between the experimental and contralateral eyes in the recovery group. HSFs were cultured with BMP-2 or transforming growth factor-β1 (TGF-β1. Type I and type III collagen synthesis was significantly up-regulated following BMP-2 treatment in culture after one and two weeks, but the ratio of type III to type I collagen mRNA was not increased. Biosynthesis of glycosaminoglycan (GAG and aggrecan was increased in HSFs treated with BMP-2. Some chondrogenesis-associated genes expression increased in HSFs treated with BMP-2. From this study, we concluded that BMP-2 is involved in scleral remodeling in the development and recovery of lens-induced myopia.

  18. BMP-2 Is Involved in Scleral Remodeling in Myopia Development

    Science.gov (United States)

    Li, Honghui; Cui, Dongmei; Zhao, Feng; Huo, Lijun; Hu, Jianmin; Zeng, Junwen

    2015-01-01

    The development of myopia is associated with scleral remodeling, but it is unclear which factors regulate this process. This study investigated bone morphogenetic protein-2 (BMP-2) expression in the sclera of guinea pigs with lens-induced myopia (LIM) and after recovery from myopia and evaluated the effect of BMP-2 on extracellular matrix (ECM) synthesis in human scleral fibroblasts (HSFs) cultured in vitro. Lens-induced myopia was brought about in two groups of guinea pigs (the lens-induced myopia and myopia recovery groups) by placing -4.00 D lenses on the right eye for three weeks. The left eye served as a contralateral control. In the recovery group, the lenses were removed after one week. The refractive power and axial length of the eyes were measured, and the BMP-2 expression levels in the sclera were measured. After three weeks, the lens-induced eyes acquired relative myopia in both groups of guinea pigs. Immunostaining of the eyeballs revealed significantly decreased BMP-2 expression in the posterior sclera of the myopic eyes compared to the contralateral eyes. One week after lens removal, BMP-2 expression recovered, and no differences were observed between the experimental and contralateral eyes in the recovery group. HSFs were cultured with BMP-2 or transforming growth factor-β1 (TGF-β1). Type I and type III collagen synthesis was significantly up-regulated following BMP-2 treatment in culture after one and two weeks, but the ratio of type III to type I collagen mRNA was not increased. Biosynthesis of glycosaminoglycan (GAG) and aggrecan was increased in HSFs treated with BMP-2. Some chondrogenesis-associated genes expression increased in HSFs treated with BMP-2. From this study, we concluded that BMP-2 is involved in scleral remodeling in the development and recovery of lens-induced myopia. PMID:25965995

  19. Delta-like 1/fetal antigen 1(DLK1/FA1) inhibits BMP2 induced osteoblast differentiation through modulation of NFκB signaling pathway

    DEFF Research Database (Denmark)

    Qiu, Weimin; Abdallah, Basem; Kassem, Moustapha

    as assessed by reduced Alp activity and osteogenic gene expression including Alp, Col1a1, Runx2 and Bglap. In addition, DLK1/FA1 inhibited BMP signaling as demonstrated by reduced gene expression of BMP-responsive genes: Junb and Id1, reduced BMP2 induced luciferase activity in C2C12 BMP luciferase reporter....... Besides, we observed that DLK1/FA1 induced strong NFκB activity evidenced by NFκB responsive luciferase reporter assay and real-time RT-PCR analysis of NFκB target genes. The inhibitory effect of NFκB signaling on BMP signaling was confirmed by luciferase assay in C2C12 BMP luciferase reporter cells...

  20. Simultaneous gene transfer of bone morphogenetic protein (BMP) -2 and BMP-7 by in vivo electroporation induces rapid bone formation and BMP-4 expression

    OpenAIRE

    Kawai, Mariko; Bessho, Kazuhisa; Maruyama, Hiroki; Miyazaki, Jun-ichi; Yamamoto, Toshio

    2006-01-01

    Background: Transcutaneous in vivo electroporation is expected to be an effective gene-transfer method for promoting bone regeneration using the BMP-2 plasmid vector. To promote enhanced osteoinduction using this method, we simultaneously transferred cDNAs for BMP-2 and BMP-7, as inserts in the non-viral vector pCAGGS.

  1. BMP-2 Is Involved in Scleral Remodeling in Myopia Development

    OpenAIRE

    Honghui Li; Dongmei Cui; Feng Zhao; Lijun Huo; Jianmin Hu; Junwen Zeng

    2015-01-01

    The development of myopia is associated with scleral remodeling, but it is unclear which factors regulate this process. This study investigated bone morphogenetic protein-2 (BMP-2) expression in the sclera of guinea pigs with lens-induced myopia (LIM) and after recovery from myopia and evaluated the effect of BMP-2 on extracellular matrix (ECM) synthesis in human scleral fibroblasts (HSFs) cultured in vitro. Lens-induced myopia was brought about in two groups of guinea pigs (the lens-induced ...

  2. Complexation and sequestration of BMP-2 from an ECM mimetic hyaluronan gel for improved bone formation.

    Directory of Open Access Journals (Sweden)

    Marta Kisiel

    Full Text Available Bone morphogenetic protein-2 (BMP-2 is considered a promising adjuvant for the treatment of skeletal non-union and spinal fusion. However, BMP-2 delivery in a conventional collagen scaffold necessitates a high dose to achieve an efficacious outcome. To lower its effective dose, we precomplexed BMP-2 with the glycosaminoglycans (GAGs dermatan sulfate (DS or heparin (HP, prior to loading it into a hyaluronic acid (HA hydrogel. In vitro release studies showed that BMP-2 precomplexed with DS or HP had a prolonged delivery compared to without GAG. BMP-2-DS complexes achieved a slightly faster release in the first 24 h than HP; however, both delivered BMP-2 for an equal duration. Analysis of the kinetic interaction between BMP-2 and DS or HP showed that HP had approximately 10 times higher affinity for BMP-2 than DS, yet it equally stabilized the protein, as determined by alkaline phosphatase activity. Ectopic bone formation assays at subcutaneous sites in rats demonstrated that HA hydrogel-delivered BMP-2 precomplexed with GAG induced twice the volume of bone compared with BMP-2 delivered uncomplexed to GAG.

  3. Biological activity of a genetically modified BMP-2 variant with inhibitory activity

    Directory of Open Access Journals (Sweden)

    Kübler Alexander C

    2009-02-01

    Full Text Available Abstract Background Alterations of the binding epitopes of bone morphogenetic protein-2 (BMP-2 lead to a modified interaction with the ectodomains of BMP receptors. In the present study the biological effect of a BMP-2 double mutant with antagonistic activity was evaluated in vivo. Methods Equine-derived collagenous carriers were loaded with recombinant human BMP-2 (rhBMP-2 in a well-known dose to provide an osteoinductive stimulus. The study was performed in a split animal design: carriers only coupled with rhBMP-2 (control were implanted into prepared cavities of lower limb muscle of rats, specimens coupled with rhBMP-2 as well as BMP-2 double mutant were placed into the opposite limb in the same way. After 28 days the carriers were explanted, measured radiographically and characterized histologically. Results As expected, the BMP-2 loaded implants showed a typical heterotopic bone formation. The specimens coupled with both proteins showed a significant decreased bone formation in a dose dependent manner. Conclusion The antagonistic effect of a specific BMP-2 double mutant could be demonstrated in vivo. The dose dependent influence on heterotopic bone formation by preventing rhBMP-2 induced osteoinduction suggests a competitive receptor antagonism.

  4. Signaling Crosstalk between PPARγ and BMP2 in Mesenchymal Stem Cells

    Directory of Open Access Journals (Sweden)

    Ichiro Takada

    2012-01-01

    Full Text Available Recent studies have revealed that PPARγ’s transactivation function is regulated by extracellular signals. In particular, cytokines and Wnt family proteins suppress the ligand-inducible transactivation function of PPARγ and attenuate adipogenesis/osteoblastogenesis switching in mesenchymal stem cells (MSCs. For example, Wnt5a suppresses PPARγ transcriptional activity through the NLK/SETDB1/CHD7 pathway. Among these factors, BMP2 strongly induces bone formation, but the effect of BMP2 on PPARγ function remains unclear. We examined the effect of BMP2 and PPARγ in ST2 cells and found that PPARγ activation affected BMP2’s signaling pathway through epigenetic regulation. Although BMP2 did not interfere with PPARγ-mediated adipogenesis, BMP2 increased mRNA expression levels of PPARγ target genes (such as Fabp4 and Nr1h3 when cells were first treated with troglitazone (TRO. Moreover, PPARγ activation affected BMP2 through enhancement of histone activation markers (acetylated histone H3 and trimethylated Lys4 of histone H3 on the Runx2 promoter. After TRO treatment for three hours, BMP2 enhanced the levels of active histone marks on the promoter of a PPARγ target gene. These results suggest that the order of treatment with BMP2 and a PPARγ ligand is critical for adipogenesis and osteoblastogenesis switching in MSCs.

  5. Repressive BMP2 gene regulatory elements near the BMP2 promoter

    International Nuclear Information System (INIS)

    The level of bone morphogenetic protein 2 (BMP2) profoundly influences essential cell behaviors such as proliferation, differentiation, apoptosis, and migration. The spatial and temporal pattern of BMP2 synthesis, particular in diverse embryonic cells, is highly varied and dynamic. We have identified GC-rich sequences within the BMP2 promoter region that strongly repress gene expression. These elements block the activity of a highly conserved, osteoblast enhancer in response to FGF2 treatment. Both positive and negative gene regulatory elements control BMP2 synthesis. Detecting and mapping the repressive motifs is essential because they impede the identification of developmentally regulated enhancers necessary for normal BMP2 patterns and concentration.

  6. Repressive BMP2 gene regulatory elements near the BMP2 promoter

    Energy Technology Data Exchange (ETDEWEB)

    Jiang, Shan [Department of Biochemistry and Molecular Biology, University of Medicine and Dentistry (UMDNJ), New Jersey Medical School (NJMS), Newark, NJ (United States); Chandler, Ronald L. [Department of Molecular Physiology and Biophysics, Center for Human Genetics Research, Vanderbilt University School of Medicine, Nashville, TN (United States); Fritz, David T. [Department of Biochemistry and Molecular Biology, University of Medicine and Dentistry (UMDNJ), New Jersey Medical School (NJMS), Newark, NJ (United States); Mortlock, Douglas P. [Department of Molecular Physiology and Biophysics, Center for Human Genetics Research, Vanderbilt University School of Medicine, Nashville, TN (United States); Rogers, Melissa B., E-mail: rogersmb@umdnj.edu [Department of Biochemistry and Molecular Biology, University of Medicine and Dentistry (UMDNJ), New Jersey Medical School (NJMS), Newark, NJ (United States)

    2010-02-05

    The level of bone morphogenetic protein 2 (BMP2) profoundly influences essential cell behaviors such as proliferation, differentiation, apoptosis, and migration. The spatial and temporal pattern of BMP2 synthesis, particular in diverse embryonic cells, is highly varied and dynamic. We have identified GC-rich sequences within the BMP2 promoter region that strongly repress gene expression. These elements block the activity of a highly conserved, osteoblast enhancer in response to FGF2 treatment. Both positive and negative gene regulatory elements control BMP2 synthesis. Detecting and mapping the repressive motifs is essential because they impede the identification of developmentally regulated enhancers necessary for normal BMP2 patterns and concentration.

  7. Sustained and promoter dependent bone morphogenetic protein expression by rat mesenchymal stem cells after BMP-2 transgene electrotransfer

    Directory of Open Access Journals (Sweden)

    E Ferreira

    2012-07-01

    Full Text Available Transplantation of mesenchymal stem cells (MSCs with electrotransferred bone morphogenetic protein-2 (BMP-2 transgene is an attractive therapeutic modality for the treatment of large bone defects: it provides both stem cells with the ability to form bone and an effective bone inducer while avoiding viral gene transfer. The objective of the present study was to determine the influence of the promoter driving the human BMP-2 gene on the level and duration of BMP-2 expression after transgene electrotransfer into rat MSCs. Cytomegalovirus, elongation factor-1α, glyceraldehyde 3-phosphate dehydrogenase, and beta-actin promoters resulted in a BMP-2 secretion rate increase of 11-, 78-, 66- and 36-fold over respective controls, respectively. In contrast, the osteocalcin promoter had predictable weak activity in undifferentiated MSCs but induced the strongest BMP-2 secretion rates in osteoblastically-differentiated MSCs. Regardless of the promoter driving the transgene, a plateau of maximal BMP-2 secretion persisted for at least 21 d after the hBMP-2 gene electrotransfer. The present study demonstrates the feasibility of gene electrotransfer for efficient BMP-2 transgene delivery into MSCs and for a three-week sustained BMP-2 expression. It also provides the first in vitro evidence for a safe alternative to viral methods that permit efficient BMP-2 gene delivery and expression in MSCs but raise safety concerns that are critical when considering clinical applications.

  8. BMP2 Regulation of CXCL12 Cellular, Temporal, and Spatial Expression is Essential During Fracture Repair

    Science.gov (United States)

    Myers, Timothy J; Longobardi, Lara; Willcockson, Helen; Temple, Joseph D; Tagliafierro, Lidia; Ye, Ping; Li, Tieshi; Esposito, Alessandra; Moats-Staats, Billie M; Spagnoli, Anna

    2016-01-01

    The cellular and humoral responses that orchestrate fracture healing are still elusive. Here we report that bone morphogenic protein 2 (BMP2)-dependent fracture healing occurs through a tight control of chemokine C-X-C motif-ligand-12 (CXCL12) cellular, spatial, and temporal expression. We found that the fracture repair process elicited an early site-specific response of CXCL12+-BMP2+ endosteal cells and osteocytes that was not present in unfractured bones and gradually decreased as healing progressed. Absence of a full complement of BMP2 in mesenchyme osteoprogenitors (BMP2cKO/+) prevented healing and led to a dysregulated temporal and cellular upregulation of CXCL12 expression associated with a deranged angiogenic response. Healing was rescued when BMP2cKO/+ mice were systemically treated with AMD3100, an antagonist of CXCR4 and agonist for CXCR7 both receptors for CXCL12. We further found that mesenchymal stromal cells (MSCs), capable of delivering BMP2 at the endosteal site, restored fracture healing when transplanted into BMP2cKO/+ mice by rectifying the CXCL12 expression pattern. Our in vitro studies showed that in isolated endosteal cells, BMP2, while inducing osteoblastic differentiation, stimulated expression of pericyte markers that was coupled with a decrease in CXCL12. Furthermore, in isolated BMP2cKO/cKO endosteal cells, high expression levels of CXCL12 inhibited osteoblastic differentiation that was restored by AMD3100 treatment or coculture with BMP2-expressing MSCs that led to an upregulation of pericyte markers while decreasing platelet endothelial cell adhesion molecule (PECAM). Taken together, our studies show that following fracture, a CXCL12+-BMP2+ perivascular cell population is recruited along the endosteum, then a timely increase of BMP2 leads to downregulation of CXCL12 that is essential to determine the fate of the CXCL12+-BMP2+ to osteogenesis while departing their supportive role to angiogenesis. Our findings have far

  9. BMP-2 Overexpression Augments Vascular Smooth Muscle Cell Motility by Upregulating Myosin Va via Erk Signaling

    Directory of Open Access Journals (Sweden)

    Ming Zhang

    2014-01-01

    Full Text Available Background. The disruption of physiologic vascular smooth muscle cell (VSMC migration initiates atherosclerosis development. The biochemical mechanisms leading to dysfunctional VSMC motility remain unknown. Recently, cytokine BMP-2 has been implicated in various vascular physiologic and pathologic processes. However, whether BMP-2 has any effect upon VSMC motility, or by what manner, has never been investigated. Methods. VSMCs were adenovirally transfected to genetically overexpress BMP-2. VSMC motility was detected by modified Boyden chamber assay, confocal time-lapse video assay, and a colony wounding assay. Gene chip array and RT-PCR were employed to identify genes potentially regulated by BMP-2. Western blot and real-time PCR detected the expression of myosin Va and the phosphorylation of extracellular signal-regulated kinases 1/2 (Erk1/2. Immunofluorescence analysis revealed myosin Va expression locale. Intracellular Ca2+ oscillations were recorded. Results. VSMC migration was augmented in VSMCs overexpressing BMP-2 in a dose-dependent manner. siRNA-mediated knockdown of myosin Va inhibited VSMC motility. Both myosin Va mRNA and protein expression significantly increased after BMP-2 administration and were inhibited by Erk1/2 inhibitor U0126. BMP-2 induced Ca2+ oscillations, generated largely by a “cytosolic oscillator”. Conclusion. BMP-2 significantly increased VSMCs migration and myosin Va expression, via the Erk signaling pathway and intracellular Ca2+ oscillations. We provide additional insight into the pathophysiology of atherosclerosis, and inhibition of BMP-2-induced myosin Va expression may represent a potential therapeutic strategy.

  10. BMP2-loaded hollow hydroxyapatite microspheres exhibit enhanced osteoinduction and osteogenicity in large bone defects.

    Science.gov (United States)

    Xiong, Long; Zeng, Jianhua; Yao, Aihua; Tu, Qiquan; Li, Jingtang; Yan, Liang; Tang, Zhiming

    2015-01-01

    The regeneration of large bone defects is an osteoinductive, osteoconductive, and osteogenic process that often requires a bone graft for support. Limitations associated with naturally autogenic or allogenic bone grafts have demonstrated the need for synthetic substitutes. The present study investigates the feasibility of using novel hollow hydroxyapatite microspheres as an osteoconductive matrix and a carrier for controlled local delivery of bone morphogenetic protein 2 (BMP2), a potent osteogenic inducer of bone regeneration. Hollow hydroxyapatite microspheres (100±25 μm) with a core (60±18 μm) and a mesoporous shell (180±42 m(2)/g surface area) were prepared by a glass conversion technique and loaded with recombinant human BMP2 (1 μg/mg). There was a gentle burst release of BMP2 from microspheres into the surrounding phosphate-buffered saline in vitro within the initial 48 hours, and continued at a low rate for over 40 days. In comparison with hollow hydroxyapatite microspheres without BMP2 or soluble BMP2 without a carrier, BMP2-loaded hollow hydroxyapatite microspheres had a significantly enhanced capacity to reconstitute radial bone defects in rabbit, as shown by increased serum alkaline phosphatase; quick and complete new bone formation within 12 weeks; and great biomechanical flexural strength. These results indicate that BMP2-loaded hollow hydroxyapatite microspheres could be a potential new option for bone graft substitutes in bone regeneration. PMID:25609957

  11. Low dose BMP-2 treatment for bone repair using a PEGylated fibrinogen hydrogel matrix.

    Science.gov (United States)

    Ben-David, Dror; Srouji, Samer; Shapira-Schweitzer, Keren; Kossover, Olga; Ivanir, Eran; Kuhn, Gisela; Müller, Ralph; Seliktar, Dror; Livne, Erella

    2013-04-01

    Bone repair strategies utilizing resorbable biomaterial implants aim to stimulate endogenous cells in order to gradually replace the implant with functional repair tissue. These biomaterials should therefore be biodegradable, osteoconductive, osteoinductive, and maintain their integrity until the newly formed host tissue can contribute proper function. In recent years there has been impressive clinical outcomes for this strategy when using osteoconductive hydrogel biomaterials in combination with osteoinductive growth factors such as human recombinant bone morphogenic protein (hrBMP-2). However, the success of hrBMP-2 treatments is not without risks if the factor is delivered too rapidly and at very high doses because of a suboptimal biomaterial. Therefore, the aim of this study was to evaluate the use of a PEGylated fibrinogen (PF) provisional matrix as a delivery system for low-dose hrBMP-2 treatment in a critical size maxillofacial bone defect model. PF is a semi-synthetic hydrogel material that can regulate the release of physiological doses of hrBMP-2 based on its controllable physical properties and biodegradation. hrBMP-2 release from the PF material and hrBMP-2 bioactivity were validated using in vitro assays and a subcutaneous implantation model in rats. Critical size calvarial defects in mice were treated orthotopically with PF containing 8 μg/ml hrBMP-2 to demonstrate the capacity of these bioactive implants to induce enhanced bone formation in as little as 6 weeks. Control defects treated with PF alone or left empty resulted in far less bone formation when compared to the PF/hrBMP-2 treated defects. These results demonstrate the feasibility of using a semi-synthetic biomaterial containing small doses of osteoinductive hrBMP-2 as an effective treatment for maxillofacial bone defects. PMID:23375953

  12. 核心结合因子α1在BMP-2调控细胞外基质蛋白表达中的作用%Study of cbfα1 on the expression of extracellular matrix proteins in dental papilla cells induced by BMP-2 in vitro

    Institute of Scientific and Technical Information of China (English)

    余擎; 朱庆林; 孙汉堂; 田宇; 何文喜; 肖明振

    2008-01-01

    目的:探讨核心结合因子α1(cbfa1)在BMP-2调控体外培养的牙乳头细胞表达细胞外基质蛋白中的作用.方法:采用反义核酸技术,体外阻断培养的牙乳头细胞中cbfα1的表达,分别用RT-PCR、Western印迹等方法观察200ng/mL BMP-2作用6h后细胞中相关基质蛋白,碱性磷酸酶(ALP)、骨钙素(OC)、骨连蛋白(ON)、骨桥素(OPN)、骨涎蛋白(BSP)、牙本质基质蛋白1(DMP-1)以及牙本质涎磷蛋白(DSPP)的表达,采用SPSS 11.0软件包对数据进行方差分析.结果:外源性BMP-2能明显上调牙乳头细胞中ALP、OC含量以及OPN、BSP和ON的表达,当反义阻断cbfα1的表达时,ALP、OC、OPN和BSP的表达显著降低(P<0.01).结论:cbfα1参与了BMP-2调控体外培养的牙乳头细胞表达细胞外基质蛋白的信号转导过程.

  13. Dexamethasone, BMP-2, and 1,25-dihydroxyvitamin D enhance a more differentiated osteoblast phenotype

    DEFF Research Database (Denmark)

    Jørgensen, Niklas Rye; Henriksen, Z; Sørensen, O H;

    2004-01-01

    D), 100 nM Dex, and/or 100 ng/ml BMP-2. The osteoblast phenotype was assessed as alkaline phosphatase (AP) activity/staining, production of osteocalcin and procollagen type 1 (P1NP), parathyroid hormone (PTH)-induced cyclic adenosine mono-phosphate (cAMP) production, and in vitro mineralization. AP...... activity was increased by Dex, but not by BMP-2 treatment. P1NP production was decreased after Dex treatment, while BMP-2 had no effect on P1NP levels. Osteocalcin production was low in cultures not stimulated with vitamin D. Dex or BMP-2 treatment alone did not affect the basic osteocalcin levels, but in...... osteoblastic cells with different phenotypic characteristics, and a selective activation of some of the most important genes and functions of the mature osteoblast can thus be performed in vitro....

  14. Subcutaneous ectopic osteogenesis induced by porous calcium phosphate cement and gelatin sponge as the carrier of recombinant bone morphogenetic protein-2 in rats:A comparative study%两种材料复合rhBMP-2诱导大鼠皮下异位成骨的比较研究

    Institute of Scientific and Technical Information of China (English)

    李想; 董纪元; 彭江; 汪爱媛; 睢翔; 赵斌; 刘道宏

    2011-01-01

    Objective To analyze the difference in subcutaneous ectopic osteogenesis induced by porous calcium phosphate cement (CPC) and gelatin sponge as a carrier of recombinant bone morphogenetic protein-2 (rhBMP-2). Methods Thirty Sprague Dawley rats with an average body weight of 200g were divided into groups A-D. CPC+rhBMP-2, CPC, gelatin sponge+rhBMP-2, and gelatin sponge were implanted into the rats after anesthesia. Ten rats were killed 2, 4 and 8 weeks after they were fed under sterile environment. Bone tissue samples were collected from the implantation sites. Tissue mineral density (TMD) and trabecular thickness were detected with micro-CT scanner and analyzed with SPSS 1 OX) statistical software. Bone tissue was fixed in 4% paraformaldehyde for 2 days, embedded in paraffin, and cut into sections. The sections were stained with H&E to observe their histological change. Results The tissue mineral density and trabecular thickness of the samples with rhBMP-2 were higher in two experimental groups 2,4 and 8 weeks after implantation, which increased with the prolongation of time (P<0.05). Conclusion Porous CPC can be used as a carrier of rhBMP-2 for osteogenesis.%目的 分析多孔自固化磷酸钙骨水泥(Calcium Phosphate Cement,CPC)和明胶海绵复合重组人骨形态发生蛋白(Recombinantion Humen Bone Morphogenetic Protein-2,rhBMP-2)诱导大鼠皮下异位成骨的区别.方法 平均质量200g SD大鼠30只,麻醉后分别植入A:多孔CPC复合rhBMP-2(2μg);B:多孔CPC;C:明胶海绵复合rhBMP-2(2μg);D:空白明胶海绵,无菌喂养后分别于2、4、8周各处死10只.对植入部位组织取材,分别进行micro-CT扫描,并使用Micview V2.1三维重建处理软件扫及ABA骨形态分析软件检测,记录组织骨密度(Tissue Mineral Density,TMD)及骨小梁厚度(Trabecular Thickness,Tb.Th).运用SPSS10.0统计软件进行统计学分析.后行甲醛固定2周,石蜡包埋切片,HE染色进行组织学观察.结果 在2、4、8周时,加入rhBMP

  15. BMP-2 regulates the formation of oral sulcus in mouse tongue by altering the balance between TIMP-1 and MMP-13.

    Science.gov (United States)

    Fukui, Tadayoshi; Suga, Takeo; Iida, Ryo-Hei; Morito, Mitsuhiko; Luan, Xianghong; Diekwisch, Thomas G H; Nakamura, Yoshiki; Yamane, Akira

    2010-08-01

    The aim of this study is to investigate whether BMP-2 regulates the oral sulcus formation of mouse embryonic tongue by modifying the expression of TIMP and MMP. The BMP-2 siRNA induced a 180% increase in the depth of oral sulcus cavity (P sulcus into the mesenchymal tissues consisting of tongue floor, whereas the recombinant BMP-2 suppressed the process in the organ culture system of mouse embryonic tongue. The BMP-2 siRNA induced a 60% decrease in the expression of TIMP-1 mRNA (P sulcus in the BMP-2 siRNA treated mandibles. The recombinant BMP-2 induced a 220% increases in the expression of TIMP-1 mRNA and the area of the immunostaining for TIMP-1 around the oral sulcus was larger in the mandibles treated with the recombinant BMP-2 than the vehicle. The BMP-2 siRNA induced a 60% increase in the expression of MMP-13 protein and a marked increase in the staining intensity for MMP-13 was observed in the epithelial region of the BMP-2 siRNA treated mandibles. The recombinant BMP-2 induced a 70% decrease in the expression of MMP-13 mRNA and the decrease was mainly observed in the tissues around oral sulcus. The expressions of BMP-2, TIMP-1, and MMP-13 were verified in the tissues around in vivo developing oral sulcus at E11, 12, and 13 by immunohistochemistry. These results suggest that BMP-2 regulates the formation of oral sulcus by altering the balance between TIMP-1 and MMP-13.

  16. Regulating the osteogenic function of rhBMP 2 by different titanium surface properties.

    Science.gov (United States)

    Xiao, Ming; Biao, Meina; Chen, Yangmei; Xie, Meiju; Yang, Bangcheng

    2016-08-01

    Bone morphogenetic protein 2 (BMP-2) is important for regulating the osteogenic differentiation of mesenchymal stem cells and the response of bone tissue. It adsorbs on the surface of biomedical implants immediately and plays a role of mediator between the materials surfaces and the host cells. Studies usually connect the material surface properties and the new bone formation directly. However, interaction between the adsorbed BMP-2 on the implant surface and the cells in the tissue is the key to explaining the osteogenic properties of the material. So, in this article, we investigated the conformational and functional changes induced by the surface modified titanium metals. We found that the α-helix and β-sheet structure of rhBMP-2 can be well maintained on the anodic oxidation treated titanium surface. The osteogenic function of rhBMP-2 can sustain for a relatively long time even though there is less amount adhere to the surface compared with that on the acid alkali treated titanium. Surface properties, especially the morphology enable a larger amount of rhBMP-2 to adsorb to the surface of the acid alkali treated titanium, but the conformation of the protein is severely influenced. The percentage of α-helix structure is also significantly decreased so that the efficacy of rhBMP-2 is only maintained in the early time. This study indicated that different surface modification of the surface could regulate the structure of rhBMP-2 and then further influence its osteogenic function. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1882-1893, 2016. PMID:26991341

  17. Induction of chronic pancreatitis by pancreatic duct ligation activates BMP2, apelin, and PTHrP expression in mice.

    Science.gov (United States)

    Rastellini, Cristiana; Han, Song; Bhatia, Vandanajay; Cao, Yanna; Liu, Ka; Gao, Xuxia; Ko, Tien C; Greeley, George H; Falzon, Miriam

    2015-10-01

    Chronic pancreatitis (CP) is a devastating disease with no treatments. Experimental models have been developed to reproduce the parenchyma and inflammatory responses typical of human CP. For the present study, one objective was to assess and compare the effects of pancreatic duct ligation (PDL) to those of repetitive cerulein (Cer)-induced CP in mice on pancreatic production of bone morphogenetic protein-2 (BMP2), apelin, and parathyroid hormone-related protein (PTHrP). A second objective was to determine the extent of cross talk among pancreatic BMP2, apelin, and PTHrP signaling systems. We focused on BMP2, apelin, and PTHrP since these factors regulate the inflammation-fibrosis cascade during pancreatitis. Findings showed that PDL- and Cer-induced CP resulted in significant elevations in expression and peptide/protein levels of pancreatic BMP2, apelin, and PTHrP. In vivo mouse and in vitro pancreatic cell culture experiments demonstrated that BMP2 stimulated pancreatic apelin expression whereas apelin expression was inhibited by PTHrP exposure. Apelin or BMP2 exposure inhibited PTHrP expression, and PTHrP stimulated upregulation of gremlin, an endogenous inhibitor of BMP2 activity. Transforming growth factor-β (TGF-β) stimulated PTHrP expression. Together, findings demonstrated that PDL- and Cer-induced CP resulted in increased production of the pancreatic BMP2, apelin, and PTHrP signaling systems and that significant cross talk occurred among pancreatic BMP2, apelin, and PTHrP. These results together with previous findings imply that these factors interact via a pancreatic network to regulate the inflammation-fibrosis cascade during CP. More importantly, this network communicated with TGF-β, a key effector of pancreatic pathophysiology. This novel network may be amenable to pharmacologic manipulations during CP in humans. PMID:26229008

  18. Tracheal cartilage regeneration and new bone formation by slow release of bone morphogenetic protein (BMP)-2.

    Science.gov (United States)

    Igai, Hitoshi; Chang, Sung Soo; Gotoh, Masashi; Yamamoto, Yasumichi; Yamamoto, Masaya; Tabata, Yasuhiko; Yokomise, Hiroyasu

    2008-01-01

    We investigated the efficiency of bone morphogenetic protein (BMP)-2 released slowly from gelatin sponge for tracheal cartilage regeneration. A 1-cm gap was made in the mid-ventral portion of each of 10 consecutive tracheal cartilages. In the control group (n = 4), the resulting gap was left untreated. In the gelatin group (n = 4), plain gelatin was implanted in the gap. In the BMP-2 group (n = 4), gelatin containing 100 microg BMP-2 was implanted. We euthanatized all dogs in each group at 1, 3, 6, and 12 months after the implantation, respectively, and then examined the implant site macro- and microscopically. In the BMP-2 group, regenerated fibrous cartilage and newly formed bone were observed at 1 and 12 months. Regenerated cartilage was observed at the ends of the host cartilage stumps, with newly formed bone in the middle portion. The gaps were filled with regenerated cartilage and newly formed bone. At 3 and 6 months, regenerated cartilage, but not newly formed bone, was evident. The regenerated cartilage was covered with perichondrium and showed continuity with the host cartilage. We succeeded in inducing cartilage regeneration and new bone formation in canine trachea by slow release of 100 microg BMP-2 from gelatin. PMID:18204324

  19. Preconditioning Human Mesenchymal Stem Cells with a Low Concentration of BMP2 Stimulates Proliferation and Osteogenic Differentiation In Vitro

    DEFF Research Database (Denmark)

    Lysdahl, Helle; Baatrup, Anette; Foldager, Casper Bindzus;

    2014-01-01

    treatment strategy in which human bone marrow-derived mesenchymal stem cells (hMSCs) are preconditioned with low concentrations of BMP2 for a short time in vitro. hMSCs in suspension were stimulated for 15 min with 10 and 20 ng/mL of BMP2. After the BMP2 was removed, the cells were seeded and cultured...... in osteogenesis was validated by findings of increased gene expression of SMAD1 and an increase in dual phosphorylation of ser 463 and ser 465 in the SMAD 1/5/8 pathway. We concluded that preconditioning hMSCs with BMP2 stimulates osteogenesis: proliferation with matrix secretion and matrix maturation of h......MSCs. This implies that preconditioning with BMP2 might be more effective at inducing proliferation and osteogenic differentiation of hMSCs than continuous stimulation. Preconditioning with BMP2 could benefit the clinical application of BMP2 since side effects from high-dose treatments could be avoided....

  20. Bmp2 Is Required for Odontoblast Differentiation and Pulp Vasculogenesis

    OpenAIRE

    Yang, W; Harris, M.A.; Y. Cui; Mishina, Y; Harris, S.E.; Gluhak-Heinrich, J.

    2012-01-01

    Using the Bmp2 floxed/3.6Col1a1-Cre (Bmp2-cKOod) mouse model, we have observed severe defects in odontogenesis and dentin formation with the removal of the Bmp2 gene in early-polarizing odontoblasts. The odontoblasts in the Bmp2-cKOod do not mature properly and fail to form proper dentin with normal dentinal tubules and activate terminal differentiation, as reflected by decreased Osterix, Col1a1, and Dspp expression. There is less dentin, and the dentin is hypomineralized and patchy. We also ...

  1. BMP-2 and BMP-2/7 Heterodimers Conjugated to a Fibrin/Hyaluronic Acid Hydrogel in a Large Animal Model of Mild Intervertebral Disc Degeneration.

    Science.gov (United States)

    Peeters, Mirte; Detiger, Suzanne E L; Karfeld-Sulzer, Lindsay S; Smit, Theo H; Yayon, Avner; Weber, Franz E; Helder, Marco N

    2015-01-01

    Intervertebral disc (IVD) degeneration is etiologically associated with low back pain and is currently only treated in severe cases with spinal fusion. Regenerative medicine attempts to restore degenerated tissue by means of cells, hydrogels, and/or growth factors and can therefore be used to slow, halt, or reverse the degeneration of the IVD in a minimally invasive manner. Previously, the growth factors bone morphogenetic proteins 2 and 7 (BMP-2, -7) were shown to enhance disc regeneration, in vitro and in vivo. Since BMPs have only a short in vivo half-life, and to prevent heterotopic ossification, we evaluated the use of a slow release system for BMP-2 homodimers and BMP-2/7 heterodimers for IVD regeneration. BMP growth factors were conjugated to a fibrin/hyaluronic acid (FB/HA) hydrogel and intradiscally injected in a goat model of mild IVD degeneration to study safety and efficacy. Mild degeneration was induced in five lumbar discs of seven adult Dutch milk goats, by injections with the enzyme chondroitinase ABC. After 12 weeks, discs were treated with either FB/HA-hydrogel only or supplemented with 1 or 5 μg/mL of BMP-2 or BMP-2/7. BMPs were linked to the FB/HA hydrogels using a transglutaminase moiety, to be released through an incorporated plasmin cleavage site. After another 12 weeks, goats were sacrificed and discs were assessed using radiography, MRI T2* mapping, and biochemical and histological analyses. All animals maintained weight throughout the study and no heterotopic bone formation or other adverse effects were noted during follow-up. Radiographs showed significant disc height loss upon induction of mild degeneration. MRI T2* mapping showed strong and significant correlations with biochemistry and histology as shown before. Surprisingly, no differences could be demonstrated in any parameter between intervention groups. To our knowledge, this is the first large animal study evaluating BMPs conjugated to an FB/HA-hydrogel for the treatment of

  2. Perlecan domain 1 recombinant proteoglycan augments BMP-2 activity and osteogenesis

    Directory of Open Access Journals (Sweden)

    DeCarlo Arthur A

    2012-09-01

    Full Text Available Abstract Background Many growth factors, such as bone morphogenetic protein (BMP-2, have been shown to interact with polymers of sulfated disacharrides known as heparan sulfate (HS glycosaminoglycans (GAGs, which are found on matrix and cell-surface proteoglycans throughout the body. HS GAGs, and some more highly sulfated forms of chondroitin sulfate (CS, regulate cell function by serving as co-factors, or co-receptors, in GF interactions with their receptors, and HS or CS GAGs have been shown to be necessary for inducing signaling and GF activity, even in the osteogenic lineage. Unlike recombinant proteins, however, HS and CS GAGs are quite heterogenous due, in large part, to post-translational addition, then removal, of sulfate groups to various positions along the GAG polymer. We have, therefore, investigated whether it would be feasible to deliver a DNA pro-drug to generate a soluble HS/CS proteoglycan in situ that would augment the activity of growth-factors, including BMP-2, in vivo. Results Utilizing a purified recombinant human perlecan domain 1 (rhPln.D1 expressed from HEK 293 cells with HS and CS GAGs, tight binding and dose-enhancement of rhBMP-2 activity was demonstrated in vitro. In vitro, the expressed rhPln.D1 was characterized by modification with sulfated HS and CS GAGs. Dose-enhancement of rhBMP-2 by a pln.D1 expression plasmid delivered together as a lyophilized single-phase on a particulate tricalcium phosphate scaffold for 6 or more weeks generated up to 9 fold more bone volume de novo on the maxillary ridge in a rat model than in control sites without the pln.D1 plasmid. Using a significantly lower BMP-2 dose, this combination provided more than 5 times as much maxillary ridge augmentation and greater density than rhBMP-2 delivered on a collagen sponge (InFuse™. Conclusions A recombinant HS/CS PG interacted strongly and functionally with BMP-2 in binding and cell-based assays, and, in vivo, the pln.247 expression plasmid

  3. RhBMP-2 microspheres-loaded chitosan/collagen scaffold enhanced osseointegration: an experiment in dog.

    Science.gov (United States)

    Shi, Shanshan; Cheng, Xiangrong; Wang, Jiawei; Zhang, Wei; Peng, Lin; Zhang, Yufeng

    2009-01-01

    The purpose of this study is to develop a novel recombinant human bone morphogenetic protein-2 (rhBMP-2) sustained release scaffold for dental implant osseointegration, and to evaluate the effect of this scaffold on promoting bone formation. RhBMP-2 was encapsulated in the poly-D,L-lactide-co-glycolide (PLGA) biodegradable microspheres, which were subsequently dispersed in a chitosan/collagen composite scaffold. This rhBMP-2 microspheres-loaded scaffold (S-MB) was compared with a chitosan/collagen scaffold without microspheres that directly encapsulated rhBMP-2 (S-B) in vitro and in vivo. The microstructure of the new scaffold was examined with scanning electron microscopy. The release profile of rhBMP-2 in vitro was measured at interval periods. The effect of rhBMP-2 encapsulated scaffolds on enhancing bone formation through implantation in dogs' mandibles was identified by histological examination of the regenerated bone after 4 weeks of implantation. Due to PLGA microspheres being loaded, the S-MB exhibited lower values at porosity and swelling rate, as well as a higher effective release dose than that of the S-B. Bone density, bone-implant contact, and bone-fill values measured from dog experiments demonstrated that the S-MB induced bone regeneration more quickly and was timely substituted by new bone. It was concluded that this sustained carrier scaffold based on microspheres was more effective to induce implant osseointegration. PMID:18667455

  4. BMP2 Transfer to Neighboring Cells and Activation of Signaling.

    Science.gov (United States)

    Alborzinia, Hamed; Shaikhkarami, Marjan; Hortschansky, Peter; Wölfl, Stefan

    2016-09-01

    Morphogen gradients and concentration are critical features during early embryonic development and cellular differentiation. Previously we reported the preparation of biologically active, fluorescently labeled BMP2 and quantitatively analyzed their binding to the cell surface and followed BMP2 endocytosis over time on the level of single endosomes. Here we show that this internalized BMP2 can be transferred to neighboring cells and, moreover, also activates downstream BMP signaling in adjacent cells, indicated by Smad1/5/8 phosphorylation and activation of the downstream target gene id1. Using a 3D matrix to modulate cell-cell contacts in culture we could show that direct cell-cell contact significantly increased BMP2 transfer. Using inhibitors of vesicular transport, transfer was strongly inhibited. Interestingly, cotreatment with the physiological BMP inhibitor Noggin increased BMP2 uptake and transfer, albeit activation of Smad signaling in neighboring cells was completely suppressed. Our findings present a novel and interesting mechanism by which morphogens such as BMP2 can be transferred between cells and how this is modulated by BMP antagonists such as Noggin, and how this influences activation of Smad signaling by BMP2 in neighboring cells. PMID:27306974

  5. Experimental Research on Ectopic Osteogenesis of BMP2-derived Peptide P24 Combined with PLGA Copolymers

    Institute of Scientific and Technical Information of China (English)

    DUAN Zhixia; ZHENG Qixin; GUO Xiaodong; YUAN Quan; CHEN Shunguang

    2007-01-01

    To experimentally evaluate the ectopic osteogenetic capacity of synthesized BMP2-derived peptide P24 combined with poly lactic-co-glycolic acid (PLGA), Wistar rats were divided into two groups: group A, in which BMP2-derived peptide P24/PLGA complex was implanted,and group B which received simple PLGA implant. The complex was respectively implanted into the back muscles of rats. Samples were taken the 1 st, 4 th, 8 th, and the 12 th week after the implantation.Their bone formation was detected by X-ray examination, and tissue response was histologically observed. Western blotting was used for the detection of the expression of collagen Ⅰ (Col- Ⅰ ) and osteopontin (OPN). There was acute inflammation in the tissue around both types of implants at early stage. The cartilage was found around implant areas 4 weeks after the implantation of BMP2-derived peptide p24/PLGA complex, 8 weeks after the implantation, osteoblasts were found, and 12 weeks after the implantation, typical trabecular bone structure was observed. In group B, after 12 weeks, no osteoblasts were found. It is concluded that PLGA is an ideal scaffold material for bone tissue engineering. BMP2-derived peptide can start endochondral ossification and is more effective in inducing ectopic osteogenesis.

  6. Enhancement of the Regenerative Potential of Anorganic Bovine Bone Graft Utilizing a Polyglutamate-Modified BMP2 Peptide with Improved Binding to Calcium-Containing Materials.

    Science.gov (United States)

    Bain, Jennifer L; Bonvallet, Paul P; Abou-Arraj, Ramzi V; Schupbach, Peter; Reddy, Michael S; Bellis, Susan L

    2015-09-01

    Autogenous bone is the gold standard material for bone grafting in craniofacial and orthopedic regenerative medicine. However, due to complications associated with harvesting donor bone, clinicians often use commercial graft materials that may lose their osteoinductivity due to processing. This study was aimed to functionalize one of these materials, anorganic bovine bone (ABB), with osteoinductive peptides to enhance regenerative capacity. Two peptides known to induce osteoblastic differentiation of mesenchymal stem cells were evaluated: (1) DGEA, an amino acid motif within collagen I and (2) a biomimetic peptide derived from bone morphogenic protein 2 (BMP2pep). To achieve directed coupling of the peptides to the graft surface, the peptides were engineered with a heptaglutamate domain (E7), which confers specific binding to calcium moieties within bone mineral. Peptides with the E7 domain exhibited greater anchoring to ABB than unmodified peptides, and E7 peptides were retained on ABB for at least 8 weeks in vivo. To assess the osteoinductive potential of the peptide-conjugated ABB, ectopic bone formation was evaluated utilizing a rat subcutaneous pouch model. ABB conjugated with full-length recombinant BMP2 (rBMP2) was also implanted as a model for current clinical treatments utilizing rBMP2 passively adsorbed to carriers. These studies showed that E7BMP2pep/ABB samples induced more new bone formation than all other peptides, and an equivalent amount of new bone as compared with rBMP2/ABB. A mandibular defect model was also used to examine intrabony healing of peptide-conjugated ABB. Bone healing was monitored at varying time points by positron emission tomography imaging with (18)F-NaF, and it was found that the E7BMP2pep/ABB group had greater bone metabolic activity than all other groups, including rBMP2/ABB. Importantly, animals implanted with rBMP2/ABB exhibited complications, including inflammation and formation of cataract-like lesions in the eye, whereas

  7. Mesenchymal stem cells with rhBMP-2 inhibits the growth of canine osteosarcoma cells

    Directory of Open Access Journals (Sweden)

    Grassi Rici Rose

    2012-02-01

    Full Text Available Abstract Background The bone morphogenetic proteins (BMPs belong to a unique group of proteins that includes the growth factor TGF-β. BMPs play important roles in cell differentiation, cell proliferation, and inhibition of cell growth. They also participate in the maturation of several cell types, depending on the microenvironment and interactions with other regulatory factors. Depending on their concentration gradient, the BMPs can attract various types of cells and act as chemotactic, mitogenic, or differentiation agents. BMPs can interfere with cell proliferation and the formation of cartilage and bone. In addition, BMPs can induce the differentiation of mesenchymal progenitor cells into various cell types, including chondroblasts and osteoblasts. The aim of this study was to analyze the effects of treatment with rhBMP-2 on the proliferation of canine mesenchymal stem cells (cMSCs and the tumor suppression properties of rhBMP-2 in canine osteocarcoma (OST cells. Osteosarcoma cell lines were isolated from biopsies and excisions of animals with osteosarcoma and were characterized by the Laboratory of Biochemistry and Biophysics, Butantan Institute. The mesenchymal stem cells were derived from the bone marrow of canine fetuses (cMSCs and belong to the University of São Paulo, College of Veterinary Medicine (FMVZ-USP stem cell bank. After expansion, the cells were cultured in a 12-well Transwell system; cells were treated with bone marrow mesenchymal stem cells associated with rhBMP2. Expression of the intracytoplasmic and nuclear markers such as Caspase-3, Bax, Bad, Bcl-2, Ki-67, p53, Oct3/4, Nanog, Stro-1 were performed by flow citometry. Results We evaluated the regenerative potential of in vitro treatment with rhBMP-2 and found that both osteogenic induction and tumor regression occur in stem cells from canine bone marrow. rhBMP-2 inhibits the proliferation capacity of OST cells by mechanisms of apoptosis and tumor suppression mediated by p

  8. Osteogenic differentiation as a result of BMP-2 plasmid DNA based gene therapy in vitro and in vivo.

    Science.gov (United States)

    Wegman, F; Bijenhof, A; Schuijff, L; Oner, F C; Dhert, W J A; Alblas, J

    2011-03-15

    Bone regeneration is one of the major focus points in the field of regenerative medicine. A well-known stimulus of bone formation is bone morphogenetic protein-2 (BMP-2), which has already been extensively used in clinical applications. We investigated the possibility of achieving osteogenic differentiation both in vitro and in vivo as a result of prolonged presence of BMP-2 using plasmid DNA-based gene therapy. By delivering BMP-2 cDNA in an alginate hydrogel, a versatile formulation is developed. High transfection efficiencies of up to 95% were obtained in both human multipotent stromal cells (MSCs) and MG-63 cells using naked DNA in vitro. Over a period of 5 weeks, an increasing amount of biologically active BMP-2 was released from the cells and remained present in the gel. In vivo, transfected cells were found after both two and six weeks implantation in naked mice, even in groups without seeded cells, thus indicating in vivo transfection of endogenous cells. The protein levels were effective in inducing osteogenic differentiation in vitro, as seen by elevated alkaline phosphatase (ALP) production and in vivo, as demonstrated by the production of collagen I and osteocalcin in a mineralised alginate matrix. We conclude that BMP-2 cDNA incorporated in alginate hydrogel appears to be a promising new strategy for minimal-invasive delivery of growth factors in bone regeneration.

  9. Bmp2 and Bmp4 accelerate alveolar bone development.

    Science.gov (United States)

    Ou, Mingming; Zhao, Yibing; Zhang, Fangming; Huang, Xiaofeng

    2015-06-01

    Alveolar bone remodeling is a continuous process that takes place during development and in response to various physiological and pathological stimuli. However, detailed knowledge regarding the underlying mechanisms involved in alveolar bone development is still lacking. This study aims at improving our understanding of alveolar bone formation and the role of bone morphogenetic proteins (Bmps) in this process. Mice at embryonic (E) day 13.5 to postnatal (PN) day 15.5 were selected to observe the process of alveolar bone development. Alveolar bone development was found to be morphologically observable at E14.5. Molar teeth isolated from mice at PN7.5 were pretreated with Bmp2, Bmp4, Noggin, or BSA, and grafted subcutaneously into mice. The subcutaneously implanted tooth germs formed alveolar bone indicating the role of the dental follicle in alveolar bone development. Alveolar bone formation was increased after pretreatment with Bmp2 and Bmp4, but not with Noggin. Gene expression levels in dental follicle cells from murine molars were also determined by real-time RT-PCR. The expression levels of Runx2, Bsp, and Ocn were significantly higher in dental follicle cells cultured with Bmp2 or Bmp4, and significantly lower in those cultured with Noggin when compared with that of the BSA controls. Our results suggest that the dental follicle participates in alveolar bone formation and Bmp2/4 appears to accelerate alveolar bone development.

  10. 重组人BMP-2诱导C3H10T1/2间质干细胞定向成骨分化早期基因表达谱分析%Identification and analysis of gene expression profiles for early osteoblastic differentiation on C3H10T1/2 mesenchymal stem cells induced by rhBMP-2

    Institute of Scientific and Technical Information of China (English)

    左长清; 汪宗桂; 钟月春; 卢旱云; 戴忠; 吴铁; 崔燎

    2014-01-01

    目的 研究间质干细胞早期定向成骨分化基因表达谱,为研究基因对早期成骨定向分化调控机制提供实验基础.方法 分别提取重组人骨形成蛋白2(rhBMP-2)诱导组和对照组C3H10T1/2细胞总RNA,进行扩增标记后,与ArraySTAR小鼠基因芯片杂交,应用生物信息学软件GeneSpring和GATHER对基因芯片数据进行分析.应用STRING在线软件对差异表达基因构建蛋白互作网络并进行网络分析.结果 C3H10T1/2早期成骨分化中,主要富集发育、器官形成等分子功能本体以及细胞因子-细胞因子受体作用信号通路.成骨分化1d和4d均上调表达基因42个,下调表达基因45个.网络分析研究表明:Egfr、Cxcl 12等信号分子参与调控rhBMP-2诱导成骨分化.结论 筛选的差异表达基因和信号分子对早期成骨分化调控具有重要作用,为进一步全面解析早期成骨定向分化提供实验基础.

  11. Smad4 mediated BMP2 signal is essential for the regulation of GATA4 and Nkx2.5 by affecting the histone H3 acetylation in H9c2 cells

    Energy Technology Data Exchange (ETDEWEB)

    Si, Lina; Shi, Jin; Gao, Wenqun [Heart Centre, Children’s Hospital of Chongqing Medical University, 136 Zhongshan 2nd Road, Yu Zhong District, Chongqing 400014 (China); Ministry of Education Key Laboratory of Child Development and Disorders, Key Laboratory of Pediatrics in Chongqing, Chongqing International Science and Technology Cooperation Center for Child Development and Disorders, 136 Zhongshan 2nd Road, Yu Zhong District, Chongqing 400014 (China); Zheng, Min [Heart Centre, Children’s Hospital of Chongqing Medical University, 136 Zhongshan 2nd Road, Yu Zhong District, Chongqing 400014 (China); Liu, Lingjuan; Zhu, Jing [Ministry of Education Key Laboratory of Child Development and Disorders, Key Laboratory of Pediatrics in Chongqing, Chongqing International Science and Technology Cooperation Center for Child Development and Disorders, 136 Zhongshan 2nd Road, Yu Zhong District, Chongqing 400014 (China); Tian, Jie, E-mail: jietian@cqmu.edu.cn [Heart Centre, Children’s Hospital of Chongqing Medical University, 136 Zhongshan 2nd Road, Yu Zhong District, Chongqing 400014 (China)

    2014-07-18

    Highlights: • BMP2 can upregulated cardiac related gene GATA4, Nkx2.5, MEF2c and Tbx5. • Inhibition of Smad4 decreased BMP2-induced hyperacetylation of histone H3. • Inhibition of Smad4 diminished BMP2-induced overexpression of GATA4 and Nkx2.5. • Inhibition of Smad4 decreased hyperacetylated H3 in the promoter of GATA4 and Nkx2.5. • Smad4 is essential for BMP2 induced hyperacetylated histone H3. - Abstract: BMP2 signaling pathway plays critical roles during heart development, Smad4 encodes the only common Smad protein in mammals, which is a pivotal nuclear mediator. Our previous studies showed that BMP2 enhanced the expression of cardiac transcription factors in part by increasing histone H3 acetylation. In the present study, we tested the hypothesis that Smad4 mediated BMP2 signaling pathway is essential for the expression of cardiac core transcription factors by affecting the histone H3 acetylation. We successfully constructed a lentivirus-mediated short hairpin RNA interference vector targeting Smad4 (Lv-Smad4) in rat H9c2 embryonic cardiac myocytes (H9c2 cells) and demonstrated that it suppressed the expression of the Smad4 gene. Cultured H9c2 cells were transfected with recombinant adenoviruses expressing human BMP2 (AdBMP2) with or without Lv-Smad4. Quantitative real-time RT-PCR analysis showed that knocking down of Smad4 substantially inhibited both AdBMP2-induced and basal expression levels of cardiac transcription factors GATA4 and Nkx2.5, but not MEF2c and Tbx5. Similarly, chromatin immunoprecipitation (ChIP) analysis showed that knocking down of Smad4 inhibited both AdBMP2-induced and basal histone H3 acetylation levels in the promoter regions of GATA4 and Nkx2.5, but not of Tbx5 and MEF2c. In addition, Lv-Smad4 selectively suppressed AdBMP2-induced expression of HAT p300, but not of HAT GCN5 in H9c2 cells. The data indicated that inhibition of Smad4 diminished both AdBMP2 induced and basal histone acetylation levels in the promoter regions of

  12. Smad4 mediated BMP2 signal is essential for the regulation of GATA4 and Nkx2.5 by affecting the histone H3 acetylation in H9c2 cells

    International Nuclear Information System (INIS)

    Highlights: • BMP2 can upregulated cardiac related gene GATA4, Nkx2.5, MEF2c and Tbx5. • Inhibition of Smad4 decreased BMP2-induced hyperacetylation of histone H3. • Inhibition of Smad4 diminished BMP2-induced overexpression of GATA4 and Nkx2.5. • Inhibition of Smad4 decreased hyperacetylated H3 in the promoter of GATA4 and Nkx2.5. • Smad4 is essential for BMP2 induced hyperacetylated histone H3. - Abstract: BMP2 signaling pathway plays critical roles during heart development, Smad4 encodes the only common Smad protein in mammals, which is a pivotal nuclear mediator. Our previous studies showed that BMP2 enhanced the expression of cardiac transcription factors in part by increasing histone H3 acetylation. In the present study, we tested the hypothesis that Smad4 mediated BMP2 signaling pathway is essential for the expression of cardiac core transcription factors by affecting the histone H3 acetylation. We successfully constructed a lentivirus-mediated short hairpin RNA interference vector targeting Smad4 (Lv-Smad4) in rat H9c2 embryonic cardiac myocytes (H9c2 cells) and demonstrated that it suppressed the expression of the Smad4 gene. Cultured H9c2 cells were transfected with recombinant adenoviruses expressing human BMP2 (AdBMP2) with or without Lv-Smad4. Quantitative real-time RT-PCR analysis showed that knocking down of Smad4 substantially inhibited both AdBMP2-induced and basal expression levels of cardiac transcription factors GATA4 and Nkx2.5, but not MEF2c and Tbx5. Similarly, chromatin immunoprecipitation (ChIP) analysis showed that knocking down of Smad4 inhibited both AdBMP2-induced and basal histone H3 acetylation levels in the promoter regions of GATA4 and Nkx2.5, but not of Tbx5 and MEF2c. In addition, Lv-Smad4 selectively suppressed AdBMP2-induced expression of HAT p300, but not of HAT GCN5 in H9c2 cells. The data indicated that inhibition of Smad4 diminished both AdBMP2 induced and basal histone acetylation levels in the promoter regions of

  13. The effects of 3D bioactive glass scaffolds and BMP-2 on bone formation in rat femoral critical size defects and adjacent bones

    International Nuclear Information System (INIS)

    Reconstruction of critical size defects in the load-bearing area has long been a challenge in orthopaedics. In the past, we have demonstrated the feasibility of using a biodegradable load-sharing scaffold fabricated from poly(propylene fumarate)/tricalcium phosphate (PPF/TCP) loaded with bone morphogenetic protein-2 (BMP-2) to successfully induce healing in those defects. However, there is limited osteoconduction observed with the PPF/TCP scaffold itself. For this reason, 13-93 bioactive glass scaffolds with local BMP-2 delivery were investigated in this study for inducing segmental defect repairs in a load-bearing region. Furthermore, a recent review on BMP-2 revealed greater risks in radiculitis, ectopic bone formation, osteolysis and poor global outcome in association with the use of BMP-2 for spinal fusion. We also evaluated the potential side effects of locally delivered BMP-2 on the structures of adjacent bones. Therefore, cylindrical 13-93 glass scaffolds were fabricated by indirect selective laser sintering with side holes on the cylinder filled with dicalcium phosphate dehydrate as a BMP-2 carrier. The scaffolds were implanted into critical size defects created in rat femurs with and without 10 μg of BMP-2. The x-ray and micro-CT results showed that a bridging callus was found as soon as three weeks and progressed gradually in the BMP group while minimal bone formation was observed in the control group. Degradation of the scaffolds was noted in both groups. Stiffness, peak load and energy to break of the BMP group were all higher than the control group. There was no statistical difference in bone mineral density, bone area and bone mineral content in the tibiae and contralateral femurs of the control and BMP groups. In conclusion, a 13-93 bioactive glass scaffold with local BMP-2 delivery has been demonstrated for its potential application in treating large bone defects. (paper)

  14. Vitapex can promote the expression of BMP-2 during the bone regeneration of periapical lesions in rats

    Directory of Open Access Journals (Sweden)

    Xianyin Xia

    2013-01-01

    Full Text Available Purpose: To investigate the effect of Vitapex on the healing of periapical lesions and the expression of bone morphogenetic protein (BMP-2 during the periapical bone regeneration. Materials and Methods: Periapical lesions were induced in Sprague-Dawley (S-D rats by an occlusal pulp exposure in the mandibular first molars and were verified by X-ray. Total of 36 rats were randomly divided into three groups, and they were obturated with Zinc Oxide Eugenol (ZOE, or with Vitapex, or non-treated as negative control group. The rats of three groups were randomly killed at week 0, 2, 4, and 8 after root canal therapy, and then the mandibles were processed for histological examination and immunohistochemistry analysis. Results: At week 0, only a few BMP-2 positive cells could be observed in all rats. While the expression of BMP-2 was dramatically increased in case of Vitapex group at week 2 and week 4, and then climaxed at week 8. However, no apparent changes were observed in ZOE group and negative group at week 2, 4, and 8. Conclusion: These observations suggested that Vitapex has a greater ability in inducing bone regeneration than ZOE by the expression of BMP-2 induction in the treatment of rats experimental periapical lesions.

  15. Disequilibrium of BMP2 Levels in the Breast Stem Cell Niche Launches Epithelial Transformation by Overamplifying BMPR1B Cell Response

    Directory of Open Access Journals (Sweden)

    Marion Chapellier

    2015-02-01

    Full Text Available Understanding the mechanisms of cancer initiation will help to prevent and manage the disease. At present, the role of the breast microenvironment in transformation remains unknown. As BMP2 and BMP4 are important regulators of stem cells and their niches in many tissues, we investigated their function in early phases of breast cancer. BMP2 production by tumor microenvironment appeared to be specifically upregulated in luminal tumors. Chronic exposure of immature human mammary epithelial cells to high BMP2 levels initiated transformation toward a luminal tumor-like phenotype, mediated by the receptor BMPR1B. Under physiological conditions, BMP2 controlled the maintenance and differentiation of early luminal progenitors, while BMP4 acted on stem cells/myoepithelial progenitors. Our data also suggest that microenvironment-induced overexpression of BMP2 may result from carcinogenic exposure. We reveal a role for BMP2 and the breast microenvironment in the initiation of stem cell transformation, thus providing insight into the etiology of luminal breast cancer.

  16. Disequilibrium of BMP2 Levels in the Breast Stem Cell Niche Launches Epithelial Transformation by Overamplifying BMPR1B Cell Response

    Science.gov (United States)

    Chapellier, Marion; Bachelard-Cascales, Elodie; Schmidt, Xenia; Clément, Flora; Treilleux, Isabelle; Delay, Emmanuel; Jammot, Alexandre; Ménétrier-Caux, Christine; Pochon, Gaëtan; Besançon, Roger; Voeltzel, Thibault; Caron de Fromentel, Claude; Caux, Christophe; Blay, Jean-Yves; Iggo, Richard; Maguer-Satta, Véronique

    2015-01-01

    Summary Understanding the mechanisms of cancer initiation will help to prevent and manage the disease. At present, the role of the breast microenvironment in transformation remains unknown. As BMP2 and BMP4 are important regulators of stem cells and their niches in many tissues, we investigated their function in early phases of breast cancer. BMP2 production by tumor microenvironment appeared to be specifically upregulated in luminal tumors. Chronic exposure of immature human mammary epithelial cells to high BMP2 levels initiated transformation toward a luminal tumor-like phenotype, mediated by the receptor BMPR1B. Under physiological conditions, BMP2 controlled the maintenance and differentiation of early luminal progenitors, while BMP4 acted on stem cells/myoepithelial progenitors. Our data also suggest that microenvironment-induced overexpression of BMP2 may result from carcinogenic exposure. We reveal a role for BMP2 and the breast microenvironment in the initiation of stem cell transformation, thus providing insight into the etiology of luminal breast cancer. PMID:25601208

  17. BMP-2-enhanced chondrogenesis involves p38 MAPK-mediated down-regulation of Wnt-7a pathway.

    Science.gov (United States)

    Jin, Eun-Jung; Lee, Sun-Young; Choi, Young-Ae; Jung, Jae-Chang; Bang, Ok-Sun; Kang, Shin-Sung

    2006-12-31

    The bone morphogenetic protein (BMP) family has been implicated in control of cartilage development. Here, we demonstrate that BMP-2 promotes chondrogenesis by activating p38 mitogen-activated protein kinase (MAPK), which in turn downregulates Wnt-7a/b-catenin signaling responsible for proteasomal degradation of Sox9. Exposure of mesenchymal cells to BMP-2 resulted in upregulation of Sox9 protein and a concomitant decrease in the level of b-catenin protein and Wnt-7a signaling. In agreement with this, the interaction of Sox9 with b-catenin was inhibited in the presence of BMP-2. Inhibition of the p38 MAPK pathway using a dominant negative mutant led to sustained Wnt-7a signaling and decreased Sox9 expression, with consequent inhibition of precartilage condensation and chondrogenic differentiation. Moreover, overexpression of b-catenin caused degradation of Sox9 via the ubiquitin/26S proteasome pathway. Our results collectively indicate that the increase in Sox9 protein resulting from downregulation of b-catenin/Wnt-7a signaling is mediated by p38 MAPK during BMP-2 induced chondrogenesis in chick wing bud mesenchymal cells. PMID:17202865

  18. BMP2-loaded hollow hydroxyapatite microspheres exhibit enhanced osteoinduction and osteogenicity in large bone defects

    Directory of Open Access Journals (Sweden)

    Xiong L

    2015-01-01

    Full Text Available Long Xiong,1 Jianhua Zeng,1 Aihua Yao,2 Qiquan Tu,3 Jingtang Li,1 Liang Yan,4 Zhiming Tang1 1Department of Osteology, People’s Hospital of Jiangxi Province, Nanchang, Jiangxi, People’s Republic of China; 2School of Materials Science and Engineering, Tongji University, Shanghai, People’s Republic of China; 3Department of Osteology, People’s Hospital of Jiujiang County, Jiujiang, Jiangxi, People’s Republic of China; 4Department of Osteology, The Third Hospital of Nanchang City, Nanchang, Jiangxi, People’s Republic of China Abstract: The regeneration of large bone defects is an osteoinductive, osteoconductive, and osteogenic process that often requires a bone graft for support. Limitations associated with naturally autogenic or allogenic bone grafts have demonstrated the need for synthetic substitutes. The present study investigates the feasibility of using novel hollow hydroxyapatite microspheres as an osteoconductive matrix and a carrier for controlled local delivery of bone morphogenetic protein 2 (BMP2, a potent osteogenic inducer of bone regeneration. Hollow hydroxyapatite microspheres (100±25 µm with a core (60±18 µm and a mesoporous shell (180±42 m2/g surface area were prepared by a glass conversion technique and loaded with recombinant human BMP2 (1 µg/mg. There was a gentle burst release of BMP2 from microspheres into the surrounding phosphate-buffered saline in vitro within the initial 48 hours, and continued at a low rate for over 40 days. In comparison with hollow hydroxyapatite microspheres without BMP2 or soluble BMP2 without a carrier, BMP2-loaded hollow hydroxyapatite microspheres had a significantly enhanced capacity to reconstitute radial bone defects in rabbit, as shown by increased serum alkaline phosphatase; quick and complete new bone formation within 12 weeks; and great biomechanical flexural strength. These results indicate that BMP2-loaded hollow hydroxyapatite microspheres could be a potential new option

  19. BMP2 and VEGF promote angiogenesis but retard terminal differentiation of osteoblasts in bone regeneration by up-regulating Id1

    Institute of Scientific and Technical Information of China (English)

    Xiaobin Song; Shaohua Liu; Xun Qu; Yingwei Hu; Xiaoying Zhang; TaoWang; FengcaiWei

    2011-01-01

    Inadequate vascularization limits the repair of bone defects,In order to improve angiogenesis and accelerate osteogenesis,the synergism of co-cultured cells with genetic modification in bone regeneration was investigated in this study.Endothelial progenitor cells (EPCs) and bone marrow stem cells (BMSCs) were transfected with the genes of vascular endothelial growth factor (VEGF) and bone morphogenetic protein 2 (BMP2) by adenovirus,respectively.The co-cultured cells,designated as four groups including BMSC + EPC,Ad-BMP2-BMSC +EPC,BMSC + Ad-VEGF-EPC,and Ad-BMP2-BMSC + Ad-VEGF-EPC groups,were seeded on an alginate gel and then implanted into rat intramuscularly to evaluate the effects on angiogenesis and osteogenesis.Both VEGF and BMP2 could induce the overexpression of inhibitor of DNA-binding 1(Id1) gene which significantly promoted tube formation in vitro and increase the amount of blood vessels in the Ad-BMP2-BMSC + Ad-VEGF-EPC group after implantation.Nevertheless,overexpression of Id1 retarded the terminal differentiation of osteoblasts and the bone formation.Later,osteogenic gene expression at transcriptional level,calcium nodules,and alkaline phosphatase (ALP) activity showed a gradual decrease and the amount of newly formed osteogenesis area exhibited a small increase in the Ad-BMP2-BMSC + Ad-VEGF-EPC group.This finding suggests that a balanced regulation of Id1 expression in VEGF-EPCs and BMP2-BMSCs may be critical to cell-based and gene-based approaches for bone regeneration.

  20. Retrovirus-mediated transfer of the fusion gene encoding EGFP-BMP_2 in mesenchymal stem cells

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Bone marrow mesenchymal stemcells(MSCs)are pluripotential stemcells that have the capacitytodifferentiate into chondrocytes and osteoblasts[1].Ithas been well documented that bone morphogeneticproteins(BMPs),a group of proteins belonging tothe TGF-βsuperfamily,can induce bone for mationbothin vivoandin vitroas well as promote osteo-blastic differentiation of MSC[2].HeterologousBMP2is successfully transferred to MSCs and genetherapy is employed based on repairing bony andcartilage defects,spinal fusion[3-5]....

  1. Bone regeneration by implantation of adipose-derived stromal cells expressing BMP-2

    International Nuclear Information System (INIS)

    In this study, we reported that the adipose-derived stromal cells (ADSCs) genetically modified by bone morphogenetic protein 2 (BMP-2) healed critical-sized canine ulnar bone defects. First, the osteogenic and adipogenic differentiation potential of the ADSCs derived from canine adipose tissue were demonstrated. And then the cells were modified by the BMP-2 gene and the expression and bone-induction ability of BMP-2 were identified. Finally, the cells modified by BMP-2 gene were applied to a β-tricalcium phosphate (TCP) carrier and implanted into ulnar bone defects in the canine model. After 16 weeks, radiographic, histological, and histomorphometry analysis showed that ADSCs modified by BMP-2 gene produced a significant increase of newly formed bone area and healed or partly healed all of the bone defects. We conclude that ADSCs modified by the BMP-2 gene can enhance the repair of critical-sized bone defects in large animals

  2. E. coli-Produced BMP-2 as a Chemopreventive Strategy for Colon Cancer: A Proof-of-Concept Study

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    Saravanan Yuvaraj

    2012-01-01

    Full Text Available Colon cancer is a serious health problem, and novel preventive and therapeutical avenues are urgently called for. Delivery of proteins with anticancer activity through genetically modified bacteria provides an interesting, potentially specific, economic and effective approach here. Interestingly, bone morphogenetic protein 2 (BMP-2 is an important and powerful tumour suppressor in the colon and is thus an attractive candidate protein for delivery through genetically modified bacteria. It has not been shown, however, that BMP production in the bacterial context is effective on colon cancer cells. Here we demonstrate that transforming E. coli with a cDNA encoding an ileal-derived mature human BMP-2 induces effective apoptosis in an in vitro model system for colorectal cancer, whereas the maternal organism was not effective in this respect. Furthermore, these effects were sensitive to cotreatment with the BMP inhibitor Noggin. We propose that prevention and treatment of colorectal cancer using transgenic bacteria is feasible.

  3. Bmp2 deletion causes an amelogenesis imperfecta phenotype via regulating enamel gene expression.

    Science.gov (United States)

    Guo, Feng; Feng, Junsheng; Wang, Feng; Li, Wentong; Gao, Qingping; Chen, Zhuo; Shoff, Lisa; Donly, Kevin J; Gluhak-Heinrich, Jelica; Chun, Yong Hee Patricia; Harris, Stephen E; MacDougall, Mary; Chen, Shuo

    2015-08-01

    Although Bmp2 is essential for tooth formation, the role of Bmp2 during enamel formation remains unknown in vivo. In this study, the role of Bmp2 in regulation of enamel formation was investigated by the Bmp2 conditional knock out (Bmp2 cKO) mice. Teeth of Bmp2 cKO mice displayed severe and profound phenotypes with asymmetric and misshaped incisors as well as abrasion of incisors and molars. Scanning electron microscopy analysis showed that the enamel layer was hypoplastic and enamel lacked a typical prismatic pattern. Teeth from null mice were much more brittle as tested by shear and compressive moduli. Expression of enamel matrix protein genes, amelogenin, enamelin, and enamel-processing proteases, Mmp-20 and Klk4 was reduced in the Bmp2 cKO teeth as reflected in a reduced enamel formation. Exogenous Bmp2 up-regulated those gene expressions in mouse enamel organ epithelial cells. This result for the first time indicates Bmp2 signaling is essential for proper enamel development and mineralization in vivo.

  4. Cell saver filtering of extravasated rhBMP-2 after degenerative scoliosis reconstruction

    Directory of Open Access Journals (Sweden)

    Gabriel Liu, MBBCh, MSc, FRCS, FAMS (Orth

    2015-06-01

    Full Text Available RhBMP-2 is a bone fusion enhancer commonly used in scoliosis reconstruction surgery. It is delivered via an absorbable collagen sponge but has been known to migrate away from its delivery site. RhBMP-2 extravasation in surgical drainage has been noted during first two days post-surgery. Cell savers are widely used in scoliosis reconstruction to limit transfusion requirements and are commonly deployed in cases where rhBMP-2 is used for fusion augmentation. It is not known whether rhBMP-2 is present in salvaged blood or filtered away during cell saver recycling. Through this case series of four patients who underwent scoliosis reconstruction, we assess cell saver efficacy in filtering rhBMP-2 molecules by quantifying the amount of rhBMP-2 present in salvaged blood obtained after postoperative drainage recycling by OrthoPAT® cell saver and comparing it to rhBMP-2 leakage in postoperative drainage without cell saver recycling. We report an almost 10-fold reduction of rhBMP-2 concentration in salvaged blood obtained after cell saver recycling of postoperative drainage, suggesting cell saver effectiveness in filtering rhBMP-2 molecules.

  5. Repair of rabbit radial bone defects using true bone ceramics combined with BMP-2-related peptide and type I collagen

    International Nuclear Information System (INIS)

    An ideal bone graft material is the one characterized with good biocompatibility, biodegradation, osteoconductivity and osteoinductivity. In this study, a novel synthetic BMP-2-related peptide (designated P24) corresponding to residues of the knuckle epitope of BMP-2 was introduced into a biomimetic scaffold based on sintered bovine bone or true bone ceramics (TBC) and type I collagen (TBC/collagen I) using a simulated body fluid (SBF). Hydroxylapatite crystal mineralization with a Ca/P molar ratio of 1.63 was observed on the surface of P24/TBC/collagen I composite by scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDX) and X-ray diffraction (XRD) techniques. Cell adhesion rate evaluation of bone marrow stromal cells (BMSCs) seeded on materials in vitro showed that the percentage of cells attached to P24/TBC/collagen I composite was significantly higher than that of the TBC/collagen I composite. A 10 mm unilateral segmental bone defect was created in the radius of New Zealand white rabbits and randomly implanted with three groups of biomaterials (Group A: P24/TBC/collagen I composite; Group B: TBC/collagen I composite and Group C: TBC alone). Based on radiographic evaluation and histological examination, the implants of P24/TBC/collagen I composite significantly stimulated bone growth, thereby confirming the enhanced rate of bone healing compared with that of TBC/collagen I composite and TBC alone. It was concluded that BMP-2-related peptide P24 could induce nucleation of calcium phosphate crystals on the surface of TBC/collagen I composite. The TBC/collagen I composite loaded with the synthetic BMP-2-related peptide is a promising scaffold biomaterial for bone tissue engineering.

  6. Expression of active hBMP2 in transgenic tobacco plants.

    Science.gov (United States)

    Suo, Guangli; Chen, Bing; Zhang, Jingyu; Gao, Yuan; Wang, Xia; He, Zhengquan; Dai, Jianwu

    2006-12-01

    Bone morphogenetic protein 2 (BMP2) is important for bone tissue repair. The goal of this research is to construct a high level human BMP2 (hBMP2) expression system using transgenic tobacco plants as a bioreactor. Cauliflower mosaic virus (CaMV) 35S promoter, alfalfa mosaic virus (AMV) enhancer, tobacco mosaic virus (TMV) enhancer, matrix attachment regions (MARs) sequence, and "Kozak" sequence were used to construct recombinant expression vectors and the high-expression vectors were screened out through GUS-fusions assay. The promoter is the most important factor; double-CaMV 35S promoter is more effective than single promoter. The AMV or TMV enhancer is able to promote the foreign protein expression. After four-step purification, the activated hBMP2 (0.02% total soluble protein) was obtained. Our results suggested that the transgenic tobacco has great potential to be used as a bioreactor to produce hBMP2. PMID:16819603

  7. Immortalization and characterization of mouse floxed Bmp2/4 osteoblasts

    International Nuclear Information System (INIS)

    Generation of a floxed Bmp2/4 osteoblast cell line is a valuable tool for studying the modulatory effects of Bmp2 and Bmp4 on osteoblast differentiation as well as relevant molecular events. In this study, primary floxed Bmp2/4 mouse osteoblasts were cultured and transfected with simian virus 40 large T-antigen. Transfection was verified by polymerase chain reaction (PCR) and immunohistochemistry. To examine the characteristics of the transfected cells, morphology, proliferation and mineralization were analyzed, expression of cell-specific genes including Runx2, ATF4, Dlx3, Osx, dentin matrix protein 1, bone sialoprotein, osteopontin, osteocalcin, osteonectin and collagen type I was detected. These results show that transfected floxed Bmp2/4 osteoblasts bypassed senescence with a higher proliferation rate, but retain the genotypic and phenotypic characteristics similar to the primary cells. Thus, we for the first time demonstrate the establishment of an immortalized mouse floxed Bmp2/4 osteoblast cell line.

  8. Immortalization and characterization of mouse floxed Bmp2/4 osteoblasts

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Li-An [Department of Pediatric Dentistry, The University of Texas Health Science Center at San Antonio, TX (United States); Department of Pediatric Dentistry, School of Stomatology, The Fourth Military Medical University, Xi-an (China); Yuan, Guohua; Yang, Guobin [Department of Pediatric Dentistry, The University of Texas Health Science Center at San Antonio, TX (United States); Key Laboratory of Oral Biomedical Engineering Ministry of Education, Wuhan (China); Ortiz-Gonzalez, Iris [Department of Pediatric Dentistry, The University of Texas Health Science Center at San Antonio, TX (United States); Yang, Wuchen; Cui, Yong [Department of Periodontics, Dental School, The University of Texas Health Science Center at San Antonio, TX (United States); MacDougall, Mary [Department of Oral/Maxillofacial Surgery, University of Alabama, Birmingham, AL (United States); Donly, Kevin J. [Department of Pediatric Dentistry, The University of Texas Health Science Center at San Antonio, TX (United States); Harris, Stephen [Department of Periodontics, Dental School, The University of Texas Health Science Center at San Antonio, TX (United States); Chen, Shuo, E-mail: chens0@uthscsa.edu [Department of Pediatric Dentistry, The University of Texas Health Science Center at San Antonio, TX (United States)

    2009-08-14

    Generation of a floxed Bmp2/4 osteoblast cell line is a valuable tool for studying the modulatory effects of Bmp2 and Bmp4 on osteoblast differentiation as well as relevant molecular events. In this study, primary floxed Bmp2/4 mouse osteoblasts were cultured and transfected with simian virus 40 large T-antigen. Transfection was verified by polymerase chain reaction (PCR) and immunohistochemistry. To examine the characteristics of the transfected cells, morphology, proliferation and mineralization were analyzed, expression of cell-specific genes including Runx2, ATF4, Dlx3, Osx, dentin matrix protein 1, bone sialoprotein, osteopontin, osteocalcin, osteonectin and collagen type I was detected. These results show that transfected floxed Bmp2/4 osteoblasts bypassed senescence with a higher proliferation rate, but retain the genotypic and phenotypic characteristics similar to the primary cells. Thus, we for the first time demonstrate the establishment of an immortalized mouse floxed Bmp2/4 osteoblast cell line.

  9. Effect of rhBMP-2 Immobilized Anorganic Bovine Bone Matrix on Bone Regeneration

    Directory of Open Access Journals (Sweden)

    Jung-Bo Huh

    2015-07-01

    Full Text Available Anorganic bovine bone matrix (Bio-Oss® has been used for a long time for bone graft regeneration, but has poor osteoinductive capability. The use of recombinant human bone morphogenetic protein-2 (rhBMP-2 has been suggested to overcome this limitation of Bio-Oss®. In the present study, heparin-mediated rhBMP-2 was combined with Bio-Oss® in animal experiments to investigate bone formation performance; heparin was used to control rhBMP-2 release. Two calvarial defects (8 mm diameter were formed in a white rabbit model and then implanted or not (controls with Bio-Oss® or BMP-2/Bio-Oss®. The Bio-Oss® and BMP-2/Bio-Oss® groups had significantly greater new bone areas (expressed as percentages of augmented areas than the non-implanted controls at four and eight weeks after surgery, and the BMP-2/Bio-Oss® group (16.50 ± 2.87 (n = 6 had significantly greater new bone areas than the Bio-Oss® group (9.43 ± 3.73 (n = 6 at four weeks. These findings suggest that rhBMP-2 treated heparinized Bio-Oss® markedly enhances bone regeneration.

  10. Effect of rhBMP-2 Immobilized Anorganic Bovine Bone Matrix on Bone Regeneration.

    Science.gov (United States)

    Huh, Jung-Bo; Yang, June-Jip; Choi, Kyung-Hee; Bae, Ji Hyeon; Lee, Jeong-Yeol; Kim, Sung-Eun; Shin, Sang-Wan

    2015-01-01

    Anorganic bovine bone matrix (Bio-Oss®) has been used for a long time for bone graft regeneration, but has poor osteoinductive capability. The use of recombinant human bone morphogenetic protein-2 (rhBMP-2) has been suggested to overcome this limitation of Bio-Oss®. In the present study, heparin-mediated rhBMP-2 was combined with Bio-Oss® in animal experiments to investigate bone formation performance; heparin was used to control rhBMP-2 release. Two calvarial defects (8 mm diameter) were formed in a white rabbit model and then implanted or not (controls) with Bio-Oss® or BMP-2/Bio-Oss®. The Bio-Oss® and BMP-2/Bio-Oss® groups had significantly greater new bone areas (expressed as percentages of augmented areas) than the non-implanted controls at four and eight weeks after surgery, and the BMP-2/Bio-Oss® group (16.50 ± 2.87 (n = 6)) had significantly greater new bone areas than the Bio-Oss® group (9.43 ± 3.73 (n = 6)) at four weeks. These findings suggest that rhBMP-2 treated heparinized Bio-Oss® markedly enhances bone regeneration. PMID:26184187

  11. Effect of rhBMP-2 Immobilized Anorganic Bovine Bone Matrix on Bone Regeneration

    OpenAIRE

    Jung-Bo Huh; June-Jip Yang; Kyung-Hee Choi; Ji Hyeon Bae; Jeong-Yeol Lee; Sung-Eun Kim; Sang-Wan Shin

    2015-01-01

    Anorganic bovine bone matrix (Bio-Oss®) has been used for a long time for bone graft regeneration, but has poor osteoinductive capability. The use of recombinant human bone morphogenetic protein-2 (rhBMP-2) has been suggested to overcome this limitation of Bio-Oss®. In the present study, heparin-mediated rhBMP-2 was combined with Bio-Oss® in animal experiments to investigate bone formation performance; heparin was used to control rhBMP-2 release. Two calvarial defects (8 mm diameter) were fo...

  12. Effects of local delivery of BMP2, zoledronate and their combination on bone microarchitecture, biomechanics and bone turnover in osteoporotic rabbits.

    Science.gov (United States)

    Jing, Da; Hao, Xuguang; Xu, Fang; Liu, Jian; Xu, Fei; Luo, Erping; Meng, Guolin

    2016-01-01

    The hip fracture is one major clinical challenge associated with osteoporosis, resulting in heavy socioeconomic burdens and high mortality. Systemic therapies of anti-osteoporosis drugs are expensive, time-consuming and also evoke substantial side effects, which fails to provide early protection from fractures. Accumulating evidence demonstrates the high bioavailability and therapeutic efficacy of local drug delivery in accelerating facture healing and bone defect repair. This study aims at investigating the effects of local delivery of BMP2 and zoledronate (two promising anabolic/anti-catobolic reagents) encapsulated by fibrin sealants into femoral necks on regulating bone quality and remodeling in osteoporotic rabbits subjected to combined ovariectomy and glucocorticoid injection. We show that 6-week BMP2 delivery exhibited more prominent effect on mitigating trabecular bone microarchitecture deterioration and mechanical strength reduction of femoral necks than local zoledronate treatment. BMP2 plus zoledronate showed more significant improvement of bone microstructure, mechanical strength and bone formation rate at 12 weeks post injection than single BMP2 or zoledronate delivery via μCT, biomechanical, histomorphometric and serum biochemical analyses. This study enriches our knowledge for understanding the availability of local drug delivery for improving bone quantity and quality, which may lead to earlier, safer and more efficient protection from osteoporosis-induced fractures in clinics. PMID:27329730

  13. BMP2, 4 and 6 and BMPR1B are altered from early stages of bovine cystic ovarian disease development.

    Science.gov (United States)

    Díaz, Pablo U; Hein, Gustavo J; Belotti, Eduardo M; Rodríguez, Fernanda M; Rey, Florencia; Amweg, Ayelén N; Matiller, Valentina; Baravalle, María E; Ortega, Hugo H; Salvetti, Natalia R

    2016-10-01

    Cystic ovarian disease (COD) is an important cause of subfertility in dairy cattle. Bone morphogenetic proteins (BMPs), mainly BMP2, BMP4 and BMP6, play a key role in female fertility. In this study, we hypothesized that an altered BMP system is associated with ovarian alterations contributing to COD pathogenesis. Therefore, we examined the expression of BMP2, BMP4 and BMP6 and BMP receptor 1B (BMPR1B) in the ovaries of animals with spontaneous or ACTH-induced COD, as well as during the development of the disease, in a model of follicular persistence induced by low doses of progesterone (at 5, 10 and 15 days of follicular persistence). Results showed changes in BMP2, BMP4 and BMP6 expression during folliculogenesis, in granulosa and theca cells in the COD groups, as well as at different stages of follicular persistence. Results also showed changes in BMPR1B expression in developing follicles in animals with COD, and at the initial stages of follicular persistence (P5). Comparison between groups showed significant differences, mainly in BMP4 and BMP6 expression, in granulosa and theca cells of different follicular categories. The expression of these BMPs also increased in cystic and persistent follicles, in relation to antral follicles of the control group. BMPR1B showed high expression in cystic follicles. Together, these results may indicate an alteration in BMPs, especially in BMP4 and BMP6, as well as in BMPR1B, which occurs early in folliculogenesis and incipiently during the development of COD, which could be a major cause of recurrence of this disease in cattle.Free Spanish abstract: A Spanish translation of this abstract is freely available at http://www.reproduction-online.org/content/early/2016/08/01/REP-15-0315/suppl/DC1. PMID:27486268

  14. Sustained release of BMP-2 in bioprinted alginate for osteogenicity in mice and rats.

    Directory of Open Access Journals (Sweden)

    Michelle T Poldervaart

    Full Text Available The design of bioactive three-dimensional (3D scaffolds is a major focus in bone tissue engineering. Incorporation of growth factors into bioprinted scaffolds offers many new possibilities regarding both biological and architectural properties of the scaffolds. This study investigates whether the sustained release of bone morphogenetic protein 2 (BMP-2 influences osteogenicity of tissue engineered bioprinted constructs. BMP-2 loaded on gelatin microparticles (GMPs was used as a sustained release system, which was dispersed in hydrogel-based constructs and compared to direct inclusion of BMP-2 in alginate or control GMPs. The constructs were supplemented with goat multipotent stromal cells (gMSCs and biphasic calcium phosphate to study osteogenic differentiation and bone formation respectively. BMP-2 release kinetics and bioactivity showed continuous release for three weeks coinciding with osteogenicity. Osteogenic differentiation and bone formation of bioprinted GMP containing constructs were investigated after subcutaneous implantation in mice or rats. BMP-2 significantly increased bone formation, which was not influenced by the release timing. We showed that 3D printing of controlled release particles is feasible and that the released BMP-2 directs osteogenic differentiation in vitro and in vivo.

  15. Effect of a Novel Nonviral Gene Delivery of BMP-2 on Bone Healing

    Directory of Open Access Journals (Sweden)

    P. Schwabe

    2012-01-01

    Full Text Available Background. Gene therapeutic drug delivery approaches have been introduced to improve the efficiency of growth factors at the site of interest. This study investigated the efficacy and safety of a new nonviral copolymer-protected gene vector (COPROG for the stimulation of bone healing. Methods. In vitro, rat osteoblasts were transfected with COPROG + luciferase plasmid or COPROG + hBMP-2 plasmid. In vivo, rat tibial fractures were intramedullary stabilized with uncoated versus COPROG+hBMP-2-plasmid-coated titanium K-wires. The tibiae were prepared for biomechanical and histological analyses at days 28 and 42 and for transfection/safety study at days 2, 4, 7, 28, and 42. Results. In vitro results showed luciferase expression until day 21, and hBMP-2-protein was measured from day 2 – day 10. In vivo, the local application of hBMP-2-plasmid showed a significantly higher maximum load after 42 days compared to that in the control. The histomorphometric analysis revealed a significantly less mineralized periosteal callus area in the BMP-2 group compared to the control at day 28. The rt-PCR showed no systemic biodistribution of luciferase RNA. Conclusion. A positive effect on fracture healing by nonviral BMP-2 plasmid application from COPROG-coated implants could be shown in this study; however, the effect of the vector may be improved with higher plasmid concentrations. Transfection showed no biodistribution to distant organs and was considered to be safe.

  16. Cell-mediated BMP-2 liberation promotes bone formation in a mechanically unstable implant environment.

    Science.gov (United States)

    Hägi, Tobias T; Wu, Gang; Liu, Yuelian; Hunziker, Ernst B

    2010-05-01

    The flexible alloplastic materials that are used in bone-reconstruction surgery lack the mechanical stability that is necessary for sustained bone formation, even if this process is promoted by the application of an osteogenic agent, such as BMP-2. We hypothesize that if BMP-2 is delivered gradually, in a cell-mediated manner, to the surgical site, then the scaffolding material's lack of mechanical stability becomes a matter of indifference. Flexible discs of Ethisorb were functionalized with BMP-2, which was either adsorbed directly onto the material (rapid release kinetics) or incorporated into a calcium-phosphate coating (slow release kinetics). Unstabilized and titanium-plate-stabilized samples were implanted subcutaneously in rats and retrieved up to 14 days later for a histomorphometric analysis of bone and cartilage volumes. On day 14, the bone volume associated with titanium-plate-stabilized discs bearing an adsorbed depot of BMP-2 was 10-fold higher than that associated with their mechanically unstabilized counterparts. The bone volume associated with discs bearing a coating-incorporated depot of BMP-2 was similar in the mechanically unstabilized and titanium-plate-stabilized groups, and comparable to that associated with the titanium-plate-stabilized discs bearing an adsorbed depot of BMP-2. Hence, if an osteogenic agent is delivered in a cell-mediated manner (via coating degradation), ossification can be promoted even within a mechanically unstable environment.

  17. Mandibular bone repair by implantation of rhBMP-2 in a slow release carrier of polylactic acid--an experimental study in rats.

    Science.gov (United States)

    Schliephake, Henning; Weich, Herbert A; Dullin, Christian; Gruber, Rudolf; Frahse, Sarah

    2008-01-01

    The aim of the present study was to test the hypothesis that human recombinant bone morphogenic protein 2 (rhBMP-2) implanted in a slow release carrier of polylactic acid (PLA) can repair a non-healing defect in the rat mandible and maintain the thickness of an augmented volume. p-DL-lactic acid discs were produced and loaded with 48 and 96 microg rhBMP-2 and inserted into non-healing defects of the mandible of 45 Wistar rats. Fifteen rats received implants with 96 microg rhBMP-2 (Group 2), 48 microg rhBMP-2 (Group 1) and blank implants without BMP (Group 0) each on one side of the mandible. Unfilled defects of the same size on the contralateral sides of the mandibles served as empty controls. After 6, 13 and 26 weeks, implants of each group were retrieved from five animals each and submitted to flat panel detector computed tomography. Bone formation and thickness of augmentation was assessed by computer-assisted histomorphometry. In Group 2 significantly more bone was produced than in Group 1. Implants of Group 1 induced significantly more bone than the blank controls only after 6 weeks, whereas the difference was not significant after 13 and 26 weeks. Differences between Group 2 and Group 1 were clearly significant after 26 weeks. The thickness of bone tissue was maintained in Group 2 whereas it decreased in Group 1 and was negligible in Group 0. It is concluded that the PLA implants with 96 microg rhBMP-2 were able to bridge a non-healing defect in the rat mandible and maintained the thickness of an augmented volume. However, continuous supply of osteogenic signals appears to be required to compensate for adverse effects during polymer degradation. PMID:17936352

  18. Chondrocyte outgrowth into a gelatin scaffold in a single impact load model of damage/repair – effect of BMP-2

    Directory of Open Access Journals (Sweden)

    Vincent Thea

    2007-12-01

    Full Text Available Abstract Background Articular cartilage has little capacity for repair in vivo, however, a small number of studies have shown that, in vitro, a damage/repair response can be induced. Recent work by our group has shown that cartilage can respond to single impact load and culture by producing repair cells on the articular surface. The purpose of this study was to identify whether chondrocyte outgrowth into a 3D scaffold could be observed following single impact load and culture. The effect of bone morphogenic-2 (BMP-2 on this process was investigated. Methods Cartilage explants were single impact loaded, placed within a scaffold and cultured for up to 20 days +/- BMP-2. Cell numbers in the scaffold, on and extruding from the articular surface were quantified and the immunohistochemistry used to identify the cellular phenotype. Results Following single impact load and culture, chondrocytes were observed in a 3D gelatin scaffold under all culture conditions. Chondrocytes were also observed on the articular surface of the cartilage and extruding out of the parent cartilage and on to the cartilage surface. BMP-2 was demonstrated to quantitatively inhibit these events. Conclusion These studies demonstrate that articular chondrocytes can be stimulated to migrate out of parent cartilage following single impact load and culture. The addition of BMP-2 to the culture medium quantitatively reduced the repair response. It may be that the inhibitory effect of BMP-2 in this experimental model provides a clue to the apparent inability of articular cartilage to heal itself following damage in vivo.

  19. Experimental study of human BMP-2 on osteogenic induction in BMSCs of dogs in vitro%人BMP-2体外定向诱导犬BMSCs向成骨方向分化的实验研究

    Institute of Scientific and Technical Information of China (English)

    许蕾; 韩建国; 李家锋

    2015-01-01

    Objective:To provide seed cells for bone tissue engineering in the late establishment by establishing the cul-ture system of bone marrow mesenchymal stem cells( BMSCs)of dogs in vitro,and using human BMP-2 to make them in-duced to differentiate into osteoblasts. Methods:The extraction of BMSCs of adult beagle dogs was made,then the whole marrow adherence method and density gradient centrifugation were used to isolate and culture BMSCs in vitro,and observe the cell growth morphology everyday. The third generation BMSCs with good growth form was divided into two groups. The experimental group were cultured with adding 200ng/ml human BMP-2 containing fetal bovine serum(FBS)while the control group were cultured only with complete medium containing FBS. Then we used the detection of alkaline phosphatase staining after 3 weeks′induction,alizarin red staining and Von-Kossa staining after 4 weeks′induction to identify the differentiation of osteoblasts. Results:After 3 weeks of induction of experimental group with alkaline phosphatase,staining showed the cyto-plasm of positive expression of black particles,and it was negative in the control group;After 4 weeks of induction of experi-mental group with alizarin red staining and Von-Kossa staining showed positive expression of calcium nodules,and it was negative in the control group. All the staining results in the experimental group showed the characteristics of osteoblasts. Conclusion:BMSCs of dogs,which are extracted and cultivated in vitro,can directionally differentiate into osteoblasts under the action of human BMP-2.%目的:通过将犬骨髓间充质干细胞( bone marrow mesenchymal stem cells,BMSCs)建立体外培养体系,运用人骨形态发生蛋白-2(bone morphogenetic protein-2,BMP-2)体外定向诱导分化为成骨细胞,为后期建立骨组织工程提供种子细胞。方法提取比格犬BMSCs,全骨髓贴壁法结合密度梯度离心法行体外分离培养,每日观察细

  20. Heterotopic ossification following single-level anterior cervical discectomy and fusion: results from the prospective, multicenter, historically controlled trial comparing allograft to an optimized dose of rhBMP-2.

    Science.gov (United States)

    Arnold, Paul M; Anderson, Karen K; Selim, Abdulhafez; Dryer, Randall F; Kenneth Burkus, J

    2016-09-01

    OBJECTIVE Heterotopic ossification (HO) has been reported following total hip, knee, cervical, and lumbar arthroplasty, as well as following posterolateral lumbar fusion using recombinant human bone morphogenetic protein-2 (rhBMP-2). Data regarding HO following anterior cervical discectomy and fusion (ACDF) with rhBMP-2 are sparse. A subanalysis was done of the prospective, multicenter, investigational device exemption trial that compared rhBMP-2 on an absorbable collagen sponge (ACS) versus allograft in ACDF for patients with symptomatic single-level cervical degenerative disc disease. METHODS To assess differences in types of HO observed in the treatment groups and effects of HO on functional and efficacy outcomes, clinical outcomes from previous disc replacement studies were compared between patients who received rhBMP-2/ACS versus allograft. Rate, location, grade, and size of ossifications were assessed preoperatively and at 24 months, and correlated with clinical outcomes. RESULTS Heterotopic ossification was primarily anterior in both groups. Preoperatively in both groups, and including osteophytes in the target regions, HO rates were high at 40.9% and 36.9% for the rhBMP-2/ACS and allograft groups, respectively (p = 0.350). At 24 months, the rate of HO in the rhBMP-2/ACS group was higher than in the allograft group (78.6% vs 59.2%, respectively; p disc spaces significantly reduced range of motion, more so in the rhBMP-2/ACS group. At 24 months, HO negatively affected Neck Disability Index scores (excluding neck/arm pain scores), neurological status, and overall success in patients in the rhBMP-2/ACS group, but not in patients in the allograft group. CONCLUSIONS Implantation of rhBMP-2/ACS at 1.5 mg/ml with polyetheretherketone spacer and titanium plate is effective in inducing fusion and improving pain and function in patients undergoing ACDF for symptomatic single-level cervical degenerative disc disease. At 24 months, the rate and dimensions (length and

  1. Repair of Rabbit Femoral Defects with a Novel BMP2-derived Oligopeptide P24

    Institute of Scientific and Technical Information of China (English)

    Zhixia DUAN; Qixin ZHENG; Xiaodong GUO; Changwen LI; Bin WU; Weigang WU

    2008-01-01

    In this study, the bioactivity of a novel BMP2-derived oligopeptide P24 was investigated by using the model of rabbit femoral defect after loaded in the biodegradable poly (lactic acid / glycolic acid / asparagic acid-co-polyethylene glycol) (PLGA-[ASP-PEG]). A 1.5-cm unilateral segmental bone defect was created in the left femoral diaphysis in each of the 30 new zealand white rabbits.The defects of 18 legs filled with BMP2-derived peptide P24 combined with PLGA-[ASP-PEG]scaffold serves as the experimental group, and the defects in the rest 12 rabbits filled with(PLGA-[ASP-PEG]) without P24 as control group. The bone-repairing capability in the target region of the two group was grossly, radiologically, histopathologically and biomechanically evaluated 4, 8and 12 weeks after the operation. Our results showed that in each group, primary healing of incision was achieved in the two groups. Radiographically, in experimental group, defects were filled with induced callus within 8 weeks, and a cortical bone-like structure was observed in some animals at the12th week. According to the standardized stage of bone defect repair, 9 (64.28%) achieved grade-4healing. In contrast, little bone formation was seen in the defects even 12 weeks after the operation,and 5 (62.50%) had grade 0 healing in this group. Histologically, tissue engineering material was mostly absorbed and cartilage was found around implants in the experimental group at the 4th week;8 weeks after operation, the engineering material was completely absorbed, and formation of woven bone was observed and typical trabecular bone structure could be seen. In control group, 8 weeks after operation, the defect was filled with fibrous tissues, and no bone-like structure was observed. Statistical analysis showed very significant difference in biomechanical indicators between the two groups (P<0.05). It is concluded that new oligopeptide P24 can induce excellent bone regeneration and promote bone repair.

  2. Binding Interactions of Keratin-Based Hair Fiber Extract to Gold, Keratin, and BMP-2.

    Directory of Open Access Journals (Sweden)

    Roche C de Guzman

    Full Text Available Hair-derived keratin biomaterials composed mostly of reduced keratin proteins (kerateines have demonstrated their utility as carriers of biologics and drugs for tissue engineering. Electrostatic forces between negatively-charged keratins and biologic macromolecules allow for effective drug retention; attraction to positively-charged growth factors like bone morphogenetic protein 2 (BMP-2 has been used as a strategy for osteoinduction. In this study, the intermolecular surface and bulk interaction properties of kerateines were investigated. Thiol-rich kerateines were chemisorbed onto gold substrates to form an irreversible 2-nm rigid layer for surface plasmon resonance analysis. Kerateine-to-kerateine cohesion was observed in pH-neutral water with an equilibrium dissociation constant (KD of 1.8 × 10(-4 M, indicating that non-coulombic attractive forces (i.e. hydrophobic and van der Waals were at work. The association of BMP-2 to kerateine was found to be greater (KD = 1.1 × 10(-7 M, within the range of specific binding. Addition of salts (phosphate-buffered saline; PBS shortened the Debye length or the electrostatic field influence which weakened the kerateine-BMP-2 binding (KD = 3.2 × 10(-5 M. BMP-2 in bulk kerateine gels provided a limited release in PBS (~ 10% dissociation in 4 weeks, suggesting that electrostatic intermolecular attraction was significant to retain BMP-2 within the keratin matrix. Complete dissociation between kerateine and BMP-2 occurred when the PBS pH was lowered (to 4.5, below the keratin isoelectric point of 5.3. This phenomenon can be attributed to the protonation of keratin at a lower pH, leading to positive-positive repulsion. Therefore, the dynamics of kerateine-BMP-2 binding is highly dependent on pH and salt concentration, as well as on BMP-2 solubility at different pH and molarity. The study findings may contribute to our understanding of the release kinetics of drugs from keratin biomaterials and allow for the

  3. No advantage to rhBMP-2 in addition to autogenous graft for fracture nonunion.

    Science.gov (United States)

    Takemoto, Richelle; Forman, Jordanna; Taormina, David P; Egol, Kenneth A

    2014-06-01

    Bone morphogenetic proteins are a necessary component of the fracture healing cascade. Few studies have delineated the efficacy of iliac crest bone graft and recombinant human bone morphogenetic protein 2 (rhBMP-2), especially, in comparison with the gold standard treatment of nonunion, which is autogenous bone graft alone. This study compared the outcome of patients with fracture nonunion treated with autogenous bone graft plus rhBMP-2 adjuvant vs patients treated with autogenous bone graft alone. A total of 118 consecutive patients who were to undergo long bone nonunion surgery with autogenous bone graft (50) or autogenous bone graft plus rhBMP-2 (68) were identified. Surgical intervention included either harvested iliac autogenous bone graft or autogenous bone graft plus 1.5 mg/mL of rhBMP-2 placed in and around the site of nonunion. No differences were found in the distribution of nonunion sites included within each group. Twelve-month follow-up was obtained on 100 of 118 patients (84.7%). Analyses of demographic characteristics (including tobacco), medical comorbidities, previous surgeries, and nonunion type (atrophic vs hypertrophic) did not differ. Postoperative complication rates did not differ. The percentage of patients who progressed to union did not differ. Mean time to union in the autogenous bone graft plus rhBMP-2 group was 6.6 months (±3.9) vs 5.4 (±2.7) months in the autogenous bone graft-only group (P=.06). Rates of revision (16.2% for rhBMP-2 plus autogenous bone graft vs 8% for autogenous bone graft) did not differ statistically (P=.19), nor did 12-month scores of pain and functional assessment. Although rhBMP-2 is a safe adjuvant, there was no benefit seen when rhBMP-2 was added to autogenous bone graft in the treatment of long bone nonunion. Given its high cost, rhBMP-2 should be reconsidered as an aid to autogenous bone graft in the treatment of nonunion. PMID:24972432

  4. Scaffold-mediated BMP-2 minicircle DNA delivery accelerated bone repair in a mouse critical-size calvarial defect model.

    Science.gov (United States)

    Keeney, Michael; Chung, Michael T; Zielins, Elizabeth R; Paik, Kevin J; McArdle, Adrian; Morrison, Shane D; Ransom, Ryan C; Barbhaiya, Namrata; Atashroo, David; Jacobson, Gunilla; Zare, Richard N; Longaker, Michael T; Wan, Derrick C; Yang, Fan

    2016-08-01

    Scaffold-mediated gene delivery holds great promise for tissue regeneration. However, previous attempts to induce bone regeneration using scaffold-mediated non-viral gene delivery rarely resulted in satisfactory healing. We report a novel platform with sustained release of minicircle DNA (MC) from PLGA scaffolds to accelerate bone repair. MC was encapsulated inside PLGA scaffolds using supercritical CO2 , which showed prolonged release of MC. Skull-derived osteoblasts transfected with BMP-2 MC in vitro result in higher osteocalcin gene expression and mineralized bone formation. When implanted in a critical-size mouse calvarial defect, scaffolds containing luciferase MC lead to robust in situ protein production up to at least 60 days. Scaffold-mediated BMP-2 MC delivery leads to substantially accelerated bone repair as early as two weeks, which continues to progress over 12 weeks. This platform represents an efficient, long-term nonviral gene delivery system, and may be applicable for enhancing repair of a broad range of tissues types. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2099-2107, 2016. PMID:27059085

  5. Transcriptional repression of Bmp2 by p21(Waf1/Cip1) links quiescence to neural stem cell maintenance.

    Science.gov (United States)

    Porlan, Eva; Morante-Redolat, José Manuel; Marqués-Torrejón, María Ángeles; Andreu-Agulló, Celia; Carneiro, Carmen; Gómez-Ibarlucea, Esther; Soto, Atenea; Vidal, Anxo; Ferrón, Sacri R; Fariñas, Isabel

    2013-11-01

    Relative quiescence and self renewal are defining features of adult stem cells, but their potential coordination remains unclear. Subependymal neural stem cells (NSCs) lacking cyclin-dependent kinase (CDK) inhibitor (CKI) 1a (p21) exhibit rapid expansion that is followed by their permanent loss later in life. Here we demonstrate that transcription of the gene encoding bone morphogenetic protein 2 (Bmp2) in NSCs is under the direct negative control of p21 through actions that are independent of CDK. Loss of p21 in NSCs results in increased levels of secreted BMP2, which induce premature terminal differentiation of multipotent NSCs into mature non-neurogenic astrocytes in an autocrine and/or paracrine manner. We also show that the cell-nonautonomous p21-null phenotype is modulated by the Noggin-rich environment of the subependymal niche. The dual function that we describe here provides a physiological example of combined cell-autonomous and cell-nonautonomous functions of p21 with implications in self renewal, linking the relative quiescence of adult stem cells to their longevity and potentiality.

  6. Effects of codon modification on human BMP2 gene expression in tobacco plants.

    Science.gov (United States)

    Suo, Guangli; Chen, Bing; Zhang, Jingyu; Duan, Ziyuan; He, Zhengquan; Yao, Wei; Yue, Chaoyin; Dai, Jianwu

    2006-07-01

    Bone morphogenetic protein 2 (BMP2) has great potential in therapeutic applications. We are working on generating transgenic plants as a bioreactor to produce BMP2. We have studied the effects of codon optimization on the expression of human BMP2 (hBMP2) in tobacco plants. Three modified hBMP2 genes were transformed into tobacco under the control of either cauliflower mosaic virus 35S (CaMV35S) promoter or double-CaMV35S promoter plus alfalfa mosaic virus (AMV) enhancer. The fused beta-glucuronidase (GUS) reporter gene was used to facilitate the assay of protein expression. The results indicated that codon optimization could increase the protein expression level obviously under CaMV35S promoter. However, under relatively stronger initiation condition (double-CaMV35S promoter plus AMV enhancer), only the gene with the lowest degree of codon optimization could increase the protein expression level. Our findings suggest that the action of codon optimization may be influenced by the factors of promoter strength and A+T content in tobacco plants. PMID:16491379

  7. Evaluation of a Novel HA/ZrO2-Based Porous Bioceramic Artificial Vertebral Body Combined with a rhBMP-2/Chitosan Slow-Release Hydrogel

    Science.gov (United States)

    Shi, Yihui; Quan, Renfu; Xie, Shangju; Li, Qiang; Cao, Guoping; Zhuang, Wei; Zhang, Liang; Shao, Rongxue; Yang, Disheng

    2016-01-01

    A new HA/ZrO2-based porous bioceramic artificial vertebral body (AVB), carried a recombinant human bone morphogenetic protein-2 (rhBMP-2)/chitosan slow-release hydrogel was prepared to repair vertebral bone defect in beagles. An ionic cross-linking was used to prepare the chitosan hydrogel (CS gel) as the rhBMP-2 slow-release carrier. The vertebral body defects were implanted with the rhBMP-2-loaded AVB in group A, or a non-drug-loaded AVB in group B, or autologous iliac in group C. The encapsulation rate of rhBMP-2 in rhBMP-2-loaded CS gel was 91.88±1.53%, with a drug load of 39.84±2.34 ng/mg. At 6, 12, 24 weeks postoperatively, radiography showed that the bone calluses gradually increased with time in group A, where the artificial vertebral body had completely fused with host-bone at 24 weeks after surgery. In group C, an apparent bone remodeling was occurred in the early stages, and the graft-bone and host-bone had also fused completely at 24 weeks postoperatively. In group B, fusion occurred less than in groups A and C. At 24 weeks after surgery, micro-computed tomography (Micro-CT) revealed that the volume of newly-formed bone in group A was significantly more than in group B (p<0.05). At 24 weeks after surgery, ultra-compressive strengths of the operated segments were 14.03±1.66 MPa in group A, 8.62±1.24 MPa in group B, and 13.78±1.43 MPa in group C. Groups A and C were both significantly higher than group B (p < 0.05). At 24 weeks postoperatively, the hard tissue sections showed that the AVB of group A had tightly fused with host bone, and that pores of the AVB had been filled with abundant nearly mature bone, and that the new bone structured similarly to a trabecular framework, which was similar to that in group C. In contrast, implant fusion of the AVB in group B was not as apparent as group A. In conclusion, the novel HA/ZrO2-based porous bioceramic AVB carried the rhBMP-2-loaded CS gel can promote the repair of bony defect, and induce bone tissue to

  8. Local expression and role of BMP-2/4 in injured spinal cord.

    Science.gov (United States)

    Cui, Z S; Zhao, P; Jia, C X; Liu, H J; Qi, R; Cui, J W; Cui, J H; Peng, Q; Lin, B; Rao, Y J

    2015-08-07

    We investigated local changes in BMP-2/4 expression in rat spinal cords 1 week following injury to study the damage effects of BMP-2/4 in spinal cord injury (SCI). Sprague Dawley rats (45, 4 months old) were randomized into three groups comprising 15 rats each: a SHAM group, an SCI without noggin group (SCIO), and an SCI with noggin group (SCID). The SCIO and SCID groups were subjected to spinal cord hemisection, and motor activity was assessed using the BBB score. Expression of BMP-2/4 in each injured spinal cord section was examined by hematoxylin and eosin staining, immunohistochemistry, and western blot. There were no significant differences in BBB scores among the three groups (P > 0.05). Following hemisection, the BBB score in the SHAM group was significantly higher than in the other two groups on the 1st day after modeling (P 0.05). Seven days after modeling, the BBB score in the SHAM group was significantly higher than in the other two groups (P < 0.05), and the BBB score in the SCID group was obviously higher than in the SCIO group (P < 0.05). The expression of BMP-2/4 was highest in the SCIO group and lowest in the SHAM group (P < 0.05). SCI can cause severe impairment of motor activity in rats. Seven days after SCI, the local expression of BMP-2/4 had obviously increased; noggin can effectively inhibit the expression of BMP-2/4 and reduce impairment.

  9. Implant Composed of Demineralized Bone and Mesenchymal Stem Cells Genetically Modified with AdBMP2/AdBMP7 for the Regeneration of Bone Fractures in Ovis aries

    Science.gov (United States)

    Hernandez-Hurtado, Adelina A.; Lara-Arias, Jorge; Romero-Diaz, Viktor J.; Abrego-Guerra, Adalberto; Vilchez-Cavazos, Jose F.; Elizondo-Riojas, Guillermo; Martinez-Rodriguez, Herminia G.; Espinoza-Juarez, Marcela A.; Mendoza Lemus, Oscar F.

    2016-01-01

    Adipose-derived mesenchymal stem cells (ADMSCs) are inducible to an osteogenic phenotype by the bone morphogenetic proteins (BMPs). This facilitates the generation of implants for bone tissue regeneration. This study evaluated the in vitro osteogenic differentiation of ADMSCs transduced individually and in combination with adenoviral vectors expressing BMP2 and BMP7. Moreover, the effectiveness of the implant containing ADMSCs transduced with the adenoviral vectors AdBMP2/AdBMP7 and embedded in demineralized bone matrix (DBM) was tested in a model of tibial fracture in sheep. This graft was compared to ewes implanted with untransduced ADMSCs embedded in the same matrix and with injured but untreated animals. In vivo results showed accelerated osteogenesis in the group treated with the AdBMP2/AdBMP7 transduced ADMSC graft, which also showed improved restoration of the normal bone morphology.

  10. Combination therapy with BMP-2 and a systemic RANKL inhibitor enhances bone healing in a mouse critical-sized femoral defect.

    Science.gov (United States)

    Bougioukli, Sofia; Jain, Ashish; Sugiyama, Osamu; Tinsley, Brian A; Tang, Amy H; Tan, Matthew H; Adams, Douglas J; Kostenuik, Paul J; Lieberman, Jay R

    2016-03-01

    Recombinant human BMP-2 (rhBMP-2) is a potent osteoinductive agent, but has been associated not only with bone formation, but also osteoclastogenesis and bone resorption. Osteoprotegerin (OPG) is a RANKL inhibitor that blocks differentiation and function of osteoclasts. We hypothesized that the combination of local BMP-2 (recombinant protein or a product of gene therapy) plus systemic OPG-Fc is more effective than BMP-2 alone in promoting bone repair. To test this hypothesis we used a mouse critical-sized femoral defect model. Col2.3eGFP (osteoblastic marker) male mice were treated with rhBMP-2 (group I), rhBMP-2 and systemic OPG (group II), rhBMP-2 and delayed administration of OPG (group III), mouse BM cells transduced with a lentiviral vector containing the BMP-2 gene (LV-BMP-2; group IV), LV-BMP-2 and systemic OPG (group V), a carrier alone (group VI) and administration of OPG alone (group VII). All bone defects treated with BMP-2 (alone or combined with OPG) healed, whereas minimal bone formation was noted in animals treated with the carrier alone or OPG alone. MicroCT analysis showed that bone volume (BV) in rhBMP-2+OPG and LV-BMP-2+OPG groups was significantly higher compared to rhBMP-2 alone (p<0.01) and LV-BMP-2 alone (p<0.001). Similar results were observed in histomorphometry, with rhBMP-2 alone defects exhibiting significantly lower bone area (B.Ar) compared to rhBMP-2+OPG defects (p<0.005) and LV-BMP-2 defects having a significantly lower B.Ar compared to all BMP-2+OPG treated groups (p≤0.01). TRAP staining demonstrated a major osteoclast response in the groups that did not receive OPG (rhBMP-2, LV-BMP-2 and sponge alone) beginning as early as 7days post-operatively. In conclusion, we demonstrated that locally delivered BMP-2 (recombinant protein or gene therapy) in combination with systemically administered OPG improved bone healing compared to BMP-2 alone in a mouse critical-sized bone defect. These data indicate that osteoclasts can diminish

  11. Biodegradable Chitosan Nanoparticle Coatings on Titanium for the Delivery of BMP-2

    Directory of Open Access Journals (Sweden)

    Nils Poth

    2015-01-01

    Full Text Available A simple method for the functionalization of a common implant material (Ti6Al4V with biodegradable, drug loaded chitosan-tripolyphosphate (CS-TPP nanoparticles is developed in order to enhance the osseointegration of endoprostheses after revision operations. The chitosan used has a tailored degree of acetylation which allows for a fast biodegradation by lysozyme. The degradability of chitosan is proven via viscometry. Characteristics and degradation of nanoparticles formed with TPP are analyzed using dynamic light scattering. The particle degradation via lysozyme displays a decrease in particle diameter of 40% after 4 days. Drug loading and release is investigated for the nanoparticles with bone morphogenetic protein 2 (BMP-2, using ELISA and the BRE luciferase test for quantification and bioactivity evaluation. Furthermore, nanoparticle coatings on titanium substrates are created via spray-coating and analyzed by ellipsometry, scanning electron microscopy and X-ray photoelectron spectroscopy. Drug loaded nanoparticle coatings with biologically active BMP-2 are obtained in vitro within this work. Additionally, an in vivo study in mice indicates the dose dependent induction of ectopic bone growth through CS-TPP-BMP-2 nanoparticles. These results show that biodegradable CS-TPP coatings can be utilized to present biologically active BMP-2 on common implant materials like Ti6Al4V.

  12. Improving the osteogenic potential of BMP-2 with hyaluronic acid hydrogel modified with integrin-specific fibronectin fragment

    NARCIS (Netherlands)

    Kisiel, M.; Martino, M.M.; Ventura, M.; Hubbell, J.A.; Hilborn, J.; Ossipov, D.A.

    2013-01-01

    While human bone morphogenetic protein-2 (rhBMP-2) is a promising growth factor for bone regeneration, its clinical efficacy has recently shown to be below expectation. In order to improve the clinical translation of rhBMP-2, there exists strong motivation to engineer better delivery systems. Hyalur

  13. Bone formation of a porous Gelatin-Pectin-biphasic calcium phosphate composite in presence of BMP-2 and VEGF.

    Science.gov (United States)

    Amirian, Jhaleh; Linh, Nguyen Thuy Ba; Min, Young Ki; Lee, Byong-Taek

    2015-05-01

    A composite scaffold of gelatin (Gel)-pectin (Pec)-biphasic calcium phosphate (BCP) was fabricated for the successful delivery of growth factors. Bone morphogenetic protein-2 (BMP-2) and vascular endothelial growth factor (VEGF) were coated on the Gel-Pec-BCP surface to investigate of effect of them on bone healing. Surface morphology was investigated by scanning electron microscopy, and BCP dispersion in the hydrogel scaffolds was measured by energy dispersive X-ray spectroscopy. The results obtained from Fourier transform infrared spectroscopy showed that BMP-2 and VEGF were successfully coated on Gel-Pec-BCP hydrogel scaffolds. MC3T3-E1 preosteoblasts were cultivated on the scaffolds to investigate the effect of BMP-2 and VEGF on cell viability and proliferation. VEGF and BMP-2 loaded on Gel-Pec-BCP scaffold facilitated increased cell spreading and proliferation compared to Gel-Pec-BCP scaffolds. In vivo, bone formation was examined using rat models. Bone formation was observed in Gel-Pec-BCP/BMP-2 and Gel-Pec-BCP/VEGF scaffolds within 4 weeks, and was greatest with Gel-Pec-BCP/BMP-2 scaffolds. In vitro and in vivo results suggest that Gel-Pec-BCP/BMP-2 and Gel-Pec-BCP/VEGF scaffolds could enhance bone regeneration.

  14. Gene gun transferring-bone morphogenetic protein 2 (BMP-2) gene enhanced bone fracture healing in rabbits

    OpenAIRE

    Li, Wenju; Wei, Haifeng; Xia, Chunmei; Zhu, Xiaomeng; Hou, Guozhu; Xu, Feng; Xinghua SONG; Zhan, Yulin

    2015-01-01

    Purpose: Transferring the bone morphogenetic protein 2 (BMP-2) genes into the tissues or cells can improve the bone healing of the fracture has been widely accepted. We evaluated the efficiency of using gene gun to transfer the BMP-2 gene thereby affected the healing of a fractured bone. Methods: The vector coding for BMP-2 was constructed by a non-replicating encephalo-myocarditis virus (ECMV)-based vector. The segmental bone defect (1.5 cm) model was created by a wire-saw at the middle part...

  15. Vergleich von BMP-4 versus BMP-2 für die osteogene Differenzierung von Periostzellen

    OpenAIRE

    Klumpp, Florian (Alexander Stephan)

    2010-01-01

    Es ist heute bekannt, dass humane periostale mesenchymale Stammzellen (PMSCs) eine aussichtsreiche Grundlage für ein erfolgreiches Knochen Tissue Engineering darstellen. Dennoch ist die osteogene Differenzierung noch nicht vollständig be-schrieben. Da BMP-2 und BMP-4 nachweislich Regulatoren der Osteogenese sind, bestand die Aufgabe der vorliegenden Arbeit darin, die Wirkung derer auf die osteo-gene Differenzierung humaner PMSCs zu untersuchen. Isolierte humane PMSCs wurden mit Hilfe von o...

  16. BMP-2 in der Therapie der Pseudarthrose langer Röhrenknochen

    OpenAIRE

    Hellriegel, Tom

    2010-01-01

    Effective therapy for long bone non-unions is still a challenge in trauma and orthopedic surgery and treatment is time and cost-intensive. Complications can lead to ensuing health-related problems for the patient and their ability to work can be restricted. An innovative approach to stimulate bone regeneration is the application of growth factors. Bone morphogenetic protein-2 (BMP-2) has a high osteoinductive capacity and might stimulate human non-union healing. The purpose of this stud...

  17. Histone deacetylases control neurogenesis in embryonic brain by inhibition of BMP2/4 signaling.

    Directory of Open Access Journals (Sweden)

    Maya Shakèd

    Full Text Available BACKGROUND: Histone-modifying enzymes are essential for a wide variety of cellular processes dependent upon changes in gene expression. Histone deacetylases (HDACs lead to the compaction of chromatin and subsequent silencing of gene transcription, and they have recently been implicated in a diversity of functions and dysfunctions in the postnatal and adult brain including ocular dominance plasticity, memory consolidation, drug addiction, and depression. Here we investigate the role of HDACs in the generation of neurons and astrocytes in the embryonic brain. PRINCIPAL FINDINGS: As a variety of HDACs are expressed in differentiating neural progenitor cells, we have taken a pharmacological approach to inhibit multiple family members. Inhibition of class I and II HDACs in developing mouse embryos with trichostatin A resulted in a dramatic reduction in neurogenesis in the ganglionic eminences and a modest increase in neurogenesis in the cortex. An identical effect was observed upon pharmacological inhibition of HDACs in in vitro-differentiating neural precursors derived from the same brain regions. A reduction in neurogenesis in ganglionic eminence-derived neural precursors was accompanied by an increase in the production of immature astrocytes. We show that HDACs control neurogenesis by inhibition of the bone morphogenetic protein BMP2/4 signaling pathway in radial glial cells. HDACs function at the transcriptional level by inhibiting and promoting, respectively, the expression of Bmp2 and Smad7, an intracellular inhibitor of BMP signaling. Inhibition of the BMP2/4 signaling pathway restored normal levels of neurogenesis and astrogliogenesis to both ganglionic eminence- and cortex-derived cultures in which HDACs were inhibited. CONCLUSIONS: Our results demonstrate a transcriptionally-based regulation of BMP2/4 signaling by HDACs both in vivo and in vitro that is critical for neurogenesis in the ganglionic eminences and that modulates cortical

  18. Effect of rhBMP-2 on tibial plateau fractures in a canine model.

    Science.gov (United States)

    Schaefer, Susan L; Lu, Yan; Seeherman, Howard; Li, X Jian; Lopez, Mandi J; Markel, Mark D

    2009-04-01

    This study was to determine the efficacy of recombinant human bone morphogenetic protien-2 (rhBMP-2)/calcium phosphate matrix (CPX) paste to accelerate healing in a canine articular fracture model with associated subchondral defect. rhBMP-2/CPX (BMP), CPX alone (CPX) or autogenous bone graft (ABG) was administered to a canine articular tibial plateau osteotomy with a subchondral defect in each of 21 female dogs. The unoperated contralateral limbs served as controls. Ground reaction forces, synovial fluid, radiographic changes, mechanical testing, bone density, and histology of bone and synovium were analyzed at 6 weeks after surgery. Radiographic analysis demonstrated that the BMP and CPX groups showed improved bony healing compared to the ABG group at week 6. Histomorphometric analysis demonstrated that the BMP group had significantly increased trabecular bone volume compared to the CPX and ABG groups. Mechanical testing revealed that the BMP group had significantly greater maximum failure loads than the ABG group. Histological analysis demonstrated that the BMP group had significantly less sub-synovial inflammation than CPX group. This study demonstrated that rhBMP-2/CPX accelerated healing of articular fractures with subchondral defect compared to ABG in most of the parameters evaluated, and had less subsynovial inflammation than the CPX alone in a canine model.

  19. BMP2 gene delivery to bone mesenchymal stem cell by chitosan-g-PEI nonviral vector

    Science.gov (United States)

    Yue, Jianhui; Wu, Jun; Liu, Di; Zhao, Xiaoli; Lu, William W.

    2015-04-01

    Nanotechnology has made a significant impact on the development of nanomedicine. Nonviral vectors have been attracting more attention for the advantage of biosafety in gene delivery. Polyethylenimine (PEI)-conjugated chitosan (chitosan-g-PEI) emerged as a promising nonviral vector and has been demonstrated in many tumor cells. However, there is a lack of study focused on the behavior of this vector in stem cells which hold great potential in regenerative medicine. Therefore, in this study, in vitro gene delivering effect of chitosan-g-PEI was investigated in bone marrow stem cells. pIRES2-ZsGreen1-hBMP2 dual expression plasmid containing both the ZsGreen1 GFP reporter gene and the BMP2 functional gene was constructed for monitoring the transgene expression level. Chitosan-g-PEI-mediated gene transfer showed 17.2% of transfection efficiency and more than 80% of cell viability in stem cells. These values were higher than that of PEI. The expression of the delivered BMP2 gene in stem cells enhanced the osteogenic differentiation. These results demonstrated that chitosan-g-PEI is capable of applying in delivering gene to stem cells and providing potential applications in stem cell-based gene therapy.

  20. 转染Ad-hBMP2的脂肪干细胞与壳聚糖/磷酸三钙复合物支架的相容性%Compatibility of Adipose-derived Stem Cells Transfected by Ad-hBMP2 Gene and CTCP Scaffold in vitro

    Institute of Scientific and Technical Information of China (English)

    方忠; 杨琴; 熊伟; 李光辉; 廖晖; 李锋; 肖骏

    2012-01-01

    Objective To observe the biological behavior of cultured adipose-derived stem cells(ADSCs)transfected by Ad-hBMP2 combined with chitosan/tricalcium phosphate(CTCP)scaffold and investigate the feasibility of the composite for cartilage tissue engineering. Methods The ADSCsQ X 106/mL) transfected with Ad-hBMP2 plasmid vector were co-cultured with the CTCP scaffold. The adhesion and proliferation of ADSCs, and the morphological changes were observed. RT-PCR, Western blot and immunohistochemistry were applied to detect the expression of Osteocalcin and collagen I in the scaffold. Results The poriferous CTCP scaffold has macro and micro poriferous structures,and the porous rate was 83%. The ADSCs transfected by Ad-hBMP2 have been successfully cultured in vitro. The induced cells adhered to the surface of the scaffold and proliferated well. The RT-PCR,Western blot and immunohistochemistry revealed that the expression of Osteocalcin and collagen I was detected after the co-culture. Conclusion The poriferous CTCP scaffold with excellent property should be a good "matrix" for ADSCs transfected by Ad-hBMP2, and could be used for bone tissue engineering.%目的 探讨转染腺病毒骨形态发生蛋白(Ad-hBMP2)基因的脂肪干细胞(ADSCs)与壳聚糖/磷酸三钙(CTCP)复合物支架的相容性,以期为ADSCs修复骨缺损寻找理想的组织工程骨支架材料.方法 将壳聚糖与磷酸三钙进行复合制成CTCP复合物材料,再将其与转染Ad-hBMP2的ADSCs(密度1×106/mL)复合培养,进行细胞复合物支架的一般与超微形态学观察,观察细胞粘附能力、增殖活力,RT-PCR及Western blot测定成骨细胞骨钙素和Ⅰ型胶原水平.结果 CTCP支架孔径200~350 μm,孔隙率83%;电镜显示转染Ad-hBMP2的ADSCs与CTCP复合物在体外培养期间支架无塌陷及形变,且其在支架上粘附、增殖良好,并能分泌细胞外基质如骨钙素和Ⅰ型胶原等;随着培养时间延长,骨的组织学特征

  1. A late role for bmp2b in the morphogenesis of semicircular canal ducts in the zebrafish inner ear.

    Directory of Open Access Journals (Sweden)

    Katherine L Hammond

    Full Text Available The Bone Morphogenetic Protein (BMP genes bmp2 and bmp4 are expressed in highly conserved patterns in the developing vertebrate inner ear. It has, however, proved difficult to elucidate the function of BMPs during ear development as mutations in these genes cause early embryonic lethality. Previous studies using conditional approaches in mouse and chicken have shown that Bmp4 has a role in semicircular canal and crista development, but there is currently no direct evidence for the role of Bmp2 in the developing inner ear.We have used an RNA rescue strategy to test the role of bmp2b in the zebrafish inner ear directly. Injection of bmp2b or smad5 mRNA into homozygous mutant swirl (bmp2b(-/- embryos rescues the early patterning defects in these mutants and the fish survive to adulthood. As injected RNA will only last, at most, for the first few days of embryogenesis, all later development occurs in the absence of bmp2b function. Although rescued swirl adult fish are viable, they have balance defects suggestive of vestibular dysfunction. Analysis of the inner ears of these fish reveals a total absence of semicircular canal ducts, structures involved in the detection of angular motion. All other regions of the ear, including the ampullae and cristae, are present and appear normal. Early stages of otic development in rescued swirl embryos are also normal.Our findings demonstrate a critical late role for bmp2b in the morphogenesis of semicircular canals in the zebrafish inner ear. This is the first demonstration of a developmental role for any gene during post-embryonic stages of otic morphogenesis in the zebrafish. Despite differences in the early stages of semicircular canal formation between zebrafish and amniotes, the role of Bmp2 in semicircular canal duct outgrowth is likely to be conserved between different vertebrate species.

  2. Parathyroid hormone stimulate osteoblast differentiation by up-regulation of BMP2 expression and function%骨形态发生蛋白2介导甲状旁腺素促进成骨细胞分化的实验研究

    Institute of Scientific and Technical Information of China (English)

    徐莹; 田野; 孟凌新

    2012-01-01

    Objective To study the important role of BMP2 in the PTH-induced osteoblast differentiation. Methods MC3T3-E1 cells were divided into 4 groups: 1) Controls; 2) PTH treatment; 3) Dorso-morphin treatment; 4) PTH + Dorsomorphin treatment. Gene and protein expression levels of BMP2, BMP2 downstream genes and osteoblastic genes and protein expressions were detected by Real-time PCR and Western blot respectively. Alkaline phosphatase (ALP) staining was performed to detect ALP activity. 12xSBE-OC luciferase activity was measured using dual luciferase reporter assays. Results The expression level of BMP2 and osteoblastic marker genes was higher in the PTH group than in controls. PTH also increases 12xSBE-OC luciferase activity significantly. In the other hand, the expression of BMP2, BMP2 downstream genes and osteoblastic genes was lower in Dorsomorphin and PTH + Dorsomorphin group, than in controls. However, the expression was similar in Dorsomorphin and PTH + Dorsomorphin groups. Conclusion PTH stimulates osteoblast differentiation by up-regulating BMP2 expression and function.%目的 探讨骨形态发生蛋白2(BMP2)在甲状旁腺素(PTH)促进成骨细胞分化过程中的重要介导作用.方法培养MC3T3-E1细胞,分为4组:1)盐水对照组;2)PTH组;3)6-[4-[2-(1-哌啶基)乙氧基]苯基]-3-(4-吡啶基)吡唑并[1,5-a]嘧啶 (Dorsomorphin) 组;4) PTH+Dorsomorphin组.Real-time PCR法和Westernblot方法检测细胞BMP2BMP2下游基因和成骨因子的表达,碱性磷酸酶(ALP)染色方法检测细胞ALP的活性;双荧光素酶报告基因检测方法检测12xSBE-OC荧光素酶的活性.结果:PTH组BMP-2、成骨因子的表达及其12xSBE-OC荧光素酶的活性,明显高于盐水对照组.Dorsomorphin组和PTH+Dorsomorphin组BMP-2BMP-2下游基因和成骨因子的表达,均明显低于盐水对照组;但其表达于两组间无明显差别.结论 BMP2介导PTH促进成骨细胞的分化,PTH可通过上调BMP2的表达,提高其功能,促进成骨细胞的成熟分化.

  3. Bone marrow stromal cells with a combined expression of BMP-2 and VEGF-165 enhanced bone regeneration

    Energy Technology Data Exchange (ETDEWEB)

    Xiao Caiwen; Zhou Huifang; Fu Yao; Gu Ping; Fan Xianqun [Department of Ophthalmology, Shanghai Ninth People' s Hospital, Shanghai JiaoTong University School of Medicine, Shanghai 200011 (China); Liu Guangpeng [Key Laboratory of Tissue Engineering, Shanghai Ninth People' s Hospital, Shanghai JiaoTong University School of Medicine, Shanghai 200011 (China); Zhang Peng [Center for Translational Medicine Research and Development, Shenzhen Institute of Advanced Technology, Chinese Academy of Science (China); Hou Hongliang; Tang Tingting, E-mail: drfanxianqun@126.com [Department of Orthopedics, Shanghai Ninth People' s Hospital, Shanghai JiaoTong University School of Medicine, Shanghai 200011 (China)

    2011-02-15

    Bone graft substitutes with osteogenic factors alone often exhibit poor bone regeneration due to inadequate vascularization. Combined delivery of osteogenic and angiogenic factors from biodegradable scaffolds may enhance bone regeneration. We evaluated the effects of bone morphogenetic protein 2 (BMP2) and vascular endothelial growth factor (VEGF), combined with natural coral scaffolds, on the repair of critical-sized bone defects in rabbit orbits. In vitro expanded rabbit bone marrow stromal cells (BMSCs) were transfected with human BMP2 and VEGF165 genes. Target protein expression and osteogenic differentiation were confirmed after gene transduction. Rabbit orbital defects were treated with a coral scaffold loaded with BMP2-transduced and VEGF-transduced BMSCs, BMP2-expressing BMSCs, VEGF-expressing BMSCs, or BMSCs without gene transduction. Volume and density of regenerated bone were determined by micro-computed tomography at 4, 8, and 16 weeks after implantation. Neovascularity, new bone deposition rate, and new bone formation were measured by immunostaining, tetracycline and calcein labelling, and histomorphometric analysis at different time points. The results showed that VEGF increased blood vessel formation relative to groups without VEGF. Combined delivery of BMP2 and VEGF increased new bone deposition and formation, compared with any single factor. These findings indicate that mimicking the natural bone development process by combined BMP2 and VEGF delivery improves healing of critical-sized orbital defects in rabbits.

  4. 慢性肾脏病患者血清PTH与BMP-2的变化及意义

    Institute of Scientific and Technical Information of China (English)

    范旗; 赵燕凌; 甘西伦

    2008-01-01

    选择慢性肾脏病(CKD)患者65例和健康查体者20例(对照组),根据肾小球滤过率(GFR)将CKD患者分为五组,分别采用化学发光法和酶联免疫吸附法测定血清血清甲状旁腺激素(PTH)及骨形态发生蛋白-2(BMP-2)浓度,分析血清PTH及BMP-2浓度变化的规律.结果 CKD患者血清PTH、BMP-2浓度均明显高于对照组(P<0.01);CKD患者血清BMP-2浓度与PTH呈正相关(r=0.678,P=0.006).认为CKD患者血清PTH及BMP-2浓度随肾功能损害程度加重逐渐升高,提示PTH、BMP-2与CKD患者病情进展有一定关系.

  5. Experimental Comparison of Cranial Particulate Bone Graft, rhBMP-2, and Split Cranial Bone Graft for Inlay Cranioplasty.

    Science.gov (United States)

    Hassanein, Aladdin H; Couto, Rafael A; Kurek, Kyle C; Rogers, Gary F; Mulliken, John B; Greene, Arin K

    2013-05-01

    Background :  Particulate bone graft and recombinant human bone morphogenetic protein-2 (rhBMP-2) are options for inlay cranioplasty in children who have not developed a diploic space. The purpose of this study was to determine whether particulate bone graft or rhBMP-2 has superior efficacy for inlay cranioplasty and to compare these substances to split cranial bone. Methods :  A 17 mm × 17 mm critical-sized defect was made in the parietal bones of 22 rabbits and managed in four ways: Group I (no implant; n=5), Group II (particulate bone graft; n=5), Group III (rhBMP-2; n=7), and Group IV (split cranial bone graft; n=5). Animals underwent microcomputed tomography and histologic analysis 16 weeks after cranioplasty. Results :  Defects without an implant (Group I) demonstrated inferior ossification (41.4%; interquartile range [IQR], 28.9% to 42.5%) compared to those treated with particulate bone graft (Group II: 99.5%; IQR, 97.8% to 100%), rhBMP-2 (Group III: 99.6%; IQR, 99.5% to 100%), or split cranial bone (Group IV: 100%) (P inlay calvarial defect areas equally, although the thickness of bone healed with rhBMP-2 is inferior. Clinically, particulate bone graft or split cranial bone graft may be superior to rhBMP-2 for inlay cranioplasty.

  6. Bone marrow stromal cells with a combined expression of BMP-2 and VEGF-165 enhanced bone regeneration

    International Nuclear Information System (INIS)

    Bone graft substitutes with osteogenic factors alone often exhibit poor bone regeneration due to inadequate vascularization. Combined delivery of osteogenic and angiogenic factors from biodegradable scaffolds may enhance bone regeneration. We evaluated the effects of bone morphogenetic protein 2 (BMP2) and vascular endothelial growth factor (VEGF), combined with natural coral scaffolds, on the repair of critical-sized bone defects in rabbit orbits. In vitro expanded rabbit bone marrow stromal cells (BMSCs) were transfected with human BMP2 and VEGF165 genes. Target protein expression and osteogenic differentiation were confirmed after gene transduction. Rabbit orbital defects were treated with a coral scaffold loaded with BMP2-transduced and VEGF-transduced BMSCs, BMP2-expressing BMSCs, VEGF-expressing BMSCs, or BMSCs without gene transduction. Volume and density of regenerated bone were determined by micro-computed tomography at 4, 8, and 16 weeks after implantation. Neovascularity, new bone deposition rate, and new bone formation were measured by immunostaining, tetracycline and calcein labelling, and histomorphometric analysis at different time points. The results showed that VEGF increased blood vessel formation relative to groups without VEGF. Combined delivery of BMP2 and VEGF increased new bone deposition and formation, compared with any single factor. These findings indicate that mimicking the natural bone development process by combined BMP2 and VEGF delivery improves healing of critical-sized orbital defects in rabbits.

  7. Plasma Treated High-Density Polyethylene (HDPE Medpor Implant Immobilized with rhBMP-2 for Improving the Bone Regeneration

    Directory of Open Access Journals (Sweden)

    Jin-Su Lim

    2014-01-01

    Full Text Available We investigate the bone generation capacity of recombinant human bone morphogenetic protein-2 (rhBMP-2 immobilized Medpor surface through acrylic acid plasma-polymerization. Plasma-polymerization was carried out at a 20 W at an acrylic acid flow rate of 7 sccm for 5 min. The plasma-polymerized Medpor surface showed hydrophilic properties and possessed a high density of carboxyl groups. The rhBMP-2 was immobilized with covalently attached carboxyl groups using 1-ethyl-3-(3-dimethylaminopropyl carbodiimide and N-hydroxysuccinimide. Carboxyl groups and rhBMP-2 immobilization on the Medpor surface were identified by Fourier transform infrared spectroscopy. The activity of Medpor with rhBMP-2 immobilized was examined using an alkaline phosphatase assay on MC3T3-E1 cultured Medpor. These results showed that the rhBMP-2 immobilized Medpor increased the level of MC3T3-E1 cell differentiation. These results demonstrated that plasma surface modification has the potential to immobilize rhBMP-2 on polymer implant such as Medpor and can be used for the binding of bioactive nanomolecules in bone tissue engineering.

  8. Does Recombinant Human Bone Morphogenetic Protein-2 (rhBMP-2) Use in Adult Spinal Deformity (ASD) Increase Complications and Are Complications Associated With Location of rhBMP-2 Use?: A Prospective, Multicenter Study of 279 Consecutive Patients.

    Science.gov (United States)

    Bess, Shay; Line, Breton G; Lafarge, Virginie; Schwab, Frank; Shaffrey, Christopher I; Hart, Robert A; Boachie-Adjei, Oheneba; Akbarnia, Behrooz A; Ames, Christopher P; Burton, Douglas C; Deverin, Vedat; Fu, Kai-Ming G; Gupta, Munish; Hostin, Richard; Kebaish, Khaled; Klineberg, Eric; Mundis, Gregory; O'Brien, Michael; Shelokov, Alexis; Smith, Justin S

    2013-11-18

    Study Design. Multi-center, prospective analysis of consecutive ASD patients.Objective. Evaluate complications associated with rhBMP-2 use in ASDSummary of Background Data. Off-label rhBMP-2 use is common, however under-reporting of rhBMP-2 associated complications has been recently scrutinized.Methods. ASD patients consecutively enrolled into a prospective, multicenter database, were evaluated for type and timing of acute perioperative complications. Inclusion criteria: age ≥ 18 years, ASD, spinal arthrodesis >4 levels, and ≥3 months follow-up. Patients divided into those receiving rhBMP-2 (BMP) or no rhBMP-2 (NOBMP). BMP divided into location of use: posterior (PBMP), interbody (IBMP), and interbody + posterior spine (I+PBMP). Correlations between acute perioperative complications and rhBMP-2 use including total dose, dose/level and location of use were evaluated.Results. 279 patients (mean age 57 years, mean spinal levels fused 12.0, mean follow-up 28.8 months) met inclusion criteria. BMP (n = 172; average posterior dose = 2.5 mg/level, average interbody dose = 5 mg/level) had similar age, smoking history, previous spine surgery, total spinal levels fused, estimated blood loss, and duration of hospital stay as NOBMP (n = 107; p>0.05). BMP had greater Charlson Comorbidity Index (1.9 vs. 1.2), greater scoliosis (43° vs. 38°), longer operative time (488.2 vs. 414.6 minutes), more osteotomies/patient (4.0 vs. 1.6) and greater percentage of anteroposterior fusion (APSF; 20.9% vs. 8.4%) than NOBMP, respectively (p0.05). Multivariate analysis demonstrated small to non-existent correlations between rhBMP-2 use and complications.Conclusions. RhBMP-2 use and location of rhBMP-2 use in ASD surgery, at reported doses, does not increase acute major, neurological or wound complications. Research is needed for higher rhBMP-2 dosing and long-term follow-up.

  9. Low-power GaAlAs laser irradiation promotes the proliferation and osteogenic differentiation of stem cells via IGF1 and BMP2.

    Directory of Open Access Journals (Sweden)

    Jyun-Yi Wu

    Full Text Available Low-power laser irradiation (LPLI has been found to induce various biological effects and cellular processes. Also, LPLI has been shown to promote fracture repair. Until now, it has been unclear how LPLI promotes bone formation and fracture healing. The aim of this study was to investigate the potential mechanism of LPLI-mediated enhancement of bone formation using mouse bone marrow mesenchymal stem cells (D1 cells. D1 cells were irradiated daily with a gallium-aluminum-arsenide (GaAlAs laser at dose of 0, 1, 2, or 4 J/cm(2. The lactate dehydrogenase (LDH assay showed no cytotoxic effects of LPLI on D1 cells, and instead, LPLI at 4 J/cm(2 significantly promoted D1 cell proliferation. LPLI also enhanced osteogenic differentiation in a dose-dependent manner and moderately increased expression of osteogenic markers. The neutralization experiments indicated that LPLI regulated insulin-like growth factor 1 (IGF1 and bone morphogenetic protein 2 (BMP2 signaling to promote cell proliferation and/or osteogenic differentiation. In conclusion, our study suggests that LPLI may induce IGF1 expression to promote both the proliferation and osteogenic differentiation of D1 cells, whereas it may induce BMP2 expression primarily to enhance osteogenic differentiation.

  10. The multifaceted effects of agmatine on functional recovery after spinal cord injury through Modulations of BMP-2/4/7 expressions in neurons and glial cells.

    Directory of Open Access Journals (Sweden)

    Yu Mi Park

    Full Text Available Presently, few treatments for spinal cord injury (SCI are available and none have facilitated neural regeneration and/or significant functional improvement. Agmatine (Agm, a guanidinium compound formed from decarboxylation of L-arginine by arginine decarboxylase, is a neurotransmitter/neuromodulator and been reported to exert neuroprotective effects in central nervous system injury models including SCI. The purpose of this study was to demonstrate the multifaceted effects of Agm on functional recovery and remyelinating events following SCI. Compression SCI in mice was produced by placing a 15 g/mm(2 weight for 1 min at thoracic vertebra (Th 9 segment. Mice that received an intraperitoneal (i.p. injection of Agm (100 mg/kg/day within 1 hour after SCI until 35 days showed improvement in locomotor recovery and bladder function. Emphasis was made on the analysis of remyelination events, neuronal cell preservation and ablation of glial scar area following SCI. Agm treatment significantly inhibited the demyelination events, neuronal loss and glial scar around the lesion site. In light of recent findings that expressions of bone morphogenetic proteins (BMPs are modulated in the neuronal and glial cell population after SCI, we hypothesized whether Agm could modulate BMP- 2/4/7 expressions in neurons, astrocytes, oligodendrocytes and play key role in promoting the neuronal and glial cell survival in the injured spinal cord. The results from computer assisted stereological toolbox analysis (CAST demonstrate that Agm treatment dramatically increased BMP- 2/7 expressions in neurons and oligodendrocytes. On the other hand, BMP- 4 expressions were significantly decreased in astrocytes and oligodendrocytes around the lesion site. Together, our results reveal that Agm treatment improved neurological and histological outcomes, induced oligodendrogenesis, protected neurons, and decreased glial scar formation through modulating the BMP- 2/4/7 expressions following

  11. BMP-2 functions independently of SHH signaling and triggers cell condensation and apoptosis in regenerating axolotl limbs

    Directory of Open Access Journals (Sweden)

    Finnson Kenneth

    2010-02-01

    Full Text Available Abstract Background Axolotls have the unique ability, among vertebrates, to perfectly regenerate complex body parts, such as limbs, after amputation. In addition, axolotls pattern developing and regenerating autopods from the anterior to posterior axis instead of posterior to anterior like all tetrapods studied to date. Sonic hedgehog is important in establishing this anterior-posterior axis of limbs in all tetrapods including axolotls. Interestingly, its expression is conserved (to the posterior side of limb buds and blastemas in axolotl limbs as in other tetrapods. It has been suggested that BMP-2 may be the secondary mediator of sonic hedgehog, although there is mounting evidence to the contrary in mice. Since BMP-2 expression is on the anterior portion of developing and regenerating limbs prior to digit patterning, opposite to the expression of sonic hedgehog, we examined whether BMP-2 expression was dependent on sonic hedgehog signaling and whether it affects patterning of the autopod during regeneration. Results The expression of BMP-2 and SOX-9 in developing and regenerating axolotl limbs corresponded to the first digits forming in the anterior portion of the autopods. The inhibition of sonic hedgehog signaling with cyclopamine caused hypomorphic limbs (during development and regeneration but did not affect the expression of BMP-2 and SOX-9. Overexpression of BMP-2 in regenerating limbs caused a loss of digits. Overexpression of Noggin (BMP inhibitor in regenerating limbs also resulted in a loss of digits. Histological analysis indicated that the loss due to BMP-2 overexpression was the result of increased cell condensation and apoptosis while the loss caused by Noggin was due to a decrease in cell division. Conclusion The expression of BMP-2 and its target SOX-9 was independent of sonic hedgehog signaling in developing and regenerating limbs. Their expression correlated with chondrogenesis and the appearance of skeletal elements has

  12. Establishment of Immortalized Mouse Bmp2 Knock-Out Dental Papilla Mesenchymal Cells Necessary for Study of Odontoblastic Differentiation and Odontogenesis

    Science.gov (United States)

    Wu, Lian; Wang, Feng; Donly, Kevin J.; Wan, Chunyan; Luo, Daoshu; Harris, Stephen E.; Macdougall, Mary; Chen, Shuo

    2016-01-01

    Bmp2 is essential for dentin formation. Bmp2 cKO mice exhibited similar phenotype to dentinogenesis imperfecta, showing dental pulp exposure, hypomineralized dentin, and delayed odontoblast differentiation. As it is relatively difficult to obtain lot of primary Bmp2 cKO dental papilla mesenchymal cells and to maintain a long-term culture of these primary cells, availability of immortalized deleted Bmp2 dental papilla mesenchymal cells is critical for studying the underlying mechanism of Bmp2 signal in odontogenesis. In this study, our goal was to generate an immortalized deleted Bmp2 dental papilla mesenchymal (iBmp2ko/ko dp) cell line by introducing Cre fluorescent protein (GFP) into the immortalized mouse floxed Bmp2 dental papilla mesenchymal (iBmp2fx/fx dp) cells. iBmp2ko/ko dp cells were confirmed by GFP and PCR. The deleted Bmp2 cells exhibited slow cell proliferation rate and cell growth was arrested in G2 phase. Expression of tooth-related marker genes and cell differentiation were decreased in the deleted cells. Importantly, extracellular matrix remodeling was impaired in the iBmp2ko/ko dp cells as reflected by the decreased Mmp-9 expression. In addition, with exogenous Bmp2 induction, these cell differentiation and mineralization were rescued as well as extracellular matrix remodeling was enhanced. Therefore, we for the first time described establishment of iBmpko/ko cells that are useful for study of mechanisms in regulating dental papilla mesenchymal cell lineages. PMID:26037045

  13. Establishment of Immortalized Mouse Bmp2 Knock-Out Dental Papilla Mesenchymal Cells Necessary for Study of Odontoblastic Differentiation and Odontogenesis.

    Science.gov (United States)

    Wu, Lian; Wang, Feng; Donly, Kevin J; Wan, Chunyan; Luo, Daoshu; Harris, Stephen E; MacDougall, Mary; Chen, Shuo

    2015-11-01

    Bmp2 is essential for dentin formation. Bmp2 cKO mice exhibited similar phenotype to dentinogenesis imperfecta, showing dental pulp exposure, hypomineralized dentin, and delayed odontoblast differentiation. As it is relatively difficult to obtain lot of primary Bmp2 cKO dental papilla mesenchymal cells and to maintain a long-term culture of these primary cells, availability of immortalized deleted Bmp2 dental papilla mesenchymal cells is critical for studying the underlying mechanism of Bmp2 signal in odontogenesis. In this study, our goal was to generate an immortalized deleted Bmp2 dental papilla mesenchymal (iBmp2(ko/ko)dp) cell line by introducing Cre recombinase and green fluorescent protein (GFP) into the immortalized mouse floxed Bmp2 dental papilla mesenchymal (iBmp2(fx/fx)dp) cells. iBmp2(ko/ko)dp cells were confirmed by GFP and PCR. The deleted Bmp2 cells exhibited slow cell proliferation rate and cell growth was arrested in G2 phase. Expression of tooth-related marker genes and cell differentiation were decreased in the deleted cells. Importantly, extracellular matrix remodeling was impaired in the iBmp2(ko/ko)dp cells as reflected by the decreased Mmp-9 expression. In addition, with exogenous Bmp2 induction, these cell differentiation and mineralization were rescued as well as extracellular matrix remodeling was enhanced. Therefore, we for the first time described establishment of iBmp(ko/ko) cells that are useful for study of mechanisms in regulating dental papilla mesenchymal cell lineages. PMID:26037045

  14. Effects of rhBMP-2 on Mandibular Distraction Osteogenesis and its OPG Expression in Rabbits%rhBMP-2对兔下颌骨牵引成骨区骨保护素表达的影响

    Institute of Scientific and Technical Information of China (English)

    周蕊; 付颖; 李新

    2011-01-01

    目的:通过动物实验,研究应用外源性rhBMP-2对兔下颌骨牵引成骨区骨保护素( osteoprotegerin,OPG)的影响.方法:在48只成年大耳白兔的一侧下颌骨前部行骨切开术,分别将空白胶原、rhBMP-2 1.5 mg胶原复合物植入下颌骨切开处,用牵引器延长一侧下颌骨4 mm,稳定期第1、3、7、14天,分别处死各组动物,取牵引区新生骨痂行组织学及OPG免疫组化染色.结果:下颌牵引延长后牵引间隙均有新骨形成,应用rhBMP-2 1.5mg效果好.免疫组化染色OPG主要定位于成骨细胞的胞浆中.在同一时间内,应用rhBMP-2组较对照组有显著性差异(P<0.05).结论:动物实验表明,rhBMP-2能促进兔下颌骨牵引成骨区新骨的生成.%Objective: To investigate the effects of rhBMP- 2 on mandibular distraction osteogenesis and the expression of OPG in the period of distraction osteogenesis. Methods: Unilateral mandibular osteotomies were performed in 48 mature rabbit. rhBMP - 2 1. 5mg with the collagen carrier was implanted in the osteotomy side of mandibles. Only collagen sponge was implanted in the control group. The mandibles of 48 rabbits were lengthened by 4 mm using a distractor , The animals were killed on 1,3,7,14 days of consolidation period. The distracted calluses were harvested and processed for histological and immunohistochemistry study of OPG. Results: The regenerated bone was found in the distraction gap after mandibular lengthening. But the rhBMP-2 was better. Staining for OPG was localized in osteoblasts of the periosteal region after completion of distraction. The mandibular side treated with rhBMP-2 had greater amount of new bone formation than that treated with collagen sponge. OPG was found in the cytoplasm of osteoblasts and stained brown or dark brown by immunohistochemistry. At the same time, OPG expression indicated that there was siganificant difference between rhBMP-2 group and control group(P<0. 05). Conclusion: rhBMP -2 could accelerate

  15. BMP2基因修饰犬脂肪源性基质细胞修复自体大段骨缺损%Repairing canine segmental bone defects using BMP2 gene modified adipose-derived stromal cells

    Institute of Scientific and Technical Information of China (English)

    李慧武; 戴尅戎; 汤亭亭; 张晓玲; 唐坚; 孙晓江; 张双燕; 楼觉人

    2008-01-01

    Objective To evaluate osteogenetic effectiveness of porous β-tricalcium phosphate(β-TCP) ceramic mixed with human bone morphogenetic protein2 gene(Adv-hBMP2)modified adipose derived stromal cells (ADSCs) in the repair of critical-sized bone defects..Methods The ADSCs taken from the back of beagle dogs were modified by the BMP2 gene.The expression and bone-induction ability of BMP2 was identified by ELISA and ectopic bone formation in nude mice.The cells were applied to a β-tricalcium phosphate (TGP)carrier and implanted into ulnar bone defects in the canine model.18 ulnar bone defects were divided into three groups randomly and filled with granular TCP alone,granular TCP and ADSCs,or TCP and ADSCs transduced with Adv-hBMP2 respectively.All dogs were followed clinically and roentgenographically for 16 weeks and then sacrificed.Results ELISA and ectopic bone formation in nude mice showed the recombinant ADSCs could express BMP2 highly and stably.No bone defects healed after implanting granular TCP alone or granular TCP and ADSCs.In the TCP and ADSCs transduced with AdvhBMP2 group,two defects healed,four partly healed.Histological examination showed woven bone at the both end of the cortices but entirelv fibrous tissue in the middle in which defects filled with TCP alone or TCP and ADSCs.Defects filled with TCP and transduced ADSCs showed substatial new bone formation.Histomorphometry showed TCP combined with ADSCs did not significantly increase new bone area compared with TCP alone.TCP and recombinant ADSCs produced a significant increase in newly formed bone area.Conclusion ADSCs tansduced with BMP2 gene in a TCP carrier can enhance bone regeneratmn to repair the critically-sized bone defect.%目的 评价BMP2基因修饰的犬脂肪源性基质细胞(ADSCs)与β-磷酸三钙(β-TCP)复合修复自体大段骨缺损的疗效.方法 从比格犬背部脂肪组织中提取基质细胞,转染腺病毒介导的人BMP2基因(Adv-hBMP2),通过ELISA和裸鼠体内异位成骨实验鉴定BMP

  16. 脊柱融合术患者BMP-2基因突变的检测及其意义%Mutational analysis of BMP-2 gene in the patients of spinal fusion

    Institute of Scientific and Technical Information of China (English)

    周传利; 陈晓亮

    2007-01-01

    目的 检测脊柱融合术患者的骨形态发生蛋白-2(BMP-2)基因突变状况.方法 从80例行脊柱融合术患者的术前空腹静脉血中提取DNA,采用聚合酶链反应-单链构象多态性分析(PCR-SSCP)及测序技术,检测其BMP-2基因部分编码区及其侧翼序列的突变.结果 脊柱融合术患者的外周静脉血中BMP-2基因有突变:TCG→GCG,TCA→TCG,并引起相应多肽的结构改变.结论 脊柱融合术患者中存在BMP-2基因突变及多态性分布,并有可能影响植骨融合效果.

  17. Influence of BMP-2 on early follicular development and mRNA expression of oocyte specific genes in bovine preantral follicles cultured in vitro.

    Science.gov (United States)

    Rossi, Rodrigo O D S; da Cunha, Ellen V; Portela, Antonia M L R; Passos, José R S; Costa, José J N; Silva, Anderson W B; Saraiva, Márcia V A; Peixoto, Christina A; Donato, Mariana A M; van den Hurk, Robert; Silva, José R V

    2016-03-01

    This study evaluates the effect of different concentrations (0, 10, 50 and 100ng/mL) of bone morphogenetic protein-2 (BMP-2) on primordial and secondary follicle development. It also investigates the effects of FSH and BMP-2 on the growth, morphology, ultrastructure and expression of mRNA for GDF9, NLRP5 and NPM2 genes in secondary follicles cultured for 18 days. The presence of BMP-2 at all tested concentrations increased the development of primordial follicles in vitro, but the highest concentration of BMP-2 (100 ng/mL) reduced the percentage of normal follicles when compared with tissues cultured with 10 ng/mL BMP-2. During culture of secondary follicles, in contrast to higher concentrations (50 or 100 ng/mL), 10 ng/mL BMP-2 kept the morphology of follicles during initial stages of in vitro culture. This concentration of BMP-2 also benefits maintenance of the ultrastructure of 18-day cultured follicles. The presence of both BMP-2 and FSH in culture medium resulted in a significant (PFSH and BMP-2 reduced follicular mRNA expression of GDF9 and NLRP5 when compared to follicles cultured in media containing only FSH. In combination with FSH, BMP-2 reduced the mRNA levels of NPM2, when compared to follicles cultured in control medium. It is concluded from these data that 10 ng/mL BMP-2 promotes the growth of primordial in vitro and it helps to maintain the ultrastructure of secondary follicles, while FSH is more important for better expression of follicular markers like GDF9 and NLRP5. PMID:26435174

  18. Expression of Human BMP-2 Gene in Different Tissues of Tobacco Plants%重组人BMP-2在烟草不同组织中的表达

    Institute of Scientific and Technical Information of China (English)

    高原; 索广力; 韩津; 何正权; 姚伟; 戴建武

    2006-01-01

    骨形态发生蛋白(BMPs)是一类调节骨组织发育的生长因子.BMP-2是BMP家族中诱骨活性最强的.在骨组织工程研究和临床应用中需要大量的BMP-2.因此,研究出一种能够有效地大量生产BMP-2的方法是十分必要的.随着植物分子生物学的进展,转基因植物被用作一种生物反应器来生产目的蛋白.以gus作为报告基因,研究了重组人bmp-2基因在烟草中的表达.通过GUS活性检测、半定量PCR和Western blotting分析了根、茎、叶组织中基因表达的水平,结果显示融合蛋白在根和茎组织中表达量显著高于叶组织.由于根和茎组织中蛋白组成与叶组织相比相对简单,提示其更易于进行目的蛋白的纯化.%The bone morphogenetic proteins (BMPs) are a family of growth factors that regulate the development of bone. BMP-2 is the most effective in the induction of bone tissue. A large amount of BMP-2 is needed for both bone tissue engineering research and clinical application. Thus, an effective way is necessary to produce sufficient BMP-2 protein. With the advance in plant biotechnology, transgenic plants have been targeted as a bioreactor to produce desired recombinant proteins. Here, the expression of recombinant human bmp-2 gene (rhbmp-2) was studied in tobacco plants using gus as a reporter gene. The difference of expression levels in root, stem and leaf tissues was analyzed by GUS activity assay, semi-quantitive RT-PCR and westem blotting.The results indicated that the expression levels of fusion protein in root and stem tissues were significantly higher than those in leaf tissue. For the protein compositions in root and stem tissues were simpler than those in leaf tissue,this suggested that the purification process with root and stem tissues would potentially be easier.

  19. Immunohistological Localization of BMP-2, BMP-7, and Their Receptors in Knee Joints with Focal Cartilage Lesions

    Directory of Open Access Journals (Sweden)

    Hagen Schmal

    2012-01-01

    Full Text Available Introduction. Although it is well known that BMP-2 and BMP-7 play significant roles in cartilage metabolism, data about intra-articular expression and localization of these proteins and their receptors in humans are rare. Methods. Biopsies of synovia and debrided cartilage were taken in patients undergoing autologous chondrocyte implantation. Expression of BMP-2, BMP-7, and their receptors BMPR-1A, BMPR-1B and BMPR-2 were semiquantitatively evaluated by immunohistological staining. Results. BMP-7 was equally highly expressed in all cartilage and synovial biopsies. Increased levels of BMPR-1A, but not of BMPR-1B, and BMPR-2, were found in all synovial and 47% of all cartilage samples (P=0.002. BMP-2 was positively scored in 47% of all cartilage and 40% of all synovial specimens. Defect size, KOSS, Henderson or Kellgren-Lawrence score did not statistically significant correlate with the expression of the analyzed proteins or Mankin and Pritzker scores. Duration of symptoms and localization of lesions were associated with KOSS (P<0.02, but there was no influence of these parameters on protein expression. Conclusions. BMP-2, BMP-7, and BMPR-1A were expressed in cartilage and synovia of knees with focal cartilage lesions. Although defect localization and duration of symptoms decisively influence KOSS, there was no associated alteration of protein expression observed.

  20. Kinetics and thermodynamics studies on the BMP-2 adsorption onto hydroxyapatite surface with different multi-morphological features

    Energy Technology Data Exchange (ETDEWEB)

    Lu, Zhiwei; Huangfu, Changxin; Wang, Yanying; Ge, Hongwei; Yao, Yao; Zou, Ping; Wang, Guangtu [College of Science, Sichuan Agricultural University, Ya' an 625014 (China); He, Hua [Institute of Animal Genetics and Breeding, Sichuan Agricultural University, Wenjiang, Sichuan 611130 (China); Rao, Hanbing, E-mail: rhbscu@gmail.com [College of Science, Sichuan Agricultural University, Ya' an 625014 (China)

    2015-07-01

    The effect of the surface topography on protein adsorption process is of great significance for designing hydroxyapatite (HA) ceramic material surfaces. In this work, three different topographies of HA materials HA-sheet, HA-rod, and HA-whisker were synthesized and testified by X-ray diffraction (XRD), Fourier transform infrared (FT-IR), Brunauer–Emmett–Teller (BET) and a field emission scanning electron microscopy (FE-SEM). We have systematically investigated the adsorption kinetics and thermodynamics of bone morphogenetic proteins (BMP-2) on the three different topography surfaces of HA, respectively. The results showed that the maximum adsorption capacities of HA-sheet, HA-rod and HA-whisker were (219.96 ± 10.18), (247.13 ± 12.35), and (354.67 ± 17.73) μg · g{sup −1}, respectively. Kinetic parameters, rate constants, equilibrium adsorption capacities and related correlation coefficients, for each kinetic model were calculated as well as discussed. It demonstrated that the adsorption of BMP-2 onto HA could be described by the pseudo second-order equation. Adsorption of BMP-2 onto HA followed the Langmuir isotherm. It confirmed that compared with other samples HA-whisker had more adsorption sites for its high specific surface area which could provide more opportunities for protein molecules. The adsorption processes were endothermic (ΔH > 0), spontaneous (ΔG < 0) and entropy increasing (ΔS > 0). A possible adsorption mechanism has been proposed. In addition, the BMP-2 could be adsorbed to the surface which existed slight conformational changes by FT-IR. - Highlights: • A novel protein adsorption studies based on sheet, rod and whisker of HA were designed. • Kinetic and thermodynamics parameters of BMP-2 and HA bonded materials were evaluated. • Surface topographies of the HA effect BMP-2 adsorption • The HA-whisker material had excellent adsorption performance for protein enrichment. • The electrostatic interaction is responsible for the

  1. In silico Mechano-Chemical Model of Bone Healing for the Regeneration of Critical Defects: The Effect of BMP-2.

    Directory of Open Access Journals (Sweden)

    Frederico O Ribeiro

    Full Text Available The healing of bone defects is a challenge for both tissue engineering and modern orthopaedics. This problem has been addressed through the study of scaffold constructs combined with mechanoregulatory theories, disregarding the influence of chemical factors and their respective delivery devices. Of the chemical factors involved in the bone healing process, bone morphogenetic protein-2 (BMP-2 has been identified as one of the most powerful osteoinductive proteins. The aim of this work is to develop and validate a mechano-chemical regulatory model to study the effect of BMP-2 on the healing of large bone defects in silico. We first collected a range of quantitative experimental data from the literature concerning the effects of BMP-2 on cellular activity, specifically proliferation, migration, differentiation, maturation and extracellular matrix production. These data were then used to define a model governed by mechano-chemical stimuli to simulate the healing of large bone defects under the following conditions: natural healing, an empty hydrogel implanted in the defect and a hydrogel soaked with BMP-2 implanted in the defect. For the latter condition, successful defect healing was predicted, in agreement with previous in vivo experiments. Further in vivo comparisons showed the potential of the model, which accurately predicted bone tissue formation during healing, bone tissue distribution across the defect and the quantity of bone inside the defect. The proposed mechano-chemical model also estimated the effect of BMP-2 on cells and the evolution of healing in large bone defects. This novel in silico tool provides valuable insight for bone tissue regeneration strategies.

  2. Retrovirus-mediated transfer of the fusion gene encoding EGFP-BMP2 in mesenchymal stem cells

    Institute of Scientific and Technical Information of China (English)

    Zhang Yingang; Guo Xiong; Liu Zheng; Wang Shijie

    2007-01-01

    Objective To develop retrovirus-mediated transfer of the fusion gene encoding EGFP-BMP2 in mesenchymal stem cells. Methods Mesenchymal stem cells from New Zealand white rabbits were transduced with retroviral pLEGFP-BMP2 vector by the optimized retroviral transduction protocol. Fluorescent microscopy's examination was to evaluate the results of the transduction, flow cytometer's analysis was to evaluate the transduction efficiency and the Fluorescence-activated cell sorting method was to sort the transduced cells. Bioactivity test from C2C12K4 cells was to show the expression and bio-activity of the fusion gene. Results Fluorescent microscopy showed the success of the transduction. By flow cytometer's analysis, the mean efficiency of the transduction with EGFP was (42.8±6.1)% SD. Transduced cells were sorted efficiently by the fluorescence-activated cell sorting method and after sorting, almost of those showed the expression of BMP2. Fluorescently and strongly bioactivity test for C2C12K4 cells demonstrated that fluorescent materials were located the surface of cells and the activity of luciferase increased compared with the control. Analysis of long-term expression showed there was no difference between 2 week-time point and 3 month-time point of culture post-sorting. Conclusion Mesenchymal stem cells can be transduced efficiently by retrovirus-mediated transfer of the fusion gene encoding EGFP-BMP2, the highly pure transduced cells are obtained by the fluorescence-activated cell sorting technique, the expressed chimeric protein embraced the double bioactivity of EGFP and BMP2, and moreover, the expression had not attenuated over time.

  3. 糖尿病对大鼠牙槽骨缺损修复中骨形态发生蛋白-2表达影响的研究%Effects of diabetes on expression of BMP-2 during bone healing of alveolar defect in rats

    Institute of Scientific and Technical Information of China (English)

    聂莹; 张志宏; 袁晟; 鲍军燕

    2011-01-01

    Objective To investigate the effects of diabetes on the expression of bone morphogenetic protein - 2 (BMP-2) during the various bone healing periods of alveolar defect. Methods 48 male SD rats were randomly divided into diabetes group ( n = 24) and control group( n=24). Diabetic rats were induced by intraperitoneal injection of streptozotocin (STZ) ,and alveolar defect was created through the diabetic duration time. 6 rats in each group were scarified respectively at the lth ,2th ,4th ,8th week ,then the alveolar bone were processed for histological examination. The expression of BMP-2 in different periods( 1,2,4,8 weeks)of alveolar defect healing of rats was investigated through immunohistochemistry method. The optical density (OD) of BMP-2 was analysed and compared between groups. Results Osteopenia in diabetes group were observed. The OD of BMP - 2 in the control group was statistically greater than that in the test group 1 and 2 weeks after alveolar defect. After 4 and 8 weeks, the expression of BMP-2 in the control group decreased,and no statistical difference was found in BMP -2 expression between these two groups. Conclusions Diabetes may affect the formation of BMP-2 ,leading to a reduction in bone healing. Diabetes is able to affect the differentiation of mesenchymal stem cells,leading to less osseointegration. Therefore, primary stability was decreased.%目的 观察糖尿病(diabetes mellitus,DM)对实验性大鼠牙槽骨缺损修复过程中不同时期骨形态发生蛋白-2(bone morphogenetic protein-2,BMP-2)表达的影响.方法 将48 只雄性SD大鼠随机分为DM组和对照组,每组24 只,DM组大鼠经腹腔注射链脲佐菌素造成DM大鼠模型,建模成功后行大鼠牙槽骨骨缺损制备,2 组均分别于骨缺损制备后1、2、4、8 周各取6 只大鼠处死,取术区组织.苏木精-伊红染色(hematoxylin-eosin staining,HE染色)镜下观察缺损区内新生骨样组织形成情况;用免疫组化法检测术后1、2、4

  4. rhBMP-2/CPC强化骨质疏松椎体力学强度的实验研究%The experimental study of the effect of rhBMP-2/CPC on biomechanical intensity for osteoporotic vertebrae

    Institute of Scientific and Technical Information of China (English)

    罗志强

    2011-01-01

    Objective To observe the dynamic efficacy of recombinant human bone morphogenetic protein-2/calcium phosphate cement ( rhBMP-2/CPC ) on the augment of biomechanical intensity of the lumbar vertebrae in ovariectomized sheep. Methods Twelve adult female sheep were ovariectomized and raised for 1 year after the surgery. Bone mineral densities ( BMD) of the lumbar vertebrae were measured before and after the surgery. L1-L6 were the experimental objects. The sheep in control group were offered no treatment. The sheep in CPC group were injected with CPC (2.0ml) via the transpedicular of the vertebra. The sheep in rhBMP-2/CPC group were injected with rhBMP-2/CPC (2. 0ml) via the transpedicular of the vertebra. Every 3 sheep were randomly killed on day 1, week 6, week 12, and week 24 after the surgery. The vertebra compression test was performed. The ultimate compressive stress ( σalt ) and energy absorption value ( EAV ) of the vertebrae in every group were measured. The biomechanical indexes were compared and analyzed among different methods at the same time and among different time points using same method. Results BMO of the sheep vertebrae significantly decreased at 1 year after the surgery ( P 0.05). However, aalt in rhBMP-2/CPC group was significantly higher than that in CPC group on week 24 ( P 0. 05). However, σalt in rhBMP-2/ CPC group on week 24 was significantly higher than that on other three time points in the same group ( P < 0. 05). Conclusion rhBMP-2/CPC not only improved the immediate mechanical strength of osteoporotic vertebrae, but also maintained the dynamic mechanical strength and further enhanced the lone-term mechanical strength of osteoporotic vertebrae, which could provide an ideal mechanical condition for firm bone fusion of the spine.%目的 观察人重组骨形态发生蛋白-2复合磷酸钙骨水泥(recombinant human bonemorphogenetic protein-2/calcium phosphate cement,rhBMP-2/CPC)强化骨质疏松绵羊腰椎生物力学

  5. N-cadherin mediated distribution of beta-catenin alters MAP kinase and BMP-2 signaling on chondrogenesis-related gene expression.

    Science.gov (United States)

    Modarresi, Rozbeh; Lafond, Toulouse; Roman-Blas, Jorge A; Danielson, Keith G; Tuan, Rocky S; Seghatoleslami, M Reza

    2005-05-01

    We have examined the effect of calcium-dependent adhesion, mediated by N-cadherin, on cell signaling during chondrogenesis of multipotential embryonic mouse C3H10T1/2 cells. The activity of chondrogenic genes, type II collagen, aggrecan, and Sox9 were examined in monolayer (non-chondrogenic), and micromass (chondrogenic) cultures of parental C3H10T1/2 cells and altered C3H10T1/2 cell lines that express a dominant negative form of N-cadherin (delta390-T1/2) or overexpress normal N-cadherin (MNCD2-T1/2). Our findings show that missexpression or inhibition of N-cadherin in C3H10T1/2 cells results in temporal and spatial changes in expression of the chondrogenic genes Sox9, aggrecan, and collagen type II. We have also analyzed activity of the serum response factor (SRF), a nuclear target of MAP kinase signaling implicated in chondrogenesis. In semi-confluent monolayer cultures (minimum cell-cell contact) of C3H10T1/2, MNCD2-T1/2, or delta390-T1/2 cells, there was no significant change in the pattern of MAP kinase or bone morphogenetic protein-2 (BMP-2) regulation of SRF. However, in micromass cultures, the effect of MAP kinase and BMP-2 on SRF activity was proportional to the nuclear localization of beta-catenin, a Wnt stabilized cytoplasmic factor that can associate with lymphoid enhancer-binding factor (LEF) to serve as a transcription factor. Our findings suggest that the extent of adherens junction formation mediated by N-cadherin can modulate the potential Wnt-induced nuclear activity of beta-catenin. PMID:15723280

  6. Fabrication of Core-Shell PEI/pBMP2-PLGA Electrospun Scaffold for Gene Delivery to Periodontal Ligament Stem Cells

    Directory of Open Access Journals (Sweden)

    Qiao Xie

    2016-01-01

    Full Text Available Bone tissue engineering is the most promising technology for enhancing bone regeneration. Scaffolds loaded with osteogenic factors improve the therapeutic effect. In this study, the bioactive PEI (polyethylenimine/pBMP2- (bone morphogenetic protein-2 plasmid- PLGA (poly(D, L-lactic-co-glycolic acid core-shell scaffolds were prepared using coaxial electrospinning for a controlled gene delivery to hPDLSCs (human periodontal ligament stem cells. The pBMP2 was encapsulated in the PEI phase as a core and PLGA was employed to control pBMP2 release as a shell. First, the scaffold characterization and mechanical properties were evaluated. Then the gene release behavior was analyzed. Our results showed that pBMP2 was released at high levels in the first few days, with a continuous release behavior in the next 28 days. At the same time, PEI/pBMP2 showed high transfection efficiency. Moreover, the core-shell electrospun scaffold showed BMP2 expression for a much longer time (more than 28 days compared with the single axial electrospun scaffold, as evaluated by qRT-PCR and western blot after culturing with hPDLSCs. These results suggested that the core-shell PEI/pBMP2-PLGA scaffold fabricated by coaxial electrospinning had a good gene release behavior and showed a prolonged expression time with a high transfection efficiency.

  7. Expression of human bone morphogenetic protein (BMP-2 and BMP-4 genes in transgenic bovine fibroblasts Expressão dos genes bone morphogenetic protein (BMP-2 e BMP-4 em fibroblastos bovinos transgênicos

    Directory of Open Access Journals (Sweden)

    C. Oleskovicz

    2004-08-01

    Full Text Available cDNAs dos genes bone morphogenetic protein-2 (BMP-2 e bone morphogenetic protein-4 (BMP-4 foram sintetizados a partir de RNA total extraído de tecidos ósseos de pacientes que apresentavam trauma facial (fraturas do maxilar entre o 7º e o 10º dia pós-trauma e clonados num vetor para expressão em células mamíferas, sob controle do promotor de citomegalovírus (CMV. Os vetores contendo os genes BMP-2 e o BMP-4 foram utilizados para a transfecção de fibroblastos bovinos. mRNAs foram indiretamente detectados por RT-PCR nas células transfectadas. As proteínas BMP-2 e BMP-4 foram detectadas mediante análises de Western blot. Os resultados demonstram a possibilidade de produção desses fatores de crescimento celular em fibroblastos bovinos. Essas células poderão ser utilizadas como fontes doadoras de material genético para a técnica de transferência nuclear na geração de animais transgênicos.

  8. Changes with Age and the Effect of Recombinant Human BMP-2 on Proteoglycan and Collagen Gene Expression in Rabbit Anulus Fibrosus Cells

    Institute of Scientific and Technical Information of China (English)

    Qin-Ming FEI; Xiao-Xing JIANG; Tong-Yi CHEN; Jun LI; Hideki MURAKAMI; Kai-Jow TSAI; William C. HUTTON

    2006-01-01

    In order to compare the difference between young and old intervertebral disc cells and their responsiveness to recombinant human bone morphogenetic protein-2 (rhBMP-2), disc cells were isolated from the anulus fibrosus (AF) and transition zones of lumbar discs from eight old and eight young New Zealand white rabbits. Compared with the cells from the young rabbits, cells from old rabbits respond less to rhBMP-2 treatment with respect to sulfated-glycosaminoglycan (sGAG) synthesis and aggrecan gene expression. But in collagen Ⅰ and collagen Ⅱ gene expressions, there are no significant differences between the old and the young. When comparing sGAG content, aggrecan, and collagen Ⅱ gene expression of the old AF cells after rhBMP-2 treatment with that of the young AF cells without rhBMP-2 treatment, the old AF cells with rhBMP-2 treatment have a greater capacity to synthesize sGAG bound in the cells and to release sGAG in the media, as well as to express aggrecan and collagen Ⅱ gene. It can be concluded that old AF cells after rhBMP-2 treatment have a greater capacity to synthesize sGAG and express aggrecan and collagen Ⅱ as compared to young AF cells without rhBMP-2 treatment. Thus rhBMP-2 can reverse the decline in the anabolic capacity of the disc cells with ageing. So it seems that rhBMP-2 has potential for use as an agent to retard a key component of disc degeneration and loss of disc matrix.

  9. Vessel formation is induced prior to the appearance of cartilage in BMP-2-mediated heterotopic ossification

    Science.gov (United States)

    Heterotopic ossification (HO), or endochondral bone formation at nonskeletal sites, often results from traumatic injury and can lead to devastating consequences. Alternatively, the ability to harness this phenomenon would greatly enhance current orthopedic tools for treating segmental bone defects. ...

  10. Effect of implantation of biodegradable magnesium alloy on BMP-2 expression in bone of ovariectomized osteoporosis rats

    Energy Technology Data Exchange (ETDEWEB)

    Guo, Yue, E-mail: 373073766@qq.com [Liaoning Medical University, 40 Songpo Road, Jinzhou, 121000 (China); Ren, Ling, E-mail: lren@imr.ac.cn [Institute of Metal Research, Chinese Academy of Sciences, 72 Wenhua Road, Shenyang, 110016 (China); Liu, Chang, E-mail: meixifan1971@163.com [Liaoning Medical University, 40 Songpo Road, Jinzhou, 121000 (China); Yuan, Yajiang, E-mail: yuan925@163.com [Liaoning Medical University, 40 Songpo Road, Jinzhou, 121000 (China); Lin, Xiao, E-mail: linx@imr.ac.cn [Institute of Metal Research, Chinese Academy of Sciences, 72 Wenhua Road, Shenyang, 110016 (China); Tan, Lili, E-mail: lltan@imr.ac.cn [Institute of Metal Research, Chinese Academy of Sciences, 72 Wenhua Road, Shenyang, 110016 (China); Chen, Shurui, E-mail: 272146792@qq.com [Liaoning Medical University, 40 Songpo Road, Jinzhou, 121000 (China); Yang, Ke, E-mail: kyang@imr.ac.cn [Institute of Metal Research, Chinese Academy of Sciences, 72 Wenhua Road, Shenyang, 110016 (China); Mei, Xifan, E-mail: meixifan1971@163.com [Liaoning Medical University, 40 Songpo Road, Jinzhou, 121000 (China)

    2013-10-01

    The study was focused on the implantation of a biodegradable AZ31 magnesium alloy into the femoral periosteal of the osteoporosis modeled rats. The experimental results showed that after 4 weeks implantation of AZ31 alloy in the osteoporosis modeled rats, the expression of BMP-2 in bone tissues of the rats was much enhanced, even higher than the control group, which should promote the bone formation and be beneficial for reducing the harmful effect of osteoporosis. Results of HE stains showed that the implantation of AZ31 alloy did not have obvious pathological changes on both the liver and kidney of the animal. - Highlights: • Mg alloy greatly increased expression of BMP-2 in osteoporosis modeled rat bone. • Mg alloy showed good biological safety. • Mg alloy is beneficial for reducing the symptom of osteoporosis.

  11. Effect of implantation of biodegradable magnesium alloy on BMP-2 expression in bone of ovariectomized osteoporosis rats

    International Nuclear Information System (INIS)

    The study was focused on the implantation of a biodegradable AZ31 magnesium alloy into the femoral periosteal of the osteoporosis modeled rats. The experimental results showed that after 4 weeks implantation of AZ31 alloy in the osteoporosis modeled rats, the expression of BMP-2 in bone tissues of the rats was much enhanced, even higher than the control group, which should promote the bone formation and be beneficial for reducing the harmful effect of osteoporosis. Results of HE stains showed that the implantation of AZ31 alloy did not have obvious pathological changes on both the liver and kidney of the animal. - Highlights: • Mg alloy greatly increased expression of BMP-2 in osteoporosis modeled rat bone. • Mg alloy showed good biological safety. • Mg alloy is beneficial for reducing the symptom of osteoporosis

  12. Mandibular bone repair by implantation of rhBMP-2 in a slow release carrier of polylactic acid--an experimental study in rats.

    OpenAIRE

    Schliephake, Henning; Weich, Herbert A.; Dullin, Christian; Gruber, Rudolf; Frahse, Sarah

    2008-01-01

    The aim of the present study was to test the hypothesis that human recombinant bone morphogenic protein 2 (rhBMP-2) implanted in a slow release carrier of polylactic acid (PLA) can repair a non-healing defect in the rat mandible and maintain the thickness of an augmented volume. p-DL-lactic acid discs were produced and loaded with 48 and 96 microg rhBMP-2 and inserted into non-healing defects of the mandible of 45 Wistar rats. Fifteen rats received implants with 96 microg rhBMP-2 (Group 2), 4...

  13. The expressions of IGF-1, BMP-2 and TGF-β1 in cartilage of condylar hyperplasia.

    Science.gov (United States)

    Meng, Q; Long, X; Deng, M; Cai, H; Li, J

    2011-01-01

    Condylar hyperplasia is a complex post-natal growth abnormality of the mandible and condyle, which leads to facial asymmetry. We investigated the distributions of insulin-like growth factors (IGF-1), bone morphogenetic protein-2 (BMP-2) and transforming growth factor-β1 (TGF-β1) in cartilage of condylar hyperplasia and revealed relationships between age and the cartilaginous thickness. Twenty patients with condylar hyperplasia were divided into four histopathological types. The cartilaginous thickness and age in different histological types were analysed, and the localizations of IGF-1, BMP-2 and TGF-β1 were detected by immunohistochemistry analysis. The cartilaginous thickness of condylar hyperplasia significantly increased. The cartilaginous thickness of type III was significantly thicker than type I and type II, Bivariate correlation revealed a significant correlations between age and the cartilaginous thickness (r = 0·68, P = 0·01). However, the expressions of IGF-1, BMP-2 and TGF-β1 were the strongest in type I. In almost all types of condylar hyperplasia, the presence of IGF-1 and BMP-2 was found mainly in the proliferative chondrocyte layer and the hypertrophic chondrocyte layer, and only a few in the calcified chondrocyte layer. The presence of TGF-β1 widely distributed from the fibrous articular surface to the calcified cartilage. These findings suggest that the proliferative activity of cartilage in condylar hyperplasia is strongly associated with age and cartilaginous thickness. Therefore, the four pathological types of condylar hyperplasia seem more likely to be four discontinuous stages. PMID:20626571

  14. Rat aortic smooth muscle cells cultured on hydroxyapatite differentiate into osteoblast-like cells via BMP-2-SMAD-5 pathway.

    Science.gov (United States)

    Nahar-Gohad, Pranjal; Gohad, Neeraj; Tsai, Chen-Chih; Bordia, Rajendra; Vyavahare, Naren

    2015-04-01

    Vascular calcification is an important pathological condition associated with increased risk of cardiovascular mortality. Hydroxyapatite (HA) found in such deposits is the same polymorph of calcium (Ca) found in bone, indicating calcification may involve mechanisms akin to bone formation. Vascular smooth muscle cells (Vsmcs) have been shown to undergo phenotypic change to osteoblast-like cells. However, the mechanisms underlying this phenotypic change are unclear, and whether the stimulus to become osteogenic is a result of loss of mineralization inhibitors or early mineral deposits is not known. Our aim in this study is to identify mechanisms and signal transduction pathways that cause differentiation of Vsmcs into osteoblast-like cells in the presence of HA. We first characterized vascular origin of Vsmcs by studying the expression of smooth muscle cell markers: myosin heavy chain and smooth muscle actin along with SM22α at both mRNA and protein levels. Vsmcs grown on HA exhibited progressive change in cellular morphology at 3-, 7-, and 14-day time points. Culturing of Vsmcs on HA disc resulted in decrease in media Ca levels and increased expression of Ca-sensing receptor (CaSR) on Vsmcs resulting in upregulation of intracellular CaSR signaling leading to increased BMP-2 secretion. BMP-2 pathway mediated differentiation of Vsmcs to osteoblast-like cells shown by expression of osteogenic markers like runt-related transcription factor 2, osteocalcin, and alkaline phosphatase at mRNA and protein levels. Blocking CaSR by NPS-2143 reduced BMP-2 secretion and blocking the BMP-2 pathway by LDN-193189, a BMP inhibitor, modulated expression of osteogenic markers confirming their role in osteogenesis of Vsmcs. PMID:25725805

  15. Full regeneration of segmental bone defects using porous titanium implants loaded with BMP-2 containing fibrin gels

    Directory of Open Access Journals (Sweden)

    J van der Stok

    2015-03-01

    Full Text Available Regeneration of load-bearing segmental bone defects is a major challenge in trauma and orthopaedic surgery. The ideal bone graft substitute is a biomaterial that provides immediate mechanical stability, while stimulating bone regeneration to completely bridge defects over a short period. Therefore, selective laser melted porous titanium, designed and fine-tuned to tolerate full load-bearing, was filled with a physiologically concentrated fibrin gel loaded with bone morphogenetic protein-2 (BMP-2. This biomaterial was used to graft critical-sized segmental femoral bone defects in rats. As a control, porous titanium implants were either left empty or filled with a fibrin gels without BMP-2. We evaluated bone regeneration, bone quality and mechanical strength of grafted femora using in vivo and ex vivo µCT scanning, histology, and torsion testing. This biomaterial completely regenerated and bridged the critical-sized bone defects within eight weeks. After twelve weeks, femora were anatomically re-shaped and revealed open medullary cavities. More importantly, new bone was formed throughout the entire porous titanium implants and grafted femora regained more than their innate mechanical stability: torsional strength exceeded twice their original strength. In conclusion, combining porous titanium implants with a physiologically concentrated fibrin gels loaded with BMP-2 improved bone regeneration in load-bearing segmental defects. This material combination now awaits its evaluation in larger animal models to show its suitability for grafting load-bearing defects in trauma and orthopaedic surgery.

  16. Experimental and computational investigation of the effect of hydrophobicity on aggregation and osteoinductive potential of BMP-2-derived peptide in a hydrogel matrix.

    Science.gov (United States)

    Moeinzadeh, Seyedsina; Barati, Danial; Sarvestani, Samaneh K; Karimi, Tahereh; Jabbari, Esmaiel

    2015-01-01

    An attractive approach to reduce the undesired side effects of bone morphogenetic proteins (BMPs) in regenerative medicine is to use osteoinductive peptide sequences derived from BMPs. Although the structure and function of BMPs have been studied extensively, there is limited data on structure and activity of BMP-derived peptides immobilized in hydrogels. The objective of this work was to investigate the effect of concentration and hydrophobicity of the BMP-2 peptide, corresponding to residues 73-92 of the knuckle epitope of BMP-2 protein, on peptide aggregation and osteogenic differentiation of human mesenchymal stem cells encapsulated in a polyethylene glycol (PEG) hydrogel. The peptide hydrophobicity was varied by capping PEG chain ends with short lactide segments. The BMP-2 peptide with a positive index of hydrophobicity had a critical micelle concentration (CMC) and formed aggregates in aqueous solution. Based on simulation results, there was a slight increase in the concentration of free peptide in solution with 1000-fold increase in peptide concentration. The dose-osteogenic response curve of the BMP-2 peptide was in the 0.0005-0.005 mM range, and osteoinductive potential of the BMP-2 peptide was significantly less than that of BMP-2 protein even at 1000-fold higher concentrations, which was attributed to peptide aggregation. Further, the peptide or PEG-peptide aggregates had significantly higher interaction energy with the cell membrane compared with the free peptide, which led to a higher nonspecific interaction with the cell membrane and loss of osteoinductive potential. Conjugation of the BMP-2 peptide to PEG increased CMC and osteoinductive potential of the peptide whereas conjugation to lactide-capped PEG reduced CMC and osteoinductive potential of the peptide. Experimental and simulation results revealed that osteoinductive potential of the BMP-2 peptide is correlated with its CMC and the free peptide concentration in aqueous medium and not the

  17. MRI of transforaminal lumbar interbody fusion: imaging appearance with and without the use of human recombinant bone morphogenetic protein-2 (rhBMP-2)

    Energy Technology Data Exchange (ETDEWEB)

    Fox, Michael G.; Goldberg, Judd M.; Gaskin, Cree M.; Barr, Michelle S.; Alford, Bennett [University of Virginia, Department of Radiology and Medical Imaging, Charlottesville, VA (United States); Patrie, James T. [University of Virginia, Department of Public Health Sciences, Charlottesville, VA (United States); Shen, Francis H. [University of Virginia, Department of Orthopedic Surgery, Charlottesville, VA (United States)

    2014-09-15

    To describe the vertebral endplate and intervertebral disc space MRI appearance following TLIF, with and without the use of rhBMP-2, and to determine if the appearance is concerning for discitis/osteomyelitis. After institutional review board approval, 116 TLIF assessments performed on 75 patients with rhBMP-2 were retrospectively and independently reviewed by five radiologists and compared to 73 TLIF assessments performed on 45 patients without rhBMP-2. MRIs were evaluated for endplate signal, disc space enhancement, disc space fluid, and abnormal paraspinal soft tissue. Endplate edema-like signal was reported when T1-weighted hypointensity, T2-weighted hyperintensity, and endplate enhancement were present. Subjective concern for discitis/osteomyelitis on MRI was graded on a five-point scale. Generalized estimating equation binomial regression model analysis was performed with findings correlated with rhBMP-2 use, TLIF level, graft type, and days between TLIF and MRI. The rhBMP-2 group demonstrated endplate edema-like signal (OR 5.66; 95 % CI [1.58, 20.24], p = 0.008) and disc space enhancement (OR 2.40; 95 % CI [1.20, 4.80], p = 0.013) more often after adjusting for the TLIF level, graft type, and the number of days following TLIF. Both groups had a similar temporal distribution for endplate edema-like signal but disc space enhancement peaked earlier in the rhBMP-2 group. Disc space fluid was only present in the rhBMP-2 group. Neither group demonstrated abnormal paraspinal soft tissue and discitis/osteomyelitis was not considered likely in any patient. Endplate edema-like signal and disc space enhancement were significantly more frequent and disc space enhancement developed more rapidly following TLIF when rhBMP-2 was utilized. The concern for discitis/osteomyelitis was similar and minimal in both groups. (orig.)

  18. MRI of transforaminal lumbar interbody fusion: imaging appearance with and without the use of human recombinant bone morphogenetic protein-2 (rhBMP-2)

    International Nuclear Information System (INIS)

    To describe the vertebral endplate and intervertebral disc space MRI appearance following TLIF, with and without the use of rhBMP-2, and to determine if the appearance is concerning for discitis/osteomyelitis. After institutional review board approval, 116 TLIF assessments performed on 75 patients with rhBMP-2 were retrospectively and independently reviewed by five radiologists and compared to 73 TLIF assessments performed on 45 patients without rhBMP-2. MRIs were evaluated for endplate signal, disc space enhancement, disc space fluid, and abnormal paraspinal soft tissue. Endplate edema-like signal was reported when T1-weighted hypointensity, T2-weighted hyperintensity, and endplate enhancement were present. Subjective concern for discitis/osteomyelitis on MRI was graded on a five-point scale. Generalized estimating equation binomial regression model analysis was performed with findings correlated with rhBMP-2 use, TLIF level, graft type, and days between TLIF and MRI. The rhBMP-2 group demonstrated endplate edema-like signal (OR 5.66; 95 % CI [1.58, 20.24], p = 0.008) and disc space enhancement (OR 2.40; 95 % CI [1.20, 4.80], p = 0.013) more often after adjusting for the TLIF level, graft type, and the number of days following TLIF. Both groups had a similar temporal distribution for endplate edema-like signal but disc space enhancement peaked earlier in the rhBMP-2 group. Disc space fluid was only present in the rhBMP-2 group. Neither group demonstrated abnormal paraspinal soft tissue and discitis/osteomyelitis was not considered likely in any patient. Endplate edema-like signal and disc space enhancement were significantly more frequent and disc space enhancement developed more rapidly following TLIF when rhBMP-2 was utilized. The concern for discitis/osteomyelitis was similar and minimal in both groups. (orig.)

  19. Experimental and computational investigation of the effect of hydrophobicity on aggregation and osteoinductive potential of BMP-2-derived peptide in a hydrogel matrix.

    Science.gov (United States)

    Moeinzadeh, Seyedsina; Barati, Danial; Sarvestani, Samaneh K; Karimi, Tahereh; Jabbari, Esmaiel

    2015-01-01

    An attractive approach to reduce the undesired side effects of bone morphogenetic proteins (BMPs) in regenerative medicine is to use osteoinductive peptide sequences derived from BMPs. Although the structure and function of BMPs have been studied extensively, there is limited data on structure and activity of BMP-derived peptides immobilized in hydrogels. The objective of this work was to investigate the effect of concentration and hydrophobicity of the BMP-2 peptide, corresponding to residues 73-92 of the knuckle epitope of BMP-2 protein, on peptide aggregation and osteogenic differentiation of human mesenchymal stem cells encapsulated in a polyethylene glycol (PEG) hydrogel. The peptide hydrophobicity was varied by capping PEG chain ends with short lactide segments. The BMP-2 peptide with a positive index of hydrophobicity had a critical micelle concentration (CMC) and formed aggregates in aqueous solution. Based on simulation results, there was a slight increase in the concentration of free peptide in solution with 1000-fold increase in peptide concentration. The dose-osteogenic response curve of the BMP-2 peptide was in the 0.0005-0.005 mM range, and osteoinductive potential of the BMP-2 peptide was significantly less than that of BMP-2 protein even at 1000-fold higher concentrations, which was attributed to peptide aggregation. Further, the peptide or PEG-peptide aggregates had significantly higher interaction energy with the cell membrane compared with the free peptide, which led to a higher nonspecific interaction with the cell membrane and loss of osteoinductive potential. Conjugation of the BMP-2 peptide to PEG increased CMC and osteoinductive potential of the peptide whereas conjugation to lactide-capped PEG reduced CMC and osteoinductive potential of the peptide. Experimental and simulation results revealed that osteoinductive potential of the BMP-2 peptide is correlated with its CMC and the free peptide concentration in aqueous medium and not the

  20. Improved Bone Formation in Osteoporotic Rabbits with the Bone Morphogenetic Protein-2 (rhBMP-2) Coated Titanium Screws Which Were Coated By Using Plasma Polymerization Technique

    OpenAIRE

    Salih Gulsen; Dilek Cokeliler; Hilal Goktas; Aysu Kucukturhan; Bilgehan Ozcil; Hakan Caner

    2014-01-01

    Delaying of bone fusion in osteoporotic patients underwent spinal stabilization surgery leads to screw loosening, and this causes pseudoarticulation, mobility and fibrosis at vertebral segments. To prevent these complications, the screws coated with recombinant bone morphogenetic protein-2 (rhBMP-2) could be used. To verify this hypothesis, we coated 5 Titanium screws with rhBMP-2 using plasma polymerization method, and also used 10 uncoated screws for making comparison between coated and unc...

  1. Medium-Term Function of a 3D Printed TCP/HA Structure as a New Osteoconductive Scaffold for Vertical Bone Augmentation: A Simulation by BMP-2 Activation

    Directory of Open Access Journals (Sweden)

    Mira Moussa

    2015-04-01

    Full Text Available Introduction: A 3D-printed construct made of orthogonally layered strands of tricalcium phosphate (TCP and hydroxyapatite has recently become available. The material provides excellent osteoconductivity. We simulated a medium-term experiment in a sheep calvarial model by priming the blocks with BMP-2. Vertical bone growth/maturation and material resorption were evaluated. Materials and methods: Titanium hemispherical caps were filled with either bare- or BMP-2 primed constructs and placed onto the calvaria of adult sheep (n = 8. Histomorphometry was performed after 8 and 16 weeks. Results: After 8 weeks, relative to bare constructs, BMP-2 stimulation led to a two-fold increase in bone volume (Bare: 22% ± 2.1%; BMP-2 primed: 50% ± 3% and a 3-fold decrease in substitute volume (Bare: 47% ± 5%; BMP-2 primed: 18% ± 2%. These rates were still observed at 16 weeks. The new bone grew and matured to a haversian-like structure while the substitute material resorbed via cell- and chemical-mediation. Conclusion: By priming the 3D construct with BMP-2, bone metabolism was physiologically accelerated, that is, enhancing vertical bone growth and maturation as well as material bioresorption. The scaffolding function of the block was maintained, leaving time for the bone to grow and mature to a haversian-like structure. In parallel, the material resorbed via cell-mediated and chemical processes. These promising results must be confirmed in clinical tests.

  2. Co-delivery of platelet-derived growth factor (PDGF-BB) and bone morphogenic protein (BMP-2) coated onto heparinized titanium for improving osteoblast function and osteointegration.

    Science.gov (United States)

    Kim, Sung Eun; Yun, Young-Pil; Lee, Jae Yong; Shim, June-Sung; Park, Kyeongsoon; Huh, Jung-Bo

    2015-12-01

    The aim of this study was to improve osteoblast function by delivering two growth factors, PDGF-BB and BMP-2, incorporated onto heparinized titanium (Hep-Ti) substrate. To achieve co-delivery of PDGF-BB and BMP-2, the surface of anodized Ti was immobilized with heparin, and then the two growth factors were coated onto the Hep-Ti surface. Incorporation of the two growth factors onto Hep-Ti was evaluated by SEM and XPS. Incorporated PDGF-BB and BMP-2 were released from the Hep-Ti substrate in a sustained manner. In vitro studies revealed that osteoblasts grown on PDGF-BB- and BMP-2-immobilized Hep-Ti increased ALP activity, calcium deposition, osteocalcin and osteopontin levels as compared to those grown on PDGF-BB alone- or BMP-2 alone-immobilized Hep-Ti. These results suggested that co-delivery of PDGF-BB and BMP-2 using Hep-Ti substrate will be a promising material for the enhancement of osteoblast function and osteointegration.

  3. Trehalose maintains bioactivity and promotes sustained release of BMP-2 from lyophilized CDHA scaffolds for enhanced osteogenesis in vitro and in vivo.

    Directory of Open Access Journals (Sweden)

    Jun Zhao

    Full Text Available Calcium phosphate (Ca-P scaffolds have been widely employed as a supportive matrix and delivery system for bone tissue engineering. Previous studies using osteoinductive growth factors loaded Ca-P scaffolds via passive adsorption often experience issues associated with easy inactivation and uncontrolled release. In present study, a new delivery system was fabricated using bone morphogenetic protein-2 (BMP-2 loaded calcium-deficient hydroxyapatite (CDHA scaffold by lyophilization with addition of trehalose. The in vitro osteogenesis effects of this formulation were compared with lyophilized BMP-2/CDHA construct without trehalose and absorbed BMP-2/CDHA constructs with or without trehalose. The release characteristics and alkaline phosphatase (ALP activity analyses showed that addition of trehalose could sufficiently protect BMP-2 bioactivity during lyophilization and achieve sustained BMP-2 release from lyophilized CDHA construct in vitro and in vivo. However, absorbed BMP-2/CDHA constructs with or without trehalose showed similar BMP-2 bioactivity and presented a burst release. Quantitative real-time PCR (RT-qPCR and enzyme-linked immunosorbent assay (ELISA demonstrated that lyophilized BMP-2/CDHA construct with trehalose (lyo-tre-BMP-2 promoted osteogenic differentiation of bone marrow stromal cells (bMSCs significantly and this formulation could preserve over 70% protein bioactivity after 5 weeks storage at 25°C. Micro-computed tomography, histological and fluorescent labeling analyses further demonstrated that lyo-tre-BMP-2 formulation combined with bMSCs led to the most percentage of new bone volume (38.79% ± 5.32% and area (40.71% ± 7.14% as well as the most percentage of fluorochrome stained bone area (alizarin red S: 2.64% ± 0.44%, calcein: 6.08% ± 1.37% and mineral apposition rate (4.13 ± 0.62 µm/day in critical-sized rat cranial defects healing. Biomechanical tests also indicated the maximum stiffness (118.17 ± 15.02 Mpa and

  4. Matrix-immobilized BMP-2 on microcontact printed fibronectin as in vitro tool to study BMP-mediated signaling and cell migration

    Directory of Open Access Journals (Sweden)

    Kristin eHauff

    2015-05-01

    Full Text Available During development, bone morphogenetic proteins (BMPs exert important functions in several tissues by regulating signaling for cell differentiation and migration. In vivo the extracellular matrix (ECM not only provides a support for adherent cells, but also presents a reservoir of growth factors (GFs. Several constituents of the ECM provide adhesive cues, which serve as binding sites for cell transmembrane receptors, such as integrins, which convey adhesion-mediated signaling to the intracellular compartment. Integrins do not function alone but rather crosstalk and cooperate with other receptors, such as GF receptors, in regulating cell responses to extracellular signals. To this, we present here the immobilization of BMP-2 onto cellular fibronectin (cFN, a key protein of the ECM, to investigate their impact on GF-mediated signaling and migration.Following biotinylation, BMP-2 was linked to biotinylated cFN using NeutrAvidin (NA as cross-linker. Characterization with QCM-D and ELISA confirmed the efficient immobilization of BMP-2 on cFN over a period of 24 h.To validate the bioactivity of matrix-immobilized BMP-2 (iBMP-2 we investigated short- and long-term responses of C2C12 myoblasts in comparison to soluble BMP-2 (sBMP-2 or in absence of GFs. Similarly to sBMP-2, iBMP-2 triggered Smad 1/5 phosphorylation and translocation into the nucleus corresponding to the activation of BMP-mediated Smad-dependent pathway. Additionally, successful suppression of myotube formation was observed after six days.We next implemented this approach to fabricate cFN micro patterned stripes by soft lithography. These stripes only allowed cell-surface interaction on the pattern due to passivation of the surface in between, thus serving as platform for studies on directed cell migration. During a 10 h-period, cells showed an increased migratory activity upon BMP-2 exposure.Thus, this versatile tool retains the GF's bioactivity and allows the presentation of ECM

  5. Construction and identification of recombinant adenovirus vector co-expressing VEGF121 and BMP2 genes and its expression in HEK293 cells%VEGF121和BMP2双基因共表达重组腺病毒载体的构建及其在HEK293中的表达

    Institute of Scientific and Technical Information of China (English)

    栗刚; 吴秀成; 钟声; 王巍; 李媛; 刘丹平

    2011-01-01

    目的 构建人血管内皮生长因子121(VEGF121)与人骨形态发生蛋白2(BMP2)双基因共表达腺病毒载体Adv-BMP2-IRES-VEGF121,并观察其在人胚肾细胞株(HEK293)中的表达情况.方法 对腺病毒质粒pShuttle-CMV-BMP2的目的基因BMP2进行PCR扩增.腺病毒质粒pShuttle-CMV-VEGF121-IRES-hrGFP-1经Kpn I/Xba I酶切后,将BMP2片段定向导入pShuttle-CMV-VEGF121-IRES,构建pShuttle-CMV-V EGF121-IRES-BMP2,并注入大肠杆菌DH5a中扩增,提取质粒.通过酶切分析、PCR检测和序列分析进行鉴定.将构建所得的质粒转染HEK293,采用RT-PCR法检测HEK293中的BMP2、VEGF121 mRNA,Western blot法检测其蛋白.结果 成功构建了Adv-BMP2-IRES-VEGF121.酶切分析及DNA序列测定证实重组质粒构建正确.质粒转染后的HEK293 BMP2和VEGF121表达阳性.结论 成功构建了Adv-BMP2-IRES-VEGF121,其转染HEK293后,VEGF121、BMP2在HEK293中共表达阳性.%Objective To construct and identify the adenovirus shuttle plasmid pShuttle-CMV-VEGF121-IRES-BMP2 and its express in HEK293 cells.Methods The DNA fragments of human BMP2 gene were changed restriction sites and subcloned by PCR.The human BMP2 genes and pShuttle-CMV-VEGF121-IRES were ligated into the plasmid by directional cloning method.The inserted target genes in the plasmid were verified by restriction enzyme digestion and nucleotide sequencing.The correct recombinant express plasmid was transfected to HEK293 cells.The expression of VEGF121, BMP2 mRNA were detected by RT-PCR, the VEGF121, BMP2 protein were detected by Western blotting.Results The adenovirus shuttle plasmid was constructed correctly.The VEGF121, BMP2 mRNA and protein were expressed in HEK293 cells.Conclusion The adenovirus shuttle plasmid is constructed, VEGF121, BMP2 mRNA and protein are successfully expressed in HEK293 cells.

  6. Enhancement of Tendon–Bone Healing for Anterior Cruciate Ligament (ACL Reconstruction Using Bone Marrow-Derived Mesenchymal Stem Cells Infected with BMP-2

    Directory of Open Access Journals (Sweden)

    Shiyi Chen

    2012-10-01

    Full Text Available At present, due to the growing attention focused on the issue of tendon–bone healing, we carried out an animal study of the use of genetic intervention combined with cell transplantation for the promotion of this process. Here, the efficacy of bone marrow stromal cells infected with bone morphogenetic protein-2 (BMP-2 on tendon–bone healing was determined. A eukaryotic expression vector containing the BMP-2 gene was constructed and bone marrow-derived mesenchymal stem cells (bMSCs were infected with a lentivirus. Next, we examined the viability of the infected cells and the mRNA and protein levels of BMP-2-infected bMSCs. Gastrocnemius tendons, gastrocnemius tendons wrapped by bMSCs infected with the control virus (bMSCs+Lv-Control, and gastrocnemius tendons wrapped by bMSCs infected with the recombinant BMP-2 virus (bMSCs+Lv-BMP-2 were used to reconstruct the anterior cruciate ligament (ACL in New Zealand white rabbits. Specimens from each group were harvested four and eight weeks postoperatively and evaluated using biomechanical and histological methods. The bMSCs were infected with the lentivirus at an efficiency close to 100%. The BMP-2 mRNA and protein levels in bMSCs were significantly increased after lentiviral infection. The bMSCs and BMP-2-infected bMSCs on the gastrocnemius tendon improved the biomechanical properties of the graft in the bone tunnel; specifically, bMSCs infected with BMP-2 had a positive effect on tendon–bone healing. In the four-week and eight-week groups, bMSCs+Lv-BMP-2 group exhibited significantly higher maximum loads of 29.3 ± 7.4 N and 45.5 ± 11.9 N, respectively, compared with the control group (19.9 ± 6.4 N and 21.9 ± 4.9 N (P = 0.041 and P = 0.001, respectively. In the eight-week groups, the stiffness of the bMSCs+Lv-BMP-2 group (32.5 ± 7.3 was significantly higher than that of the bMSCs+Lv-Control group (22.8 ± 7.4 or control groups (12.4 ± 6.0 (p = 0.036 and 0.001, respectively. Based on the

  7. BMP-2,3,4,5在颌面部神经鞘瘤中的表达分析%Analysis of the Expression of BMP-2,3,4,5 in Nerve Sheath Tumors of Maxillofacial Region

    Institute of Scientific and Technical Information of China (English)

    金岩; 吕红兵; Tipoe GL; 李媛

    2000-01-01

    目的:探讨BMPs家族成员与外周神经肿瘤的关系。方法:用原位杂交方法对BMP-2,3,4,5在人良、恶性神经鞘瘤中的表达进行观察。结果:显示BMP-2,3,4,5 mRNA在外周神经的良恶性神经鞘瘤中均有分布。良性肿瘤中,呈栅栏状排列,肿瘤细胞聚集的区域BMPs表达升高;恶性肿瘤中BMPs的表达高于良性肿瘤。结论:确定了BMPs在外周神经肿瘤中的表达和分布,揭示部分BMPs可能参与了外周神经肿瘤的发生发展过程。

  8. The effect of SDF-1α on low dose BMP-2 mediated bone regeneration by release from heparinized mineralized collagen type I matrix scaffolds in a murine critical size bone defect model.

    Science.gov (United States)

    Zwingenberger, Stefan; Langanke, Robert; Vater, Corina; Lee, Geoffrey; Niederlohmann, Eik; Sensenschmidt, Markus; Jacobi, Angela; Bernhardt, Ricardo; Muders, Michael; Rammelt, Stefan; Knaack, Sven; Gelinsky, Michael; Günther, Klaus-Peter; Goodman, Stuart B; Stiehler, Maik

    2016-09-01

    The treatment of critical size bone defects represents a challenge. The growth factor bone morphogenetic protein 2 (BMP-2) is clinically established but has potentially adverse effects when used at high doses. The aim of this study was to evaluate if stromal derived factor-1 alpha (SDF-1α) and BMP-2 released from heparinized mineralized collagen type I matrix (MCM) scaffolds have a cumulative effect on bone regeneration. MCM scaffolds were functionalized with heparin, loaded with BMP-2 and/or SDF-1α and implanted into a murine critical size femoral bone defect (control group, low dose BMP-2 group, low dose BMP-2 + SDF-1α group, and high dose BMP-2 group). After 6 weeks, both the low dose BMP-2 + SDF-1α group (5.8 ± 0.6 mm³, p = 0.0479) and the high dose BMP-2 group (6.5 ± 0.7 mm³, p = 0.008) had a significantly increased regenerated bone volume compared to the control group (4.2 ± 0.5 mm³). There was a higher healing score in the low dose BMP-2 + SDF-1α group (median grade 8; Q1-Q3 7-9; p = 0.0357) than in the low dose BMP-2 group (7; Q1-Q3 5-9) histologically. This study showed that release of BMP-2 and SDF-1α from heparinized MCM scaffolds allows for the reduction of the applied BMP-2 concentration since SDF-1α seems to enhance the osteoinductive potential of BMP-2. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2126-2134, 2016. PMID:27060915

  9. Effect of rhBMP- 2 on bone regeneration and osseointegration in peri- implant defects- histological observation%rhBMP-2在种植体周围骨缺损修复中应用的组织学观察

    Institute of Scientific and Technical Information of China (English)

    黄元瑾; 章锦才; 刘曙光; 蔡德鸿

    2012-01-01

    目的:研究rhBMP- 2及不同载体在种植体周围骨缺损修复中的应用.方法:在beagle犬下颌骨植入种植体,颊侧形成裂开性骨缺损,置入复合了不同浓度rhBMP- 2的珊瑚羟基磷灰石人造骨(CHA)或可吸收胶原海绵(ACS).种植体植入后2、4、8、12 周,获取含种植体骨标本,进行组织学观察.结果:2 周时,rhBMP- 2组可见极少量的新生骨组织.4 周时,rhBMP- 2/ACS组新骨组织由牙槽骨顶端向缺损区中心方向生长;rhBMP- 2/CHA组人造骨颗粒内部和周围出现呈岛状生长的新生骨组织.8 周时,rhBMP- 2/ACS组的新骨形成大片状结构;rhBMP- 2/CHA组人造骨颗粒周围较多骨岛形成.12 周时,rhBMP- 2组的缺损区内骨量和骨高度进一步增加,与种植体形成骨性结合.浓度为0.05 mg/ml和0.2 mg/ml,载体为CHA或ACS促进骨再生作用差异无统计学意义.结论:以CHA或ACS为载体rhBMP- 2能促进种植体周围骨缺损区内的骨组织再生并与种植体表面较好地结合.%Objective: To investigate the effects of rhBMP-2 in bone formation and osseointegration in peri-implant defects. Methods: 8 implants were placed in each of 8 beagle dogs. Dehiscence defects were surgically created on the buccal side of each implant. rhBMP-2 at 0. 05 mg/ml or 0. 2 mg/ml was combined into absorbable collagen sponge( ACS ) or coraline hydroxyapatite( CHA ) respectively and applied into the defects. ACS or CHA alone were used as the control. Animals were sacrificed 2,4,8 and 12 weeks after implantation respectively, non- decalcified ground sections of the bone samples with the implants were made and observed under microscope. Results: 2 weeks after implantation, the newly generated bone was minimal. 4 weeks after implantation, in rhBMP-2/ACS group formations of trabeculae of woven bone could be seen in the defects, in rhBMP-2/CHA the CHA particles were surrounded by newly formed bone. 8 weeks after implantation, in rhBMP-2/ACS group the newly formed bone

  10. Abrogation of epithelial BMP2 and BMP4 causes Amelogenesis Imperfecta by reducing MMP20 and KLK4 expression

    Science.gov (United States)

    Xie, Xiaohua; Liu, Chao; Zhang, Hua; Jani, Priyam H.; Lu, Yongbo; Wang, Xiaofang; Zhang, Bin; Qin, Chunlin

    2016-01-01

    Amelogenesis Imperfecta (AI) can be caused by the deficiencies of enamel matrix proteins, molecules responsible for the transportation and secretion of enamel matrix components, and proteases processing enamel matrix proteins. In the present study, we discovered the double deletion of bone morphogenetic protein 2 (Bmp2) and bone morphogenetic protein 4 (Bmp4) in the dental epithelium by K14-cre resulted in hypoplastic enamel and reduced density in X-ray radiography as well as shortened enamel rods under scanning electron microscopy. Such enamel phenotype was consistent with the diagnosis of hypoplastic amelogenesis imperfecta. Histological and molecular analyses revealed that the removal of matrix proteins in the mutant enamel was drastically delayed, which was coincided with the greatly reduced expression of matrix metalloproteinase 20 (MMP20) and kallikrein 4 (KLK4). Although the expression of multiple enamel matrix proteins was down-regulated in the mutant ameloblasts, the cleavage of ameloblastin was drastically impaired. Therefore, we attributed the AI primarily to the reduction of MMP20 and KLK4. Further investigation found that BMP/Smad4 signaling pathway was down-regulated in the K14-cre;Bmp2f/f;Bmp4f/fameloblasts, suggesting that the reduced MMP20 and KLK4 expression may be due to the attenuated epithelial BMP/Smad4 signaling. PMID:27146352

  11. Cardiogenic induction of pluripotent stem cells streamlined through a conserved SDF-1/VEGF/BMP2 integrated network.

    Directory of Open Access Journals (Sweden)

    Anca Chiriac

    Full Text Available BACKGROUND: Pluripotent stem cells produce tissue-specific lineages through programmed acquisition of sequential gene expression patterns that function as a blueprint for organ formation. As embryonic stem cells respond concomitantly to diverse signaling pathways during differentiation, extraction of a pro-cardiogenic network would offer a roadmap to streamline cardiac progenitor output. METHODS AND RESULTS: To resolve gene ontology priorities within precursor transcriptomes, cardiogenic subpopulations were here generated according to either growth factor guidance or stage-specific biomarker sorting. Innate expression profiles were independently delineated through unbiased systems biology mapping, and cross-referenced to filter transcriptional noise unmasking a conserved progenitor motif (55 up- and 233 down-regulated genes. The streamlined pool of 288 genes organized into a core biological network that prioritized the "Cardiovascular Development" function. Recursive in silico deconvolution of the cardiogenic neighborhood and associated canonical signaling pathways identified a combination of integrated axes, CXCR4/SDF-1, Flk-1/VEGF and BMP2r/BMP2, predicted to synchronize cardiac specification. In vitro targeting of the resolved triad in embryoid bodies accelerated expression of Nkx2.5, Mef2C and cardiac-MHC, enhanced beating activity, and augmented cardiogenic yield. CONCLUSIONS: Transcriptome-wide dissection of a conserved progenitor profile thus revealed functional highways that coordinate cardiogenic maturation from a pluripotent ground state. Validating the bioinformatics algorithm established a strategy to rationally modulate cell fate, and optimize stem cell-derived cardiogenesis.

  12. Gelatin Tight-Coated Poly(lactide-co-glycolide Scaffold Incorporating rhBMP-2 for Bone Tissue Engineering

    Directory of Open Access Journals (Sweden)

    Juan Wang

    2015-03-01

    Full Text Available Surface coating is the simplest surface modification. However, bioactive molecules can not spread well on the commonly used polylactone-type skeletons; thus, the surface coatings of biomolecules are typically unstable due to the weak interaction between the polymer and the bioactive molecules. In this study, a special type of poly(lactide-co-glycolide (PLGA-based scaffold with a loosened skeleton was fabricated by phase separation, which allowed gelatin molecules to more readily diffuse throughout the structure. In this application, gelatin modified both the internal substrate and external surface. After cross-linking with glutaraldehyde, the surface layer gelatin was tightly bound to the diffused gelatin, thereby preventing the surface layer gelatin coating from falling off within 14 days. After gelatin modification, PLGA scaffold demonstrated enhanced hydrophilicity and improved mechanical properties (i.e., increased compression strength and elastic modulus in dry and wet states. Furthermore, a sustained release profile of recombinant human bone morphogenetic protein-2 (rhBMP-2 was achieved in the coated scaffold. The coated scaffold also supported the in vitro attachment, proliferation, and osteogenesis of rabbit bone mesenchymal stem cells (BMSCs, indicating the bioactivity of rhBMP-2. These results collectively demonstrate that the cross-linked-gelatin-coated porous PLGA scaffold incorporating bioactive molecules is a promising candidate for bone tissue regeneration.

  13. Mineralization of three-dimensional osteoblast cultures is enhanced by the interaction of 1α,25-dihydroxyvitamin D3 and BMP2 via two specific vitamin D receptors.

    Science.gov (United States)

    Chen, Jiaxuan; Dosier, Christopher R; Park, Jung Hwa; De, Subhendu; Guldberg, Robert E; Boyan, Barbara D; Schwartz, Zvi

    2016-01-01

    1α,25-Dihydroxyvitamin D3 [1α,25(OH)2D3] and bone morphogenetic protein-2 (BMP2) are both used to stimulate osteoblastic differentiation. 1α,25(OH)2D3 regulates osteoblasts through classical steroid hormone receptor mechanisms and through rapid responses that are mediated by two receptors, the traditional vitamin D receptor (VDR) and protein disulphide isomerase family A member 3 (Pdia3). The interaction between 1α,25(OH)2D3 and BMP2, especially in three-dimensional (3D) culture, and the roles of the two vitamin D receptors in this interaction are not well understood. We treated wild-type (WT), Pdia3-silenced (Sh-Pdia3) and VDR-silenced (Sh-VDR) pre-osteoblastic MC3T3-E1 cells with either 1α,25(OH)2D3, or BMP2, or with 1α,25(OH)2D3 and BMP2 together, and measured osteoblast marker expression in 2D culture and mineralization in a 3D poly(ε-caprolactone)-collagen scaffold model. Quantitative PCR showed that silencing Pdia3 or VDR had a differential effect on baseline expression of osteoblast markers. 1α,25(OH)2D3 + BMP2 caused a synergistic increase in osteoblast marker expression in WT cells, while silencing either Pdia3 or VDR attenuated this effect. 1α,25(OH)2D3 + BMP2 also caused a synergistic increase in Dlx5 in both silenced cell lines. Micro-computed tomography (μCT) showed that the mineralized volume of untreated Sh-Pdia3 and Sh-VDR 3D cultures was greater than that of WT. 1α,25(OH)2D3 reduced mineral in WT and Sh-VDR cultures; BMP2 increased mineralization; and 1α,25(OH)2D3 + BMP2 caused a synergistic increase, but only in WT cultures. SEM showed that mineralized matrix morphology in 3D cultures differed for silenced cells compared to WT cells. These data indicate a synergistic crosstalk between 1α,25(OH)2D3 and BMP2 toward osteogenesis and mineral deposition, involving both VDR and Pdia3.

  14. Interplay between self-assembled structure of bone morphogenetic protein-2 (BMP-2) and osteoblast functions in three-dimensional titanium alloy scaffolds: Stimulation of osteogenic activity.

    Science.gov (United States)

    Nune, K C; Kumar, A; Murr, L E; Misra, R D K

    2016-02-01

    Three-dimensional cellular scaffolds are receiving significant attention in bone tissue engineering to treat segmental bone defects. However, there are indications of lack of significant osteoinductive ability of three-dimensional cellular scaffolds. In this regard, the objective of the study is to elucidate the interplay between bone morphogenetic protein (BMP-2) and osteoblast functions on 3D mesh structures with different porosities and pore size that were fabricated by electron beam melting. Self-assembled dendritic microstructure with interconnected cellular-type morphology of BMP-2 on 3D scaffolds stimulated osteoblast functions including adhesion, proliferation, and mineralization, with prominent effect on 2-mm mesh. Furthermore, immunofluorescence studies demonstrated higher density and viability of osteoblasts on lower porosity mesh structure (2 mm) as compared to 3- and 4-mm mesh structures. Enhanced filopodia cellular extensions with extensive cell spreading was observed on BMP-2 treated mesh structures, a behavior that is attributed to the unique self-assembled structure of BMP-2 that effectively communicates with the cells. The study underscores the potential of BMP-2 in imparting osteoinductive capability to the 3D printed scaffolds.

  15. Enhancement of tendon-to-bone healing after anterior cruciate ligament reconstruction using bone marrow-derived mesenchymal stem cells genetically modified with bFGF/BMP2

    Science.gov (United States)

    Chen, Biao; Li, Bin; Qi, Yong-Jian; Ni, Qu-Bo; Pan, Zheng-Qi; Wang, Hui; Chen, Liao-Bin

    2016-01-01

    Many strategies, including various growth factors and gene transfer, have been used to augment healing after anterior cruciate ligament (ACL) reconstruction. The biological environment regulated by the growth factors during the stage of tendon-bone healing was considered important in controlling the integrating process. The purpose of this study was to evaluate the effects of bone marrow-derived mesenchymal stem cells (BMSCs) genetically modified with bone morphogenetic protein 2 (BMP2) and basic fibroblast growth factor (bFGF) on healing after ACL reconstruction. BMSCs were infected with an adenoviral vector encoding BMP2 (AdBMP2) or bFGF (AdbFGF). Then, the infected BMSCs were surgically implanted into the tendon-bone interface. At 12 weeks postoperatively, the formation of abundant cartilage-like cells, smaller tibial bone tunnel and significantly higher ultimate load and stiffness levels, through histological analysis, micro-computed tomography and biomechanical testing, were observed. In addition, the AdBMP2-plus-AdbFGF group had the smallest bone tunnel and the best mechanical properties among all the groups. The addition of BMP2 or bFGF by gene transfer resulted in better cellularity, new bone formation and higher mechanical property, which contributed to the healing process after ACL reconstruction. Furthermore, the co-application of these two genes was more powerful and efficient than either single gene therapy. PMID:27173013

  16. Sustained release of VH and rhBMP-2 from nanoporous magnesium-zinc-silicon xerogels for osteomyelitis treatment and bone repair.

    Science.gov (United States)

    Li, Fengqian; Wu, Wen; Xiang, Li; Weng, Gan; Hong, Hua; Jiang, Hong; Qian, Jun

    2015-01-01

    Nanoporous magnesium-zinc-silicon (n-MZS) xerogels with a pore size ∼4 nm, a surface area of 718 cm(2)/g, and a pore volume of 1.24 cm(3)/g were synthesized by a sol-gel method. The n-MZS xerogels had high capacity to load vancomycin hydrochloride (VH) and human bone morphogenetic protein-2 (rhBMP-2), after soaking in phosphate buffered saline (PBS) for 24 hours (1.5 and 0.8 mg/g, respectively). Moreover, the n-MZS xerogels exhibited the sustained release of VH and rhBMP-2 as compared with magnesium-zinc-silicon (MZS) xerogels without nanopores (showing a burst release). The VH/rhBMP-2/n-MZS system not only exhibited a good antibacterial property but also promoted the MG63 cell proliferation and differentiation demonstrating good bactericidal activity and cytocompatibility. The results suggested that n-MZS with larger surface area and high pore volume might be a promising carrier for loading and sustained release of VH and rhBMP-2. Hence, the VH/rhBMP-2/n-MZS system might be one of the promising biomaterials for osteomyelitis treatment and bone repair.

  17. Enhancement of tendon-to-bone healing after anterior cruciate ligament reconstruction using bone marrow-derived mesenchymal stem cells genetically modified with bFGF/BMP2.

    Science.gov (United States)

    Chen, Biao; Li, Bin; Qi, Yong-Jian; Ni, Qu-Bo; Pan, Zheng-Qi; Wang, Hui; Chen, Liao-Bin

    2016-01-01

    Many strategies, including various growth factors and gene transfer, have been used to augment healing after anterior cruciate ligament (ACL) reconstruction. The biological environment regulated by the growth factors during the stage of tendon-bone healing was considered important in controlling the integrating process. The purpose of this study was to evaluate the effects of bone marrow-derived mesenchymal stem cells (BMSCs) genetically modified with bone morphogenetic protein 2 (BMP2) and basic fibroblast growth factor (bFGF) on healing after ACL reconstruction. BMSCs were infected with an adenoviral vector encoding BMP2 (AdBMP2) or bFGF (AdbFGF). Then, the infected BMSCs were surgically implanted into the tendon-bone interface. At 12 weeks postoperatively, the formation of abundant cartilage-like cells, smaller tibial bone tunnel and significantly higher ultimate load and stiffness levels, through histological analysis, micro-computed tomography and biomechanical testing, were observed. In addition, the AdBMP2-plus-AdbFGF group had the smallest bone tunnel and the best mechanical properties among all the groups. The addition of BMP2 or bFGF by gene transfer resulted in better cellularity, new bone formation and higher mechanical property, which contributed to the healing process after ACL reconstruction. Furthermore, the co-application of these two genes was more powerful and efficient than either single gene therapy. PMID:27173013

  18. Gene delivery nanocarriers of bioactive glass with unique potential to load BMP2 plasmid DNA and to internalize into mesenchymal stem cells for osteogenesis and bone regeneration

    Science.gov (United States)

    Kim, Tae-Hyun; Singh, Rajendra K.; Kang, Min Sil; Kim, Joong-Hyun; Kim, Hae-Won

    2016-04-01

    The recent development of bioactive glasses with nanoscale morphologies has spurred their specific applications in bone regeneration, for example as drug and gene delivery carriers. Bone engineering with stem cells genetically modified with this unique class of nanocarriers thus holds great promise in this avenue. Here we report the potential of the bioactive glass nanoparticle (BGN) system for the gene delivery of mesenchymal stem cells (MSCs) targeting bone. The composition of 15% Ca-added silica, proven to be bone-bioactive, was formulated into surface aminated mesoporous nanospheres with enlarged pore sizes, to effectively load and deliver bone morphogenetic protein-2 (BMP2) plasmid DNA. The enlarged mesopores were highly effective in loading BMP2-pDNA with an efficiency as high as 3.5 wt% (pDNA w.r.t. BGN), a level more than twice than for small-sized mesopores. The BGN nanocarriers released the genetic molecules in a highly sustained manner (for as long as 2 weeks). The BMP2-pDNA/BGN complexes were effectively internalized to rat MSCs with a cell uptake level of ~73%, and the majority of cells were transfected to express the BMP2 protein. Subsequent osteogenesis of the transfected MSCs was demonstrated by the expression of bone-related genes, including bone sialoprotein, osteopontin, and osteocalcin. The MSCs transfected with BMP2-pDNA/BGN were locally delivered inside a collagen gel to the target calvarium defects. The results showed significantly improved bone regeneration, as evidenced by the micro-computed tomographic, histomorphometric and immunohistochemical analyses. This study supports the excellent capacity of the BGN system as a pDNA-delivery nanocarrier in MSCs, and the engineered system, BMP2-pDNA/BGN with MSCs, may be considered a new promising candidate to advance the therapeutic potential of stem cells through genetic modification, targeting bone defects and diseases.The recent development of bioactive glasses with nanoscale morphologies has

  19. Effect of rhBMP2 and rhTGF-β1 on alkaline phosphatase activity of human dental pulp cells in vitro%rhBMP2和rhTGF-β1联合应用对人牙髓细胞碱性磷酸酶活性的影响

    Institute of Scientific and Technical Information of China (English)

    刘嘉利; 张郁; 王晓方; 汪平

    2000-01-01

    目的:探讨rhBMP2和rhTGF-β1联合应用对人牙髓细胞ALPase活性的影响.方法:采用酶动力学的方法,比较不同浓度rhBMP2和rhTGF-β1单独或联合应用对人牙髓细胞的ALPase活性的影响.结果 :rhBMP2对人牙髓细胞的ALPase活性呈浓度依赖性增强,rhTGF-β1对人牙髓细胞ALPase活性的影响与其本身浓度有关 .当rhTGF-β1浓度为1μg/L与rhBMP2联合应用时, ALPa se活性比rhBMP2单独应用明显增高.结论:rhBMP2、rhTGF-β1单独及联合应用于人牙髓细胞时,对人牙髓细胞的ALPase活性作用不同,其对人牙髓细胞的生理功能可能有调节作用.

  20. Off-label innovation: characterization through a case study of rhBMP-2 for spinal fusion.

    Science.gov (United States)

    Schnurman, Zane; Smith, Michael L; Kondziolka, Douglas

    2016-09-01

    OBJECTIVE Off-label therapies are widely used in clinical practice by spinal surgeons. Some patients and practitioners have advocated for increased regulation of their use, and payers have increasingly questioned reimbursment for off-label therapies. In this study, the authors applied a model that quantifies publication data to analyze the developmental process from initial on-label use to off-label innovation, using as an example recombinant human bone morphogenetic protein 2 (rhBMP-2) because of its wide off-label use. METHODS As a case study of off-label innovation, the developmental patterns of rhBMP-2 from FDA-approved use for anterior lumbar interbody fusion to several of its off-label uses, including posterolateral lumbar fusion, anterior cervical discectomy and fusion, and posterior lumbar interbody fusion/transforaminal lumbar interbody fusion, were evaluated using the "progressive scholarly acceptance" (PSA) model. In this model, PSA is used as an end point indicating acceptance of a therapy or procedure by the relevant scientific community and is reached when the total number of peer-reviewed studies devoted to refinement or improvement of a therapy surpasses the total number assessing initial efficacy. Report characteristics, including the number of patients studied and study design, were assessed in addition to the time to and pattern of community acceptance, and results compared with previous developmental study findings. Disclosures and reported conflicts of interest for all articles were reviewed, and these data were also used in the analysis. RESULTS Publication data indicated that the acceptance of rhBMP-2 off-label therapies occurred more rapidly and with less evidence than previously studied on-label therapies. Additionally, the community appeared to respond more robustly (by rapidly changing publication patterns) to reports of adverse events than to new questions of efficacy. CONCLUSIONS The development of off-label therapies, including the

  1. Effects of BMP-2 and dexamethasone on osteogenic differentiation of rat dental follicle progenitor cells seeded on three-dimensional beta-TCP

    Energy Technology Data Exchange (ETDEWEB)

    Xu Lulu; Jin Zuolin; Duan Yinzhong [Department of Orthodontics, Stomatological College, Fourth Military Medical University, Xi' an 710032 (China); Liu Hongchen; Wang Dongsheng; E Lingling [Department of Stomatology, China PLA General Hospital, Beijing 100853 (China); Xu Lin, E-mail: jinzuolin88@yahoo.com.c, E-mail: duanyinzhong@yahoo.com.c [Department of Stomatology, the First Hospital of PLA, Lanzhou 730000 (China)

    2009-12-15

    The aim of this study was to investigate the effects of BMP-2 and dexamethasone (Dex) on osteogenic differentiation of rat dental follicle progenitor cells (RDFCs) seeded on three-dimensional beta-TCP. The alkaline phosphatase (ALP), the calcium and phosphonium, the osteocalcin in media of the third passage RDFCs on biomaterial beta-TCP after 1-3, 3-7, 7-14 days of culture were examined respectively. The growth of cells on the scaffolds was observed by scanning electron microscope (SEM) after 3, 7 days of culture and by implanting in the backs of severe combined immunodeficient (SCID) mice for bone regeneration. The third passage RDFCs could be seen adhered, extended and proliferated on the beta-TCP by scanning electron microscopy. The ALP activity, the calcium and phosphoniums and the osteocalcin content of dexamethasone (10{sup -8} M) or/and BMP-2 (100 ng ml{sup -1}) were significantly higher than their existence in the control group. They were the significantly highest among four groups after joint application of BMP-2 and dexamethasone. After 8 weeks of implantation, the percentage of the new bones formed area in the RDFCs+beta-TCP+BMP-2+Dex group was significantly higher than that in the RDFCs+beta-TCP+BMP-2 group. In contrast, beta-TCP, RDFCs+beta-TCP+Dex and control constructs lacked new bone formation by histological staining and histomorphometric analysis. The BMP-2+Dex could significantly promote osteogenic differentiation of RDFCs on beta-TCP. beta-TCP supported fast cellular adhesion, proliferation and differentiation of RDFCs. The feasibility of its application in periodontal tissue engineering was also proved.

  2. Effects of BMP-2 and dexamethasone on osteogenic differentiation of rat dental follicle progenitor cells seeded on three-dimensional β-TCP

    International Nuclear Information System (INIS)

    The aim of this study was to investigate the effects of BMP-2 and dexamethasone (Dex) on osteogenic differentiation of rat dental follicle progenitor cells (RDFCs) seeded on three-dimensional β-TCP. The alkaline phosphatase (ALP), the calcium and phosphonium, the osteocalcin in media of the third passage RDFCs on biomaterial β-TCP after 1-3, 3-7, 7-14 days of culture were examined respectively. The growth of cells on the scaffolds was observed by scanning electron microscope (SEM) after 3, 7 days of culture and by implanting in the backs of severe combined immunodeficient (SCID) mice for bone regeneration. The third passage RDFCs could be seen adhered, extended and proliferated on the β-TCP by scanning electron microscopy. The ALP activity, the calcium and phosphoniums and the osteocalcin content of dexamethasone (10-8 M) or/and BMP-2 (100 ng ml-1) were significantly higher than their existence in the control group. They were the significantly highest among four groups after joint application of BMP-2 and dexamethasone. After 8 weeks of implantation, the percentage of the new bones formed area in the RDFCs+β-TCP+BMP-2+Dex group was significantly higher than that in the RDFCs+β-TCP+BMP-2 group. In contrast, β-TCP, RDFCs+β-TCP+Dex and control constructs lacked new bone formation by histological staining and histomorphometric analysis. The BMP-2+Dex could significantly promote osteogenic differentiation of RDFCs on β-TCP. β-TCP supported fast cellular adhesion, proliferation and differentiation of RDFCs. The feasibility of its application in periodontal tissue engineering was also proved.

  3. Diabetes mellitus affects the biomechanical function of the callus and the expression of TGF-beta1 and BMP2 in an early stage of fracture healing

    OpenAIRE

    Xu, M. T.; Sun, S.; Zhang, L.; Xu, F.; Du, S.L.; Zhang, X. D.; Wang, D. W.

    2015-01-01

    Transforming growth factor beta 1 (TGF-β1) and bone morphogenetic protein-2 (BMP-2) are important regulators of bone repair and regeneration. In this study, we examined whether TGF-β1 and BMP-2 expressions were delayed during bone healing in type 1 diabetes mellitus. Tibial fractures were created in 95 diabetic and 95 control adult male Wistar rats of 10 weeks of age. At 1, 2, 3, 4, and 5 weeks after fracture induction, five rats were sacrificed from each group. The expressions of TGF-β1 and ...

  4. Regulació de la migració cel·lular induïda per BMP-2

    OpenAIRE

    Gamell Fullà, Cristina

    2009-01-01

    EN CATALÀ :Les proteïnes morfogenètiques òssies (BMPs) són membres de la superfamília del TGF-beta i s'ha demostrat que participen en la determinació i especificació de varis teixits i òrgans durant el desenvolupament dels vertebrats i que regulen la proliferació, l'apoptosi i la diferenciació de múltiples tipus cel·lulars. Les BMPs van ser originàriament identificades per a la seva habilitat d'induir la formació ectòpica d'os i entre ells, BMP-2, -4 and -7 resulten essencials perquè tingui l...

  5. Differential expression of Bmp2, Bmp4 and Bmp3 in embryonic development of mouse anterior and posterior palate

    Institute of Scientific and Technical Information of China (English)

    NIE Xu-guang

    2005-01-01

    Background The palate is differently regulated and developed along the anterior-posterior axis. The Bmp signal pathway plays a crucial role in palatogenesis. Conditioned-inactivation of Bmp type I receptor Alk2 or Alk3 in the neural crest or craniofacial region leads to palatal cleft in mice. However, how different Bmp members are involved in palatogenesis remains to be elucidated. In the present study, mRNA expression patterns of Bmp2, Bmp3 and Bmp4 in the developing anterior and posterior palates were examined and compared, focusing on the fusion stage. Methods To detect the expression of Bmp mRNA, antisense riboprobes were synthesized by in vitro transcription. Radioactive in situ hybridization was performed on sagital and coronal sections of mice head from E13 to E18. Results The expression of these Bmps were developmentally regulated in the anterior and posterior palates prior to, during and after palatal fusion. During palatal fusion, Bmp4 expression shifted from the anterior to the posterior palate, Bmp2 was highly expressed in both the anterior and posterior palates in this process, whereas Bmp3 was only localized in the posterior palate. They showed generally non-overlapping pattern in their expression domains. Thereafter, their expression was detected in both the anterior and posterior palates regulating osteogenesis and myogenesis respectively. Conclusions Bmp signalling is involved in palatogenesis in multiple stages and has multiple roles in regulating anterior and posterior palatal development. Disturbances of Bmp signalling during palatogenesis might be a possible mechanism of cleft palate.

  6. The origin of bmp16, a novel Bmp2/4 relative, retained in teleost fish genomes

    Directory of Open Access Journals (Sweden)

    Meyer Axel

    2009-12-01

    Full Text Available Abstract Background Whole genome sequences have allowed us to have an overview of the evolution of gene repertoires. The target of the present study, the TGFβ superfamily, contains many genes involved in vertebrate development, and provides an ideal system to explore the relationships between evolution of gene repertoires and that of developmental programs. Results As a result of a bioinformatic survey of sequenced vertebrate genomes, we identified an uncharacterized member of the TGFβ superfamily, designated bmp16, which is confined to teleost fish species. Our molecular phylogenetic study revealed a high affinity of bmp16 to the Bmp2/4 subfamily. Importantly, further analyses based on the maximum-likelihood method unambiguously ruled out the possibility that this teleost-specific gene is a product of teleost-specific genome duplication. This suggests that the absence of a bmp16 ortholog in tetrapods is due to a secondary loss. In situ hybridization showed embryonic expression of the zebrafish bmp16 in the developing swim bladder, heart, tail bud, and ectoderm of pectoral and median fin folds in pharyngula stages, as well as gut-associated expression in 5-day embryos. Conclusion Comparisons of expression patterns revealed (1 the redundancy of bmp16 expression with its homologs in presumably plesiomorphic expression domains, such as the fin fold, heart, and tail bud, which might have permitted its loss in the tetrapod lineage, and (2 the loss of craniofacial expression and gain of swim bladder expression of bmp16 after the gene duplication between Bmp2, -4 and -16. Our findings highlight the importance of documenting secondary changes of gene repertoires and expression patterns in other gene families.

  7. Effects of rhBMP-2 on Sandblasted and Acid Etched Titanium Implant Surfaces on Bone Regeneration and Osseointegration: Spilt-Mouth Designed Pilot Study

    Directory of Open Access Journals (Sweden)

    Nam-Ho Kim

    2015-01-01

    Full Text Available This study was conducted to evaluate effects of rhBMP-2 applied at different concentrations to sandblasted and acid etched (SLA implants on osseointegration and bone regeneration in a bone defect of beagle dogs as pilot study using split-mouth design. Methods. For experimental groups, SLA implants were coated with different concentrations of rhBMP-2 (0.1, 0.5, and 1 mg/mL. After assessment of surface characteristics and rhBMP-2 releasing profile, the experimental groups and untreated control groups (n = 6 in each group, two animals in each group were placed in split-mouth designed animal models with buccal open defect. At 8 weeks after implant placement, implant stability quotients (ISQ values were recorded and vertical bone height (VBH, mm, bone-to-implant contact ratio (BIC, %, and bone volume (BV, % in the upper 3 mm defect areas were measured. Results. The ISQ values were highest in the 1.0 group. Mean values of VBH (mm, BIC (%, and BV (% were greater in the 0.5 mg/mL and 1.0 mg/mL groups than those in 0.1 and control groups in buccal defect areas. Conclusion. In the open defect area surrounding the SLA implant, coating with 0.5 and 1.0 mg/mL concentrations of rhBMP-2 was more effective, compared with untreated group, in promoting bone regeneration and osseointegration.

  8. Improved Bone Formation in Osteoporotic Rabbits with the Bone Morphogenetic Protein-2 (rhBMP-2 Coated Titanium Screws Which Were Coated By Using Plasma Polymerization Technique

    Directory of Open Access Journals (Sweden)

    Salih Gulsen

    2014-06-01

    Full Text Available Delaying of bone fusion in osteoporotic patients underwent spinal stabilization surgery leads to screw loosening, and this causes pseudoarticulation, mobility and fibrosis at vertebral segments. To prevent these complications, the screws coated with recombinant bone morphogenetic protein-2 (rhBMP-2 could be used. To verify this hypothesis, we coated 5 Titanium screws with rhBMP-2 using plasma polymerization method, and also used 10 uncoated screws for making comparison between coated and uncoated screws in different groups. And 15 skeletally mature white New Zealand female rabbits were assigned into three different groups: Group 1(N = 5: No osteoporosis induction and insertion of uncoated Titanium screw into right sacrum of each rabbit in group 1; group 2 (N = 5: Osteoporosis induction and insertion of uncoated Titanium screw into right sacrum of each rabbit in group 2; group 3 (N = 5 rhBMP-2 coated Titanium screw inserted into right sacrum of each rabbit in group 3. In summary, using of these coated screws provides new bone formation, but causes less fibrosis and less inflammation than uncoated screws at the interface between the coated screw and bone. Then the plasma polymerization technique provides controlled releasing of rhBMP-2 from the screw to the bone tissue in osteoporotic rabbits.

  9. Intestinal Mucosal Barrier Is Injured by BMP2/4 via Activation of NF-κB Signals after Ischemic Reperfusion

    Directory of Open Access Journals (Sweden)

    Kang Chen

    2014-01-01

    Full Text Available Intestinal ischemic reperfusion (I/R can cause dysfunction of the intestinal mucosal barrier; however, the mechanism of the intestinal mucosal barrier dysfunction caused by I/R remains unclear. In this study, using intestinal epithelial cells under anaerobic cultivation and an in vivo rat intestinal I/R model, we found that hypoxia and I/R increased the expression of BMP2/4 and upregulated BMP type Ia receptor and BMP type II receptor expression. We also found that exogenous BMP2/4 can activate the ERK and AKT signaling pathways in rat small intestine (IEC-6 cells, thereby activating NF-κB signaling, which leads to increased levels of inflammatory factors, such as TNF-α and IL-6. Furthermore, recombinant BMP2/4 decreased the expression of the tight junction protein occludin via the activation of the NF-κB pathway; these effects were abolished by treatment with the BMP-specific antagonist noggin or the NF-κB inhibitor pyrrolidine dithiocarbamate (PDTC. All these factors can destroy the intestinal mucosal barrier, thereby leading to weaker barrier function. On the basis of these data, we conclude that BMP2/4 may act as the pathogenic basis for intestinal mucosal barrier dysfunction when the intestines suffer an I/R injury. Our results provide background for the development pharmacologic interventions in the management of I/R injury.

  10. Effects of rhBMP-2 on Sandblasted and Acid Etched Titanium Implant Surfaces on Bone Regeneration and Osseointegration: Spilt-Mouth Designed Pilot Study

    Science.gov (United States)

    Kim, Nam-Ho; Lee, So-Hyoun; Ryu, Jae-Jun; Choi, Kyung-Hee; Huh, Jung-Bo

    2015-01-01

    This study was conducted to evaluate effects of rhBMP-2 applied at different concentrations to sandblasted and acid etched (SLA) implants on osseointegration and bone regeneration in a bone defect of beagle dogs as pilot study using split-mouth design. Methods. For experimental groups, SLA implants were coated with different concentrations of rhBMP-2 (0.1, 0.5, and 1 mg/mL). After assessment of surface characteristics and rhBMP-2 releasing profile, the experimental groups and untreated control groups (n = 6 in each group, two animals in each group) were placed in split-mouth designed animal models with buccal open defect. At 8 weeks after implant placement, implant stability quotients (ISQ) values were recorded and vertical bone height (VBH, mm), bone-to-implant contact ratio (BIC, %), and bone volume (BV, %) in the upper 3 mm defect areas were measured. Results. The ISQ values were highest in the 1.0 group. Mean values of VBH (mm), BIC (%), and BV (%) were greater in the 0.5 mg/mL and 1.0 mg/mL groups than those in 0.1 and control groups in buccal defect areas. Conclusion. In the open defect area surrounding the SLA implant, coating with 0.5 and 1.0 mg/mL concentrations of rhBMP-2 was more effective, compared with untreated group, in promoting bone regeneration and osseointegration. PMID:26504807

  11. Recombinant human bone morphogenetic protein induces bone formation

    International Nuclear Information System (INIS)

    The authors have purified and characterized active recombinant human bone morphogenetic protein (BMP) 2A. Implantation of the recombinant protein in rats showed that a single BMP can induce bone formation in vivo. A dose-response and time-course study using the rat ectopic bone formation assay revealed that implantation of 0.5-115 μg of partially purified recombinant human BMP-2A resulted in cartilage by day 7 and bone formation by day 14. The time at which bone formation occurred was dependent on the amount of BMP-2A implanted; at high doses bone formation could be observed at 5 days. The cartilage- and bone-inductive activity of the recombinant BMP-2A is histologically indistinguishable from that of bone extracts. Thus, recombinant BMP-2A has therapeutic potential to promote de novo bone formation in humans

  12. Mesoporous calcium–silicon xerogels with mesopore size and pore volume influence hMSC behaviors by load and sustained release of rhBMP-2

    Directory of Open Access Journals (Sweden)

    Song W

    2015-03-01

    Full Text Available Wenhua Song,1,* Xiangde Li,1,* Jun Qian,1 Guoyu Lv,2 Yonggang Yan,2 Jiacan Su,3 Jie Wei1 1Key Laboratory for Ultrafine Materials of Ministry of Education, East China University of Science and Technology, Shanghai, People’s Republic of China; 2College of Physical Science and Technology, Sichuan University, Chengdu, People’s Republic of China; 3Changhai Hospital, Second Military Medical University, Shanghai, People’s Republic of China *These authors contributed equally to this paper Abstract: Mesoporous calcium–silicon xerogels with a pore size of 15 nm (MCS-15 and pore volume of 1.43 cm3/g were synthesized by using 1,3,5-mesitylene (TMB as the pore-expanding agent. The MCS-15 exhibited good degradability with the weight loss of 50 wt% after soaking in Tris-HCl solution for 56 days, which was higher than the 30 wt% loss shown by mesoporous calcium–silicon xerogels with a pore size of 4 nm (MCS-4. The pore size and pore volume of MCS-15 had significant influences on load and release of recombinant human bone morphogenetic protein-2 (rhBMP-2. The MCS-15 had a higher capacity to encapsulate a large amount of rhBMP-2; it could adsorb 45 mg/g of rhBMP-2 in phosphate-buffered saline after 24 hours, which was more than twice that with MCS-4 (20 mg/g. Moreover, the MCS-15 system exhibited sustained release of rhBMP-2 as compared with MCS-4 system (showing a burst release. The MCS-15/rhBMP-2 system could promote the proliferation and differentiation of human mesenchymal stem cells, showing good cytocompatibility and bioactivity. The results indicated that MCS-15, with larger mesopore size and higher pore volume, might be a promising carrier for loading and sustained release of rhBMP-2, which could be used as bone repair material with built-in osteoinduction function in bone reconstruction. Keywords: mesoporous calcium–silicon xerogels, pore size, pore volume, load-release, rhBMP-2

  13. Dual Delivery of BMP-2 and bFGF from a New Nano-Composite Scaffold, Loaded with Vascular Stents for Large-Size Mandibular Defect Regeneration

    Directory of Open Access Journals (Sweden)

    Hang Zhao

    2013-06-01

    Full Text Available The aim of this study was to investigate the feasibility and advantages of the dual delivery of bone morphogenetic protein-2 (BMP-2 and basic fibroblast growth factor (bFGF from nano-composite scaffolds (PLGA/PCL/nHA loaded with vascular stents (PLCL/Col/nHA for large bone defect regeneration in rabbit mandibles. Thirty-six large bone defects were repaired in rabbits using engineering bone composed of allogeneic bone marrow mesenchymal stem cells (BMSCs, bFGF, BMP-2 and scaffolds composed of PLGA/PCL/nHA loaded with PLCL/Col/nHA. The experiments were divided into six groups: BMSCs/bFGF/BMP-2/scaffold, BMSCs/BMP-2/scaffold, BMSCs/bFGF/scaffold, BMSCs/scaffold, scaffold alone and no treatment. Sodium alginate hydrogel was used as the carrier for BMP-2 and bFGF and its features, including gelling, degradation and controlled release properties, was detected by the determination of gelation and degradation time coupled with a controlled release study of bovine serum albumin (BSA. AlamarBlue assay and alkaline phosphatase (ALP activity were used to evaluate the proliferation and osteogenic differentiation of BMSCs in different groups. X-ray and histological examinations of the samples were performed after 4 and 12 weeks post-implantation to clarify new bone formation in the mandible defects. The results verified that the use of sodium alginate hydrogel as a controlled release carrier has good sustained release ability, and the combined application of bFGF and BMP-2 could significantly promote the proliferation and osteogenic differentiation of BMSCs (p < 0.05 or p < 0.01. In addition, X-ray and histological examinations of the samples exhibited that the dual release group had significantly higher bone formation than the other groups. The above results indicate that the delivery of both growth factors could enhance new bone formation and vascularization compared with delivery of BMP-2 or bFGF alone, and may supply a promising way of repairing large

  14. Sustained release of VH and rhBMP-2 from nanoporous magnesium–zinc–silicon xerogels for osteomyelitis treatment and bone repair

    Directory of Open Access Journals (Sweden)

    Li FQ

    2015-06-01

    Full Text Available Fengqian Li,1,* Wen Wu,2,* Li Xiang,1 Gan Weng,1 Hua Hong,3 Hong Jiang,4 Jun Qian31Department of Pharmacy, Shanghai Xuhui Dahua Hospital, 2Department of Orthopaedics, Ninth People’s Hospital, School of Medicine, Shanghai Jiaotong University, 3Key Laboratory for Ultrafine Materials of Ministry of Education, East China University of Science and Technology, 4School of Materials Science and Engineering, University of Shanghai for Science and Technology, Shanghai, People’s Republic of China*Co-first authors contributed equally to this workAbstract: Nanoporous magnesium–zinc–silicon (n-MZS xerogels with a pore size of ~4 nm, a surface area of 718 cm2/g, and a pore volume of 1.24 cm3/g were synthesized by a sol–gel method. The n-MZS xerogels had high capacity to load vancomycin hydrochloride (VH and human bone morphogenetic protein-2 (rhBMP-2, after soaking in phosphate buffered saline (PBS for 24 hours (1.5 and 0.8 mg/g, respectively. Moreover, the n-MZS xerogels exhibited the sustained release of VH and rhBMP-2 as compared with magnesium–zinc–silicon (MZS xerogels without nanopores (showing a burst release. The VH/rhBMP-2/n-MZS system not only exhibited a good antibacterial property but also promoted the MG63 cell proliferation and differentiation demonstrating good bactericidal activity and cytocompatibility. The results suggested that n-MZS with larger surface area and high pore volume might be a promising carrier for loading and sustained release of VH and rhBMP-2. Hence, the VH/rhBMP-2/n-MZS system might be one of the promising biomaterials for osteomyelitis treatment and bone repair.Keywords: nanoporous xerogels, sustained release, drugs, osteomyelitis, bone regeneration, bactericidal activity, cytocompatibility

  15. Transforming growth factor β1 inhibits bone morphogenic protein (BMP-2 and BMP-7 signaling via upregulation of Ski-related novel protein N (SnoN: possible mechanism for the failure of BMP therapy?

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    Ehnert Sabrina

    2012-09-01

    Full Text Available Abstract Background Bone morphogenic proteins (BMPs play a key role in bone formation. Consequently, it was expected that topical application of recombinant human (rhBMP-2 and rhBMP-7 would improve the healing of complex fractures. However, up to 36% of fracture patients do not respond to this therapy. There are hints that a systemic increase in transforming growth factor β1 (TGFβ1 interferes with beneficial BMP effects. Therefore, in the present work we investigated the influence of rhTGFβ1 on rhBMP signaling in primary human osteoblasts, with the aim of more specifically delineating the underlying regulatory mechanisms. Methods BMP signaling was detected by adenoviral Smad-binding-element-reporter assays. Gene expression was determined by reverse transcription polymerase chain reaction (RT-PCR and confirmed at the protein level by western blot. Histone deacetylase (HDAC activity was determined using a test kit. Data sets were compared by one-way analysis of variance. Results Our findings showed that Smad1/5/8-mediated rhBMP-2 and rhBMP-7 signaling is completely blocked by rhTGFβ1. We then investigated expression levels of genes involved in BMP signaling and regulation (for example, Smad1/5/8, TGFβ receptors type I and II, noggin, sclerostin, BMP and activin receptor membrane bound inhibitor (BAMBI, v-ski sarcoma viral oncogene homolog (Ski, Ski-related novel protein N (SnoN and Smad ubiquitination regulatory factors (Smurfs and confirmed the expression of regulated genes at the protein level. Smad7 and SnoN were significantly induced by rhTGFβ1 treatment while expression of Smad1, Smad6, TGFβRII and activin receptor-like kinase 1 (Alk1 was reduced. Elevated SnoN expression was accompanied by increased HDAC activity. Addition of an HDAC inhibitor, namely valproic acid, fully abolished the inhibitory effect of rhTGFβ1 on rhBMP-2 and rhBMP-7 signaling. Conclusions rhTGFβ1 effectively blocks rhBMP signaling in osteoblasts. As possible

  16. Bone morphogenetic protein 2-induced human dental pulp cell differentiation involves p38 mitogen-activated protein kinase-activated canonical WNT pathway

    Institute of Scientific and Technical Information of China (English)

    Jing Yang; Ling Ye; Tian-Qian Hui; Dong-Mei Yang; Ding-Ming Huang; Xue-Dong Zhou; Jeremy J Mao; Cheng-Lin Wang

    2015-01-01

    Both bone morphogenetic protein 2 (BMP2) and the wingless-type MMTV integration site (WNT)/b-catenin signalling pathway play important roles in odontoblast differentiation and dentinogenesis. Cross-talk between BMP2 and WNT/b-catenin in osteoblast differentiation and bone formation has been identified. However, the roles and mechanisms of the canonical WNT pathway in the regulation of BMP2 in dental pulp injury and repair remain largely unknown. Here, we demonstrate that BMP2 promotes the differentiation of human dental pulp cells (HDPCs) by activating WNT/b-catenin signalling, which is further mediated by p38 mitogen-activated protein kinase (MAPK) in vitro. BMP2 stimulation upregulated the expression of b-catenin in HDPCs, which was abolished by SB203580 but not by Noggin or LDN193189. Furthermore, BMP2 enhanced cell differentiation, which was not fully inhibited by Noggin or LDN193189. Instead, SB203580 partially blocked BMP2-induced b-catenin expression and cell differentiation. Taken together, these data suggest a possible mechanism by which the elevation of b-catenin resulting from BMP2 stimulation is mediated by the p38 MAPK pathway, which sheds light on the molecular mechanisms of BMP2-mediated pulp reparative dentin formation.

  17. BMP-2基因修饰自体BMSCs移植促进兔下颌骨牵张成骨新骨形成的实验研究%EXPERIMENTAL STUDY ON TRANSPLANTATION OF BMP-2 GENE TRANSFECTED AUTOGENOUS BONE MESENCHYMAL STEM CELLS FOR PROMOTING BONE REGENERATION IN RABBIT MANDIBULAR DISTRACTION OSTEOGENESIS

    Institute of Scientific and Technical Information of China (English)

    黄旋平; 周诺; 江献芳; 杨媛媛; 李华; 谢庆条

    2012-01-01

    目的:检测骨形态发生蛋白-2(BMP-2)基因mRNA及其蛋白的表达,探讨BMP-2基因修饰自体骨髓间充质干细胞(BMSCs)移植对兔下颌骨牵张成骨新骨形成的促进作用.方法:取新西兰白兔36只随机分为3组,每组12只.建立牵张成骨动物模型,在固定期第2天,实验组于牵张间隙注射200 μL的BMP-2基因修饰的自体BMSCs液;对照组注射等量自体BMSCs液;空白组注射等量生理盐水.分别于固定2,6周通过逆转录多聚酶链式反应(RT-PCR)、免疫组化等手段检测BMP-2基因mRNA及其蛋白的表达情况.结果:实验组牵张间隙新生骨组织均可见BMP-2基因mRNA和其蛋白强阳性表达.结论:BMP-2基因修饰的自体BMSCs移植能有效促进兔下颌骨牵张成骨新骨形成.%Objective:To examine the expressions of both bone morphogenetic protein-2 (BMP-2) gene mR-NA and related proteins and investigate the promotive effect of transplantation of BMP-2 gene transfected autogenous bone mesenchymal stem cells on bone regeneration in rabbit mandibular distraction osteogene-sis. Methods: Thirty-six New Zealand's white rabbits were randomly divided into three groups with twelve in each. All objects -were prepared into distraction osteogenesis surgical model on right mandibles. On the 2nd day of consolidation, experimental, control, and blank groups -were injected -with the same amount of 200 juL of the solution with BMP-2 gene transfected autogenous bone mesenchymal stem cells, the solution with autogenous bone mesenchymal stem cells, and physiological saline at distraction gap, respectively. The expressions of BMP-2 mRNA and related proteins -were examined by RT-PCR and immunohistochem-istry at the ends of the 2nd and 6th -week consolidations, respectively. Results: Strongly positive expression of both BMP-2 gene mRNA and related proteins were confirmed on regenerated bone in distraction gap. Conclusion: The transplantation of BMP-2 gene transfected autogenous bone

  18. Wnt1 and BMP2: two factors recruiting multipotent neural crest progenitors isolated from adult bone marrow.

    Science.gov (United States)

    Glejzer, A; Laudet, E; Leprince, P; Hennuy, B; Poulet, C; Shakhova, O; Sommer, L; Rogister, B; Wislet-Gendebien, S

    2011-06-01

    Recent studies have shown that neural crest-derived progenitor cells can be found in diverse mammalian tissues including tissues that were not previously shown to contain neural crest derivatives, such as bone marrow. The identification of those "new" neural crest-derived progenitor cells opens new strategies for developing autologous cell replacement therapies in regenerative medicine. However, their potential use is still a challenge as only few neural crest-derived progenitor cells were found in those new accessible locations. In this study, we developed a protocol, based on wnt1 and BMP2 effects, to enrich neural crest-derived cells from adult bone marrow. Those two factors are known to maintain and stimulate the proliferation of embryonic neural crest stem cells, however, their effects have never been characterized on neural crest cells isolated from adult tissues. Using multiple strategies from microarray to 2D-DIGE proteomic analyses, we characterized those recruited neural crest-derived cells, defining their identity and their differentiating abilities. PMID:20976520

  19. Efficacy of rhBMP-2 loaded PCL/PLGA/β-TCP guided bone regeneration membrane fabricated by 3D printing technology for reconstruction of calvaria defects in rabbit

    International Nuclear Information System (INIS)

    We successfully fabricated a three-dimensional (3D) printing-based PCL/PLGA/β-TCP guided bone regeneration (GBR) membrane that slowly released rhBMP-2. To impregnate the GBR membrane with intact rhBMP-2, collagen solution encapsulating rhBMP-2 (5 µg ml−1) was infused into pores of a PCL/PLGA/β-TCP membrane constructed using a 3D printing system with four dispensing heads. In a release profile test, sustained release of rhBMP-2 was observed for up to 28 d. To investigate the efficacy of the GBR membrane on bone regeneration, PCL/PLGA/β-TCP membranes with or without rhBMP-2 were implanted in an 8 mm calvaria defect of rabbits. Bone formation was evaluated at weeks 4 and 8 histologically and histomorphometrically. A space making ability of the GBR membrane was successfully maintained in both groups, and significantly more new bone was formed at post-implantation weeks 4 and 8 by rhBMP-2 loaded GBR membranes. Interestingly, implantation with rhBMP-2 loaded GBR membranes led to almost entire healing of calvaria defects within 8 weeks. (paper)

  20. Efficacy of rhBMP-2 loaded PCL/PLGA/β-TCP guided bone regeneration membrane fabricated by 3D printing technology for reconstruction of calvaria defects in rabbit.

    Science.gov (United States)

    Shim, Jin-Hyung; Yoon, Min-Chul; Jeong, Chang-Mo; Jang, Jinah; Jeong, Sung-In; Cho, Dong-Woo; Huh, Jung-Bo

    2014-11-10

    We successfully fabricated a three-dimensional (3D) printing-based PCL/PLGA/β-TCP guided bone regeneration (GBR) membrane that slowly released rhBMP-2. To impregnate the GBR membrane with intact rhBMP-2, collagen solution encapsulating rhBMP-2 (5 µg ml(-1)) was infused into pores of a PCL/PLGA/β-TCP membrane constructed using a 3D printing system with four dispensing heads. In a release profile test, sustained release of rhBMP-2 was observed for up to 28 d. To investigate the efficacy of the GBR membrane on bone regeneration, PCL/PLGA/β-TCP membranes with or without rhBMP-2 were implanted in an 8 mm calvaria defect of rabbits. Bone formation was evaluated at weeks 4 and 8 histologically and histomorphometrically. A space making ability of the GBR membrane was successfully maintained in both groups, and significantly more new bone was formed at post-implantation weeks 4 and 8 by rhBMP-2 loaded GBR membranes. Interestingly, implantation with rhBMP-2 loaded GBR membranes led to almost entire healing of calvaria defects within 8 weeks.

  1. The effects of substrate-streching strain on the BMP-2 mRNA expression in three kinds of mouse cell lines%基底拉伸应变对小鼠三种骨组织细胞BMP-2 mRNA表达的影响

    Institute of Scientific and Technical Information of China (English)

    闫玉仙; 宋梅; 郭春; 郭勇; 宫元伟; 李瑞欣; 张西正

    2010-01-01

    目的 研究基底拉伸应变对小鼠成骨细胞系MC3T3-E1、破骨细胞系RAW264.7及骨细胞MLO-Y4三种细胞BMP-2 mRNA表达的影响.方法 三种细胞随机分为0 με、1 000 με、1 500 με、2 000 με、2 500 με和5 000 με组,最佳拉伸时间和周期为1次/d,每次1 h,连续3 d,频率为0.5 Hz.采用卫生装备研究所自行设计研制的四点弯曲装置对小鼠三种细胞进行拉伸加载.采用RT-PCR技术分别研究不同应变对小鼠三种细胞BMP-2 mRNA表达.结果 MC3T3-E1细胞RT-PCR结果显示:1 500 με、2 000 με组和2 500 με组与0 με组相比BMP-2 mRNA表达显著增强(P<0.01);5 000 με组与0 με组相比BMP-2 mRNA表达显著降低(P<0.01);RAW264.7细胞RT-PCR结果显示:1 500 με、2 000 με组和2 500 με组与0 με组相比BMP-2 mRNA表达显著降低(P<0.01);5 000με组与0 με组相比BMP-2 mRNA表达显著降低(P<0.01);MLO-Y4细胞BMP2基因表达结果与MC3T3-E1一致.结论 ①BMP-2在成骨细胞系MC3T3-E1、破骨细胞系RAW-264.7及骨细胞系MLO-Y4三种细胞中均有表达;②1 500 με、2 000 με、2 500 με三种生理剂量的拉伸应变可以显著增加MC3T3-E1、MLO-Y4 细胞BMP-2的表达,并呈剂量依赖性,超生理剂量5 000 με可以显著降低MC3T3-E1、MLO-Y4细胞BMP-2的表达;③相同的力学拉伸作用条件下,BMP-2在RAW-264.7细胞中表达与MC3T3-E1、MLO-Y4细胞的表达趋势相反.

  2. Multifunctional Thin Film Biomatrice Biosensor in a Degradable Scaffold Containing Bone Morphogenetic Protein-2 (BMP-2) for Controlled Release in Skeletal Tissue Engineering

    Science.gov (United States)

    McDaniel, Harvey; Lomax, Linda

    2001-03-01

    Bone morphonogenetic proteins (BMP-2) have been under investigation for three decades. Deminerialized bone and extracts of deminerialized bone are o steoinductive with a temporal sequence of bone induction. Native and recombi nant BMP's have shown the ability, thru growth and differentiative factors t o induce de novo bone formation both invitro and invivo. Their principle fun ction is to induce transformation of undifferentiated mesenchymal cells into osteoblasts. Native and recombinant BMP's, when purified and used without carrier disp erse after implantation and exert no effect on bone induction. The delivery system provides the missing component to successsfully applying osteogenic p roteins for clinical need. Biological and physio-chemical properties are str ictly adhered tofor a successful delivery system. The BMP delivery system ca rrier for osteo inductive payload provided; 1)non tumorgenic genecity, 2) no n immunogenecity, 3) water insoluble, 4) biosorbability with predictable enz ymatic degradation, and 5) an optimized surface for compatibility, cell migr ation and attachment with a negative surface change that encouraged target c ell attachment. Being a controlled Release System, it binded the proteins wi th predictible BMP released kinetics. Porosity with interconnecting voids pr otected the BMP from noon specific proteolysis and promoted rapid vascular a nd mesenchymal invasion. Far wide ranging clinical applications of mechanica l and biofunctional requirements were met with the BMP delivery system. Cohe sion and malleability were reqiured forcontour augmentation, and reconstruct ion of the discontinuity defects, prevented dislocation and retained the sha pe and bone replaced the system. Biological systems have elastic activity associated with them. The activi ty was current associated with a time dependant biological/biochemical react ion (enzymic activity). Bioelectric phoenomena associated with charged molec ules in a biologic structure caused

  3. Posterior tooth replacement with dental implants in sites augmented with rhBMP-2 at time of extraction--a case series.

    Science.gov (United States)

    Levin, Barry P; Tawil, Peter

    2012-02-01

    This case series demonstrates seven molar-site implants placed in six consecutively treated patients. All sites were augmented with rhBMP-2 (1.50 mg/cc)/ACS (recombinant human Bone Morphogenetic Protein-2/Absorbable Collagen Sponge) at extraction to regenerate bone-facilitating implant placement. In four patients, osteotomies were initiated with trephines to evaluate qualitatively for native bone and for the absence of residual ACS. All sites facilitated implant placement after augmentation. All seven implants achieved primary stabilization and were functionally loaded. No implants were lost or developed complications. It can be concluded that augmenting molar extraction sockets with rhBMP-2/ACS can allow standard implant placement in the posterior dentition that is capable of withstanding a functional load.

  4. Self-assembled Biodegradable Nanoparticles and Polysaccharides as Biomimetic ECM Nanostructures for the Synergistic effect of RGD and BMP-2 on Bone Formation.

    Science.gov (United States)

    Wang, Zhenming; Dong, Li; Han, Lu; Wang, Kefeng; Lu, Xiong; Fang, Liming; Qu, Shuxin; Chan, Chun Wai

    2016-01-01

    Producing biomimetic extracellular matrix (ECM) is an effective approach to improve biocompatibility of medical devices. In this study, biomimetic ECM nanostructures are constructed through layer-by-layer self-assembling positively charged chitosan (Chi), negatively charged oxidized sodium alginate (OAlg), and positively charged bovine serum albumin (BSA)-based nanoparticles. The BSA-based nanoparticles in the self-assembled films not only result in porous nanostructures similar to natural ECM, but also preserve the activity and realize the sustained release of Bone morphogenetic protein-2 (BMP-2). The results of bone marrow stem cells (BMSCs) culture demonstrate that the penta-peptide glycine-arginine-glycine-aspartate-serine (GRGDS) grafted Chi/OAlg films favor cell adhesion and proliferation. GRGDS and BMP-2 in biomimetic ECM nanostructures synergistically promote BMSC functions and new bone formation. The RGD and BMP incorporated biomimetic ECM coatings could be applied on a variety of biomedical devices to improve the bioactivity and biocompatibility. PMID:27121121

  5. Treatment of critically sized femoral defects with recombinant BMP-2 delivered by a modified mPEG-PLGA biodegradable thermosensitive hydrogel

    OpenAIRE

    Peng, Kuo-Ti; Hsieh, Meng-Yow; Lin, Carl T.; Chen, Chin-Fu; Lee, Mel S.; Huang, Yi-You; CHANG, PEY-JIUM

    2016-01-01

    Background Reconstruction of a segmental fracture with massive bone loss is still a challenge for orthopaedic surgeons. The aim of our study was to develop a suitable biodegradable thermosensitive hydrogel system as a carrier for bone morphogenetic protein (BMP)-2 delivery in the treatment of critical-sized femoral defects. Methods A block copolymer composed of monomethoxypoly(ethylene glycol) (mPEG), poly(lactic-co-glycolic acid) (PLGA) and 2, 2’-Bis (2-oxazolin) (Box) was synthesized by rin...

  6. Preparation of porous bioceramics using reverse thermo-responsive hydrogels in combination with rhBMP-2 carriers: in vitro and in vivo evaluation.

    Science.gov (United States)

    Fu, Yin-Chih; Chen, Chung-Hwan; Wang, Chau-Zen; Wang, Yan-Hsiung; Chang, Je-Ken; Wang, Gwo-Jaw; Ho, Mei-Ling; Wang, Chih-Kuang

    2013-11-01

    Porous biphasic calcium phosphates (BCP) were fabricated using reverse thermo-responsive hydrogels with hydroxyapatite (HAp) and β-tricalcium (β-TCP) powder and planetary centrifugal mixer. This hydrogel mixture slurry will shrink and compress the HAp powder during the sintering process. The porous bioceramics are expected to have good mechanical properties after sintering at 1200°C. Reverse thermo-responsive hydrogels of poly[(N-isopropylacrylamide)-co-(methacrylic acid)] p(NiPAAm-MAA) were synthesized by free-radical cross-linking copolymerization, and their chemical properties were evaluated by nuclear magnetic resonance spectroscopy, infrared spectroscopy, and electrospray-ionization mass spectrometry. The lower critical solution temperature (LCST) of the hydrogel was determined using turbidity measurements. A thermogravimetric analysis was used to examine the thermal properties. The porous bioceramic properties were analyzed by X-ray diffraction, scanning electron microscopy, bulk density, compressive strength testing and cytotoxicity. The compressive strength and average porosity of the porous bioceramics were examined at approximately 6.8MPa and 66% under 10wt% p(NiPAAm-MAA)=99:1 condition. The ratio of HAp/β-TCP can adjust two different compositional behaviors during the 1200°C sintering process without resulting in cell toxicity. The (rhBMP-2)-HAp-PLGA carriers were fabricated as in our previous study of the double emulsion and drop-coating technique. Results of animal study included histological micrographs of the 1-mm defect in the femurs, with the rhBMP-2 carrier group, the bioceramic spacer group and the bioceramic spacer with rhBMP-2 carriers group showing better callus formation around the femur defect site than the control group. The optimal dual effects of the bone growth factors from osteoconductive bioceramics and osteoinductive rhBMP-2 carriers produced better bone formation. PMID:23880039

  7. The Value of SPECT/CT in Monitoring Prefabricated Tissue-Engineered Bone and Orthotopic rhBMP-2 Implants for Mandibular Reconstruction.

    Directory of Open Access Journals (Sweden)

    Miao Zhou

    Full Text Available Bone tissue engineering shows good prospects for mandibular reconstruction. In recent studies, prefabricated tissue-engineered bone (PTEB by recombinant human bone morphogenetic proteins (rhBMPs applied in vivo has found to be an effective alternative for autologous bone grafts. However, the optimal time to transfer PTEB for mandibular reconstruction is still not elucidated. Thus, here in an animal experiment of rhesus monkey, the suitable transferring time for PTEB to reconstruct mandibular defects was evaluated by 99mTc-MDP SPECT/CT, and its value in monitoring orthotopic rhBMP-2 implants for mandibular reconstruction was also evaluated. The result of SPECT/CT showed higher 99mTc-MDP uptake, indicating osteoinductivity, in rhBMP-2 incorporated demineralized freeze-dried bone allograft (DFDBA and coralline hydroxyapatite (CHA implants than those without BMP stimulation. 99mTc-MDP uptake of rhBMP-2 implant peaked at 8 weeks following implantation while CT showed the density of these implants increased after 13 weeks' prefabrication. Histology confirmed that mandibular defects were repaired successfully with PTEB or orthotopically rhBMP-2 incorporated CHA implants, in accordance with SPECT/CT findings. Collectively, data shows 99mTc-MDP SPECT/CT is a sensitive and noninvasive tool to monitor osteoinductivity and bone regeneration of PTEB and orthotopic implants. The PTEB achieved peak osteoinductivity and bone density at 8 to 13 weeks following ectopic implantation, which would serve as a recommendable time frame for its transfer to mandibular reconstruction.

  8. Effect of recombinant human bone morphogenetic protein 2/polylactide-co-glycolic acid (rhBMP-2/PLGA) with core decompression on repair of rabbit femoral head necrosis

    Institute of Scientific and Technical Information of China (English)

    Zhao-Xun; Pan; Hong-Xin; Zhang; Ye-Xin; Wang; Long-Di; Zhai; Wei; Du

    2014-01-01

    Objective:To observe the effect of recombinant human bone morphogenetic protein 2/polylactide-co-glycolic acid(rhBMP-2/PLGA) with core decompression on repair of rabbit femoral head necrosis.Methods:Bilateral femoral head necrosis models of rabbit were established by steroid injection.A total of 48 rabbits(96 femoral head necrosis) were randomly divided into 4groups:Group A,control group with12 rabbits,24 femoral head necrosis;Group B,treated with rhBMP-2/PLCA implantation after core depression,with 12 rabbits,24 femoral head necrosis;Group C,treated with rhBMP-2 implantation after core depression,with 12 rabbits,24 femoral head necrosis;Croup D treated with core depression group without implantation,with 12 rabbits,24 femoral head necrosis.All animals were sacrificed after 12 weeks.The ability of repairing bone defect was evaluated by X-ray radiograph.Bone mineral density analysis of the defect regions were used to evaluate the level of ossification.The morphologic change and bone formation was assessed by HE staining.The angiogenesis was evaluated by VEGF immunohistochemistry.Results:The osteogenetic ability and quality of femoral head necrosis in group B were better than those of other groups after 12 weeks by X-ray radiograph and morphologic investigation.And the angiogenesis in group B was better than other groups.Group C had similar osteogenetic quality of femoral head necrosis and angiogenesis with group D.Conclusions:The treatment of rhBMP-2/PLCA implantation after core depression can promote the repair of rabbit femoral head necrosis.It is a promising and efficient synthetic bone material to treat the femoral head necrosis.

  9. The effect of a slow mode of BMP-2 delivery on the inflammatory response provoked by bone-defect-filling polymeric scaffolds.

    Science.gov (United States)

    Wu, Gang; Liu, Yuelian; Iizuka, Tateyuki; Hunziker, Ernst Bruno

    2010-10-01

    We investigated the inflammatory response to, and the osteoinductive efficacies of, four polymers (collagen, Ethisorb, PLGA and Polyactive) that bore either an adsorbed (fast-release kinetics) or a calcium-phosphate-coating-incorporated (slow-release kinetics) depot of BMP-2. Titanium-plate-supported discs of each polymer (n = 6 per group) were implanted at an ectopic (subcutaneous) ossification site in rats (n = 48). Five weeks later, they were retrieved for a histomorphometric analysis of the volumes of ectopic bone and foreign-body giant cells (a gauge of inflammatory reactivity), and the degree of polymer degradation. For each polymer, the osteoinductive efficacy of BMP-2 was higher when it was incorporated into a coating than when it was directly adsorbed onto the material. This mode of BMP-2 carriage was consistently associated with an attenuation of the inflammatory response. For coated materials, the volume density of foreign-body giant cells was inversely correlated with the volume density of bone (r(2) = 0.96), and the volume density of bone was directly proportional to the surface-area density of the polymer (r(2) = 0.97). Following coating degradation, other competitive factors, such as the biocompatibility and the biodegradability of the polymer itself, came into play.

  10. High-purity magnesium interference screws promote fibrocartilaginous entheses regeneration in the anterior cruciate ligament reconstruction rabbit model via accumulation of BMP-2 and VEGF.

    Science.gov (United States)

    Cheng, Pengfei; Han, Pei; Zhao, Changli; Zhang, Shaoxiang; Wu, Hongliu; Ni, Jiahua; Hou, Peng; Zhang, Yuanzhuang; Liu, Jingyi; Xu, Haidong; Liu, Shen; Zhang, Xiaonong; Zheng, Yufeng; Chai, Yimin

    2016-03-01

    Interference screw in the fixation of autologous tendon graft to the bone tunnel is widely accepted for the reconstruction of anterior cruciate ligament (ACL), but the regeneration of fibrocartilaginous entheses could hardly be achieved with the traditional interference screw. In the present work, biodegradable high-purity magnesium (HP Mg) showed good cytocompatibility and promoted the expression of bone morphogenetic protein-2 (BMP-2) and vascular endothelial growth factor (VEGF), fibrocartilage markers (Aggrecan, COL2A1 and SOX-9), and glycosaminoglycan (GAG) production in vitro. The HP Mg screw was applied to fix the semitendinosus autograft to the femoral tunnel in a rabbit model of ACL reconstruction with titanium (Ti) screw as the control. The femur-tendon graft-tibia complex was retrieved at 3, 6, 9 and 12 weeks. Gross observation and range of motion (ROM) of the animal model reached normal levels at 12 weeks. No sign of host reaction was found in the X-ray scanning. The HP Mg group was comparable to the Ti group with respect to biomechanical properties of the reconstructed ACL, and the ultimate load to failure and stiffness increased 12 weeks after surgery. In the histological analysis, the HP Mg group formed distinct fibrocartilage transition zones at the tendon-bone interface 12 weeks after surgery, whereas a disorganized fibrocartilage layer was found in the Ti group. In the immunohistochemical analysis, highly positive staining of BMP-2, VEGF and the specific receptor for BMP-2 (BMPR1A) was shown at the tendon-bone interface of the HP Mg group compared with the Ti group. Furthermore, the HP Mg group had significantly higher expression of BMP-2 and VEGF than the Ti group in the early phase of tendon-bone healing, followed by enhanced expression of fibrocartilage markers and GAG production. Therefore we proposed that the stimulation of BMP-2 and VEGF by Mg ions was responsible for the fibrochondrogenesis of Mg materials. HP Mg was promising as a

  11. Effects of recombinant human Bone Morphogenetic Protein-2 (rhBMP-2) in grade III open tibia fractures treated with unreamed nails-A clinical and health-economic analysis.

    Science.gov (United States)

    Alt, Volker; Borgman, Benny; Eicher, Alexander; Heiss, Christian; Kanakaris, Nikolaos K; Giannoudis, Peter V; Song, Fujian

    2015-11-01

    Recombinant human Bone Morphogenetic Protein-2 (rhBMP-2) is licensed in Europe for open tibia fractures treated with unreamed nails. However, there is limited data available on the specific use of rhBMP-2 in combination with unreamed nails for open tibia fractures. The intention of the current study was to evaluate the medical and health-economic effects of rhBMP-2 in Gustilo-Anderson grade III open tibia fractures treated with unreamed nails based on individual patient data from two previously published studies. Linear regression analysis was performed on raw data of 90 patients that were either treated by standard of care with soft tissue management and unreamed nailing (SOC group) (n=50) or with rhBMP-2 in addition to soft tissue management and unreamed nailing (rhBMP-2 group) (n=40). For all types of revision, a significant lower percentage of patients (27.5%) of the rhBMP-2 group had to be revised compared to 48% of the patients of the SOC group (p=0.04). When only invasive secondary interventions such as bone grafting and nail exchange were considered, there was also a statistically significant reduction in the rhBMP-2 group with a revision rate of 10.0% (4 of 40 patients) compared to the SOC group with a revision rate of 28.0% (14 of 50 patients) (p=0.01). Mean fracture healing time of 228 days in the rhBMP-2 compared to 266 days in the SOC group was not statistically significant (p=0.24). Health-economic analysis based on a societal perspective with calculation of overall treatment costs after initial surgery and including productivity losses revealed savings of €6,239 per patient for Germany and €4,752 for the UK in favour of rhBMP-2 which was mainly driven by reduction of productivity losses. In conclusion, rhBMP-2 reduces secondary interventions in patients with grade III open tibia fractures treated with an unreamed nail and its use leads to financial savings for Germany and the UK from a societal perspective. PMID:26374949

  12. Generation of an rhBMP-2-loaded beta-tricalcium phosphate/hydrogel composite and evaluation of its efficacy on peri-implant bone formation

    International Nuclear Information System (INIS)

    Dental implant insertion on a site with low bone quality or bone defect should be preceded by a bone graft or artificial bone graft insertion to heal the defect. We generated a beta-tricalcium phosphate (β-TCP) and poloxamer 407-based hydrogel composite and penetration of the β-TCP/hydrogel composite into the peri-implant area of bone was evaluated by porous bone block experiments. The maximum penetration depth for porous bone blocks and dense bone blocks were 524 μm and 464 μm, respectively. We report the in-vivo performance of a composite of β-TCP/hydrogel composite as a carrier of recombinant human bone morphogenetic protein (rhBMP-2), implanted into a rabbit tibial defect model. Three holes drilled into each tibia of eight male rabbits were (1) grafted with dental implant fixtures; (2) filled with β-TCP/hydrogel composite (containing 5 μg of rhBMP-2), followed by grafting of the dental implant fixtures. Four weeks later, bone-implant contact ratio and peri-implant bone formation were analyzed by radiography, micro-CT and histology of undecalcified specimens. The micro-CT results showed a significantly higher level of trabecular thickness and new bone and peri-implant new bone formation in the experimental treatment compared to the control treatment. Histomorphometry revealed a significantly higher bone-implant contact ratio and peri-implant bone formation with the experimental treatment. The use of β-TCP/poloxamer 407 hydrogel composite as a carrier of rhBMP-2 significantly promoted new bone formation around the dental implant fixture and it also improved the quality of the new bone formed in the tibial marrow space. (paper)

  13. CONSTRUCTION OF RECOMBINANT PLASMID pcDNA3.1/BMP-2 AND ITS INVOLVEMENT IN DIFFERENTIATION OF HUMAN DENTAL PULP-DERIVED CELLS INTO AN ODONTOBLASTIC LINEAGE

    Directory of Open Access Journals (Sweden)

    Boy M. Bachtiar

    2009-06-01

    Full Text Available Experimental studies have shown that dental pulp tissue has potential to regenerate dentine in response to adverse stimuli, such as caries and associated operative procedures. However, the potential of dental pulp regeneration seems to be limited by regenerative capacity of the cell involved. In this study, we report the effect of transfection of a recombinant plasmid containing human BMP-2 gene in proliferation and differentiation of dental pulp tissue in vitro. The regenerative capacity was analyzed by ALP production and calcium content. Results showed that the transfected dental pulp cell was able to differentiate into the odontoblast phenotype, indicating the presence of odontoblast progentitor cells in dental pulp tissue.

  14. The toxic effects of Tris-(2,3-dibromopropyl)isocyanurate(TBC) on genes expression of bmp2b and bmp4 of zebrafish embryos

    Institute of Scientific and Technical Information of China (English)

    JIA Wan-jun

    2016-01-01

    We exposed zebrafish embryos to Tris-(2,3-dibromopropyl)isocyanurate(TBC)at the concentration of 20ppb, 100ppb, 400ppb, 1000ppb for 120h and 0.1%DMSO was set as the control group. Bmp2b and bmp4 were chosen perform RT-PCR to determine their genes expression level. The results showed that, TBC influenced their genes expression level in some extent and it significantly raised the genes expression level at the concentration of 20ppb.

  15. Research of quaternized chitosan based hybrid scaffold as a delivery system for rhBMP-2%壳聚糖季铵盐基杂化支架的制备及其作为rhBMP-2载体的研究*

    Institute of Scientific and Technical Information of China (English)

    胡园园; 王靖; 刘昌胜

    2014-01-01

    Quaternized chitosan was synthesized by the reaction of chitosan and glycidyltrimethylammonium chloride (GTMAC)and named as N-[(2-hydroxy-3-trimethylammonium)propyl]chitosan chloride (HTCC). A hydrogel system composed of HTCC andβ-glycerophosphate (β-GP)was obtained by intermolecular forces. Introduction ofβ-TCP granules improved the mechanical strength and controlled the swelling behavior and pro-longed the releasing period for rhBMP-2 of the hydrogel scaffold.Moreover,rhBMP-2 loaded scaffolds were as-sessed in ectopic bone formation.The results indicate that porous HTCC/β-GP/β-TCP/rhBMP-2 scaffolds are promising candidates for application in tissue engineering of bone.%采用环氧衍生物开环法制备壳聚糖季铵盐,通过其与甘油磷酸钠的分子间作用力交联成凝胶,冻干后得多孔支架,用于装载骨形态发生蛋白-2应用于骨修复领域;同时引入β-TCP 作为物理交联点,在提高支架力学强度的同时,更好地调控支架的溶胀行为,延长rhBMP-2的释放时间,并且在异位诱导成骨的动物实验中取得良好效果。

  16. Hereditary hemochromatosis type 1 phenotype modifiers in Italian patients. The controversial role of variants in HAMP, BMP2, FTL and SLC40A1 genes.

    Science.gov (United States)

    Radio, Francesca Clementina; Majore, Silvia; Aurizi, Caterina; Sorge, Fiammetta; Biolcati, Gianfranco; Bernabini, Sara; Giotti, Irene; Torricelli, Francesca; Giannarelli, Diana; De Bernardo, Carmelilia; Grammatico, Paola

    2015-06-01

    Hereditary hemochromatosis (HH) is a heterogeneous disorder of iron metabolism. The most common form of the disease is Classic or type 1 HH, mainly caused by a biallelic missense p.Cys282Tyr (c.845G>A) mutation in the HFE gene. However, the penetrance of p.Cys282Tyr/p.Cys282Tyr genotype is incomplete in terms of both biochemical and clinical expressivity. Lack of penetrance is thought to be caused by several genetic and environmental factors. Recently, a lot of evidences on HH genetic modifiers were produced, often without conclusive results. We investigated 6 polymorphisms (rs10421768 in HAMP gene, rs235756 in BMP2 gene, rs2230267 in FTL gene, rs1439816 in SLC40A1 gene, rs41295942 in TFR2 gene and rs2111833 in TMPRSS6 gene) with uncertain function in order to further evaluate their role in an independent cohort of 109 HH type 1 patients. Our results make it likely the role of rs10421768, rs235756, rs2230267 and rs1439816 polymorphisms, respectively in HAMP, BMP2, FTL and SLC40A1 genes in HH expressivity. In addition, previous and our findings support a hypothetical multifactorial model of HH, characterized by a principal gene (HFE in HH type 1) and minor genetic and environmental factors that still have to be fully elucidated.

  17. 辽宁绒山羊BMP-2基因的克隆及序列比较分析%Cloning and Sequence Analyzing of B MP-2 Gene from Liaoning Cashmere Goats

    Institute of Scientific and Technical Information of China (English)

    薛冰; 郭丹; 王春艳; 郑旭; 高月; 张世伟

    2012-01-01

    根据GenBank上绵羊的BMP-2基因序列设计特异性引物,以辽宁绒山羊基因组DNA为模板,利用聚合酶链式反应,成功克隆了常年长绒型和季节长绒型辽宁绒山羊BMP-2部分基因片段,丰富了绒山羊BMP-2基因序列。经与绵羊、牛、鼠、猪和人的BMP-2基因进行的比对结果表明,季节与常年长绒型辽宁绒山羊的BMP-2基因同源片段的同源性达到99.7%,二者与绵羊同源性为98.2%和98.4%;与牛同源性为98.2%和97.9%;与鼠同源性为86.3%和86%;与人同源性为88.1%和88.1%。结果表明,辽宁绒山羊BMP-2基因部分核苷酸序列与其他哺乳动物同源性很高,与绵羊、牛的同源性高达97%以上,这与它们的种属关系相近一致。与人、鼠的同源性也在86%以上,说明BMP-2基因在不同物种之间具有较高的保守性。%According to the BMP-2 gene sequence of sheep on the GenBank, specific primers were designed and perennial and seasonal long-staple Cashmere goat BMP type-2 partial gene fragments were successfully cloned from the Liaoning cashmere goat genomic DNA, using the polymerase chain reaction. With the sheep, cat- tie, rats, pigs and human BMP-2 gene than on the results show that seasonal and perennial long-staple type of Liaoning cashmere goats homologous fragment of BMP-2 homology 99.7%, respeciively homology with the sheep was 98.2% and 98.4%; and bovine homology was 98.2% and 97.9%; and rat homolgy 86.3% and 86%; and human homology was 88.1% and 88.1%. The results showed that BMP-2 in Liaoning Cashmere goat gene partial nucleotide sequence homology with other mammals, which is similar to their relationship of species, and BMP-2 gene were conserved in different species.

  18. Vascular Calcification in Chronic Kidney Disease is Induced by Bone Morphogenetic Protein-2 via a Mechanism Involving the Wnt/β-Catenin Pathway

    Directory of Open Access Journals (Sweden)

    Shu Rong

    2014-11-01

    Full Text Available Background: Vascular calcification (VC, in which vascular smooth muscle cells (VSMCs undergo a phenotypic transformation into osteoblast-like cells, is one of the emergent risk factors for the accelerated atherosclerosis process characteristic of chronic kidney disease (CKD. Phosphate is an important regulator of VC. Methods: The expression of different smooth muscle cell or osteogenesis markers in response to high concentrations of phosphate or exogenous bone morphogenetic protein 2 (BMP-2 was examined by qRT-PCR and western blotting in rat VSMCs. Osteocalcin secretion was measured by radioimmunoassay. Differentiation and calcification of VSMCs were examined by alkaline phosphatase (ALP activity assay and Alizarin staining. Short hairpin RNA-mediated silencing of β-catenin was performed to examine the involvement of Wnt/β-catenin signaling in VSMC calcification and osteoblastic differentiation induced by high phosphate or BMP-2. Apoptosis was determined by TUNEL assay and immunofluorescence imaging. Results: BMP-2 serum levels were significantly higher in CKD patients than in controls. High phosphate concentrations and BMP-2 induced VSMC apoptosis and upregulated the expression of β-catenin, Msx2, Runx2 and the phosphate cotransporter Pit1, whereas a BMP-2 neutralization antibody reversed these effects. Knockdown of β-catenin abolished the effect of high phosphate and BMP-2 on VSMC apoptosis and calcification. Conclusions: BMP-2 plays a crucial role in calcium deposition in VSMCs and VC in CKD patients via a mechanism involving the Wnt/β-catenin pathway.

  19. A new heterologous fibrin sealant as scaffold to recombinant human bone morphogenetic protein-2 (rhBMP-2) and natural latex proteins for the repair of tibial bone defects.

    Science.gov (United States)

    Machado, Eduardo Gomes; Issa, João Paulo Mardegan; Figueiredo, Fellipe Augusto Tocchini de; Santos, Geovane Ribeiro Dos; Galdeano, Ewerton Alexandre; Alves, Mariana Carla; Chacon, Erivelto Luis; Ferreira Junior, Rui Seabra; Barraviera, Benedito; Cunha, Marcelo Rodrigues da

    2015-04-01

    Tissue engineering has special interest in bone tissue aiming at future medical applications Studies have focused on recombinant human bone morphogenetic protein-2 (rhBMP-2) and natural latex proteins due to the osteogenic properties of rhBMP-2 and the angiogenic characteristic of fraction 1 protein (P-1) extracted from the rubber tree Hevea brasiliensis. Furthermore, heterologous fibrin sealant (FS) has been shown as a promising alternative in regenerative therapies. The aim of this study was to evaluate these substances for the repair of bone defects in rats. A bone defect measuring 3mm in diameter was created in the proximal metaphysis of the left tibia of 60 rats and was implanted with rhBMP-2 or P-1 in combination with a new heterologous FS derived from snake venom. The animals were divided into six groups: control (unfilled bone defect), rhBMP-2 (defect filled with 5μg rhBMP-2), P-1 (defect filled with 5μg P-1), FS (defect filled with 8μg FS), FS/rhBMP-2 (defect filled with 8μg FS and 5μg rhBMP-2), FS/P-1 (defect filled with 8μg FS and 5μg P-1). The animals were sacrificed 2 and 6 weeks after surgery. The newly formed bone projected from the margins of the original bone and exhibited trabecular morphology and a disorganized arrangement of osteocyte lacunae. Immunohistochemical analysis showed intense expression of osteocalcin in all groups. Histometric analysis revealed a significant difference in all groups after 2 weeks (p0.05). A statistically significant difference (p<0.05) was observed in all groups after 6 weeks in relation to the volume of newly formed bone in the surgical area. In conclusion, the new heterologous fibrin sealant was found to be biocompatible and the combination with rhBMP-2 showed the highest osteogenic and osteoconductive capacity for bone healing. These findings suggest a promising application of this combination in the regeneration surgery. PMID:25825118

  20. 丝素蛋白增强型磷酸钙复合rhBMP-2用于绵羊腰椎椎体间融合的实验研究%Experimental study on lumbar interbody fusion with silk fibroin enhanced calcium phosphate cement composite loaded with recombinant human bone morphogenetic protein-2 in sheep

    Institute of Scientific and Technical Information of China (English)

    陈亮; 顾勇; 陈晓庆; 干旻峰; 朱雪松; 杨惠林; 唐天驷

    2010-01-01

    Objective To evaluate the osteogenic characteristics of an injectable silk fibroin (SF) enhanced calcium phosphate cement (CPC) composite loaded with recombinant human bone morphogenetic protein-2 (rhBMP-2) on lumbar interbody fusion in sheep. Methods Twenty-four mature sheep were randomly divided into two groups. Each sheep underwent L1.2, L3.4 and L5.6 lumber interbody fusion, and the three disc spaces were randomly implanted with three of the following materials: SF/CPC, CPC/rhBMP-2, SF/CPC/rhBMP2 and autogenous iliac crest bone. One group was killed at 6 months and the other at 12 months. The fusion segments were observed and analyzed by manual palpation, CT scan, undestructive biomechanical testing, undecalcified histology, and histomorphology. Results The fusion rates of SF/CPC, CPC/rhBMP-2, SF/CPC/rhBMP-2 and autogenous bone assessed by manual palpation were 0, 33.33%, 55.56% and 77.78% respectively at 6 months. At 12 months, the fusion rates improved to 11.11%, 44.44%, 77.78% and 77.78%, respectively.The biomechanical results showed that fusion stiffness was significantly greater in autograft compared with SF/CPC/rhBMP-2, CPC/rhBMP-2, and SF/CPC in 4 degrees of freedom (flexion, extension, right bending, and left bending) at 6 months. The SF/CPC/rhBMP-2 composite showed similar stiffness as autograft, which was significantly greater than CPC/rhBMP-2 and SF/CPC at 12 nonths. Both CPC/rhBMP-2 and SF/CPC/rhBMP-2 showed significantly greater stiffness at 12 months compared with that of at 6 months. The results showed that bone volume was significantly greater in autograft compared with SF/CPC/rhBMP-2, CPC/rhBMP-2, and SF/CPC at 6 months. There was significant difference among ceramic residue among SF/CPC, CPC/rhBMP-2 and SF/CPC/rhBMP-2, with SF/CPC the greatest and SF/CPC/thBMP-2 the least. At 12 months, the bone volume of SF/CPC/rhBMP-2 composite was comparable with autograft, and greater than that of CPC/rhBMP-2 and SF/CPC. The bone volume of SF/CPC, CPC/rhBMP

  1. Construction and identification of human BMP2-IRES-HIF1αmu adenovirus expressing carrier and its expression in HEK293 cells%人BMP2-IRES-HIF1αmu腺病毒表达载体的构建及其在HEK293细胞中的表达

    Institute of Scientific and Technical Information of China (English)

    李全营; 李谌; 郭威; 吴秀成; 王巍; 刘丹平

    2011-01-01

    目的 构建人BMP2-IRES-HIF1 αmu腺病毒表达载体,并转染HEK293细胞,为下一步转染骨髓基质细胞和体内实验打下基础.方法 PCR扩增HIF1αmu片段,用BstXⅠ和XbaⅠ双酶切回收目的片段.pIRES2-EGFP用BstXⅠ和Xba Ⅰ进行双酶切后回收大片段.将上述回收的目的基因与载体片段连接,然后转化感受态大肠杆菌DH5α扩增;PCR扩增BMP2片段,用Nhe Ⅰ和BamH Ⅰ双酶切后回收目的片段.把目的基因与载体片段连接,转化感受态大肠杆菌DH5α扩增重组腺病毒表达载体,通过酶切分析、PCR和测序进行鉴定.将构建好的质粒转染HEK293细胞,检测病毒液滴度.结果 构建了人BMP2-1RES-HIF1 αmu腺病毒表达载体,转染HEK293细胞见绿色荧光表达.结论 成功构建了人BMP2 -IRES-HIF1 αmu腺病毒表达载体,酶切分析及DNA测序证实质粒构建正确,质粒成功转染HEK293细胞,并见绿色荧光蛋白表达.%Objective To construct and identify human BMP2-IRES-HIFlotmu Adenovirus expressing carrier, trans-feet it in HEK293 cells, and determinate the virus droplet degrees. Methods PCR was used to amplify HIFlamu segments, BstX I and Xba I double enzyme cut pIRES2-EGFP and recycling purpose extract. Connecting the recovery target gene with carrier segment. Then introduced it into E. Coli for amplification. PCR was used to amplify BMP2 segments, Nhe I and BamH I double enzyme cut and recycling purpose extract. Connecting the recovery target gene with carrier segment. Then introduced it into E. Coli for amplification and restructuring adenovirus expressing carrier. Using the enzyme cut analysis, PCR for identification. The correct recombinant express plasmid was transfected into HEK293 cells, and detecting the virus droplet degrees. Results The adenovirus shuttle plasmid was constructed. Green fluorescent expression was seen in transfected HEK293 cells. Conclusion The adenovirus shuttle plasmid is constructed, it is successfully expressed in HEK

  2. Characteristics and Stimulation Potential with BMP-2 and BMP-7 of Tenocyte-Like Cells Isolated from the Rotator Cuff of Female Donors

    Science.gov (United States)

    Klatte-Schulz, Franka; Pauly, Stephan; Scheibel, Markus; Greiner, Stefan; Gerhardt, Christian; Hartwig, Jelka; Schmidmaier, Gerhard; Wildemann, Britt

    2013-01-01

    Tendon bone healing of the rotator cuff is often associated with non-healing or recurrent defects, which seems to be influenced by the patient’s age and sex. The present study aims to examine cellular biological characteristics of tenocyte-like cells that may contribute to this impaired rotator cuff healing. Moreover, a therapeutic approach using growth factors could possibly stimulate tendon bone healing. Therefore, our second aim was to identify patient groups who would particularly benefit from growth factor stimulation. Tenocyte-like cells isolated from supraspinatus tendons of female donors younger and older than 65 years of age were characterized with respect to different cellular biological parameters, such as cell density, cell count, marker expression, collagen-I protein synthesis, and stem cell potential. Furthermore, cells of the donor groups were stimulated with BMP-2 and BMP-7 (200 and 1000 ng/ml) in 3D-culture and analyzed for cell count, marker expression and collagen-I protein synthesis. Female donors older than 65 years of age showed significantly decreased cell count and collagen-I protein synthesis compared to cells from donors younger than 65 years. Cellular biological parameters including cell count, collagen-I and –III expression, and collagen-I protein synthesis of cells from both donor groups were stimulated with BMP-2 and BMP-7. The cells from donors older than 65 years revealed a decreased stimulation potential for cell count compared to the younger group. Cells from female donors older than 65 years of age showed inferior cellular biological characteristics. This may be one reason for a weaker healing potential observed in older female patients and should be taken into consideration for tendon bone healing of the rotator cuff. PMID:23825642

  3. Characteristics and stimulation potential with BMP-2 and BMP-7 of tenocyte-like cells isolated from the rotator cuff of female donors.

    Directory of Open Access Journals (Sweden)

    Franka Klatte-Schulz

    Full Text Available Tendon bone healing of the rotator cuff is often associated with non-healing or recurrent defects, which seems to be influenced by the patient's age and sex. The present study aims to examine cellular biological characteristics of tenocyte-like cells that may contribute to this impaired rotator cuff healing. Moreover, a therapeutic approach using growth factors could possibly stimulate tendon bone healing. Therefore, our second aim was to identify patient groups who would particularly benefit from growth factor stimulation. Tenocyte-like cells isolated from supraspinatus tendons of female donors younger and older than 65 years of age were characterized with respect to different cellular biological parameters, such as cell density, cell count, marker expression, collagen-I protein synthesis, and stem cell potential. Furthermore, cells of the donor groups were stimulated with BMP-2 and BMP-7 (200 and 1000 ng/ml in 3D-culture and analyzed for cell count, marker expression and collagen-I protein synthesis. Female donors older than 65 years of age showed significantly decreased cell count and collagen-I protein synthesis compared to cells from donors younger than 65 years. Cellular biological parameters including cell count, collagen-I and -III expression, and collagen-I protein synthesis of cells from both donor groups were stimulated with BMP-2 and BMP-7. The cells from donors older than 65 years revealed a decreased stimulation potential for cell count compared to the younger group. Cells from female donors older than 65 years of age showed inferior cellular biological characteristics. This may be one reason for a weaker healing potential observed in older female patients and should be taken into consideration for tendon bone healing of the rotator cuff.

  4. Effects of administration rhBMP-2/rhVEGF165 on tendon-bone healing after anterior cruciate ligament reconstruction in rabbits%rhBMP-2联合rhVEGF165对兔前交叉韧带重建后腱-骨愈合的影响

    Institute of Scientific and Technical Information of China (English)

    周平; 赵其纯; 尚希福; 王姚斐; 李旭; 纪小枫; 凌晓冬; 朱亚林

    2013-01-01

    目的 探讨局部联合应用重组人骨形态发生蛋白(rhBMP)-2和重组人血管内皮生长因子165 (rhVEGF165) 对兔前叉韧带重建后腱-骨早期愈合的影响.方法 78只健康成年雄性新西兰大白兔,随机分为VB、B、V、F及正常组,前4组建立双膝自体半腱肌前交叉韧带重建模型,正常组未行手术.VB组腱-骨界面注入以纤维蛋白胶(FG)为载体的rhBMP-2/rhVEGF165混合物;B组注入rhBMP-2和FG混合物;V组注入rhVEGF165和FG混合物;F组单纯注入FG.术后第2、4、8周,每组随机抽取6只兔子,右膝标本行组织学观察,左膝标本行生物力学测试.结果 术后第2周:VB组腱-骨连接紧密,成纤维细胞大量增生;B组连接紧密,可见少量软骨细胞;V、F组连接疏松,主要为纤维血管组织构成.术后第4周:VB组腱-骨界面初步形成四层结构;V、B、F组则主要由成熟的成纤维细胞构成,腱-骨连接紧密,骨隧道壁出现一定量成骨反应;术后第8周:VB组四层结构更明显,可见潮线;B组骨隧道壁侧成骨反应进步加强;V、F组腱-骨界面宽度进步变窄,成纤维细胞数目明显减少.直至术后第4、8周,VB组平均最大载负荷及刚度才较V、B、F组大(P<0.05),均低于正常组;同时V、B组生物力学性能优于F组(P<0.05).结论 rhBMP-2联合rhVEGF165对兔前交叉韧带重建术后腱-骨早期愈合具有促进作用,且联合效应强于各自单独效应.%Objective To explore effects of local administration rhBMP-2/rhVEGF165 on tendon-bone ealy healing after anterior cruciate ligament reconsctruction in rabbits. Methods Seventy eight male New Zealand white rabbits were randomly divided into Group VB,B,V,F and normal group. Bilateral anterior cruciate ligaments of each animal were removed and reconstructed with autogenetic tendon of semitendinosus muscles while normal group did not receive any operation. The fibrin glue ( FG ) containing rhBMP-2/rhVEGF165 was injected into tendon-bone interface

  5. A Novel Human TGF-β1 Fusion Protein in Combination with rhBMP-2 Increases Chondro-Osteogenic Differentiation of Bone Marrow Mesenchymal Stem Cells

    Science.gov (United States)

    Claros, Silvia; Rico-Llanos, Gustavo A.; Becerra, José; Andrades, José A.

    2014-01-01

    Transforming growth factor-beta (TGF-β) is involved in processes related to the differentiation and maturation of osteoprogenitor cells into osteoblasts. Rat bone marrow (BM) cells were cultured in a collagen-gel containing 0.5% fetal bovine serum (FBS) for 10 days in the presence of rhTGF (recombinant human TGF)-β1-F2, a fusion protein engineered to include a high-affinity collagen-binding decapeptide derived from von Willebrand factor. Subsequently, cells were moderately expanded in medium with 10% FBS for 4 days and treated with a short pulse of rhBMP (recombinant human bone morphogenetic protein)-2 for 4 h. During the last 2 days, dexamethasone and β-glycerophosphate were added to potentiate osteoinduction. Concomitant with an up-regulation of cell proliferation, DNA synthesis levels were determined. Polymerase chain reaction was performed to reveal the possible stemness of these cells. Osteogenic differentiation was evaluated in terms of alkaline phosphatase activity and mineralized matrix formation as well as by mRNA expression of osteogenic marker genes. Moreover, cells were placed inside diffusion chambers and implanted subcutaneously into the backs of adult rats for 4 weeks. Histological study provided evidence of cartilage and bone-like tissue formation. This experimental procedure is capable of selecting cell populations from BM that, in the presence of rhTGF-β1-F2 and rhBMP-2, achieve skeletogenic potential in vitro and in vivo. PMID:24968268

  6. A Novel Human TGF-β1 Fusion Protein in Combination with rhBMP-2 Increases Chondro-Osteogenic Differentiation of Bone Marrow Mesenchymal Stem Cells

    Directory of Open Access Journals (Sweden)

    Silvia Claros

    2014-06-01

    Full Text Available Transforming growth factor-beta (TGF-β is involved in processes related to the differentiation and maturation of osteoprogenitor cells into osteoblasts. Rat bone marrow (BM cells were cultured in a collagen-gel containing 0.5% fetal bovine serum (FBS for 10 days in the presence of rhTGF (recombinant human TGF-β1-F2, a fusion protein engineered to include a high-affinity collagen-binding decapeptide derived from von Willebrand factor. Subsequently, cells were moderately expanded in medium with 10% FBS for 4 days and treated with a short pulse of rhBMP (recombinant human bone morphogenetic protein-2 for 4 h. During the last 2 days, dexamethasone and β-glycerophosphate were added to potentiate osteoinduction. Concomitant with an up-regulation of cell proliferation, DNA synthesis levels were determined. Polymerase chain reaction was performed to reveal the possible stemness of these cells. Osteogenic differentiation was evaluated in terms of alkaline phosphatase activity and mineralized matrix formation as well as by mRNA expression of osteogenic marker genes. Moreover, cells were placed inside diffusion chambers and implanted subcutaneously into the backs of adult rats for 4 weeks. Histological study provided evidence of cartilage and bone-like tissue formation. This experimental procedure is capable of selecting cell populations from BM that, in the presence of rhTGF-β1-F2 and rhBMP-2, achieve skeletogenic potential in vitro and in vivo.

  7. Regulation of Axolotl (Ambystoma mexicanum) Limb Blastema Cell Proliferation by Nerves and BMP2 in Organotypic Slice Culture.

    Science.gov (United States)

    Lehrberg, Jeffrey; Gardiner, David M

    2015-01-01

    We have modified and optimized the technique of organotypic slice culture in order to study the mechanisms regulating growth and pattern formation in regenerating axolotl limb blastemas. Blastema cells maintain many of the behaviors that are characteristic of blastemas in vivo when cultured as slices in vitro, including rates of proliferation that are comparable to what has been reported in vivo. Because the blastema slices can be cultured in basal medium without fetal bovine serum, it was possible to test the response of blastema cells to signaling molecules present in serum, as well as those produced by nerves. We also were able to investigate the response of blastema cells to experimentally regulated changes in BMP signaling. Blastema cells responded to all of these signals by increasing the rate of proliferation and the level of expression of the blastema marker gene, Prrx-1. The organotypic slice culture model provides the opportunity to identify and characterize the spatial and temporal co-regulation of pathways in order to induce and enhance a regenerative response. PMID:25923915

  8. Regulation of Axolotl (Ambystoma mexicanum) Limb Blastema Cell Proliferation by Nerves and BMP2 in Organotypic Slice Culture.

    Science.gov (United States)

    Lehrberg, Jeffrey; Gardiner, David M

    2015-01-01

    We have modified and optimized the technique of organotypic slice culture in order to study the mechanisms regulating growth and pattern formation in regenerating axolotl limb blastemas. Blastema cells maintain many of the behaviors that are characteristic of blastemas in vivo when cultured as slices in vitro, including rates of proliferation that are comparable to what has been reported in vivo. Because the blastema slices can be cultured in basal medium without fetal bovine serum, it was possible to test the response of blastema cells to signaling molecules present in serum, as well as those produced by nerves. We also were able to investigate the response of blastema cells to experimentally regulated changes in BMP signaling. Blastema cells responded to all of these signals by increasing the rate of proliferation and the level of expression of the blastema marker gene, Prrx-1. The organotypic slice culture model provides the opportunity to identify and characterize the spatial and temporal co-regulation of pathways in order to induce and enhance a regenerative response.

  9. Regulation of Axolotl (Ambystoma mexicanum Limb Blastema Cell Proliferation by Nerves and BMP2 in Organotypic Slice Culture.

    Directory of Open Access Journals (Sweden)

    Jeffrey Lehrberg

    Full Text Available We have modified and optimized the technique of organotypic slice culture in order to study the mechanisms regulating growth and pattern formation in regenerating axolotl limb blastemas. Blastema cells maintain many of the behaviors that are characteristic of blastemas in vivo when cultured as slices in vitro, including rates of proliferation that are comparable to what has been reported in vivo. Because the blastema slices can be cultured in basal medium without fetal bovine serum, it was possible to test the response of blastema cells to signaling molecules present in serum, as well as those produced by nerves. We also were able to investigate the response of blastema cells to experimentally regulated changes in BMP signaling. Blastema cells responded to all of these signals by increasing the rate of proliferation and the level of expression of the blastema marker gene, Prrx-1. The organotypic slice culture model provides the opportunity to identify and characterize the spatial and temporal co-regulation of pathways in order to induce and enhance a regenerative response.

  10. Sustained Release of Bone Morphogenetic Protein 2 via Coacervate improves Muscle Derived Stem Cell Mediated Cartilage Regeneration in MIA-induced Osteoarthritis

    Science.gov (United States)

    Hicks, Justin James; Rocha, Jorge Luis; Li, Hongshuai; Huard, Johnny; Wang, Yadong; Hogan, MaCalus Vinson

    2016-01-01

    Objectives: Individuals who participate in sports have an increased risk of osteoarthritis (OA), characterized by articular cartilage degeneration. Currently, there is no cure for OA with treatment aimed at symptom relief and improved function. Muscle-derived stem cells (MDSCs) have been shown to exhibit long-term proliferation, high self-renewal, and multipotent differentiation capabilities in vitro. Previously, we have demonstrated that murine MDSCs retrovirally transduced to express chondrogenic proteins (BMPs) differentiate into chondrocytes and enhance cartilage repair in vivo. Direct injection of therapeutic proteins can promote cartilage healing; however, they have relatively short half-lives requiring muitiple injections of high dosages. This presents a challenge in terms of maintaining adequate local BMP levels and could negatively affect both injured and normal structures and lead to side effects such as osteophyte formation. Gene therapy is a promising approach that addresses this problem; however, its utilization in clinical applications is much further down the road. In order to circumvent viral transduction of cells for cartilage regeneration, we developed a unique growth factor delivery platform comprised of native heparin and a synthetic polycation, poly(ethylene argininylaspartate diglyceride) (PEAD) incorporated with BMP2 (BMP2 coacervate). In this study, we show that sustained delivery of BMP2 via a BMP2 coacervate can induce the differentiation of MDSCs to a chondrocyte lineage for in vivo cartilage regeneration and healing in a Monoiodoacetate (MIA)-induced osteoarthritis model. Methods: mMDSCs were isolated from muscle biopsies via a modified pre-plated technique. The BMP2 coacervates were prepared as previously described. The release profiles of BMP2 coacervate were tested by ELISA. The chondrogenic effects that delivery of BMP2 had on MDSCs were evaluated by RT-PCR. The efficacy of MDSC with BMP2 coacervate were evaluated in vivo in a MIA-induced

  11. Effect of recombinant human bone morphogenetic protein 2/poly-lactide-co-glycolic acid (rhBMP-2/PLGA) with core decompression on repair of rabbit femoral head necrosis

    Institute of Scientific and Technical Information of China (English)

    Zhao-Xun Pan; Hong-Xin Zhang; Ye-Xin Wang; Long-Di Zhai; Wei Du

    2014-01-01

    Objective:To observe the effect of recombinant human bone morphogenetic protein 2/poly-lactide-co-glycolic acid (rhBMP-2/PLGA) with core decompression on repair of rabbit femoral head necrosis. Methods: Bilateral femoral head necrosis models of rabbit were established by steroid injection. A total of 48 rabbits (96 femoral head necrosis) were randomly divided into 4 groups: Group A, control group with12 rabbits, 24 femoral head necrosis;Group B, treated with rhBMP-2/PLGA implantation after core depression, with 12 rabbits, 24 femoral head necrosis;Group C, treated with rhBMP-2 implantation after core depression, with 12 rabbits, 24 femoral head necrosis;Group D treated with core depression group without implantation, with 12 rabbits, 24 femoral head necrosis. All animals were sacrificed after 12 weeks. The ability of repairing bone defect was evaluated by X-ray radiograph. Bone mineral density analysis of the defect regions were used to evaluate the level of ossification. The morphologic change and bone formation was assessed by HE staining. The angiogenesis was evaluated by VEGF immunohistochemistry. Results: The osteogenetic ability and quality of femoral head necrosis in group B were better than those of other groups after 12 weeks by X-ray radiograph and morphologic investigation. And the angiogenesis in group B was better than other groups. Group C had similar osteogenetic quality of femoral head necrosis and angiogenesis with group D. Conclusions:The treatment of rhBMP-2/PLGA implantation after core depression can promote the repair of rabbit femoral head necrosis. It is a promising and efficient synthetic bone material to treat the femoral head necrosis.

  12. Histological and radiographic evaluation of the muscle tissue of rats after implantation of bone morphogenic protein (rhBMP-2 in a scaffold of inorganic bone and after stimulation with low-power laser light

    Directory of Open Access Journals (Sweden)

    Bengtson Antonio

    2010-01-01

    Full Text Available Objective: The present study histologically and radiologically evaluates the muscle tissue of rats after implantation of bone morphogenic protein (rhBMP-2 in a natural inorganic bone mineral scaffold from a bull calf femur and irradiation with low-power light laser. Materials and Methods: The right and left hind limbs of 16 rats were shaved and an incision was made in the muscle on the face corresponding to the median portion of the tibia, into which rhBMP-2 in a scaffold of inorganic bone was implanted. Two groups of limbs were formed: control (G1 and laser irradiation (G2. G2 received diode laser light applied in the direction of the implant, at a dose of 8 J/cm2 for three minutes. On the 7th, 21st, 40th and 112th days after implantation, hind limbs of 4 animals were radiographed and their implants removed together with the surrounding tissue for study under the microscope. The histological results were graded as 0=absence, 1=slight presence, 2=representative and 3=very representative, with regard to the following events: formation of osteoid structure, acute inflammation, chronic inflammation, fibrin deposition, neovascularization, foreign-body granuloma and fibrosis. Results: There were no statistically significant differences in these events at each evaluation times, between the two groups (P > 0.05; Mann-Whitney test. Nevertheless, it could be concluded that the natural inorganic bone matrix with rhBMP-2, from the femur of a bull calf, is a biocompatible combination. Conclusions: Under these conditions, the inductive capacity of rhBMP-2 for cell differentiation was inhibited. There was a slight acceleration in tissue healing in the group that received irradiation with low-power laser light.

  13. Study on the Drug-loading Pattern of BMP2 Slow-release Microspheres%载骨形态发生蛋白2缓释微球载药形式研究

    Institute of Scientific and Technical Information of China (English)

    陈发明; 吴织芬; 王勤涛; 金岩; 王国芳; 杜岩

    2005-01-01

    目的:探讨右旋糖酐-甲基丙烯酸缩水甘油酯载骨形态发生蛋白 2(BMP2-DEX-GMA)凝胶微球的载药形式.方法:采用放射免疫分析法测定.结果: BMP2-DEX-GMA凝胶微球载药形式为内部包埋(DE)与表面吸附(DA)并存,且随着粒径增大, DA减少、 DE增加,但统计学检验结果显示粒径为 20μ m~ 40μ m的凝胶微球载药形式 DA、 DE间比较无显著性差异(P>0. 05).结论:粒径的改变可以影响 BMP2-DEX-GMA凝胶微球的载药形式,但不会改变其释药特征,尚需对载药材料进行改性才能实现对药物的控释.

  14. Co-dependence of the neural and humoral pathways in the mechanism of remote ischemic conditioning

    OpenAIRE

    Pickard, J. M.; Davidson, S M; Hausenloy, D.J.; Yellon, D M

    2016-01-01

    The cardioprotection afforded by remote ischaemic conditioning (RIC) is mediated via a complex mechanism involving sensory afferent nerves, the vagus nerve, and release of a humoral blood-borne factor. However, it is unknown whether release of the protective factor depends on vagal activation or occurs independently. This study aimed to evaluate the co-dependence of the neural and humoral pathways of RIC, focussing on the vagus nerve and intrinsic cardiac ganglia. In the first study, anesthet...

  15. Co-dependence of Extreme Events in High Frequency FX Returns

    OpenAIRE

    Arnold Polanski; Evarist Stoja

    2013-01-01

    In this paper, we investigate extreme events in high frequency, multivariate FX returns within a purposely built framework. We generalize univariate tests and concepts to multidimensional settings and employ these novel techniques for parametric and nonparametric analysis. In particular, we investigate and quantify the co-dependence of cross-sectional and intertemporal extreme events. We find evidence of the cubic law of extreme returns, their increasing and asymmetric dependence and of the s...

  16. 聚乳酸及其复合物修复下颌骨缺损的实验研究%THE EXPERIMENTAL STUDY OF REPAIRING THE MANDIBULAR BONE DEFECT USING PLA-rhBMP-2

    Institute of Scientific and Technical Information of China (English)

    黄相道; 刘境华; 赵明; 王会信

    2001-01-01

    Purpose A new synthetic material consists of Polylac tic acid[PLA] and recombinant human bone morphogenetic protein-2[PLA-rhBMP -2]. The capacity of repairing bone defect of biodegradable PLA and the effica cy of PLA as a carrier for bone morphogenetic protein [BMP] are determined wit h detecting the osteogenetic process. Materials and Methods Eighteen rabbits were picked up and divided i nto three groups randomly. The defects of 12mm×6mm size were made at bilateral mandibul ar edges. PLA-rhBMP-2, PLA were implanted in the defect respectively. The 18 r abbits were killed at 2,4,8 and 12 weeks after implanting. The sample was analyz ed by the methods of X-rays and histological examination. Results After 2 weeks, the new bone began to form in the defects. A fter 8 weeks, bulk bone could be obviously observed. After 12 weeks, most of the PLA in the defects were already biodegraded. The defects were restored with n ew bone. The results in PLA-rhBMP-2 group were better than those of other grou ps. Conclusions PLA could be a promising carrier for BMP. PLA-rhBM P-2 has also been considered a better biodegradable material for repairing mand ibular defect.%目的 聚乳酸与骨形成蛋白复合,研究该材料修复颌骨缺损的能力,探讨聚乳酸作为骨形成蛋白载体的有效性。方法 18只日本大耳白兔,随机分组,在双侧下颌骨体部形成12mm×6mm的缺损,分别植入聚乳酸-人骨形成蛋白-2复合物(PLA-rhBMP-2)、单纯聚乳酸(PLA),于2、4、8、12周分批处死。通过X线、组织学染色等方法进行观察。结果 PLA-rhBMP-2植入组于术后2周,缺损区部分新骨形成;术后8周,大片新骨形成并开始改建,术后12周,PLA大部分降解,由骨组织修复。结果优于对照组。结论 PLA可作为BMP的有效载体,PLA-rhBMP-2是良好的颌骨缺损修复材料。

  17. Possible Involvement of Smad Signaling Pathways in Induction of Odontoblastic Properties in KN-3 Cells by Bone Morphogenetic Protein-2: A Growth Factor to Induce Dentin Regeneration

    Directory of Open Access Journals (Sweden)

    Ayako Washio

    2012-01-01

    Full Text Available We examined the effects of bone morphogenetic protein-2 (BMP-2 on growth, differentiation, and intracellular signaling pathways of odontoblast-like cells, KN-3 cells, to clarify molecular mechanisms of odontoblast differentiation during pulp regeneration process. After treatment with BMP-2, the cell morphology, growth, alkaline phosphatase (ALP activity, and the activation and expression of BMP-induced intracellular signaling molecules, such as Smad1/5/8 and Smad6/7, as well as activities of dentin sialoprotein (DSP and dentin matrix protein 1 (DMP1, were examined. BMP-2 had no effects on the morphology, growth, or ALP activity of KN-3 cells, whereas it induced the phosphorylation of Smad1/5/8 and expression of Smad6/7. BMP-2 also induced the expressions of DSP and DMP-1. Our results suggest that KN-3 cells may express an odontoblastic phenotype with the addition of BMP-2 through the activation of Smad signaling pathways.

  18. Effects of secretive bone morphogenetic protein 2 induced by gene transfection on the biological changes of NIH3T3 cells

    Institute of Scientific and Technical Information of China (English)

    SUN Wei-bin; WANG Juan; LU Chun; TANG Gui-xia

    2005-01-01

    Background Bone morphogenetic proteins (BMPs), which belong to the transforming growth factor beta superfamily, are powerful regulators of cartilage and bone formation. This study investigated the biological changes of NIH3T3 cells incubated with secretive BMP2 that was induced by gene transfection through transwell. Methods Eukaryonic expression vector (pcDNA3.1-B2) was transfered into NIH3T3 cells with SofastTM,a positive compound transfection agent. The positive cell clones were selected with G418. The cytoplasmic and extracellular expressions of BMP2 were determined by immunohistochemical stain and enzyme-linked immunosorbent assay. NIH3T3 cells were co-cultured with hBMP2 gene transfecting cells through transwell, and the ultrastructure, alkaline phosphatase activity and the expression of osteocalcin (the marker of osteogenetic differentiation) changes were observed. Results There were cytoplasmic and extracellular expressions of BMP2 in transfecting NIH3T3 cells. The ultrastructural changes, the high activity of alkaline phosphatase and the positive stain of osteocalcin suggested the osteogenetic differentiation tendency of NIH3T3 cells co-cultured with transfecting NIH3T3 cells. Conclusion Secretive BMP2 that is induced by gene transfection could promote the osteogenetic differentiation of fibroblast cells.

  19. Autologous serum improves bone formation in a primary stable silica-embedded nanohydroxyapatite bone substitute in combination with mesenchymal stem cells and rhBMP-2 in the sheep model

    Directory of Open Access Journals (Sweden)

    Boos AM

    2014-11-01

    Full Text Available Anja M Boos,1,* Annika Weigand,1,* Gloria Deschler,1 Thomas Gerber,2 Andreas Arkudas,1 Ulrich Kneser,1 Raymund E Horch,1 Justus P Beier11Department of Plastic and Hand Surgery, University Hospital of Erlangen, Friedrich-Alexander-University of Erlangen-Nürnberg FAU, Erlangen, 2Institute of Physics, University of Rostock, Rostock, Germany *These authors contributed equally to this work Abstract: New therapeutic strategies are required for critical size bone defects, because the gold standard of transplanting autologous bone from an unharmed area of the body often leads to several severe side effects and disadvantages for the patient. For years, tissue engineering approaches have been seeking a stable, axially vascularized transplantable bone replacement suitable for transplantation into the recipient bed with pre-existing insufficient conditions. For this reason, the arteriovenous loop model was developed and various bone substitutes have been vascularized. However, it has not been possible thus far to engineer a primary stable and axially vascularized transplantable bone substitute. For that purpose, a primary stable silica-embedded nanohydroxyapatite (HA bone substitute in combination with blood, bone marrow, expanded, or directly retransplanted mesenchymal stem cells, recombinant human bone morphogenetic protein 2 (rhBMP-2, and different carrier materials (fibrin, cell culture medium, autologous serum was tested subcutaneously for 4 or 12 weeks in the sheep model. Autologous serum lead to an early matrix change during degradation of the bone substitute and formation of new bone tissue. The best results were achieved in the group combining mesenchymal stem cells expanded with 60 µg/mL rhBMP-2 in autologous serum. Better ingrowth of fibrovascular tissue could be detected in the autologous serum group compared with the control (fibrin. Osteoclastic activity indicating an active bone remodeling process was observed after 4 weeks, particularly

  20. Effects of TiO2 sandblasted and acid-etched titanium on expression of bone morphogenetic protein 2 in human osteoblasts%TiO2喷砂酸蚀处理对钛片表面人成骨细胞BMP-2表达水平的影响

    Institute of Scientific and Technical Information of China (English)

    陆斌; 李建武; 郭义; 杨艳

    2013-01-01

    目的 探讨钛片经过TiO2喷砂酸蚀处理后对人成骨细胞系MG63细胞骨形态发生蛋白2(bone morphogenetic protein,BMP-2)表达水平的影响.方法 将钛片分为3组进行处理:机械打磨组、喷砂组及喷砂酸蚀组,分别进行机械打磨、TiO2喷砂和喷砂酸蚀处理.将人成骨细胞系MG63细胞接种于钛片表面,采用实时定量聚合酶链反应(real-time polymerase chain reaction,RT-PCR)、Western blot检测BMP-2 mRNA及蛋白表达水平.结果 喷砂组及喷砂酸蚀组BMP-2 mRNA及蛋白水平增高,与机械打磨组相比差异有统计学意义(P<0.05),而喷砂组与喷砂酸蚀组之间差异无统计学意义(P>0.05).结论 使用经过TiO2喷砂及喷砂酸蚀处理的钛片进行人成骨细胞培养可促进BMP-2表达.%Objective To explore the effect of TiO 2 sandblasted and acid -etched titanium on the expression of bone morphogenetic pro -tein 2 (BMP-2) in human MG63 cells.Methods Titanium discs (15 mm diameter and 1 mm thickness ) were divided into 3 groups: machine polished group , sandblasted group , sandblasted and acid -etched group.Titanium discs were treated with mechanical polishing , TiO2 sandblasting, sandblasting and acid-etching in three groups , respectively.MG63 cells were cultured on the titanium.The mRNA and protein expression of BMP-2 in MG63 cells were analyzed by real-time polymerase chain reaction (RT-PCR) and Western blot.Results The mRNA and protein levels of BMP -2 were significantly higher in sandblasted group and sandblasted and acid -etched group than in machine polished group ( P 0.05 ).Conclusion After sandblasting and acid -etching, titanium could promote the expression of BMP-2 in human osteoblast.

  1. BMP-2联合温热化疗对SW480中GDF15和TFF3表达的影响%Effect of bone morphogenetic protein-2 combined with hyperthermic chemotherapy on GDF15 and TFF3 expression in SW480

    Institute of Scientific and Technical Information of China (English)

    毕德利; 王亚旭; 舒宁波; 谢凯

    2012-01-01

    目的:探讨骨形态发生蛋白-2(Bone morphogenetic protein-2,BMP-2)联合温热化疗对SW480中GDF15和TFF3表达的影响.方法:BMP-2作用于大肠癌SW480细胞系,置于43℃温热化疗30 min,培养6h.(1)流式细胞法检测SW480细胞的凋亡;(2) Western blot法检测GDF15和TFF3蛋白表达情况;(3) RT-PCR半定量检测GDF15和TFF3的mRNA表达.结果:BMP-2联合43℃温热化疗后SW480细胞凋亡增加,GDF15和TFF3蛋白表达水平下降,GDF15和TFF3的mRNA表达亦下调.结论:BMP-2联合温热化疗通过抑制大肠癌SW480的GDF15和TFF3蛋白及其相关基因表达,增强抑制SW480的增殖及转移复发的作用;温热疗法联合化疗对GDF15和TFF3表达抑制有协同作用.%Objective: To explore the effect of bone morphogenetic protein-2(BMP-2) combined with hyperthermic chemotherapy on GDF15 and TFF3 expression in SW480. Methods:BMP-2 was acted on SW480 colorectal cancer cell lines,placed in 43 t hyperthermic chemotherapy for 30 min and cultured for 6 h. (1 )Apoptosis of SW480 cells was detected by flow cytometry assay; (2)GDF15 and TFF3 protein expressions were detected by Western blot; (3)GDF15 and TFF3 mRNA expressions were detected by RT-PCR. Results: SW480 cells apoptosis was increased, GDF15 and TFF3 protein levels were decreased after BMP-2 combined with 43 t hyperthermic chemotherapy. GDF 15 and TFF3 mRNA expressions were also reduced. Conclusions: BMP-2 combined hyperthermic chemotherapy can inhibit proliferation and metastasis of SW480 by inhibiting GDF15 and TFF3 protein and mRNA expressions. Hyperthermia combined with chemotherapy has synergistic effect on the inhibition of GDF15 and TFF3 expression.

  2. 活血化瘀补肾壮骨中药促进BMP基因克隆转染犬牙髓细胞增殖的实验研究%THE EXPERIMENTAL STUDY ON THE PROMOTIVE EFFECT OF CHINESE TRADITION MEDICINE ON PROLIFERATION OF DOG DENTAL PULP CELLS TRANSFECTED BY BMP2 GENE

    Institute of Scientific and Technical Information of China (English)

    刁志虹; 高毅; 李威

    2012-01-01

    Objective To observe the effect of Chinese tradition medicine serum on the proliferation of dog dental pulp cells( DDPCs )transfected with pEGFP - Nl - BMP2 eukaryotic expression plasmid in vitro. To investigate the mechanism of Chinese tradition medicine on formation of dentin. Methods BMP2 - DDPCs were cultivated respectively in Chinese tradition medicine serum group( group A),non - medicine serum group( group B ) and fetal bovine serum group( group C ). The proliferation activity of BMP2 - DDPCs was detected respectively by the 3 -(4,5 - dimethythiazol -2-yl)-2,5-diphenyl tetrazolium bromide( MTT )after 24 hours ,48 hours and 72hours. Results After BMP2 - DDPCs were cultivated in three kinds of serum, there were no differences in the cells morphology, but there were differences in the number of the cells. With the prolongation of culture time, the number of the cells gradually increased in the 3 groups, among which medicine serum group increased more prominently. There were significant differences between Chinese traditional medicine serum group and the other two groups( P <0. 05 ). Conclusion The Chinese tradition medicine could promote proliferation of BMP2 - DDPCs and obviously increase the quantity of seed cells in dentin tissue engineering.%目的 观察活血化瘀补肾壮骨含药血清对骨形成蛋白2(bone morphogenetic proteins 2,BMP2)绿色荧光融合蛋白(green-fluorescent protein,GFP)真核表达质粒(pEGFP-N1-BMP2)在体外转染的犬牙髓细胞(dog dental pulp cells,DDPCs)增殖情况的影响,探讨活血化瘀补肾壮骨中药在牙本质改建形成中的作用机制.方法 将 BMP2-DDPCs分别于活血化瘀补肾壮骨含药血清组(A组)、无药血清组(B组)和胎牛血清组(C组)中培养.分别于24、48、72h用溴化-3-(4,5-二甲基噻唑基-2)-2,5二苯基四氮唑[3-(4,5-dimethythiazol-2-yl)-2,5-diphenyl tetrazolium bromide,MTT]法检测BMP2-DDPCs增殖活性.结果 BMP2-DDPCs分别在A、B、C 3组中

  3. In vivo experimental study of hollow porous femoral prosthesis filled with rhBMP-2%中空多孔股骨柄假体骨长入方式的在体实验研究

    Institute of Scientific and Technical Information of China (English)

    蔡谞; 王达文; 樊宇平; 赵斌; 王岩

    2008-01-01

    Objective To study hone formation and osteointegration at the interface and inside the hollow porous femoral porsthesis filled with recombinant human bone morphogentic protein-2 (rhBMP-2). Methods 18 health adult hybrid dogs were divided into 3 groups randomly. Each animal received total hip arthroplasty at right hip joint. The femoral stems implanted were solid center prosthesis (group A), hollow porous prosthesis filled with cancellous bone taken from the femur head and neck (group B), and hollow porous prosthesis filled with gelfoam and 5 mg rhBMP-2(group C), respectively. All prosthesis were made of CoCrMo alloy with hydroxyapatite coating at the proximal half. The animals were sacrificed at 2,4,8 months post operation and X-ray of the femur samples were taken. The histological changes, interface osseointega- tion rate and bone ingrowth rate round and inside prosthesis were evaluated. Results The bone formation of group C was faster than group A and B histologically. The interface osteointegration rate of group C was sig- nificantly higher than that of group A and B (P< 0.05) at 2, 4 months, but there was no significantly differ- ence between them at 8 months (P 0.05). Also the bone ingrowth rate of group C was higher than that of group B(P<0.05), but no significant difference at 8 months(P 0.05). There was nosignificant difference be- tween goup A and B at interface osteointegration rate. Conclusion The hollow porous femoral prosthesis filled with rhBMP-2 can enhance interface osteointegration and bone ingrowth effectively, which can make the prosthesis fast fixed in the bone bed right at the early stage. And this may provide reliable experimental evidence for developing a kind of hollow porous femoral prosthesis for human.%目的 观察多孔中空人工股骨柄假体周围骨床骨质经界面长入金属空腔及其在腔室内成骨的特征,比较腔内复合骨诱导因子(rhBMP-2)与自身骨长入的成骨差异.方法 健康成年杂交犬18

  4. Allogeneic Platelet Releasate Preparations Derived via a Novel Rapid Thrombin Activation Process Promote Rapid Growth and Increased BMP-2 and BMP-4 Expression in Human Adipose-Derived Stem Cells.

    Science.gov (United States)

    McLaughlin, Michael; Gagnet, Paul; Cunningham, Elizabeth; Yeager, Randi; D'Amico, Michael; Guski, Katie; Scarpone, Michael; Kuebler, Daniel

    2016-01-01

    The administration of human adipose-derived stem cells (ASCs) represents a promising regenerative therapy for the treatment of orthopedic injuries. While ASCs can be easily isolated from liposuction-derived adipose tissue, most clinical applications will likely require in vitro culture expansion of these cells using nonxenogeneic components. In this study, platelet releasate was generated using a novel rapid thrombin activation method (tPR). ASCs grown in media supplemented with tPR proliferated much faster than ASCs grown in media supplemented with 10% fetal bovine serum. The cells also retained the ability to differentiate along chondrogenic, adipogenic, and osteogenic lineages. The tPR cultured ASCs displayed elevated expression of BMP-4 (5.7 ± 0.97-fold increase) and BMP-2 (4.7 ± 1.3-fold increase) and decreased expression of PDGF-B (4.0 ± 1.4-fold decrease) and FGF-2 (33 ± 9.0-fold decrease). No significant changes in expression were seen with TGF-β and VEGF. This pattern of gene expression was consistent across different allogeneic tPR samples and different ASC lines. The use of allogeneic rapidly activated tPR to culture ASCs is associated with both an increased cell yield and a defined gene expression profile making it an attractive option for cell expansion prior to cell-based therapy for orthopedic applications.

  5. Allogeneic Platelet Releasate Preparations Derived via a Novel Rapid Thrombin Activation Process Promote Rapid Growth and Increased BMP-2 and BMP-4 Expression in Human Adipose-Derived Stem Cells

    Directory of Open Access Journals (Sweden)

    Michael McLaughlin

    2016-01-01

    Full Text Available The administration of human adipose-derived stem cells (ASCs represents a promising regenerative therapy for the treatment of orthopedic injuries. While ASCs can be easily isolated from liposuction-derived adipose tissue, most clinical applications will likely require in vitro culture expansion of these cells using nonxenogeneic components. In this study, platelet releasate was generated using a novel rapid thrombin activation method (tPR. ASCs grown in media supplemented with tPR proliferated much faster than ASCs grown in media supplemented with 10% fetal bovine serum. The cells also retained the ability to differentiate along chondrogenic, adipogenic, and osteogenic lineages. The tPR cultured ASCs displayed elevated expression of BMP-4 (5.7 ± 0.97-fold increase and BMP-2 (4.7 ± 1.3-fold increase and decreased expression of PDGF-B (4.0 ± 1.4-fold decrease and FGF-2 (33 ± 9.0-fold decrease. No significant changes in expression were seen with TGF-β and VEGF. This pattern of gene expression was consistent across different allogeneic tPR samples and different ASC lines. The use of allogeneic rapidly activated tPR to culture ASCs is associated with both an increased cell yield and a defined gene expression profile making it an attractive option for cell expansion prior to cell-based therapy for orthopedic applications.

  6. Mechanical loading induced expression of bone morphogenetic protein-2,alkaline phosphatase activity,and collagen synthesis in osteoblastic MC3T3-E1 cells

    Institute of Scientific and Technical Information of China (English)

    LU Hong-fei; MAI Zhi-hui; XU Ye; WANG Wei; AI Hong

    2012-01-01

    Background Bone morphogenetic protein(BMP)-2,alkaline phosphatase(ALP),and collagen typeⅠ?are known to play a critical role in the process of bone remodeling.However,the relationship between mechanical strain and the expression of BMP-2,ALP,and COL-Ⅰ?in osteoblasts was still unknown.The purpose of this study was to investigate the effects of different magnitudes of mechanical strain on osteoblast morphology and on the expression of BMP-2,ALP,and COL-Ⅰ.Methods Osteoblast-like cells were flexed at four deformation rates(0,6%,12%,and 18% elongation).The expression of BMP-2 mRNA,ALP,and COL-Ⅰ?in osteoblast-like cells were determined by real-time quantitative reverse transcription polymerase chain reaction,respectively.The results were subjected to analysis of variance(ANOVA)using SPSS 13.0 statistical software.Results The cells changed to fusiform and grew in the direction of the applied strain after the mechanical strain was loaded.Expression level of the BMP-2,ALP,and COL-Ⅰ?increased magnitude-dependently with mechanical loading in the experimental groups,and the 12% elongation group had the highest expression(P<0.05).Conclusion Mechanical strain can induce morphological change and a magnitude-dependent increase in the expression of BMP-2,ALP,and COL-Ⅰ?mRNA in osteoblast-like cells,which might influence bone remodeling in orthodontic treatment.

  7. Role of bone morphogenetic protein 2 in early acetabulum development and dysplastic acetabulum remodeling%BMP-2在髋臼软骨发育早期及发育不良髋臼软骨可逆性恢复过程中的作用研究

    Institute of Scientific and Technical Information of China (English)

    莫越强; 裴新红; 马瑞雪

    2015-01-01

    目的 研究BMP-2在髋臼软骨发育早期及发育不良髋臼软骨可逆性恢复过程中的作用.方法 通过伸髋内收、模拟襁褓体位固定新生大鼠双后肢,建立发育不良髋臼软骨模型.将髋臼标本经HE染色后观察比较正常及发育不良髋臼软骨组织形态学变化特点,同时用ELISA方法和PCR方法分别检测BMP-2、BMP-4、BMP-6、BMP-7的分泌及基因表达情况.将捆绑不同时间后的大鼠松绑,其中部分当场处死,其余大鼠继续喂养,最终至30日龄,建立发育不良髋臼软骨可逆性恢复模型.研究其髋臼软骨组织形态学恢复及BMP-2分泌变化情况.结果 正常大鼠髋臼软骨呈半圆形、容积大、表面光滑.发育不良髋臼软骨髋臼上缘肥厚,软骨发生变性,与周围组织分界不清.髋臼软骨BMP-2的分泌在正常大鼠7日龄和9日龄时出现高峰,分别为(13.7±0.29) ng/ml和(13.9±0.38) ng/ml.而在发育不良髋臼软骨中这一分泌高峰消失.在发育不良髋臼软骨可逆性恢复组,捆绑4d和6d的大鼠,BMP-2的分泌高峰出现延迟,都在15日龄时出现;而在捆绑8d及以上的大鼠,在松绑后继续喂养至30日龄,髋臼软骨组织形态无法恢复正常,并且BMP-2的分泌高峰未出现.结论 BMP-2的分泌可能是髋臼软骨早期发育情况的生物学标记之一.%Objective To explore the early-stage acetabulum development in normal and dysplastic acetabula and elucidate the function of bone morphogenetic protein 2 (BMP-2) in early acetabulum development and dysplastic acetabulum remodeling.Methods The rat model of dysplastic acetabulum was established by maintaining hips in a swaddling position.By analyzing the cartilage histologic characteristics,early-stage acetabulum developments were examined in normal and dysplastic acetabulum animals.Meantime,the mRNA expression and chondrocyte secretion of functional BMP-2,bone morphogenetic protein 4 (BMP-4),bone morphogenetic protein 6 (BMP-6) and bone

  8. Bone morphogenic protein-2 regulates the myogenic differentiation of PMVECs in CBDL rat serum-induced pulmonary microvascular remodeling

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Chang; Chen, Lin; Zeng, Jing; Cui, Jian; Ning, Jiao-nin [Department of Anesthesia, Southwest Hospital, The Third Military Medical University, Chongqing 400038 (China); Wang, Guan-song [Institute of Respiratory Disease, Xinqiao Hospital, The Third Military Medical University, Chongqing 400037 (China); Belguise, Karine; Wang, Xiaobo [Université P. Sabatier Toulouse III and CNRS, LBCMCP, 31062 Toulouse Cedex 9 (France); Qian, Gui-sheng [Institute of Respiratory Disease, Xinqiao Hospital, The Third Military Medical University, Chongqing 400037 (China); Lu, Kai-zhi [Department of Anesthesia, Southwest Hospital, The Third Military Medical University, Chongqing 400038 (China); Yi, Bin, E-mail: yibin1974@163.com [Department of Anesthesia, Southwest Hospital, The Third Military Medical University, Chongqing 400038 (China)

    2015-08-01

    Hepatopulmonary syndrome (HPS) is characterized by an arterial oxygenation defect induced by intrapulmonary vasodilation (IPVD) that increases morbidity and mortality. In our previous study, it was determined that both the proliferation and the myogenic differentiation of pulmonary microvascular endothelial cells (PMVECs) play a key role in the development of IPVD. However, the molecular mechanism underlying the relationship between IPVD and the myogenic differentiation of PMVECs remains unknown. Additionally, it has been shown that bone morphogenic protein-2 (BMP2), via the control of protein expression, may regulate cell differentiation including cardiomyocyte differentiation, neuronal differentiation and odontoblastic differentiation. In this study, we observed that common bile duct ligation (CBDL)-rat serum induced the upregulation of the expression of several myogenic proteins (SM-α-actin, calponin, SM-MHC) and enhanced the expression levels of BMP2 mRNA and protein in PMVECs. We also observed that both the expression levels of Smad1/5 and the activation of phosphorylated Smad1/5 were significantly elevated in PMVECs following exposure to CBDL-rat serum, which was accompanied by the down-regulation of Smurf1. The blockage of the BMP2/Smad signaling pathway with Noggin inhibited the myogenic differentiation of PMVECs, a process that was associated with relatively low expression levels of both SM-α-actin and calponin in the setting of CBDL-rat serum exposure, although SM-MHC expression was not affected. These findings suggested that the BMP2/Smad signaling pathway is involved in the myogenic differentiation of the PMVECs. In conclusion, our data highlight the pivotal role of BMP2 in the CBDL-rat serum-induced myogenic differentiation of PMVECs via the activation of both Smad1 and Smad5 and the down-regulation of Smurf1, which may represent a potential therapy for HPS-induced pulmonary vascular remodeling. - Highlights: • CBDL-rat serum promotes the myogenic

  9. Bone morphogenetic protein 2 promotes transforming growth factor β3-induced chondrogenesis of human osteoarthritic synovium-derived stem cells

    Institute of Scientific and Technical Information of China (English)

    RUI Yun-feng; DU Lin; WANG You; WANG Yang; LUI Pauline po-yee; TANG Ting-ting; CHAN Kai-ming; DAI Ke-rong

    2010-01-01

    Background Synovium-derived stem cells (SDSCs) with higher chondrogenic potential are attracting considerable attention as a cell source for cartilage regeneration. We investigated the effect of bone morphogenetic protein 2 (BMP-2) on transforming growth factor beta3 (TGF-β3)-induced chondrogenesis of SDSCs isolated from human osteoarthritic synovium in a pellet culture system. Methods The clonogenicity, stem cell marker expression and multi-differentiation potential of isolated SDSCs were determined by colony forming unit assay, flow cytometry and specific staining including alizarin red S, Oil red O and alcian blue staining, respectively. SDSCs pellet was cultured in chondrogenic medium with or without TGF-β3 or/and BMP-2. At day 21, the diameter and the weight of the pellets were measured. Chondrogenic differentiation of SDSCs was evaluated by Safranin O staining, immunohistochemical staining of collagen type Ⅱ, sulfated glycosaminoglycan (sGAG) synthesis and mRNA expression of collagen type Ⅱ, aggrecan, SOX9, link-protein, collagen type X and BMP receptor Ⅱ. Results Cells isolated under the optimized culturing density (104/60 cm2) showed clonogenicity and multi-differentiation potential. These cells were positive (>99%) for CD44, CD90, CD105 and negative (<10%) for CD34 and CD71. SDSCs differentiated to a chondrocytic phenotype in chondrogenic medium containing TGF-β3 with or without BMP-2. Safranin O staining of the extracellular matrix was positive and the expression of collagen type Ⅱ was detected. Cell pellets treated with TGF-β3 and BMP-2 were larger in diameter and weight, produced more sGAGs, and expressed higher levels of collagen type Ⅱ and other chondrogenic markers, except COL10A1, than medium with TGF-β3 alone. Conclusions SDSCs could be isolated from human osteoarthritic synovium. Supplementation with BMP-2 significantly promoted the in vitro TGF-β3-induced chondrogenic differentiation of SDSCs.

  10. Tissue transglutaminase is involved in mechanical load-induced osteogenic differentiation of human ligamentum flavum cells.

    Science.gov (United States)

    Chao, Yuan-Hung; Huang, Shih-Yung; Yang, Ruei-Cheng; Sun, Jui-Sheng

    2016-07-01

    Mechanical load-induced osteogenic differentiation might be the key cellular event in the calcification and ossification of ligamentum flavum. The aim of this study was to investigate the influence of tissue transglutaminase (TGM2) on mechanical load-induced osteogenesis of ligamentum flavum cells. Human ligamentum flavum cells were obtained from 12 patients undergoing lumbar spine surgery. Osteogenic phenotypes of ligamentum flavum cells, such as alkaline phosphatase (ALP), Alizarin red-S stain, and gene expression of osteogenic makers were evaluated following the administration of mechanical load and BMP-2 treatment. The expression of TGM2 was evaluated by real-time PCR, Western blotting, and enzyme-linked immunosorbent assay (ELISA) analysis. Our results showed that mechanical load in combination with BMP-2 enhanced calcium deposition and ALP activity. Mechanical load significantly increased ALP and OC gene expression on day 3, whereas BMP-2 significantly increased ALP, OPN, and Runx2 on day 7. Mechanical load significantly induced TGM2 gene expression and enzyme activity in human ligamentum flavum cells. Exogenous TGM2 increased ALP and OC gene expression; while, inhibited TG activity significantly attenuated mechanical load-induced and TGM2-induced ALP activity. In summary, mechanical load-induced TGM2 expression and enzyme activity is involved in the progression of the calcification of ligamentum flavum.

  11. Adenovirus-mediated siRNA targeting TNF-α and overexpression of bone morphogenetic protein-2 promotes early osteoblast differentiation on a cell model of Ti particle-induced inflammatory response in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Guo, H.H.; Yu, C.C.; Sun, S.X. [Affiliated Hospital of Ningxia Medical University, Department of Orthopedic Surgery, Yinchuan (China); Ma, X.J. [Ningxia Medical Autonomous Region of the First People' s Hospital, Department of Orthopedic Surgery, Yinchuan (China); Yang, X.C.; Sun, K.N.; Jin, Q.H. [Affiliated Hospital of Ningxia Medical University, Department of Orthopedic Surgery, Yinchuan (China)

    2013-10-02

    Wear particles are phagocytosed by macrophages and other inflammatory cells, resulting in cellular activation and release of proinflammatory factors, which cause periprosthetic osteolysis and subsequent aseptic loosening, the most common causes of total joint arthroplasty failure. During this pathological process, tumor necrosis factor-alpha (TNF-α) plays an important role in wear-particle-induced osteolysis. In this study, recombination adenovirus (Ad) vectors carrying both target genes [TNF-α small interfering RNA (TNF-α-siRNA) and bone morphogenetic protein 2 (BMP-2)] were synthesized and transfected into RAW264.7 macrophages and pro-osteoblastic MC3T3-E1 cells, respectively. The target gene BMP-2, expressed on pro-osteoblastic MC3T3-E1 cells and silenced by the TNF-α gene on cells, was treated with titanium (Ti) particles that were assessed by real-time PCR and Western blot. We showed that recombinant adenovirus (Ad-siTNFα-BMP-2) can induce osteoblast differentiation when treated with conditioned medium (CM) containing RAW264.7 macrophages challenged with a combination of Ti particles and Ad-siTNFα-BMP-2 (Ti-ad CM) assessed by alkaline phosphatase activity. The receptor activator of nuclear factor-κB ligand was downregulated in pro-osteoblastic MC3T3-E1 cells treated with Ti-ad CM in comparison with conditioned medium of RAW264.7 macrophages challenged with Ti particles (Ti CM). We suggest that Ad-siTNFα-BMP-2 induced osteoblast differentiation and inhibited osteoclastogenesis on a cell model of a Ti particle-induced inflammatory response, which may provide a novel approach for the treatment of periprosthetic osteolysis.

  12. Novel mouse model of spinal cord injury-induced heterotopic ossification

    Directory of Open Access Journals (Sweden)

    Heejae Kang, BA

    2014-11-01

    Full Text Available Heterotopic ossification (HO develops in about 20% to 30% of patients with spinal cord injury (SCI and significantly impairs their rehabilitation. There is no effective prevention or treatment for this condition at this time. Our current understanding of its etiology and pathophysiology is limited partially due to the lack of clinically relevant animal models. In this study, we report a novel mouse model of SCI-induced HO by administering a subthreshold dose of bone morphogenetic protein (BMP-2 to muscles in mice after SCI. Microcomputed tomography scanning showed that an intramuscular injection of 0.25 micrograms of BMP-2 causes significant HO in mice with SCI but not in control (sham surgery mice. Our analysis of gene expression showed significantly increased BMP signaling in quadriceps following SCI, suggesting that BMP signaling may play a role in SCI-induced HO. Administering 0.25 micrograms of BMP-2 to the front arms of the mice with SCI also results in the development of significant HO but not in control mice. This suggests that SCI causes a systematic osteogenic effect, which is not limited to paralyzed limbs. This novel mouse model will serve as a powerful tool in exploring the molecular mechanisms of SCI-induced HO, which may lead to novel treatment for this disease.

  13. Ovariectomy-Induced Osteoporosis Does Not Impact Fusion Rates in a Recombinant Human Bone Morphogenetic Protein-2-Dependent Rat Posterolateral Arthrodesis Model.

    Science.gov (United States)

    Ghodasra, Jason H; Nickoli, Michael S; Hashmi, Sohaib Z; Nelson, John T; Mendoza, Marco; Nicolas, Joseph D; Bellary, Sharath S; Sonn, Kevin; Ashtekar, Amruta; Park, Christian J; Babu, Jacob; Yun, Chawon; Ghosh, Anjan; Kannan, Abhishek; Stock, Stuart R; Hsu, Wellington K; Hsu, Erin L

    2016-02-01

    Study Design Randomized, controlled animal study. Objective Recombinant human bone morphogenetic protein-2 (rhBMP-2) is frequently utilized as a bone graft substitute in spinal fusions to overcome the difficult healing environment in patients with osteoporosis. However, the effects of estrogen deficiency and poor bone quality on rhBMP-2 efficacy are unknown. This study sought to determine whether rhBMP-2-induced healing is affected by estrogen deficiency and poor bone quality in a stringent osteoporotic posterolateral spinal fusion model. Methods Aged female Sprague-Dawley rats underwent an ovariectomy (OVX group) or a sham procedure, and the OVX animals were fed a low-calcium, low-phytoestrogen diet. After 12 weeks, the animals underwent a posterolateral spinal fusion with 1 μg rhBMP-2 on an absorbable collagen sponge. Representative animals were sacrificed at 1 week postoperative for alkaline phosphatase (ALP) and osteocalcin serum analyses. The remaining animals underwent radiographs 2 and 4 weeks after surgery and were subsequently euthanized for fusion analysis by manual palpation, micro-computed tomography (CT) imaging, and histologic analysis. Results The ALP and osteocalcin levels were similar between the control and OVX groups. Manual palpation revealed no significant differences in the fusion scores between the control (1.42 ± 0.50) and OVX groups (1.83 ± 0.36; p = 0.07). Fusion rates were 100% in both groups. Micro-CT imaging revealed no significant difference in the quantity of new bone formation, and histologic analysis demonstrated bridging bone across the transverse processes in fused animals from both groups. Conclusions This study demonstrates that estrogen deficiency and compromised bone quality do not negatively influence spinal fusion when utilizing rhBMP-2, and the osteoinductive capacity of the growth factor is not functionally reduced under osteoporotic conditions in the rat. Although osteoporosis is a risk factor

  14. The effects of BMP-2 gene medication on the reconstruction of osteolytic bone defect around implant%假体周围骨溶解性骨缺损的转骨形态发生蛋白-2基因治疗

    Institute of Scientific and Technical Information of China (English)

    严孟宁; 戴尅戎; 汤亭亭

    2008-01-01

    目的 模拟假体周围骨溶解环境,观察骨形态发生蛋白-2(BMP-2)基因治疗假体周围骨溶解性骨缺损的效果.方法 成年雄性Beagle犬6条,于股骨外髁造成假体周围3mm骨缺损区.1条动物的左侧缺损区植入1ml平均直径1μm的钛合金颗粒混悬液,右侧植入1ml磷酸盐缓冲液(PBS),观察造模结果;其他5条动物双侧植入1ml钛合金颗粒混悬液,于术后2个月取出假体,植入转BMP-2基因冻干骨或单纯冻干骨,二次术后3个月取材,行组织学、组织形态计量学观察植骨愈合替代及界面骨整合情况.结果 颗粒造模术后2个月可见典型的骨溶解界膜组织形成.翻修术后3个月,冻干骨组见较多植骨残余,假体-骨界面基本为软组织界膜,假体骨接触率(BIC)为(1.38±1.22)%;基因治疗组见少量植骨残余,假体-骨界面有点状骨接触,BIC为(12.96±1.61)%,两组差异有统计学意义(P<0.01).结论 采用BMP-2基因治疗可提高假体周围骨溶解性骨缺损的界面骨整合.%Objective With the osteolystic model,the simulating revision was done to investigate the effects of BMP-2 gene therapy on the reconstruction of periprosthetic bone defect.Methods A 3 mm bone defect around Ti alloy implant was created in both femoral lateral condyla of 6 adult Beagle dogs.One animal was left as a model to evaluate the effects of particles on the defect,with 1 ml Ti alloy particles averaged diameter of 1μm implanted on the left bone defect and 1 ml PBS on the right.Ten defects of the other 5 animals were implanted 1 ml Ti alloy particle and the revisions were done 2 months postoperatively.With the impaction grafting technique,two defects of each animal were reconstructed with freeze-dried allograft (FDB group),freeze-dried allograft loading autogenous bone marrow stromal cells transfected by Adv-BMP2 gene (gene group) respectively.The allograft healing and osseointegration of bone-implant interface were evaluated by histological

  15. Abnormal expression of key genes and proteins in the canonical Wnt/β-catenin pathway of articular cartilage in a rat model of exercise-induced osteoarthritis

    OpenAIRE

    LIU, SHEN-SHEN; ZHOU, PU; Zhang, Yanqiu

    2016-01-01

    To investigate the molecular pathogenesis of the canonical Wnt/β-catenin pathway in exercise-induced osteoarthritis (OA), 30 male healthy Sprague Dawley rats were divided into three groups (control, normal exercise-induced OA and injured exercise-induced OA groups) in order to establish the exercise-induced OA rat model. The mRNA and protein expression levels of Runx-2, BMP-2, Ctnnb1, Sox-9, collagen II, Mmp-13, Wnt-3a and β-catenin in chon-drocytes were detected by reverse transcription-quan...

  16. Restoration of segmental bone defects by using chitosan-coated pressed calcium sulfate pellet com-bined with rhBMP-2%壳聚糖包衣加压硫酸钙片复合重组人骨形态发生蛋白-2修复兔节段性骨缺损

    Institute of Scientific and Technical Information of China (English)

    崔旭; 张伯勋

    2009-01-01

    Objective To compare the effect of calcium sulfate pellets made by different methods in repair of segmental radial defect of rabbits. Methods Eighty white New Zealand rabbits were sub-jected to defects of middle part of the left radial bone and divided into four groups according to repair ma-terials: control group (Group A, implanted with no artificial bone substitute), uncoated pressed calcium sulfate pellets (Group B), coated pressed calcium sulfate pellets (Group C) and coated pressed calcium sulfate pellets combined with rhBMP-2 (Group D). Histologic examination and biological test were done at 4, 8 and 12 weeks after operation. The data were processed with mono-factor variance analysis. Re-sults New bone formation was found on the defected bone in Group D and Group C, with better in Group D. The bone strength test showed that the anti-bending strength was (39.6±1.7) % in Group C and (47.5±2.1) % in Group D, which were higher than (21.3±2.7) % in Group A and (23.6±3.3) % in Group B, with higher anti-bending strength in Group D than that in Group C (F = 125.3 ,P <0.01). Conclusions For restoration of segmental bone defects, chitosan-coated pressed calcium sulfate pellet shows relatively high density and slightly slow resorption, which closely coincides with the growth rate of new bone. The coated pellet combined with rhBMP-2 can enhance its osteogeneais in restoring segmental Done defects.%目的 比较不同方法 制备的硫酸钙片修复兔桡骨节段性骨缺损的效果. 方法 新西兰大白兔80只随机数字表法分为A、B、C、D组,造成左桡骨中段骨缺损,采用三种经不同方法 制备的硫酸钙片修复.A组:空白对照组;B组:加压方法 制备的硫酸钙组;C组:壳聚糖包衣的加压硫酸钙组;D组:壳聚糖包衣的复合重组人骨形态发生蛋白-2(rhBMP-2)加压硫酸钙组.术后4,8,12周进行组织学检查和生物力学测试,实验数据采用单因素方差分析. 结果 D组、C组骨缺损愈合,而

  17. 复合骨形态蛋白-2的聚乳酸-乙醇酸共聚物/磷酸三钙人工骨结合带血供组织修复羊大段骨缺损的试验研究%An experimental research of composite of BMP-2 and PLGA/tricalcium phosphate with vascularized ulna or vascularized periosteum in repairing large segmental defect of sheeps' radius

    Institute of Scientific and Technical Information of China (English)

    徐建强; 张树明; 周密; 李长庚

    2012-01-01

    Objective To study the effects of the composite of PLGA-TCP-BMP-2 artificial bone with vascularized ulna or vascularized periosteum in repairing the large segmental defect of sheep's radius. Methods Thirty millimeter defects were made in middle segments of sheep's radius and ulna. In group A, artificial bone with vascularized ulna were implanted into the radial defects. Artificial bone with vascularized periosteum were implanted into the radial defects in group B. Artificial bone were implanted into the radial defects in group C. No material was implanted in group D. Plates were used to fix the bone. X ray was used to evaluate the repairing effects. Animals were sacrificed 24 weeks after operation to make CT analysis and histological evaluation. Radiological and scoring histological systems were used to evaluate the plains. Results Twenty four weeks after surgery, radiological scoring systems revealed that group A was better than other groups. Evaluation of the morphologic features of the regenerating bone showed that active osteogenesis occurred at the site of bone defect and complete bony union was confirmed in animals of group A. In group B, corporation between new bone and fracture site could be seen. However, the lamellar bone was rather slim. In group C, new lamellar bone and lacuna were found in deranged alignment. In group D, deranged collagenous fibrous tissue, instead of osseointegration was found at the site of bone defect. Within the porous structure in animals of group A, B, and C, no residual artificial materials or muscle fibers were observed. According to histological scoring systems revealed that group A was better than other groups. Scores of group D was lower than other groups. Conclusion The composite of BMP-2 and PLGA/tricalcium phosphate with vascularized ulna or vascularized periosteum could repair large segmental defect of sheeps' radius satisfactorily.%目的 研究复合骨形态蛋白-2的聚乳酸-乙醇酸共聚物/磷酸三钙(PLGA-TCP-BMP

  18. Is 1, 25-dihydroxyvitamin D3 an ideal substitute for dexamethasone for inducing osteogenic differentiation of human adipose tissue-derived stromal cells in vitro?

    Institute of Scientific and Technical Information of China (English)

    ZHOU Yong-sheng; LIU Yun-song; TAN Jian-guo

    2006-01-01

    Background Human adipose tissue-derived stromal cells (hADSCs) can be induced to differentiate along anosteoblastic lineage under stimulation of dexamethasone (DEX). Recent studies, however, have questioned theefficacy of glucocorticoids such as DEX in mediating the osteogenesis process of skeletal progenitor cells andprocessed lipoaspirate cells. Is it possible to find a substitute for DEX? Therefore, this study was designed toinvestigate osteogenic capacity and regulating mechanisms for osteoblastic differentiation of hADSCs bycomparing osteogenic media (OM) containing either 1, 25-dihydroxyvitamin D3 (VD) or DEX and determine ifVD was an ideal substitute for DEX as an induction agent for the osteogenesis of hADSCs.Methods Osteogenic differentiation of hADSCs was induced by osteogenic medium (OM) containing either 10nmol/L VD or 100 nmol/L DEX. Differentiation of hADSCs into osteoblastic lineage was identified by alkalinephosphatase (ALP) staining, von Kossa staining, and reverse transcription-polymerase chain reaction assays formRNA expression of osteogenesis-related genes such as type Ⅰ collagen (COL Ⅰ), bone sialoprotein (BSP),osteocalcin (OC), bone morphogenetic protein (BMP)-2, BMP-4, BMP-6, BMP-7, runt-related transcriptionfactor 2/core binding factor α1 (Runx2/Cbfal), osterix (Osx), and LIM mineralization protein-1 (LMP-1).Results von Kossa staining revealed that the differentiated cells induced by both VD and DEX weremineralized in vitro. They also expressed osteoblast-related markers, such as ALP, COL I, BSP, and OC.Runx2/Cbfal, Osx, BMP-6, and LMP-1 were upregulated during VD and DEX-induced hADSC osteoblasticdifferentiation, but BMP-4, BMP-7 were not. BMP-2 was only expressed in VD-induced differentiated cells.Conclusions VD or DEX-induced hADSCs differentiate toward the osteoblastic lineage in vitro. Runx2/Cbfa1,Osx, BMP-2, BMP-6, and LMP-1 are involved in regulating osteoblastic differentiation of hADSCs, but BMP-4,BMP-7 are not. VD, but not DEX

  19. Autophagy inhibits PDGF-BB-induced calcification in vascular smooth muscle cells

    Institute of Scientific and Technical Information of China (English)

    PEI Qian-qian; MEI Han; ZHANG Xu-hui; DONG Li-hua

    2016-01-01

    AIM:To investigate the relationship between autophagy and calcification in vascular smooth muscle cells ( VSMCs) after platelet-derived growth factor (PDGF)-BB stimulation.METHODS:Cultured VSMCs were stimulated with PDGF-BB for different time, the expression of vascular calcification-related proteins and autophagy-related proteins were detected by Western blot .The interaction be-tween Beclin1 and PI3KC3 was detected by co-immunoprecipitation.RESULTS: The expression of BMP2 and ALP showed a trend from decline to rise.ALP slumped at 12 h, and BMP2 slumped at 6 h.Moreover, the expression of Beclin-1 showed a trend from rise to decline, and peaked at 12 h.The conversion of LC3-ⅠtoⅡincreased in a time-dependent manner , and peaked at 24 h.The ex-pression of BMP2 and ALP was increased in VSMCs incubated with PDGF-BB and autophagy inhibitor 3-MA, compared with PDGF-BB-stimulated VSMCs.Furthermore, the interaction between Beclin1 and PI3KC3 was enhanced at 6 h after PDGF-BB stimulated, peaked at 12 h, and kept in high level at 24 h.Moreover, the phosphorylation level of Beclin 1 was enhanced by PDGF-BB stimulation, and peaked at 6 h.CONCLUSION:Our findings demonstrate that PDGF-BB-induced autophagy inhibits VSMC calcification by en-hancing Beclin1 phosphorylation and interaction between Beclin 1 and PI3KC3.

  20. Feasibility of determination of low-head hydroelectric power development at existing sites. Big Blue River Co-dependent Hydroelectric Development: feasibility study

    Energy Technology Data Exchange (ETDEWEB)

    Wacker, H. Steve; Feuerberg, Stan; Lawrence, John D.; Pal, Parimal C.; Trick, Dr., William T.

    1979-03-01

    The technical, economic, environmental, safety, and financial aspects of redeveloping 7 dam sites in Nebraska for hydroelectric power generation were studied. The Big Blue River Co-dependent Hydroelectric Development was found to be a technically feasible concept, for both redevelopment and in some cases rehabilitation of seven existing sites. The proposed redevelopment project will include seven installations with a recommended nominally rated redeveloped capacity of 3920 kW ranging from 120 kW at the northernmost site in Seward County to 1500 kW at Barneston. The average annual gross generation expected from the seven redeveloped sites totals 11,555,000 kWh. It is estimated that the total cost of redevelopment of these seven sites will be $14,090,000 at 1979 price levels, providing power at an average levelized cost of about 5.3 cents per kWh based on 7% cost of money, a mid-1983 commissioning date, and allowing for funds during construction and cost escalation over a 30-year period. Rehabilitation of original installations at Crete, Dewitt, Blue Springs and Barneston is technically feasible for a total installed capacity of 1415 kW with annual average gross generation of 6,675,000 kWh. The total cost of this rehabilitation is estimated as $3,372,000 at 1979 price levels, or about 2.4 cents per kWh, levelized on a similar basis. Rehabilitation of the Barneston site alone for an installed capacity of 760 kW and annual generation of 3,581,000 kWh is both technically and economically feasible. The total estimated cost of this alternative is $668,000, providing power at a cost of about 1.9 cents per kWh at 1979 price levels. The benefit-cost ratio for Barneston rehabilitation is estimated as 1.23.

  1. 重组人骨形态发生蛋白2缓释体对铬磨损颗粒诱导的溶骨效应的影响%Slow-release recombinant human bone morphogenetic protein-2 suppresses chromium wear particle-induced osteolysis in rats

    Institute of Scientific and Technical Information of China (English)

    李干; 李奇; 林荔军; 段鑫; 张西旗

    2012-01-01

    Objective To observe the effect of a slow-release recombinant human bone morphogenetic protein-2 (rhBMP-2) formulation on the expressions of receptor activator of nuclear factor-KB ligand (RANKL) and osteoprotegerin (OPG) in a murine air pouch model of bone implantation. Methods A cranial bone allograft was implanted in the air pouch induced on the back of the recipients. The rat models were then randomized into 5 groups, including a blank control group, chromium particle group, and 3 rhBMP-2 groups receiving 50,100 or 200 μg/L slow-release rhBMP-2 in addition to chromium particles. Three weeks later, the expressions of RANKL and OPG in the air pouch was detected using Western blotting and RT-PCR, and the positively stained area for osteoclasts in the bone graft was determined with TRAP staining for drug effect assessment. Results RANKL and OPG expressions were found in the air pouches in all the 5 groups. RANKL and OPG protein and mRNA expressions, RANKL/OPG ratio and osteoclast staining area in the bone graft were the highest in chromium particle group (P0.05). Conclusion Chromium particles can cause osteolysis by increasing the RANKL/OPG ratio in rats, and intervention with slow-release rhBMP-2 can significantly promote bone formation and suppress bone resorption by decreasing RANKL/OPG ratio.%目的 建立大鼠植骨气囊模型,观察在不同浓度重组人骨形态发生蛋白2(rhBMP-2)缓释体干预下气囊内组织的破骨细胞分化因子(RANKL)、骨破坏素(OPG)表达情况.方法 在大鼠背部注入空气形成气囊,取同源大鼠的颅骨植入气囊内.将已制成的植骨气囊模型大鼠分成5组:空白组、铬颗粒组、50 μg/L rhBMP-2缓释体+铬颗粒组、100 μg/L rhBMP-2缓释体+铬颗粒组和200 μg/L rhBMP-2缓释体+铬颗粒组.各组分别用药处理,2周后取出囊腔内组织进行RANKL、OPG的Wester-blot、Rt-PCR检测,并对囊腔内骨片行TRAP染色,用计算机图像分析技术测定骨片破骨细胞染

  2. Strenuous Treadmill Running Induces a Chondrocyte Phenotype in Rat Achilles Tendons

    Science.gov (United States)

    Xu, Shao-Yong; Li, Shu-Fen; Ni, Guo-Xin

    2016-01-01

    Background Although tendinopathy is common, its underlying pathogenesis is poorly understood. This study aimed to investigate the possible pathogenesis of tendinopathy. Material/Methods In this study, a total of 24 rats were randomly and evenly divided into a control (CON) group and a strenuous treadmill running (STR) group. Animals in the STR group were subjected to a 12-week treadmill running protocol. Subsequently, all Achilles tendons were harvested to perform histological observation or biochemical analyses. Results Histologically, hypercellularity and round cells, as well as disorganized collagen fibrils, were presented in rat Achilles tendon sections from the STR group. Furthermore, our results showed that the expression of aggrecan, collagen type II (Col II), and Sex-Determining Region Y Box 9 (Sox 9) were markedly increased in the STR group compared with that in the CON group. Additionally, the mRNA expression of bone morphogenetic protein-2 (BMP-2) and biglycan was significantly up-regulated in the STR group in contrast to that in CON group. Conclusions These results suggest that a 12-week strenuous treadmill running regimen can induce chondrocyte phenotype in rat Achilles tendons through chondrogenic differentiation of tendon stem cells (TSCs) by BMP-2 signaling. PMID:27742920

  3. BMP type I receptor ALK2 is required for angiotensin II-induced cardiac hypertrophy.

    Science.gov (United States)

    Shahid, Mohd; Spagnolli, Ester; Ernande, Laura; Thoonen, Robrecht; Kolodziej, Starsha A; Leyton, Patricio A; Cheng, Juan; Tainsh, Robert E T; Mayeur, Claire; Rhee, David K; Wu, Mei X; Scherrer-Crosbie, Marielle; Buys, Emmanuel S; Zapol, Warren M; Bloch, Kenneth D; Bloch, Donald B

    2016-04-15

    Bone morphogenetic protein (BMP) signaling contributes to the development of cardiac hypertrophy. However, the identity of the BMP type I receptor involved in cardiac hypertrophy and the underlying molecular mechanisms are poorly understood. By using quantitative PCR and immunoblotting, we demonstrated that BMP signaling increased during phenylephrine-induced hypertrophy in cultured neonatal rat cardiomyocytes (NRCs), as evidenced by increased phosphorylation of Smads 1 and 5 and induction of Id1 gene expression. Inhibition of BMP signaling with LDN193189 or noggin, and silencing of Smad 1 or 4 using small interfering RNA diminished the ability of phenylephrine to induce hypertrophy in NRCs. Conversely, activation of BMP signaling with BMP2 or BMP4 induced hypertrophy in NRCs. Luciferase reporter assay further showed that BMP2 or BMP4 treatment of NRCs repressed atrogin-1 gene expression concomitant with an increase in calcineurin protein levels and enhanced activity of nuclear factor of activated T cells, providing a mechanism by which BMP signaling contributes to cardiac hypertrophy. In a model of cardiac hypertrophy, C57BL/6 mice treated with angiotensin II (A2) had increased BMP signaling in the left ventricle. Treatment with LDN193189 attenuated A2-induced cardiac hypertrophy and collagen deposition in left ventricles. Cardiomyocyte-specific deletion of BMP type I receptor ALK2 (activin-like kinase 2), but not ALK1 or ALK3, inhibited BMP signaling and mitigated A2-induced cardiac hypertrophy and left ventricular fibrosis in mice. The results suggest that BMP signaling upregulates the calcineurin/nuclear factor of activated T cell pathway via BMP type I receptor ALK2, contributing to cardiac hypertrophy and fibrosis. PMID:26873969

  4. TGF-β prevents phosphate-induced osteogenesis through inhibition of BMP and Wnt/β-catenin pathways.

    Directory of Open Access Journals (Sweden)

    Fátima Guerrero

    Full Text Available BACKGROUND: Transforming growth factor-β (TGF-β is a key cytokine during differentiation of mesenchymal stem cells (MSC into vascular smooth muscle cells (VSMC. High phosphate induces a phenotypic transformation of vascular smooth muscle cells (VSMC into osteogenic-like cells. This study was aimed to evaluate signaling pathways involved during VSMC differentiation of MSC in presence or not of high phosphate. RESULTS: Our results showed that TGF-β induced nuclear translocation of Smad3 as well as the expression of vascular smooth muscle markers, such as smooth muscle alpha actin, SM22α, myocardin, and smooth muscle-myosin heavy chain. The addition of high phosphate to MSC promoted nuclear translocation of Smad1/5/8 and the activation of canonical Wnt/β-catenin in addition to an increase in BMP-2 expression, calcium deposition and alkaline phosphatase activity. The administration of TGF-β to MSC treated with high phosphate abolished all these effects by inhibiting canonical Wnt, BMP and TGF-β pathways. A similar outcome was observed in high phosphate-treated cells after the inhibition of canonical Wnt signaling with Dkk-1. Conversely, addition of both Wnt/β-catenin activators CHIR98014 and lithium chloride enhanced the effect of high phosphate on BMP-2, calcium deposition and alkaline phosphatase activity. CONCLUSIONS: Full VSMC differentiation induced by TGF-β may not be achieved when extracellular phosphate levels are high. Moreover, TGF-β prevents high phosphate-induced osteogenesis by decreasing the nuclear translocation of Smad 1/5/8 and avoiding the activation of Wnt/β-catenin pathway.

  5. In vascular smooth muscle cells paricalcitol prevents phosphate-induced Wnt/β-catenin activation.

    Science.gov (United States)

    Martínez-Moreno, Julio M; Muñoz-Castañeda, Juan R; Herencia, Carmen; Oca, Addy Montes de; Estepa, Jose C; Canalejo, Rocio; Rodríguez-Ortiz, Maria E; Perez-Martinez, Pablo; Aguilera-Tejero, Escolástico; Canalejo, Antonio; Rodríguez, Mariano; Almadén, Yolanda

    2012-10-15

    The present study investigates the differential effect of two vitamin D receptor agonists, calcitriol and paricalcitol, on human aortic smooth muscle cells calcification in vitro. Human vascular smooth muscle cells were incubated in a high phosphate (HP) medium alone or supplemented with either calcitriol 10(-8)M (HP + CTR) or paricalcitol 3·10(-8) M (HP + PC). HP medium induced calcification, which was associated with the upregulation of mRNA expression of osteogenic factors such as bone morphogenetic protein 2 (BMP2), Runx2/Cbfa1, Msx2, and osteocalcin. In these cells, activation of Wnt/β-catenin signaling was evidenced by the translocation of β-catenin into the nucleus and the increase in the expression of direct target genes as cyclin D1, axin 2, and VCAN/versican. Addition of calcitriol to HP medium (HP + CTR) further increased calcification and also enhanced the expression of osteogenic factors together with a significant elevation of nuclear β-catenin levels and the expression of cyclin D1, axin 2, and VCAN. By contrast, the addition of paricalcitol (HP + PC) not only reduced calcification but also downregulated the expression of BMP2 and other osteoblastic phenotype markers as well as the levels of nuclear β-catenin and the expression of its target genes. The role of Wnt/β-catenin on phosphate- and calcitriol-induced calcification was further demonstrated by the inhibition of calcification after addition of Dickkopf-related protein 1 (DKK-1), a specific natural antagonist of the Wnt/β-catenin signaling pathway. In conclusion, the differential effect of calcitriol and paricalcitol on vascular calcification appears to be mediated by a distinct regulation of the BMP and Wnt/β-catenin signaling pathways.

  6. Mineral trioxide aggregate induces osteoblastogenesis via Atf6

    Directory of Open Access Journals (Sweden)

    Toyonobu Maeda

    2015-06-01

    Full Text Available Mineral trioxide aggregate (MTA has been recommended for various uses in endodontics. To understand the effects of MTA on alveolar bone, we examined whether MTA induces osteoblastic differentiation using MC3T3-E1 cells. MTA enhanced mineralization concomitant with alkaline phosphatase activity in a dose- and time-dependent manner. MTA increased production of collagens (Type I and Type III and matrix metalloproteinases (MMP-9 and MMP-13, suggesting that MTA affects bone matrix remodeling. MTA also induced Bglap (osteocalcin but not Bmp2 (bone morphogenetic protein-2 mRNA expression. We observed induction of Atf6 (activating transcription factor 6, an endoplasmic reticulum (ER stress response transcription factor mRNA expression and activation of Atf6 by MTA treatment. Forced expression of p50Atf6 (active form of Atf6 markedly enhanced Bglap mRNA expression. Chromatin immunoprecipitation assay was performed to investigate the increase in p50Atf6 binding to the Bglap promoter region by MTA treatment. Furthermore, knockdown of Atf6 gene expression by introduction of Tet-on Atf6 shRNA expression vector abrogated MTA-induced mineralization. These results suggest that MTA induces in vitro osteoblastogenesis through the Atf6–osteocalcin axis as ER stress signaling. Therefore, MTA in endodontic treatment may affect alveolar bone healing in the resorbed region caused by pulpal infection.

  7. Surface functionalization of nanoporous alumina with bone morphogenetic protein 2 for inducing osteogenic differentiation of mesenchymal stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Song, Yuanhui; Ju, Yang; Morita, Yasuyuki; Xu, Baiyao [Department of Mechanical Science and Engineering, Nagoya University, Nagoya 464-8603 (Japan); Song, Guanbin [Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044 (China)

    2014-04-01

    Many studies have demonstrated the possibility to regulate cellular behavior by manipulating the specific characteristics of biomaterials including the physical features and chemical properties. To investigate the synergistic effect of chemical factors and surface topography on the growth behavior of mesenchymal stem cells (MSCs), bone morphorgenic protein 2 (BMP2) was immobilized onto porous alumina substrates with different pore sizes. The BMP2-immobilized alumina substrates were characterized with scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS). Growth behavior and osteogenic differentiation of MSCs cultured on the different substrates were investigated. Cell adhesion and morphological changes were observed with SEM, and the results showed that the BMP2-immobilized alumina substrate was able to promote adhesion and spreading of MSCs. MTT assay and immunofluorescence staining of integrin β1 revealed that the BMP2-immobilized alumina substrates were favorable for cell growth. To evaluate the differentiation of MSCs, osteoblastic differentiation markers, such as alkaline phosphatase (ALP) activity and mineralization, were investigated. Compared with those of untreated alumina substrates, significantly higher ALP activities and mineralization were detected in cells cultured on BMP2-immobilized alumina substrates. The results suggested that surface functionalization of nanoporous alumina substrates with BMP2 was beneficial for cell growth and osteogenic differentiation. With the approach of immobilizing growth factors onto material substrates, it provided a new insight to exploit novel biofunctional materials for tissue engineering. - Highlights: • BMP2 was immobilized onto nanoporous alumina substrates with different pore sizes. • BMP2-immobilized substrates were able to promote adhesion and spreading of MSCs. • BMP2-immobilized substrates were favorable for cell growth of MSCs. • BMP2-immobilized substrates promoted osteogenic

  8. Human bone morphogenetic protein-2 gene transfer induces human mesenchymal stem cell proliferation and differentiation in vitro

    Institute of Scientific and Technical Information of China (English)

    李军; 范清宇; 钱济先; 马保安; 周勇; 张明华

    2004-01-01

    Objective: To identify eukaryotic expression vector of human bone morphogenetic protein 2 pcDNA3/BMP2, verify its expression in transfected human mesenchymal stem cells (hMSCs) and the effect on hMSCs differentiation.Methods: The BMP2 gene was cloned into a eukaryotic expression vector pcDNA3. Transfected the recombinant into hMSCs by liposome. Immunnohistochemistry and in situ hybridization methods were used to identify the expression of BMP2 mRNA and protein; ALP and Von Kossa stains were performed to identify the BMP2 gene differentiated effect on the hMSCs. Results: The pcDNA3/BMP2 fragments were as large as theory. BMP2 mRNA and protein were expressed and synthesized both in 48 h and 4 weeks after transfection, the ALP and Ca deposit exhibition, which marked the osteogenic lineage of hMSCs,were enhanced and sped. Conclusion: Transfection of pcDNA3/BMP2 is able to provide transient and persistent expression in hMSCs, and promote the MSCs differentiation to osteogenic lineage.

  9. Bone marrow mesenchymal stem cells, collagen scaffold and BMP-2 for rat spinal fusio

    OpenAIRE

    Arrabal, Pilar M.; de Visser, R; Cifuentes, Manuel; Becerra Ratia, José; Jiménez-Enjuto, E.

    2013-01-01

    The use of autograft for posterolateral spinal fusion, continue being considered the gold standard for the treatment of spine pathologies. However, due to complications such as donor site morbidity, increased operating time, and limited supply, the use of allograft has become an acceptable practice especially in multisegment arthrodesis or in patients with previous graft harvests. Since their use involves the risk of immune response or disease transmission and fusion rates are not as good as ...

  10. Stimulation of porcine bone marrow stromal cells by hyaluronan, dexamethasone and rhBMP-2

    DEFF Research Database (Denmark)

    Zou, Xuenong; Li, Haisheng; Chen, Li;

    2004-01-01

    In the interest of optimizing osteogenesis in in vitro, the present study sought to determine how porcine bone marrow stromal cell (BMSc) would respond to different concentrations of hyaluronan (HY) and its different combinations with dexamethasone (Dex) and recombinant human bone morphogenic pro...

  11. Derivation of a novel undifferentiated human foetal phenotype in serum-free cultures with BMP-2

    OpenAIRE

    Mirmalek-Sani, Sayed-Hadi; Stokes, Paula J; Tare, Rahul S; Ralph, Esther J; Inglis, Stefanie; Hanley, Neil A.; Franchesca D. Houghton; Oreffo, Richard OC

    2009-01-01

    Skeletal stem and progenitor populations provide a platform for cell-based tissue regeneration strategies. Optimized conditions for ex vivo expansion will be critical and use of serum-free culture may allow enhanced modelling of differentiation potential. Maintenance of human foetal femur-derived cells in a chemically defined medium (CDM) with activin A and fibroblast growth factor-2 generated a unique undifferentiated cell population in comparison to basal cultures, with significantly reduce...

  12. Iron transferrin regulates hepcidin synthesis in primary hepatocyte culture through hemojuvelin and BMP2/4

    OpenAIRE

    Lin, Lan; Valore, Erika V.; Nemeth, Elizabeta; Goodnough, Julia B; Gabayan, Victoria; Ganz, Tomas

    2007-01-01

    The peptide hormone hepcidin is the principal regulator of systemic iron homeostasis. We examined the pathway by which iron stimulates the production of hepcidin. In humans who ingested 65 mg of iron, the increase in transferrin saturation preceded by hours the increase in urinary hepcidin excretion. Increases in urinary hepcidin concentrations were proportional to the increment in transferrin saturation. Paradoxically, in previous studies in primary hepatocytes and cell lines, hepcidin respo...

  13. Sustained Release of BMP-2 in Bioprinted Alginate for Osteogenicity in Mice and Rats

    NARCIS (Netherlands)

    Poldervaart, M.T.; Wang, H.; Stok, J. van der; Weinans, H.; Leeuwenburgh, S.C.G.; Oner, F.C.; Dhert, W.J.; Alblas, J.

    2013-01-01

    The design of bioactive three-dimensional (3D) scaffolds is a major focus in bone tissue engineering. Incorporation of growth factors into bioprinted scaffolds offers many new possibilities regarding both biological and architectural properties of the scaffolds. This study investigates whether the s

  14. Sustained release of BMP-2 in bioprinted alginate for osteogenicity in mice and rats

    NARCIS (Netherlands)

    Poldervaart, M.T.; Wang, H.; Van der Stok, J.; Weinans, H.H.; Leeuwenburgh, S.C.G.; Cumhur Öner, F.; Dhert, W.J.A.; Alblas, J.

    2013-01-01

    The design of bioactive three-dimensional (3D) scaffolds is a major focus in bone tissue engineering. Incorporation of growth factors into bioprinted scaffolds offers many new possibilities regarding both biological and architectural properties of the scaffolds. This study investigates whether the s

  15. Effect of local sequential VEGF and BMP-2 delivery on ectopic and orthotopic bone regeneration

    NARCIS (Netherlands)

    Kempen, Diederik H. R.; Lu, Lichun; Heijink, Andras; Hefferan, Theresa E.; Creemers, Laura B.; Maran, Avudaiappan; Yaszemski, Michael J.; Dhert, Wouter J. A.

    2009-01-01

    Bone regeneration is a coordinated cascade of events regulated by several cytokines and growth factors. Angiogenic growth factors are predominantly expressed during the early phases for re-establishment of the vascularity, whereas osteogenic growth factors are continuously expressed during bone form

  16. Lineage tracking of mesenchymal and endothelial progenitors in BMP-induced bone formation.

    Science.gov (United States)

    Kolind, Mille; Bobyn, Justin D; Matthews, Brya G; Mikulec, Kathy; Aiken, Alastair; Little, David G; Kalajzic, Ivo; Schindeler, Aaron

    2015-12-01

    To better understand the relative contributions of mesenchymal and endothelial progenitor cells to rhBMP-2 induced bone formation, we examined the distribution of lineage-labeled cells in Tie2-Cre:Ai9 and αSMA-creERT2:Col2.3-GFP:Ai9 reporter mice. Established orthopedic models of ectopic bone formation in the hind limb and spine fusion were employed. Tie2-lineage cells were found extensively in the ectopic bone and spine fusion masses, but co-staining was only seen with tartrate-resistant acid phosphatase (TRAP) activity (osteoclasts) and CD31 immunohistochemistry (vascular endothelial cells), and not alkaline phosphatase (AP) activity (osteoblasts). To further confirm the lack of a functional contribution of Tie2-lineage cells to BMP-induced bone, we developed conditional knockout mice where Tie2-lineage cells are rendered null for key bone transcription factor osterix (Tie2-cre:Osx(fx/fx) mice). Conditional knockout mice showed no difference in BMP-induced bone formation compared to littermate controls. Pulse labeling of mesenchymal cells with Tamoxifen in mice undergoing spine fusion revealed that αSMA-lineage cells contributed to the osteoblastic lineage (Col2.3-GFP), but not to endothelial cells or osteoclast populations. These data indicate that the αSMA+ and Tie2+ progenitor lineages make distinct cellular contributions to bone formation, angiogenesis, and resorption/remodeling. PMID:26141839

  17. Effects on differentiation of steroid-induced bone marrow mesenchymal stem cells of rats by targeting regulation of microRNA-27a on peroxisome proliferator activated receptor-γ and bone morphogenetic protein-2%微小RNA-27a靶向调控过氧化物酶体增殖子活化受体-γ和骨形态发生蛋白-2对激素诱导大鼠骨髓间充质干细胞分化的影响

    Institute of Scientific and Technical Information of China (English)

    王光辉; 李月白; 李明; 谷晨熙; 宋石; 单杰; 赵国强; 王义生

    2015-01-01

    目的 检测微小RNA(miRNA,miR)-27a调控过氧化物酶体增殖子活化受体-γ(PPAR-γ)和骨形态发生蛋白-2(BMP-2)对骨髓间充质干细胞(BMSCs)分化的影响.方法 将培养的40只大鼠BMSCs,随机分4组,正常对照组:细胞不作特殊处理;模型组:细胞给予1×10-7 mol/L地塞米松;无关序列组:将无关序列基因电转入细胞,给予1×10-7 mol/L地塞米松;实验组:将具有双向靶向作用的miR-27a电转入细胞,给予1×10-7 mol/L地塞米松.采用实时荧光定量聚合酶链反应(RT-qPCR)技术测定PPAR-γ和BMP-2 mRNA的相对表达量.结果 处理细胞7d时,实验组细胞中PPAR-γmRNA的相对表达量(1.203±0.111)较模型组(1.877±0.225)、无关序列组(1.913±0.195)明显降低(P<0.05),近似于正常组(1.000)且与其差异无统计学意义(P>0.05).实验组细胞中BMP-2 mRNA的相对表达量(0.832±0.105)较模型组(0.455±0.051)、无关序列组(0.422±0.038)明显升高(P<0.05),近似于正常组(1.000)且与其差异无统计学意义(P>0.05).结论 miR-27a能够有效抑制PPAR-γ表达,维持BMP-2表达.%Objective To explore the effect on the differentiation of steroid-induced bone marrow mesenchymal stem cells (BMSCs) of rats by tarteting regulation of microRNA (miRNA, miR)-27a on peroxisome proliferator-activated receptor-γ (PPAR-γ) and bone morphogenetic protein-2 (BMP-2).Methods BMSCs of 40 rats were expanded and randomly divided into 4 groups.In normal control group, the cells were not treated.In model group, the cells were treated with 1 × 10-7 mol/L dexamethasone.In irrelative sequence group, the cells were electroporated with the irrelative sequence that was ineffective at targeting the PPAR-γgene, and treated with 1 × 10-7 mol/L dexamethasone.In experimental group, the cells were electroporated with miR-27a and treated with 1 × 10-7 mol/L dexamethasone.The real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) was used to detected the

  18. Extracellular Vesicles Derived from Osteogenically Induced Human Bone Marrow Mesenchymal Stem Cells Can Modulate Lineage Commitment

    Directory of Open Access Journals (Sweden)

    Margarida Martins

    2016-03-01

    Full Text Available The effective osteogenic commitment of human bone marrow mesenchymal stem cells (hBMSCs is critical for bone regenerative therapies. Extracellular vesicles (EVs derived from hBMSCs have a regenerative potential that has been increasingly recognized. Herein, the osteoinductive potential of osteogenically induced hBMSC-EVs was examined. hBMSCs secreted negatively charged nanosized vesicles (∼35 nm with EV-related surface markers. The yield of EVs over 7 days was dependent on an osteogenic stimulus (standard chemical cocktail or RUNX2 cationic-lipid transfection. These EVs were used to sequentially stimulate homotypic uncommitted cells during 7 days, matching the seeding density of EV parent cells, culture time, and stimuli. Osteogenically committed hBMSC-EVs induced an osteogenic phenotype characterized by marked early induction of BMP2, SP7, SPP1, BGLAP/IBSP, and alkaline phosphatase. Both EV groups outperformed the currently used osteoinductive strategies. These data show that naturally secreted EVs can guide the osteogenic commitment of hBMSCs in the absence of other chemical or genetic osteoinductors.

  19. Effects of icariin on cytokine-induced ankylosing spondylitis with fibroblastic osteogenesis and its molecular mechanism.

    Science.gov (United States)

    Jia, Chunrong; Liu, Hongxiao; Li, Min; Wu, Zhikui; Feng, Xinghua

    2014-01-01

    The aim of this study is to explore the effects of icariin on cytokine induced ankylosing spondylitis fibroblast osteogenesis type expression and its molecular mechanism. The normal fibroblasts were collected as normal control group, and the fibroblasts of hip joint capsule of AS patients were collected, which were respectively added in fetal bovine serum (group AS), fetal bovine serum and cytokines (BMP-2+TGF-beta 1) (group AS), and cell factor solution (icariin group), and observed of the osteogenic expression of fibroblast, to evaluate the impact of Icariin on it. The ALP activity, the content of collagen, osteocalcin content and cbfa1mRNA and OCmRNA of fibroblast of AS group increased compared to the normal control group and AS control group (P < 0.01), indicating that icariin can significantly inhibit the above changes (P < 0.01). Icariin can inhibit fibroblast further osteogenic differentiation through inhibiting the effect of cytokines on the fibroblast osteogenesis type markers and osteogenic gene expression and osteogenic differentiation.

  20. Mechanism involved in enhancement of osteoblast differentiation by hyaluronic acid

    Energy Technology Data Exchange (ETDEWEB)

    Kawano, Michinao [Division of Maxillofacial Diagnostic and Surgical Science, Department of Oral and Maxillofacial Surgery, Kyushu Dental College, Kitakyushu 803-8580 (Japan); Division of Infections and Molecular Biology, Department of Health Promotion, Kyushu Dental College, Kitakyushu 803-8580 (Japan); Ariyoshi, Wataru [Division of Infections and Molecular Biology, Department of Health Promotion, Kyushu Dental College, Kitakyushu 803-8580 (Japan); Iwanaga, Kenjiro [Division of Maxillofacial Diagnostic and Surgical Science, Department of Oral and Maxillofacial Surgery, Kyushu Dental College, Kitakyushu 803-8580 (Japan); Okinaga, Toshinori [Division of Infections and Molecular Biology, Department of Health Promotion, Kyushu Dental College, Kitakyushu 803-8580 (Japan); Habu, Manabu [Division of Maxillofacial Diagnostic and Surgical Science, Department of Oral and Maxillofacial Surgery, Kyushu Dental College, Kitakyushu 803-8580 (Japan); Yoshioka, Izumi [Division of Oral and Maxillofacial Surgery, Department of Medicine of Sensory and Motor Organs, University of Miyazaki, Kiyotake, Miyazaki 889-1692 (Japan); Tominaga, Kazuhiro [Division of Maxillofacial Diagnostic and Surgical Science, Department of Oral and Maxillofacial Surgery, Kyushu Dental College, Kitakyushu 803-8580 (Japan); Oral Bioresearch Center, Kyushu Dental College, Kitakyushu 803-8580 (Japan); Nishihara, Tatsuji, E-mail: tatsujin@kyu-dent.ac.jp [Division of Infections and Molecular Biology, Department of Health Promotion, Kyushu Dental College, Kitakyushu 803-8580 (Japan); Oral Bioresearch Center, Kyushu Dental College, Kitakyushu 803-8580 (Japan)

    2011-02-25

    Research highlights: {yields} In this study was to investigate the effects of HA on osteoblast differentiation induced by BMP-2. {yields} MG63 cells were incubated with BMP-2 and HA for various time periods. {yields} Phosphorylation of Smad 1/5/8, p38, and ERK proteins was determined by western blot analysis. To elucidate the nuclear translocation of phosphorylated Smad 1/5/8, stimulated cells were subjected to immunofluorescence microscopy. {yields} HA enhanced BMP-2 induces osteoblastic differentiation in MG63 cells via down-regulation of BMP-2 antagonists and ERK phosphorylation. -- Abstract: Objectives: Bone morphogenetic protein-2 (BMP-2) is expected to be utilized to fill bone defects and promote healing of fractures. However, it is unable to generate an adequate clinical response for use in bone regeneration. Recently, it was reported that glycosaminoglycans, including heparin, heparan sulfate, keratan sulfate, dermatan sulfate, chondroitin-4-sulfate, chondroitin-6-sulfate, and hyaluronic acid (HA), regulate BMP-2 activity, though the mechanism by which HA regulates osteogenic activities has not been fully elucidated. The aim of this study was to investigate the effects of HA on osteoblast differentiation induced by BMP-2. Materials and methods: Monolayer cultures of osteoblastic lineage MG63 cells were incubated with BMP-2 and HA for various time periods. To determine osteoblastic differentiation, alkaline phosphatase (ALP) activity in the cell lysates was quantified. Phosphorylation of Smad 1/5/8, p38, and ERK proteins was determined by Western blot analysis. To elucidate the nuclear translocation of phosphorylated Smad 1/5/8, stimulated cells were subjected to immunofluorescence microscopy. To further elucidate the role of HA in enhancement of BMP-2-induced Smad signaling, mRNA expressions of the BMP-2 receptor antagonists noggin and follistatin were detected using real-time RT-PCR. Results: BMP-2-induced ALP activation, Smad 1/5/8 phosphorylation, and

  1. Methylsulfonylmethane enhances BMP‑2‑induced osteoblast differentiation in mesenchymal stem cells.

    Science.gov (United States)

    Kim, Don Nam; Joung, Youn Hee; Darvin, Pramod; Kang, Dong Young; Sp, Nipin; Byun, Hyo Joo; Cho, Kwang Hyun; Park, Kyung Do; Lee, Hak Kyo; Yang, Young Mok

    2016-07-01

    As human lifespans have increased, the incidence of osteoporosis has also increased. Methylsulfonylmethane (MSM) affects the process of mesenchymal stem cell (MSC) differentiation into osteoblasts via the Janus kinase 2 (Jak2)/signal transducer and activator of transcription (STAT)5b signaling pathway, and bone morphogenetic protein 2 (BMP‑2) is also known to significantly affect bone health. In addition, the phosphorylation of small mothers against decapentaplegic (Smad)1/5/8 regulates the Runt‑related transcription factor 2 (Runx2) gene, which encodes a transcription factor for osteoblast differentiation markers. In the present study, the differentiation of MSCs treated with MSM, BMP‑2, and their combination were examined. The differentiation of osteoblasts was demonstrated through observation of morphological changes and mineralization, using alizarin red and Von Kossa staining. Western blotting analysis demonstrated that the combination of MSM and BMP-2 increased the phosphorylation of the BMP signaling-associated protein, Smad1/5/8. Combination of MSM and BMP-2 significantly increased osteogenic differentiation and mineralization of the MSCs compared with either MSM or BMP-2 alone. Additionally, reverse transcription-polymerase chain reaction analysis demonstrated that combination of MSM and BMP-2 increased the expression level of the Runx2 gene and the osteoblast differentiation marker genes, alkaline phosphatase, bone sialoprotein and osteocalcin, in MSCs compared with controls. Thus, the combination of MSM and BMP-2 may promote the differentiation of MSCs into osteoblasts. PMID:27175741

  2. The Expression of Bone Morphogenetic Protein 2 and Matrix Metalloproteinase 2 through Retinoic Acid Receptor Beta Induced by All-Trans Retinoic Acid in Cultured ARPE-19 Cells.

    Directory of Open Access Journals (Sweden)

    Zhenya Gao

    Full Text Available All-trans retinoic acid (ATRA plays an important role in ocular development. Previous studies found that retinoic acid could influence the metabolism of scleral remodeling by promoting retinal pigment epithelium (RPE cells to secrete secondary signaling factors. The purpose of this study was to investigate whether retinoic acid affected secretion of bone morphogenetic protein 2 (BMP-2 and matrix metalloproteinase 2 (MMP-2 and to explore the signaling pathway of retinoic acid in cultured acute retinal pigment epithelial 19 (ARPE-19 cells.The effects of ATRA (concentrations from 10-9 to 10-5 mol/l on the expression of retinoic acid receptors (RARs in ARPE-19 cells were examined at the mRNA and protein levels using reverse transcription-polymerase chain reaction (RT-PCR and western blot assay, respectively. The effects of treating ARPE-19 cells with ATRA concentrations ranging from 10-9 to 10-5 mol/l for 24 h and 48 h or with 10-6mol/l ATRA at different times ranging from 6h to 72h were assessed using real-time quantitative PCR (qPCR and enzyme-linked immunosorbent assay (ELISA. The contribution of RARβ-induced activation of ARPE-19 cells was confirmed using LE135, an antagonist of RARβ.RARβ mRNA levels significantly increased in the ARPE-19 cells treated with ATRA for 24h and 48h. These increases in RARβ mRNA levels were dose dependent (at concentrations of 10-9 to 10-5 mol/l with a maximum effect observed at 10-6 mol/l. There were no significant changes in the mRNA levels of RARα and RARγ. Western blot assay revealed that RARβ protein levels were increased significantly in a time-dependent manner in ARPE-19 cells treated with 10-6 mol/l ATRA from 12 h to 72 h, with a marked increase observed at 24 h and 48 h. The upregulation of RARβ and the ATRA-induced secretion in ARPE-19 cells could be inhibited by the RARβ antagonist LE135.ATRA induced upregulation of RARβ in ARPE-19 cells and stimulated these cells to secrete BMP-2 and MMP-2.

  3. The Expression of Bone Morphogenetic Protein 2 and Matrix Metalloproteinase 2 through Retinoic Acid Receptor Beta Induced by All-Trans Retinoic Acid in Cultured ARPE-19 Cells

    Science.gov (United States)

    Gao, Zhenya; Huo, Lijun; Cui, Dongmei; Yang, Xiao; Zeng, Junwen

    2016-01-01

    Purpose All-trans retinoic acid (ATRA) plays an important role in ocular development. Previous studies found that retinoic acid could influence the metabolism of scleral remodeling by promoting retinal pigment epithelium (RPE) cells to secrete secondary signaling factors. The purpose of this study was to investigate whether retinoic acid affected secretion of bone morphogenetic protein 2 (BMP-2) and matrix metalloproteinase 2 (MMP-2) and to explore the signaling pathway of retinoic acid in cultured acute retinal pigment epithelial 19 (ARPE-19) cells. Methods The effects of ATRA (concentrations from 10−9 to 10−5 mol/l) on the expression of retinoic acid receptors (RARs) in ARPE-19 cells were examined at the mRNA and protein levels using reverse transcription-polymerase chain reaction (RT-PCR) and western blot assay, respectively. The effects of treating ARPE-19 cells with ATRA concentrations ranging from 10−9 to 10−5 mol/l for 24 h and 48 h or with 10-6mol/l ATRA at different times ranging from 6h to 72h were assessed using real-time quantitative PCR (qPCR) and enzyme-linked immunosorbent assay (ELISA). The contribution of RARβ-induced activation of ARPE-19 cells was confirmed using LE135, an antagonist of RARβ. Results RARβ mRNA levels significantly increased in the ARPE-19 cells treated with ATRA for 24h and 48h. These increases in RARβ mRNA levels were dose dependent (at concentrations of 10−9 to 10−5 mol/l) with a maximum effect observed at 10−6 mol/l. There were no significant changes in the mRNA levels of RARα and RARγ. Western blot assay revealed that RARβ protein levels were increased significantly in a time-dependent manner in ARPE-19 cells treated with 10−6 mol/l ATRA from 12 h to 72 h, with a marked increase observed at 24 h and 48 h. The upregulation of RARβ and the ATRA-induced secretion in ARPE-19 cells could be inhibited by the RARβ antagonist LE135. Conclusion ATRA induced upregulation of RARβ in ARPE-19 cells and stimulated

  4. Differentiation and Molecular Properties of Mesenchymal Stem Cells Derived from Murine Induced Pluripotent Stem Cells Derived on Gelatin or Collagen.

    Science.gov (United States)

    Obara, Chizuka; Takizawa, Kazuya; Tomiyama, Kenichi; Hazawa, Masaharu; Saotome-Nakamura, Ai; Gotoh, Takaya; Yasuda, Takeshi; Tajima, Katsushi

    2016-01-01

    The generation of induced-pluripotential stem cells- (iPSCs-) derived mesenchymal stem cells (iMSCs) is an attractive and promising approach for preparing large, uniform batches of applicable MSCs that can serve as an alternative cell source of primary MSCs. Appropriate culture surfaces may influence their growth and differentiation potentials during iMSC derivation. The present study compared molecular properties and differentiation potential of derived mouse iPS-MSCs by deriving on gelatin or collagen-coated surfaces. The cells were derived by a one-step method and expressed CD73 and CD90, but CD105 was downregulated in iMSCs cultured only on gelatin-coated plates with increasing numbers of passages. A pairwise scatter analysis revealed similar expression of MSC-specific genes in iMSCs derived on gelatin and on collagen surfaces as well as in primary mouse bone marrow MSCs. Deriving iMSCs on gelatin and collagen dictated their osteogenic and adipose differentiation potentials, respectively. Derived iMSCs on gelatin upregulated Bmp2 and Lif prior to induction of osteogenic or adipose differentiation, while PPARγ was upregulated by deriving on collagen. Our results suggest that extracellular matrix components such as gelatin biases generated iMSC differentiation potential towards adipose or bone tissue in their derivation process via up- or downregulation of these master genes. PMID:27642306

  5. Comparative proteome approach demonstrates that platelet-derived growth factor C and D efficiently induce proliferation while maintaining multipotency of hMSCs

    Energy Technology Data Exchange (ETDEWEB)

    Sotoca, Ana M., E-mail: a.sotoca@science.ru.nl [Department of Cell and Applied Biology, Radboud University, Heijendaalseweg 135, 6525 AJ Nijmegen (Netherlands); Roelofs-Hendriks, Jose [Department of Cell and Applied Biology, Radboud University, Heijendaalseweg 135, 6525 AJ Nijmegen (Netherlands); Boeren, Sjef [Laboratory of Biochemistry, Wageningen University, Dreijenlaan 3, 6703 HA Wageningen (Netherlands); Kraan, Peter M. van der [Department of Rheumatology Research and Advanced Therapeutics, Radboud University Nijmegen Medical Centre, Nijmegen (Netherlands); Vervoort, Jacques [Laboratory of Biochemistry, Wageningen University, Dreijenlaan 3, 6703 HA Wageningen (Netherlands); Zoelen, Everardus J.J. van; Piek, Ester [Department of Cell and Applied Biology, Radboud University, Heijendaalseweg 135, 6525 AJ Nijmegen (Netherlands)

    2013-10-15

    This is the first study that comprehensively describes the effects of the platelet-derived growth factor (PDGF) isoforms C and D during in vitro expansion of human mesenchymal stem cells (hMSCs). Our results show that PDGFs can enhance proliferation of hMSCs without affecting their multipotency. It is of great value to culture and expand hMSCs in a safe and effective manner without losing their multipotency for manipulation and further development of cell-based therapies. Moreover, differential effects of PDGF isoforms have been observed on lineage-specific differentiation induced by BMP2 and Vitamin D3. Based on label-free LC-based quantitative proteomics approach we have furthermore identified specific pathways induced by PDGFs during the proliferation process, showing the importance of bioinformatics tools to study cell function. - Highlights: • PDGFs (C and D) significantly increased the number of multipotent undifferentiated hMSCs. • Enhanced proliferation did not impair the ability to undergo lineage-specific differentiation. • Proteomic analysis confirmed the overall signatures of the ‘intact’ cells.

  6. Induced Abortion

    Science.gov (United States)

    ... Education & Events Advocacy For Patients About ACOG Induced Abortion Home For Patients Search FAQs Induced Abortion Page ... Induced Abortion FAQ043, May 2015 PDF Format Induced Abortion Special Procedures What is an induced abortion? What ...

  7. The Co-Dependent Relationship of Technology and Communities

    Science.gov (United States)

    Surry, Daniel W.; Baker, Fredrick W., III

    2016-01-01

    Technology is one the defining features of humanity. It is ubiquitous in modern society and plays an important role in nearly everything that humans do. New technologies frequently spur our imagination, can evoke powerful emotions and often serve as the topic of heated debate. Many people are in awe of the power and potential of new technologies…

  8. Bone morphogenetic protein-2 is a negative regulator of hepatocyte proliferation downregulated in the regenerating liver

    Institute of Scientific and Technical Information of China (English)

    Cui-Ping Xu; Wen-Min Ji; Gijs R van den Brink; Maikel P Peppelenbosch

    2006-01-01

    AIM: To characterize the expression and dynamic changes of bone morphogenetic protein (BMP)-2 in hepatocytes in the regenerating liver in rats after partial hepatectomy (PH), and examine the effects of BMP-2 on proliferation of human Huh7 hepatoma cells.METHODS: Fifty-four adult male Wistar rats were randomly divided into three groups: A normal control (NC) group, a partial hepatectomized (PH) group and a sham operated (SO) group. To study the effect of liver regeneration on BMP-2 expression, rats were sacrificed before and at different time points after PH or the sham intervention (6, 12, 24 and 48 h). For each time point, six rats were used in parallel. Expression and distribution of BMP-2 protein were determined in regenerating liver tissue by Western blot analysis and immunohistochemistry. Effects of BMP-2 on cell proliferation of human Huh7 hepatoma cell line were assessed using an MTT assay.RESULTS: In the normal liver strong BMP-2 expression was observed around the central and portal veins. The expression of BMP-2 decreased rapidly as measured by both immunohistochemistry and Western blot analysis.This decrease was at a maximum of 3.22 fold after 12 h and returned to normal levels at 48 h after PH. No significant changes in BMP-2 immunoreactivity were observed in the SO group. BMP-2 inhibited serum induced Huh7 cell proliferation.CONCLUSION: BMP-2 is expressed in normal adult rat liver and negatively regulates hepatocyte proliferation.The observed down regulation of BMP-2 following partial hepatectomy suggests that such down regulation may be necessary for hepatocyte proliferation.

  9. E. coli-Produced BMP-2 as a Chemopreventive Strategy for Colon Cancer : A Proof-of-Concept Study

    NARCIS (Netherlands)

    Yuvaraj, Saravanan; Al-Lahham, Sa'ad H.; Somasundaram, Rajesh; Figaroa, Patrick A.; Peppelenbosch, Maikel P.; Bos, Nicolaas A.

    2012-01-01

    Colon cancer is a serious health problem, and novel preventive and therapeutical avenues are urgently called for. Delivery of proteins with anticancer activity through genetically modified bacteria provides an interesting, potentially specific, economic and effective approach here. Interestingly, bo

  10. BMP2 sensitizes glioblastoma stem-like cells to Temozolomide by affecting HIF-1α stability and MGMT expression

    OpenAIRE

    Persano, L; Pistollato, F; Rampazzo, E; Della Puppa, A; Abbadi, S; Frasson, C; Volpin, F; S. Indraccolo; Scienza, R; G. Basso

    2012-01-01

    Glioblastoma multiforme (GBM) is the most common brain tumour, characterized by a central and partially necrotic (i.e., hypoxic) core enriched in cancer stem cells (CSCs). We previously showed that the most hypoxic and immature (i.e., CSCs) GBM cells were resistant to Temozolomide (TMZ) in vitro, owing to a particularly high expression of O6-methylguanine-DNA-methyltransferase (MGMT), the most important factor associated to therapy resistance in GBM. Bone morphogenetic proteins (BMPs), and in...

  11. Radiographic Assessment of Bone Formation Using rhBMP2 at Maxillary Periapical Surgical Defects: A Case Series.

    Science.gov (United States)

    Kumar, M Siva; Kumar, M Hari; Vishalakshi, K; Sabitha, H

    2016-04-01

    Periapical cysts are the most common inflammatory odontogenic cysts arising from untreated dental caries with pulp necrosis and periapical infection. The choice of treatment is often influenced by various factors like size, extension of the lesion, proximity to vital structures, systemic condition and compliance of the patient too. The treatment protocol for management of periapical cysts is still under discussion and options vary from conservative treatment by means of endodontic technique to surgical treatment like decompression or a marsupialisation or even to enucleation. Large bony defect secondary to periapical surgery compromising the tooth integrity often requires bone graft to enhance bone formation and thus restoring function at the earliest. The present case series included 10 patients who had established periapical pathology secondary to history of trauma on upper anterior teeth as well patients with history of carious teeth with an apparent failure in root canal therapy. All ten patients were treated with cyst enucleation and apiceotomy along with 1.4cc Recombinant Human Bone Morphogenetic Protein-2 soaked Absorbable Collagen Sponge implantation at surgical defect. Radiographs and clinical examinations were done upto 3 months to evaluate healing. Radiographic and clinical assessments revealed bone regeneration and restoration of the maxillary surgical defects in all 10 patients. No evidence of graft failure was noted. The Recombinant Human Bone Morphogenetic Protein-2 soaked Absorbable Collagen Sponge carrier is thus proved to be a viable option for the treatment of maxillary periapical surgical defects. PMID:27190972

  12. Radiographic Assessment of Bone Formation Using rhBMP2 at Maxillary Periapical Surgical Defects: A Case Series

    Science.gov (United States)

    Kumar, M. Hari; Vishalakshi, K.; Sabitha, H.

    2016-01-01

    Periapical cysts are the most common inflammatory odontogenic cysts arising from untreated dental caries with pulp necrosis and periapical infection. The choice of treatment is often influenced by various factors like size, extension of the lesion, proximity to vital structures, systemic condition and compliance of the patient too. The treatment protocol for management of periapical cysts is still under discussion and options vary from conservative treatment by means of endodontic technique to surgical treatment like decompression or a marsupialisation or even to enucleation. Large bony defect secondary to periapical surgery compromising the tooth integrity often requires bone graft to enhance bone formation and thus restoring function at the earliest. The present case series included 10 patients who had established periapical pathology secondary to history of trauma on upper anterior teeth as well patients with history of carious teeth with an apparent failure in root canal therapy. All ten patients were treated with cyst enucleation and apiceotomy along with 1.4cc Recombinant Human Bone Morphogenetic Protein-2 soaked Absorbable Collagen Sponge implantation at surgical defect. Radiographs and clinical examinations were done upto 3 months to evaluate healing. Radiographic and clinical assessments revealed bone regeneration and restoration of the maxillary surgical defects in all 10 patients. No evidence of graft failure was noted. The Recombinant Human Bone Morphogenetic Protein-2 soaked Absorbable Collagen Sponge carrier is thus proved to be a viable option for the treatment of maxillary periapical surgical defects. PMID:27190972

  13. Evaluation of collagen/heparin coated TCP/HA granules for long-term delivery of BMP-2

    NARCIS (Netherlands)

    Hannink, G.J.; Geutjes, P.J.; Daamen, W.F.; Buma, P.

    2013-01-01

    Bone morphogenetic proteins (BMPs) are the most potent osteoinductive growth factors. However, a delivery system is essential to take advantage of the osteoinductive effect of BMPs. The purpose of this study was to develop a sustained delivery system for recombinant human bone morphogenetic protein-

  14. Gelatin Tight-Coated Poly(lactide-co-glycolide) Scaffold Incorporating rhBMP-2 for Bone Tissue Engineering

    OpenAIRE

    Juan Wang; Dongsong Li; Tianyi Li; Jianxun Ding; Jianguo Liu; Baosheng Li; Xuesi Chen

    2015-01-01

    Surface coating is the simplest surface modification. However, bioactive molecules can not spread well on the commonly used polylactone-type skeletons; thus, the surface coatings of biomolecules are typically unstable due to the weak interaction between the polymer and the bioactive molecules. In this study, a special type of poly(lactide-co-glycolide) (PLGA)-based scaffold with a loosened skeleton was fabricated by phase separation, which allowed gelatin molecules to more readily diffuse th...

  15. Recombinant human bone morphogenetic protein 2-induced heterotopic ossification of the retroperitoneum, psoas muscle, pelvis and abdominal wall following lumbar spinal fusion

    Energy Technology Data Exchange (ETDEWEB)

    Shah, Raj K. [The George Washington University School of Medicine, Washington, DC (United States); Moncayo, Valeria M.; Pierre-Jerome, Claude; Terk, Michael R. [Emory University School of Medicine, Radiology Department, Musculoskeletal Division, Atlanta, GA (United States); Smitson, Robert D. [Emory University School of Medicine, Atlanta, GA (United States)

    2010-05-15

    A 45-year-old man presented with vertebral collapse at L5 as an initial manifestation of multiple myeloma and underwent spinal fusion surgery using recombinant human bone morphogenetic protein-2 (rhBMP-2). Subsequent computed tomography (CT) scans and X-rays revealed heterotopic ossification of the left psoas muscle, pelvis, and anterior abdominal wall. While the occurrence of heterotopic ossification has previously been reported when rhBMP-2 has been used for spinal fusion surgery, this case demonstrates that it can occur to a much greater degree than previously seen. (orig.)

  16. Form-deprivation myopia induces decreased expression of bone morphogenetic protein-2, 5 in guinea pig sclera

    Institute of Scientific and Technical Information of China (English)

    Qing; Wang; Mei-Lan; Xue; Gui-Qiu; Zhao; Mei-Guang; Liu; Yu-Na; Ma; Yan; Ma

    2015-01-01

    AIM: To identify the presence of various bone morphogenetic proteins(BMPs) and their receptors in normal sclera of human, rat and guinea pigs, and to determine whether their expression changed with form-deprivation myopia(FDM) in guinea pig sclera.METHODS: The expression of BMPs and BMP receptors were detected using reverse transcription polymerase chain reaction(RT-PCR) and immunofluorescence. Two-week-old guinea pigs were monocularly form-deprived with a translucent lens. After fourteen days induction of FDM, total RNA was isolated and subjected to RT-PCR to examine the changes of BMPs and BMP receptors in tissues from the posterior sclera. Western blotting analysis was used to investigate their changes in protein levels.RESULTS: Human sclera expressed m RNAs for BMP-2,-4,-5,-7,-RIA,-RIB and BMP-RII. Conversely, rat sclera only expressed m RNA for BMP-7 and BMP-RIB,while the expression of BMPs and BMP receptors in guinea pigs were similar to that of humans. Human sclera also expresses BMP-2,-4,-5,-7 in protein level.Fourteen days after the induction of myopia, significant decreased expressions for BMP-2 and BMP-5 in the posterior sclera of FDM-affected eyes(P <0.05 vs internal control eyes).· CONCLUSION: Various BMPs were expressed in human and guinea pig sclera. In the posterior sclera,expressions of BMP-2 and BMP-5 significantly decreased in FDM eyes. This finding indicates that various BMPs as components of the scleral cytokines regulating tissue homeostasis and provide evidence that alterations in the expression of BMP-2 and BMP-5 are associated with sclera remodeling during myopia induction.

  17. BMP treatment of C3H10T1/2 mesenchymal stem cells induces both chondrogenesis and osteogenesis.

    Science.gov (United States)

    Shea, Colleen M; Edgar, Cory M; Einhorn, Thomas A; Gerstenfeld, Louis C

    2003-12-15

    The molecular mechanisms by which bone morphogenetic proteins (BMPs) promote skeletal cell differentiation were investigated in the murine mesenchymal stem cell line C3H10T1/2. Both BMP-7 and BMP-2 induced C3H10T1/2 cells to undergo a sequential pattern of chondrogenic followed by osteogenic differentiation that was dependent on both the concentration and the continuous presence of BMP in the growth media. Differentiation was determined by the expression of chondrogenesis and osteogenesis associated matrix genes. Subsequent experiments using BMP-7 demonstrated that withdrawal of BMP from the growth media led to a complete loss of skeletal cell differentiation accompanied by adipogenic differentiation of these cells. Continuous treatment with BMP-7 increased the expression of Sox9, Msx 2, and c-fos during the periods of chondrogenic differentiation after which point their expression decreased. In contrast, Dlx 5 expression was induced by BMP-7 treatment and remained elevated throughout the time-course of skeletal cell differentiation. Runx2/Cbfa1 was not detected by ribonuclease protection assay (RPA) and did not appear to be induced by BMP-7. The sequential nature of differentiation of chondrocytic and osteoblastic cells and the necessity for continuous BMP treatment to maintain skeletal cell differentiation suggests that the maintenance of selective differentiation of the two skeletal cell lineages might be dependent on BMP-7-regulated expression of other morphogenetic factors. An examination of the expression of Wnt, transforming growth factor-beta (TGF-beta), and the hedgehog family of morphogens showed that Wnt 5b, Wnt 11, BMP-4, growth and differentiation factor-1 (GDF-1), Sonic hedgehog (Shh), and Indian hedgehog (Ihh) were endogenously expressed by C3H10T1/2 cells. Wnt 11, BMP-4, and GDF-1 expression were inhibited by BMP-7 treatment in a dose-dependent manner while Wnt 5b and Shh were selectively induced by BMP-7 during the period of chondrogenic

  18. Bone induction at physiological doses of BMP through localization by clay nanoparticle gels.

    Science.gov (United States)

    Gibbs, D M R; Black, C R M; Hulsart-Billstrom, G; Shi, P; Scarpa, E; Oreffo, R O C; Dawson, J I

    2016-08-01

    Bone Morphogenic Protein 2 (BMP2) can induce ectopic bone. This ability, which first motivated the widespread application of BMP2 in fracture healing and spinal arthrodesis has, more recently, been indicated as one of several serious adverse effects associated with the supra-physiological doses of BMP2 relied upon for clinical efficacy. Key to harnessing BMPs and other agents safely and effectively will be the ability to localize activity at a target site at substantially reduced doses. Clay (Laponite) nanoparticles can self assemble into gels under physiological conditions and bind growth factors for enhanced and localized efficacy. Here we show the ability to localize and enhance the activity of BMP2 to achieve ectopic bone formation at doses within the sub-microgram per ml range of concentrations sufficient to induce differentiation of responsive cell populations in vitro and at approximately 3000 fold lower than those employed in clinical practice. PMID:27209259

  19. Genetically modified mesenchymal stem cells induce mechanically stable posterior spine fusion

    OpenAIRE

    Sheyn, D; Rüthemann, M; Mizrahi, O; Kallai, I; Zilberman, Y.; Tawackoli, W; Kanim, L E A; Zhao, L; Bae, H; Pelled, G.; Snedeker, J G; Gazit, D.

    2010-01-01

    Most spine fusion procedures involve the use of prosthetic fixation devices combined with autologous bone grafts rather than biological treatment. We had shown that spine fusion could be achieved by injection of bone morphogenetic protein-2 (BMP-2)-expressing mesenchymal stem cells (MSCs) into the paraspinal muscle. In this study, we hypothesized that posterior spinal fusion achieved using genetically modified MSCs would be mechanically comparable to that realized using a mechanical fixation....

  20. Expression of Bone Morphogenetic Protein-2 in the Chondrogenic and Ossifying Sites of Calcific Tendinopathy and Traumatic Tendon Injury Rat Models

    Directory of Open Access Journals (Sweden)

    Chan Lai

    2009-07-01

    Full Text Available Abstract Background Ectopic chondrogenesis and ossification were observed in a degenerative collagenase-induced calcific tendinopathy model and to a lesser extent, in a patellar tendon traumatic injury model. We hypothesized that expression of bone morphogenetic protein-2 (BMP-2 contributed to ectopic chondrogenesis and ossification. This study aimed to study the spatial and temporal expression of BMP-2 in our animal models. Methods Seventy-two rats were used, with 36 rats each subjected to central one-third patellar tendon window injury (C1/3 group and collagenase-induced tendon injury (CI group, respectively. The contralateral limb served as controls. At week 2, 4 and 12, 12 rats in each group were sacrificed for immunohistochemistry and RT-PCR of BMP-2. Results For CI group, weak signal was observed at the tendon matrix at week 2. At week 4, matrix around chondrocyte-like cells was also stained in some samples. In one sample, calcification was observed and the BMP-2 signal was observed both in the calcific matrix and the embedded chondrocyte-like cells. At week 12, the staining was observed mainly in the calcific matrix. Similar result was observed in C1/3 group though the immunopositive staining of BMP-2 was generally weaker. There was significant increase in BMP-2 mRNA compared to that in the contralateral side at week 2 and the level became insignificantly different at week 12 in CI group. No significant increase in BMP-2 mRNA was observed in C1/3 group at all time points. Conclusion Ectopic expression of BMP-2 might induce tissue transformation into ectopic bone/cartilage and promoted structural degeneration in calcific tendinopathy.

  1. Intermittent Hypoxia Influences Alveolar Bone Proper Microstructure via Hypoxia-Inducible Factor and VEGF Expression in Periodontal Ligaments of Growing Rats

    Science.gov (United States)

    Oishi, Shuji; Shimizu, Yasuhiro; Hosomichi, Jun; Kuma, Yoichiro; Maeda, Hideyuki; Nagai, Hisashi; Usumi-Fujita, Risa; Kaneko, Sawa; Shibutani, Naoki; Suzuki, Jun-ichi; Yoshida, Ken-ichi; Ono, Takashi

    2016-01-01

    Intermittent hypoxia (IH) recapitulates morphological changes in the maxillofacial bones in children with obstructive sleep apnea (OSA). Recently, we found that IH increased bone mineral density (BMD) in the inter-radicular alveolar bone (reflecting enhanced osteogenesis) in the mandibular first molar (M1) region in the growing rats, but the underlying mechanism remains unknown. In this study, we focused on the hypoxia-inducible factor (HIF) pathway to assess the effect of IH by testing the null hypothesis of no significant differences in the mRNA-expression levels of relevant factors associated with the HIF pathway, between control rats and growing rats with IH. To test the null hypothesis, we investigated how IH enhances mandibular osteogenesis in the alveolar bone proper with respect to HIF-1α and vascular endothelial growth factor (VEGF) in periodontal ligament (PDL) tissues. Seven-week-old male Sprague–Dawley rats were exposed to IH for 3 weeks. The microstructure and BMD in the alveolar bone proper of the distal root of the mandibular M1 were evaluated using micro-computed tomography (micro-CT). Expression of HIF-1α and VEGF mRNA in PDL tissues were measured, whereas osteogenesis was evaluated by measuring mRNA levels for alkaline phosphatase (ALP) and bone morphogenetic protein-2 (BMP-2). The null hypothesis was rejected: we found an increase in the expression of all of these markers after IH exposure. The results provided the first indication that IH enhanced osteogenesis of the mandibular M1 region in association with PDL angiogenesis during growth via HIF-1α in an animal model. PMID:27695422

  2. Intermittent Hypoxia Influences Alveolar Bone Proper Microstructure via Hypoxia-Inducible Factor and VEGF Expression in Periodontal Ligaments of Growing Rats

    Science.gov (United States)

    Oishi, Shuji; Shimizu, Yasuhiro; Hosomichi, Jun; Kuma, Yoichiro; Maeda, Hideyuki; Nagai, Hisashi; Usumi-Fujita, Risa; Kaneko, Sawa; Shibutani, Naoki; Suzuki, Jun-ichi; Yoshida, Ken-ichi; Ono, Takashi

    2016-01-01

    Intermittent hypoxia (IH) recapitulates morphological changes in the maxillofacial bones in children with obstructive sleep apnea (OSA). Recently, we found that IH increased bone mineral density (BMD) in the inter-radicular alveolar bone (reflecting enhanced osteogenesis) in the mandibular first molar (M1) region in the growing rats, but the underlying mechanism remains unknown. In this study, we focused on the hypoxia-inducible factor (HIF) pathway to assess the effect of IH by testing the null hypothesis of no significant differences in the mRNA-expression levels of relevant factors associated with the HIF pathway, between control rats and growing rats with IH. To test the null hypothesis, we investigated how IH enhances mandibular osteogenesis in the alveolar bone proper with respect to HIF-1α and vascular endothelial growth factor (VEGF) in periodontal ligament (PDL) tissues. Seven-week-old male Sprague–Dawley rats were exposed to IH for 3 weeks. The microstructure and BMD in the alveolar bone proper of the distal root of the mandibular M1 were evaluated using micro-computed tomography (micro-CT). Expression of HIF-1α and VEGF mRNA in PDL tissues were measured, whereas osteogenesis was evaluated by measuring mRNA levels for alkaline phosphatase (ALP) and bone morphogenetic protein-2 (BMP-2). The null hypothesis was rejected: we found an increase in the expression of all of these markers after IH exposure. The results provided the first indication that IH enhanced osteogenesis of the mandibular M1 region in association with PDL angiogenesis during growth via HIF-1α in an animal model.

  3. Establishment and identification of fibroblast clones expressing human bone morphogenetic protein 2

    Institute of Scientific and Technical Information of China (English)

    Juan Wang; Weibin Sun; Chun Lu; Guixia Tang

    2005-01-01

    Objective:To establish fibroblasts stably expressing human bone morphogenetic protein 2 (hBMP2). Methods:Eukaryonic expression vector(pcDNA3.1-B2) was transduced into NIH3T3 cells using SofastTM, a new generation cationic polymer gene transfection reagent. The positive cell clones were selected with G418. The stable transfection and expression of BMP2 in the NIH3T3 cells were determined by RT-PCR and immunohistochemical stain. Results: BMP2 mRNA was transcripted and expressed in the transfected NIH3T3 cells. Conclusion: With positive compound transfection, outside human BMP2 gene can be successfully transducted into NIH3T3 cells, which is the key step to induce periodontal cells to osseous phenotypes.

  4. Bone morphogenetic protein 2 signaling negatively modulates lymphatic development in vertebrate embryos

    DEFF Research Database (Denmark)

    Dunworth, William P; Cardona-Costa, Jose; Bozkulak, Esra Cagavi;

    2014-01-01

    : Our aim was to delineate the role of bone morphogenetic protein (BMP) 2 signaling in lymphatic development. METHODS AND RESULTS: BMP2 signaling negatively regulates the formation of LECs. Developing LECs lack any detectable BMP signaling activity in both zebrafish and mouse embryos, and excess BMP2......RATIONALE: The emergence of lymphatic endothelial cells (LECs) seems to be highly regulated during development. Although several factors that promote the differentiation of LECs in embryonic development have been identified, those that negatively regulate this process are largely unknown. OBJECTIVE...... signaling in zebrafish embryos and mouse embryonic stem cell-derived embryoid bodies substantially decrease the emergence of LECs. Mechanistically, BMP2 signaling induces expression of miR-31 and miR-181a in a SMAD-dependent mechanism, which in turn results in attenuated expression of prospero homeobox...

  5. Using poly(lactic-co-glycolic acid microspheres to encapsulate plasmid of bone morphogenetic protein 2/polyethylenimine nanoparticles to promote bone formation in vitro and in vivo

    Directory of Open Access Journals (Sweden)

    Qiao C

    2013-08-01

    phosphatase (ALP, runt-related transcription factor 2 (RUNX2, SP7 and I type collagen (COLL I, and finally induce MC3T3-E1 cell differentiation. Importantly, in vivo data from micro-computed tomography (micro-CT and histological staining demonstrated that the human BMP-2 released from PLGA@pBMP-2/PEI had a long-term effect locally and efficiently promoted bone formation in the bone defect area compared to control animals. All our data suggest that our PLGA-nanoparticle delivery system efficiently and functionally delivers the human BMP-2 cDNA and has potential clinical application in the future after further modification.Keywords: gene therapy, bone regeneration, biodegradable polymer, human BMP-2

  6. Testosterone delivered with a scaffold is as effective as bone morphologic protein-2 in promoting the repair of critical-size segmental defect of femoral bone in mice.

    Directory of Open Access Journals (Sweden)

    Bi-Hua Cheng

    Full Text Available Loss of large bone segments due to fracture resulting from trauma or tumor removal is a common clinical problem. The goal of this study was to evaluate the use of scaffolds containing testosterone, bone morphogenetic protein-2 (BMP-2, or a combination of both for treatment of critical-size segmental bone defects in mice. A 2.5-mm wide osteotomy was created on the left femur of wildtype and androgen receptor knockout (ARKO mice. Testosterone, BMP-2, or both were delivered locally using a scaffold that bridged the fracture. Results of X-ray imaging showed that in both wildtype and ARKO mice, BMP-2 treatment induced callus formation within 14 days after initiation of the treatment. Testosterone treatment also induced callus formation within 14 days in wildtype but not in ARKO mice. Micro-computed tomography and histological examinations revealed that testosterone treatment caused similar degrees of callus formation as BMP-2 treatment in wildtype mice, but had no such effect in ARKO mice, suggesting that the androgen receptor is required for testosterone to initiate fracture healing. These results demonstrate that testosterone is as effective as BMP-2 in promoting the healing of critical-size segmental defects and that combination therapy with testosterone and BMP-2 is superior to single therapy. Results of this study may provide a foundation to develop a cost effective and efficient therapeutic modality for treatment of bone fractures with segmental defects.

  7. Ectopic bone formation of human bone morphogenetic protein-2 gene transfected goat bone marrow-derived mesenchymal stem cells in nude mice

    Institute of Scientific and Technical Information of China (English)

    汤亭亭; 徐小良; 戴尅戎; 郁朝锋; 岳冰; 楼觉人

    2005-01-01

    Objective: To evaluate the osteogenic potential of bone morphogenetic protein (BMP)-2 gene transfected goat bone marrow-derived mesenchymal stem cells (MSCs). Methods: Goat bone marrow- derived MSCs were transfected by Adv-human bone morphogenetic protein (hBMP)-2 gene(Group 1), Adv-beta gal transfected MSCs (Group 2)and uninfected MSCs(Group 3). Western blot analysis, alkaline phosphatase staining, Von Kossa staining and transmission electron microscopy were adopted to determine the phenotype of MSCs. Then the cells were injected into thigh muscles of the nude mice. Radiographical and histological evaluations were performed at different intervals. Results: Only Adv-hBMP-2 transfected MSCs produced hBMP-2. These cells were positive for alkaline phosphatase staining at the 12th day and were positive for Von Kossa staining at the 16th day after gene transfer. Electron microscopic observation showed that there were more rough endoplasmic reticulum, mitochondria and lysosomes in Adv-hBMP-2 transfected MSCs compared to MSCs of other two groups. At the 3rd and 6th weeks after cell injection, ectopic bones were observed in muscles of nude mice of Group 1. Only fibrous tissue or a little bone was found in other two groups. Conclusions: BMP-2 gene transfected MSCs can differentiate into osteoblasts in vitro and induce bone formation in vivo.

  8. Effect on cochlea function of guinea pig after controlled release recombinant human bone morphogenetic protein 2 transplanted into the middle ear

    Institute of Scientific and Technical Information of China (English)

    LI Xue-sheng; SUN Jian-jun; JIANG Wei; LIU Xiao

    2010-01-01

    Background The recombinant human bone morphogenetic protein 2 (rhBMP-2) has been used to induce osteogenesis in animals' middle ear and this technique is possible to be used to reconstruct the defects of ossicles. The side effects of the rhBMP-2 in middle ear should be observed before using in clinic. Thus we prepared the controlled release rhBMP-2 and implanted it into the acoustic bulla of guinea pigs. The effect on the cochlea was observed. Methods We prepared the acellular cancellous bone, accompanied with rhBMP-2. The material accompanied with rhBMP-2 was implanted into one acoustic bulla of the animal and the opposite side of the acoustic bulla was implanted with acellular cancellous bone without rhBMP-2. Totally 20 guinea pigs were undergone this procedure. After the operation, the auditory brainstem response (ABR) of the animals was tested according to the time sequence. Three months after the operation, the animals were sacrificed. The osteogenesis induced by rhBMP-2, the acoustic bulla and cochlea affected by rhBMP-2 were observed. The structures of hair cells were observed after silver nitrate staining. Results The animals were recovered soon after surgery. The hearing thresholds of the animals were declined slightly just after the surgery and come back completely after 3 months. Also, the bulla and cochlea were normal in shape. The osteogenesis occurred in the pore of the acellular cancellous bone with rhBMP-2. There was not any abnormal hyperplasia of bone in the bulla and cochlea. The articulation between the stapes and oval window was not merged. The shapes of the hair cells were normal and there was no obvious deletion of the hair cells compared with control group. Conclusions The controlled release rhBMP-2 transplanted into the middle ear could induce osteogenesis in the bulla of the animals. It did not affect the shape of the bulla and the hearing threshold of the animal, and did not induce the abnormal hyperplasia of bone in the bulla and might

  9. Inducing autophagy

    DEFF Research Database (Denmark)

    Harder, Lea M; Bunkenborg, Jakob; Andersen, Jens S.

    2014-01-01

    Autophagy is a lysosomal-mediated catabolic process, which through degradation of different cytoplasmic components aids in maintaining cellular homeostasis and survival during exposure to extra- or intracellular stresses. Ammonia is a potential toxic and stress-inducing byproduct of glutamine...... catabolism, which has recently been found to induce autophagy in an MTOR independent way and support cancer cell survival. In this study, quantitative phosphoproteomics was applied to investigate the initial signaling events linking ammonia to the induction of autophagy. The MTOR inhibitor rapamycin was used...... as a reference treatment to emphasize the differences between an MTOR-dependent and -independent autophagy-induction. By this means 5901 phosphosites were identified of which 626 were treatment-specific regulated and 175 were coregulated. Investigation of the ammonia-specific regulated sites supported that MTOR...

  10. Safety and efficacy of rhBMP2 in posterior cervical spinal fusion for subaxial degenerative spine disease: Analysis of outcomes in 204 patients

    OpenAIRE

    Xu, Risheng; Bydon, Mohamad; Sciubba, Daniel M.; Witham, Timothy F.; Wolinsky, Jean-Paul; Gokaslan, Ziya L; Bydon, Ali

    2011-01-01

    Background: Many studies offer excellent demonstration of the ability of bone morphogenic protein (BMP) to enhance fusion rates in anterior as well as posterior lumbar surgery. Recently, BMP has also been shown to increase arthrodesis rates in anterior cervical surgery, albeit with concomitant increases in complication rates. To date, however, few studies have investigated the safety and efficacy of BMP in cervical surgeries approached posteriorly. Methods: We retrospectively reviewed 204 con...

  11. 突变受体阻断NIH3T3细胞中rhBMP-2诱导的信号转导

    Institute of Scientific and Technical Information of China (English)

    刘源; 金岩; George L Tipoe; Thomas YH Lau; 赵宇

    2000-01-01

    @@ 在脊椎动物中胚层的发育诱导过程中,骨形成蛋白(bone morphogenetic protein, BMP)是重要的背-腹化发育促进因子.BMPs在细胞表面与BMP的Ⅰ、Ⅱ型受体相互作用.为研究BMPs信号转导在组织发育和细胞分化中的作用,我们以BMPs Ⅱ型突变受体的cDNA为目的基因,以NIH3T3细胞为载体细胞,构建了稳定表达BMPs Ⅱ型突变受体的细胞株.从而为从信号转导水平探讨BMPs对细胞分化及组织器官发育的调控作用奠定了基础.

  12. Characteristics and Stimulation Potential with BMP-2 and BMP-7 of Tenocyte-Like Cells Isolated from the Rotator Cuff of Female Donors

    OpenAIRE

    Franka Klatte-Schulz; Stephan Pauly; Markus Scheibel; Stefan Greiner; Christian Gerhardt; Jelka Hartwig; Gerhard Schmidmaier; Britt Wildemann

    2013-01-01

    Tendon bone healing of the rotator cuff is often associated with non-healing or recurrent defects, which seems to be influenced by the patient's age and sex. The present study aims to examine cellular biological characteristics of tenocyte-like cells that may contribute to this impaired rotator cuff healing. Moreover, a therapeutic approach using growth factors could possibly stimulate tendon bone healing. Therefore, our second aim was to identify patient groups who would particularly benefit...

  13. Minimally traumatic alveolar ridge augmentation with a tunnel injectable thermo-sensitive alginate scaffold

    Directory of Open Access Journals (Sweden)

    Yifen LI

    2015-04-01

    Full Text Available Injectable bone substitutes and techniques have been developed for use in minimally invasive procedures for bone augmentation. Objective : To develop a novel injectable thermo-sensitive alginate hydrogel (TSAH as a scaffold to induce bone regeneration, using a minimally invasive tunnelling technique. Material and Methods : An injectable TSAH was prepared from a copolymer solution of 8.0 wt% Poly(N-isopropylacrylamide (PNIPAAm and 8.0 wt% AAlg-g-PNIPAAm. In vitro properties of the material, such as its microstructure and the sustained release of recombinant human bone morphogenetic protein-2 (rhBMP-2, were investigated. Then, with the subperiosteal tunnelling technique, this material, carrying rhBMP-2, was injected under the labial periosteum of the maxillary anterior alveolar ridge in a rabbit model. New bone formation was evaluated by means of X-ray, micro-computed tomography (micro-CT, fluorescence labelling, histological study, and immunohistochemistry study. Results : The material exhibited good injectability and thermo-irreversible properties. SEM showed an interconnected porous microstructure of the TSAH. The result of ALP activity indicated sustained delivery of BMP-2 from the TSAH from days 3 to 15. In a rabbit model, both TSAH and TSAH/rhBMP-2 induced alveolar ridge augmentation. The percentage of mineralised tissue in the TSAH/rhBMP-2 group (41.6±3.79% was significantly higher than in the TSAH group (31.3±7.21%; p<0.05. The density of the regenerating tissue was higher in the TSAH/rhBMP-2 group than in the other groups (TSAH group, positive control, blank control; p<0.05. Conclusions : The TSAH provided convenient handling properties for clinical application. To some extent, TSAH could induce ridge augmentation and mineral deposition, which can be enhanced when combined with rhBMP-2 for a minimally invasive tunnelling injection.

  14. Exercise-Induced Asthma

    Science.gov (United States)

    ... Melon Smoothie Pregnant? Your Baby's Growth Exercise-Induced Asthma KidsHealth > For Parents > Exercise-Induced Asthma Print A ... previous continue Tips for Kids With Exercise-Induced Asthma For the most part, kids with exercise-induced ...

  15. Exercise-Induced Bronchoconstriction

    Science.gov (United States)

    ... Conditions & Treatments ▸ Conditions Dictionary ▸ Exercise-Induced Bronchoconstriction Share | Exercise-Induced Bronchoconstriction (EIB) « Back to A to Z Listing Exercise-Induced Bronchoconstriction, (EIB), often known as exercise-induced ...

  16. Transient brown adipocyte-like cells derive from peripheral nerve progenitors in response to bone morphogenetic protein 2.

    Science.gov (United States)

    Salisbury, Elizabeth A; Lazard, Zawaunyka W; Ubogu, Eroboghene E; Davis, Alan R; Olmsted-Davis, Elizabeth A

    2012-12-01

    Perineurial-associated brown adipocyte-like cells were rapidly generated during bone morphogenetic protein 2 (BMP2)-induced sciatic nerve remodeling in the mouse. Two days after intramuscular injection of transduced mouse fibroblast cells expressing BMP2 into wild-type mice, there was replication of beta-3 adrenergic receptor(+) (ADRB3(+)) cells within the sciatic nerve perineurium. Fluorescence-activated cell sorting and analysis of cells isolated from these nerves confirmed ADRB3(+) cell expansion and their expression of the neural migration marker HNK1. Similar analysis performed 4 days after BMP2 delivery revealed a significant decrease in ADRB3(+) cells from isolated sciatic nerves, with their concurrent appearance within the adjacent soft tissue, suggesting migration away from the nerve. These soft tissue-derived cells also expressed the brown adipose marker uncoupling protein 1 (UCP1). Quantification of ADRB3-specific RNA in total hind limb tissue revealed a 3-fold increase 2 days after delivery of BMP2, followed by a 70-fold increase in UCP1-specific RNA after 3 days. Expression levels then rapidly returned to baseline by 4 days. Interestingly, these ADRB3(+) UCP1(+) cells also expressed the neural guidance factor reelin. Reelin(+) cells demonstrated distinct patterns within the injected muscle, concentrated toward the area of BMP2 release. Blocking mast cell degranulation-induced nerve remodeling resulted in the complete abrogation of UCP1-specific RNA and protein expression within the hind limbs following BMP2 injection. The data collectively suggest that local BMP2 administration initiates a cascade of events leading to the expansion, migration, and differentiation of progenitors from the peripheral nerve perineurium to brown adipose-like cells in the mouse, a necessary prerequisite for associated nerve remodeling. PMID:23283549

  17. Human adipose tissue-derived multilineage progenitor cells exposed to oxidative stress induce neurite outgrowth in PC12 cells through p38 MAPK signaling

    Directory of Open Access Journals (Sweden)

    Moriyama Mariko

    2012-08-01

    Full Text Available Abstract Background Adipose tissues contain populations of pluripotent mesenchymal stem cells that also secrete various cytokines and growth factors to support repair of damaged tissues. In this study, we examined the role of oxidative stress on human adipose-derived multilineage progenitor cells (hADMPCs in neurite outgrowth in cells of the rat pheochromocytoma cell line (PC12. Results We found that glutathione depletion in hADMPCs, caused by treatment with buthionine sulfoximine (BSO, resulted in the promotion of neurite outgrowth in PC12 cells through upregulation of bone morphogenetic protein 2 (BMP2 and fibroblast growth factor 2 (FGF2 transcription in, and secretion from, hADMPCs. Addition of N-acetylcysteine, a precursor of the intracellular antioxidant glutathione, suppressed the BSO-mediated upregulation of BMP2 and FGF2. Moreover, BSO treatment caused phosphorylation of p38 MAPK in hADMPCs. Inhibition of p38 MAPK was sufficient to suppress BMP2 and FGF2 expression, while this expression was significantly upregulated by overexpression of a constitutively active form of MKK6, which is an upstream molecule from p38 MAPK. Conclusions Our results clearly suggest that glutathione depletion, followed by accumulation of reactive oxygen species, stimulates the activation of p38 MAPK and subsequent expression of BMP2 and FGF2 in hADMPCs. Thus, transplantation of hADMPCs into neurodegenerative lesions such as stroke and Parkinson’s disease, in which the transplanted hADMPCs are exposed to oxidative stress, can be the basis for simple and safe therapies.

  18. The Expression of Bone Morphogenetic Protein 2 and Matrix Metalloproteinase 2 through Retinoic Acid Receptor Beta Induced by All-Trans Retinoic Acid in Cultured ARPE-19 Cells

    OpenAIRE

    Zhenya Gao; Lijun Huo; Dongmei Cui; Xiao Yang; Junwen Zeng

    2016-01-01

    Purpose All-trans retinoic acid (ATRA) plays an important role in ocular development. Previous studies found that retinoic acid could influence the metabolism of scleral remodeling by promoting retinal pigment epithelium (RPE) cells to secrete secondary signaling factors. The purpose of this study was to investigate whether retinoic acid affected secretion of bone morphogenetic protein 2 (BMP-2) and matrix metalloproteinase 2 (MMP-2) and to explore the signaling pathway of retinoic acid in cu...

  19. 血管内皮生长因子和骨形成蛋白2诱导犬恒牙原位牙髓再生%Regeneration of dental pulp tissue in mature dog teeth with apical periodontitis using vascular endothelial growth factor and bone morphogenetic protein 2

    Institute of Scientific and Technical Information of China (English)

    周俊; 王兆晶; 陈文瑨; 陈文霞

    2016-01-01

    目的 通过选择犬根尖孔发育完成的恒牙建立根尖周炎模型,探索血管内皮生长因子(VEGF)和骨形态生成蛋白2(BMP2)诱导原位牙髓再生的可能性.方法 2只10~12月龄的杂种犬,选择根尖孔发育完成的14颗恒前牙建立根尖周炎模型,分别将VEGF(VEGF组)、BMP2(BMP2组)单独和VEGF+BMP2联合(VEGF+BMP2组)与水凝胶复合植入感染控制后的根管腔内,对照组仅植入水凝胶.8周后组织学观察根管内组织再生情况.结果 植入8周后,VEGF组和VEGF+BMP2组根管腔内可见含有大量成纤维样细胞和血管的新生组织形成;而BMP2组和对照组根管腔内见均质状物质,未见细胞、血管形成.结论 VEGF或VEGF+BMP2复合水凝胶支架可以诱导犬根尖发育成熟的根尖周炎患牙在根管腔内生成含有血管的疏松结缔组织.%Objective To investigate the feasibility of dental pulp regeneration in mature teeth with apical periodontitis on situ using vascular endothelial growth factor(VEGF)and bone morphogenetic protein 2(BMP2). Methods Apical periodontitis model was established in 14 mature anterior teeth in 2 dogs(10-12 months). The disinfected root canals were filled with peptide hydrogel scaffold composited with different cytokines:VEGF group,BMP2 group,VEGF+BMP2 group and a control group(without cytokines). Eight weeks after the operation,a histological observation was undertaken to evaluate the regeneration tissue in the root canals. Results Eight weeks after the operation,newly formed vascularized connective tissue were found in the root canals which filled with VEGF and VEGF+BMP2. No cells and vessels were observed in the root canals in BMP2 group and control group. Conclusion VEGF alone or combinated with BMP2 can induce pulp-like tissue regeneration within the root canals of the mature teeth with apical periodontitis.

  20. Endocardial to myocardial notch-wnt-bmp axis regulates early heart valve development.

    Directory of Open Access Journals (Sweden)

    Yidong Wang

    Full Text Available Endocardial to mesenchymal transformation (EMT is a fundamental cellular process required for heart valve formation. Notch, Wnt and Bmp pathways are known to regulate this process. To further address how these pathways coordinate in the process, we specifically disrupted Notch1 or Jagged1 in the endocardium of mouse embryonic hearts and showed that Jagged1-Notch1 signaling in the endocardium is essential for EMT and early valvular cushion formation. qPCR and RNA in situ hybridization assays reveal that endocardial Jagged1-Notch1 signaling regulates Wnt4 expression in the atrioventricular canal (AVC endocardium and Bmp2 in the AVC myocardium. Whole embryo cultures treated with Wnt4 or Wnt inhibitory factor 1 (Wif1 show that Bmp2 expression in the AVC myocardium is dependent on Wnt activity; Wnt4 also reinstates Bmp2 expression in the AVC myocardium of endocardial Notch1 null embryos. Furthermore, while both Wnt4 and Bmp2 rescue the defective EMT resulting from Notch inhibition, Wnt4 requires Bmp for its action. These results demonstrate that Jagged1-Notch1 signaling in endocardial cells induces the expression of Wnt4, which subsequently acts as a paracrine factor to upregulate Bmp2 expression in the adjacent AVC myocardium to signal EMT.

  1. Efficiently engineered cell sheet using a complex of polyethylenimine–alginate nanocomposites plus bone morphogenetic protein 2 gene to promote new bone formation

    Directory of Open Access Journals (Sweden)

    Jin H

    2014-05-01

    Full Text Available Han Jin,1 Kai Zhang,2 Chunyan Qiao,1 Anliang Yuan,1 Daowei Li,1 Liang Zhao,1 Ce Shi,1 Xiaowei Xu,1 Shilei Ni,1 Changyu Zheng,3 Xiaohua Liu,4 Bai Yang,2 Hongchen Sun11Department of Pathology, School of Stomatology, Jilin University, Changchun, People’s Republic of China; 2State Key Laboratory of Supramolecular Structure and Materials, College of Chemistry, Jilin University, Changchun, People’s Republic of China; 3Molecular Physiology and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA; 4Department of Biomedical Sciences, Texas A&M University Baylor College of Dentistry, Dallas, TX, USAAbstract: Regeneration of large bone defects is a common clinical problem. Recently, stem cell sheet has been an emerging strategy in bone tissue engineering. To enhance the osteogenic potential of stem cell sheet, we fabricated bone morphogenetic protein 2 (BMP-2 gene-engineered cell sheet using a complex of polyethylenimine–alginate (PEI–al nanocomposites plus human BMP-2 complementary(cDNA plasmid, and studied its osteogenesis in vitro and in vivo. PEI–al nanocomposites carrying BMP-2 gene could efficiently transfect bone marrow mesenchymal stem cells. The cell sheet was made by culturing the cells in medium containing vitamin C for 10 days. Assays on the cell culture showed that the genetically engineered cells released the BMP-2 for at least 14 days. The expression of osteogenesis-related gene was increased, which demonstrated that released BMP-2 could effectively induce the cell sheet osteogenic differentiation in vitro. To further test the osteogenic potential of the cell sheet in vivo, enhanced green fluorescent protein or BMP-2-producing cell sheets were treated on the cranial bone defects. The results indicated that the BMP-2-producing cell sheet group was more efficient than other groups in promoting bone formation in the defect area. Our results suggested that PEI

  2. Extrachromosomal inducible expression

    NARCIS (Netherlands)

    Veltman, Douwe M; Van Haastert, Peter J M; Eichinger, L.; Rivero, F.

    2013-01-01

    Inducible expression systems are very convenient for proteins that induce strong side effects such as retardation of growth or development and are essential for the expression of toxic proteins. In this chapter we describe the doxycycline-inducible expression system, optimized for the controlled exp

  3. Cavitation-resistant inducer

    Science.gov (United States)

    Dunn, C.; Subbaraman, M.R.

    1989-06-13

    An improvement in an inducer for a pump is disclosed wherein the inducer includes a hub, a plurality of radially extending substantially helical blades and a wall member extending about and encompassing an outer periphery of the blades. The improvement comprises forming adjacent pairs of blades and the hub to provide a substantially rectangular cross-sectional flow area which cross-sectional flow area decreases from the inlet end of the inducer to a discharge end of the inducer, resulting in increased inducer efficiency improved suction performance, reduced susceptibility to cavitation, reduced susceptibility to hub separation and reduced fabrication costs. 11 figs.

  4. Non-viral gene therapy for bone tissue engineering

    NARCIS (Netherlands)

    Wegman, F.

    2013-01-01

    In bone tissue engineering bone morphogentic protein-2 (BMP-2) is one of the most commonly used growth factors. It induces stem cells to differentiate into the osteogenic lineage to form new bone. Clinically however, high dosages of protein are administered due to fast degradation, which is associat

  5. Induction of bone formation in biphasic calcium phosphate scaffolds by bone morphogenetic protein-2 and primary osteoblasts.

    Science.gov (United States)

    Strobel, L A; Rath, S N; Maier, A K; Beier, J P; Arkudas, A; Greil, P; Horch, R E; Kneser, U

    2014-03-01

    Bone tissue engineering strategies mainly depend on porous scaffold materials. In this study, novel biphasic calcium phosphate (BCP) matrices were generated by 3D-printing. High porosity was achieved by starch consolidation. This study aimed to characterise the porous BCP-scaffold properties and interactions of osteogenic cells and growth factors under in vivo conditions. Five differently treated constructs were implanted subcutaneously in syngeneic rats: plain BCP constructs (group A), constructs pre-treated with BMP-2 (group B; 1.6 µg BMP-2 per scaffold), seeded with primary osteoblasts (OB) (group C), seeded with OB and BMP-2 (group D) and constructs seeded with OB and pre-cultivated in a flow bioreactor for 6 weeks (group E). After 2, 4 and 6 weeks, specimens were explanted and subjected to histological and molecular biological analyses. Explanted scaffolds were invaded by fibrovascular tissue without significant foreign body reactions. Morphometric analysis demonstrated significantly increased bone formation in samples from group D (OB + BMP-2) compared to all other groups. Samples from groups B-E displayed significant mRNA expression of bone-specific genes after 6 weeks. Pre-cultivation in the flow bioreactor (group E) induced bone formation comparable with group B. In this study, differences in bone distribution between samples with BMP-2 or osteoblasts could be observed. In conclusion, combination of osteoblasts and BMP-2 synergistically enhanced bone formation in novel ceramic scaffolds. These results provide the basis for further experiments in orthotopic defect models with a focus on future applications in orthopaedic and reconstructive surgery.

  6. Wnt5a signaling is a substantial constituent in bone morphogenetic protein-2-mediated osteoblastogenesis.

    Science.gov (United States)

    Nemoto, Eiji; Ebe, Yukari; Kanaya, Sousuke; Tsuchiya, Masahiro; Nakamura, Takashi; Tamura, Masato; Shimauchi, Hidetoshi

    2012-06-15

    Wnts are secreted glycoproteins that mediate developmental and post-developmental physiology by regulating cellular processes including proliferation, differentiation, and apoptosis through β-catenin-dependent canonical and β-catenin-independent noncanonical pathway. It has been reported that Wnt5a activates noncanonical Wnt signaling through receptor tyrosine kinase-like orphan receptor 2 (Ror2). Although it appears that Wnt5a/Ror2 signaling supports normal bone physiology, the biological significance of noncanonical Wnts in osteogenesis is essentially unknown. In this study, we identified expression of Wnt5a in osteoblasts in the ossification zone of the tibial growth plate as well as bone marrow of the rat tibia as assessed by immunohistochemistry. In addition, we show that osteoblastic differentiation mediated by BMP-2 is associated with increased expression of Wnt5a and Ror2 using cultured pre-osteoblasts, MC3T3-E1 cells. Silencing gene expression of Wnt5a and Ror2 in MC3T3-E1 cells results in suppression of BMP-2-mediated osteoblastic differentiation, suggesting that Wnt5a and Ror2 signaling are of substantial importance for BMP-2-mediated osteoblastic differentiation. BMP-2 stimulation induced phosphorylation of Smad1/5/8 in a similar fashion in both siWnt5a-treated cells and control cells, suggesting that Wnt5a was dispensable for the phosphorylation of Smads by BMP-2. Taken together, our results suggest that Wnt5a/Ror2 signaling appears to be involved in BMP-2-mediated osteoblast differentiation in a Smad independent pathway.

  7. Repair of rat cranial bone defect by using bone morphogenetic protein-2-related peptide combined with microspheres composed of polylactic acid/polyglycolic acid copolymer and chitosan.

    Science.gov (United States)

    Li, Jingfeng; Jin, Lin; Wang, Mingbo; Zhu, Shaobo; Xu, Shuyun

    2015-07-08

    The effects of the transplanted bone morphogenetic protein-2 (BMP2) -related peptide P24 and rhBMP2 combined with poly(lactic-co-glycolic acid) (PLGA)/chitosan (CS) microspheres were investigated in promoting the repair of rat cranial bone defect. Forty white rats were selected and equally divided into four groups (group A: 1 μg of rhBMP2/PLGA/CS composite; group B: 3 mg of P24/PLGA/CS composite; group C: 0.5 μg of rhBMP2 + 1.5 mg of P24/PLGA/CS composite; group D: blank PLGA/CS material), and rat cranial bone defect models with a diameter of 5 mm were established. The materials were transplanted to the cranial bone defects. The animals were sacrificed on weeks 6 and 12 post-operation. Radiographic examinations (x-ray imaging and 3D CT scanning) and histological evaluations were performed. The repaired areas of cranial bone defects were measured, and the osteogenetic abilities of various materials were compared. Cranial histology, imaging, and repaired area measurements showed that the osteogenetic effects at two time points (weeks 6 and 12) in group C were better than those in groups A and B. The effects in groups A and B were similar. Group D achieved the worst repair effect of cranial bone defects, where a large number of fibrous connective tissues were observed. The PLGA/CS composite microspheres loaded with rhBMP2 and P24 had optimal concrescence and could mutually increase their osteogenesis capability. rhBMP2 + P24/PLGA/CS composite is a novel material for bone defect repair with stable activity to induce bone formation.

  8. Antibiotic induced meningitis.

    OpenAIRE

    1994-01-01

    Three patients with antibiotic induced meningitis, one following penicillin with seven episodes, are reported on--the first well documented description of penicillin induced meningitis. In this patient episodes of headache and nuchal rigidity appeared with and without CSF pleocytosis. Two patients had a total of five episodes of antibiotic induced meningitis after trimethoprim-sulphamethoxazole (co-trimoxazole) administration. The features common to all three patients were myalgia, confusion ...

  9. Isoniazid-induced alopecia

    OpenAIRE

    Gupta, K. B.; Kumar, V.; Vishvkarma, S.; R Shandily

    2011-01-01

    Isoniazid is a safe and very effective antituberculosis drug. Antimitotic agents routinely cause alopecia. Drug-induced alopecia is usually reversible upon withdrawal of the drug. Isoniazid, thiacetazone and ethionamide are the antituberculosis drugs which have been associated with alopecia. Isoniazid-induced alopecia was observed in one case and confirmed by the finding that hair growth resumed when drug removed from the regimen.

  10. Material Induced Anisotropic Damage

    NARCIS (Netherlands)

    Niazi, M.S.; Wisselink, H.H.; Meinders, V.T.; Boogaard, van den A.H.; Hora, P.

    2012-01-01

    The anisotropy in damage can be driven by two different phenomena; anisotropic defor-mation state named Load Induced Anisotropic Damage (LIAD) and anisotropic (shape and/or distribution) second phase particles named Material Induced Anisotropic Damage (MIAD). Most anisotropic damage models are based

  11. Induced radioactivity at CERN

    CERN Multimedia

    1970-01-01

    A description of some of the problems and some of the advantages associated with the phenomenon of induced radioactivity at accelerator centres such as CERN. The author has worked in this field for several years and has recently written a book 'Induced Radioactivity' published by North-Holland.

  12. Diet induced thermogenesis

    Directory of Open Access Journals (Sweden)

    Westerterp KR

    2004-08-01

    Full Text Available Objective Daily energy expenditure consists of three components: basal metabolic rate, diet-induced thermogenesis and the energy cost of physical activity. Here, data on diet-induced thermogenesis are reviewed in relation to measuring conditions and characteristics of the diet. Methods Measuring conditions include nutritional status of the subject, physical activity and duration of the observation. Diet characteristics are energy content and macronutrient composition. Results Most studies measure diet-induced thermogenesis as the increase in energy expenditure above basal metabolic rate. Generally, the hierarchy in macronutrient oxidation in the postprandial state is reflected similarly in diet-induced thermogenesis, with the sequence alcohol, protein, carbohydrate, and fat. A mixed diet consumed at energy balance results in a diet induced energy expenditure of 5 to 15 % of daily energy expenditure. Values are higher at a relatively high protein and alcohol consumption and lower at a high fat consumption. Protein induced thermogenesis has an important effect on satiety. In conclusion, the main determinants of diet-induced thermogenesis are the energy content and the protein- and alcohol fraction of the diet. Protein plays a key role in body weight regulation through satiety related to diet-induced thermogenesis.

  13. Recombinant human bone morphogenetic protein 2 induced cranial neural crest cells differentiating into adrenal neurons%重组人骨形成蛋白2诱导颅神经嵴细胞向肾上腺能神经元分化的研究

    Institute of Scientific and Technical Information of China (English)

    吕红兵; 金岩; 李媛; Tipoe GL

    2003-01-01

    目的:研究重组人骨形成蛋白2(rhBMP2)诱导小鼠颅神经嵴细胞(CNCC)分化后所产生的神经元类型是否为肾上腺能神经元.方法:用50 ng/ml rhBMP2诱导CNCC分化为神经元.提取诱导前后细胞内的总RNA,用反转录聚合酶链反应(RT-PCR)分别检测细胞中酪氨酸羟化酶(TH)和γ-氨基丁酸受体(GABAAR)亚单位的表达情况.结果:诱导前的CNCC中,TH和GABAAR亚单位均无mRNA水平的表达,诱导后二者均有表达,但表达的量均低于脑组织中的表达.结论:rhBMP2诱导CNCC后所分化的神经元为肾上腺能神经元,但在功能上可能弱于正常的肾上腺能神经元.

  14. 上颌窦底增高过程中重组人骨形成蛋白2/明胶海绵复合物诱导成骨的系统评价%A systematic review of osteogenesis induced by recombinant human bone morphogenetic protein-2/absorbable collagen sponge for maxillary sinus floor augmentation

    Institute of Scientific and Technical Information of China (English)

    宁静; 刘雅莉; 杨克虎; 王琳; 马鹏; 刘斌

    2011-01-01

    BACKGROUND: Maxillary antrum limits the application of implant in maxillary molar region; the application of guided bone regeneration (GBR) provides chance and security for the elevation maxillary sinus floor. Although pharmacology, animal experiment, and some clinical research have verified the osteoinductive of recombinant human bone morphogenetic protein-2/absorbable collagen sponge (rhBMP-2/ACS), the existence of the limitations of the study, cases of self-limiting, the reliability of the results is not very clear.OBJECTIVE: To systematically evaluate curative effect and safety of thBMP-2/ ACS on the incrementation of alveolar crest in process of maxillary sinus floor augmentation.METHODS: A computer based online search of PubMed database (1996/2009-12), Embase database (1974/2009-12),Cochrane Library database (the 4th period, 2009), CBM database (1978/2009-12), and CNKI database (1994/2009-12), VIP database (1989/2009-12) was performed with the key words "rhBMP-2, ACS, autogenous bone graft" in English, and "rhBMP-2,ACS, autogenous bone graft" in Chinese. The literatures were retrieved by the way of free words combined with key words. The studies of randomized controlled trials (RCTs) which addressed the efficiency of rhBMP-2/ACS compared with an autogenous bone graft were selected and reviewed. And RevMan 5 software was used for Meta-analysis.RESULTS AND CONCLUSION: Three RCTs was finally included, a total of 288 patients. Meta-analysis results showed that there was significant difference between 1.5 g/L rhBMP-2/ACS and autogenous bone graft in height changes and width changes of alveolar ridge. While for 0.75 g/L rhBMP-2/ACS group, there was no significant difference in height changes of alveolar ridge.There was significant difference in width changes of alveolar ridge. After 6 months rhBMP-2/ACS, the bone density can be improved in implant region, no reports of untoward reaction. 1.5 g/L thBMP-2/ACS, 0.75 g/L rhBMP-2/ACS and autogenous bone graft had good

  15. Mania induced by opipramol

    Directory of Open Access Journals (Sweden)

    Kazhungil Firoz

    2015-01-01

    Full Text Available Antidepressants have propensity to induce manic switch in patients with bipolar disorder. Opipramol is an atypical anxiolytic and antidepressant drug which predominantly acts on sigma receptors. Although structurally resembles tricyclic antidepressant imipramine it does not have inhibitory action on the reuptake of norepinephrine/serotonin and hence it is not presumed to cause manic switch in bipolar depression. Here, we describe a case of mania induced by opipramol, in a patient with bipolar affective disorder who was treated for moderate depressive episode with lithium and opipramol and we discuss neurochemical hypothesis of opipramol-induced mania.

  16. The balance of Id3 and E47 determines neural stem/precursor cell differentiation into astrocytes.

    Science.gov (United States)

    Bohrer, Christian; Pfurr, Sabrina; Mammadzada, Könül; Schildge, Sebastian; Plappert, Leandra; Hils, Miriam; Pous, Lauriane; Rauch, Katharina S; Dumit, Verónica I; Pfeifer, Dietmar; Dengjel, Jörn; Kirsch, Matthias; Schachtrup, Kristina; Schachtrup, Christian

    2015-11-12

    Adult neural stem/precursor cells (NSPCs) of the subventricular zone (SVZ) are an endogenous source for neuronal replacement in CNS disease. However, adult neurogenesis is compromised after brain injury in favor of a glial cell fate, which is mainly attributed to changes in the NSPC environment. Yet, it is unknown how this unfavorable extracellular environment translates into a transcriptional program altering NSPC differentiation. Here, we show that genetic depletion of the transcriptional regulator Id3 decreased the number of astrocytes generated from SVZ-derived adult NSPCs in the cortical lesion area after traumatic brain injury. Cortical brain injury resulted in rapid BMP-2 and Id3 up-regulation in the SVZ stem cell niche. Id3(-/-) adult NSPCs failed to differentiate into BMP-2-induced astrocytes, while NSPCs deficient for the Id3-controlled transcription factor E47 readily differentiated into astrocytes in the absence of BMP-2. Mechanistically, E47 repressed the expression of several astrocyte-specific genes in adult NSPCs. These results identify Id3 as the BMP-2-induced transcriptional regulator, promoting adult NSPC differentiation into astrocytes upon CNS injury and reveal a molecular link between environmental changes and NSPC differentiation in the CNS after injury. PMID:26438726

  17. NELL-1:a novel highly efficient and specific growth factor%NELL-1:高效特异的新型生长因子

    Institute of Scientific and Technical Information of China (English)

    秦雪嫣; 赵华翔; 张倩; 陈峰; 林久祥

    2016-01-01

    SUMMARY Regenerationofbonetissue,aswellasothertissues,requiresinvolvementandinteraction of cells,scaffolds and relevant growth factors,among which growth factors play a crucial role in maintai-ning the stability of microenvironment.Nel-like-type 1 molecule (NELL-1 ),a novel growth factor in tis-sue engineering,has been studied intensively in recent years.Researches mainly covered gene and pro-tein structure and their expression profiling,biological function,molecular mechanisms and disease rele-vance.NELL-1 expressed in embryonic tissue is essential for growth and development of bone tissue. NELL-1 presents excellent abilities of inducing bone and cartilage regeneration,especially with high spe-cificity to chondrocyte lineage.Compared with classic osteogenic growth factor bone morphogenetic pro-tein 2 (BMP-2),the process of osteogenesis interacted with NELL-1 exhibits stronger specificity,higher bone density and fewerside effects.Furthermore,a recent study shows synergistic effects of NELL-1 and BMP-2.NELL-1 enhances the osteogenic reaction induced by BMP-2 of cells and notably declines in-flammation response caused by BMP-2.This review evaluates the current research progress of the function and application of NELL-1 by the systematic method of evidence-based medicine.

  18. Drug-induced hepatitis

    Science.gov (United States)

    Toxic hepatitis ... to get liver damage. Some drugs can cause hepatitis with small doses, even if the liver breakdown ... liver. Many different drugs can cause drug-induced hepatitis. Painkillers and fever reducers that contain acetaminophen are ...

  19. LASER-INDUCED PHOTODISSOCIATION

    OpenAIRE

    Rahman, N.

    1985-01-01

    The richness of the field of laser-induced photodissociation is pointed out. Some of the recent works in this area comprising theoretical, computational as well as experimental research are discussed.

  20. Vitiligo, drug induced (image)

    Science.gov (United States)

    ... this person's face have resulted from drug-induced vitiligo. Loss of melanin, the primary skin pigment, occasionally ... is the case with this individual. The typical vitiligo lesion is flat (macular) and depigmented, but maintains ...

  1. Topological Induced Gravity

    CERN Document Server

    Oda, Ichiro

    2016-01-01

    We propose a topological model of induced gravity (pregeometry) where both Newton's coupling constant and the cosmological constant appear as integration constants in solving field equations. The matter sector of a scalar field is also considered, and by solving field equations it is shown that various types of cosmological solutions in the FRW universe can be obtained. A detailed analysis is given of the meaning of the BRST transformations, which make the induced gravity be a topological field theory, by means of the canonical quantization analysis, and the physical reason why such BRST transformations are needed in the present formalism is clarified. Finally, we propose a dynamical mechanism for fixing the Lagrange multiplier fields by following the Higgs mechanism. The present study clearly indicates that the induced gravity can be constructed at the classical level without recourse to quantum fluctuations of matter and suggests an interesting relationship between the induced gravity and the topological qu...

  2. Exercise-induced asthma

    Science.gov (United States)

    Wheezing - exercise-induced; Reactive airway disease - exercise ... Having asthma symptoms when you exercise does not mean you cannot or should not exercise. But be aware of your EIA triggers. Cold or dry air may ...

  3. Optomechanically induced transparency

    CERN Document Server

    Weis, S; Deleglise, S; Gavartin, E; Arcizet, O; Schliesser, A; Kippenberg, T J

    2010-01-01

    Coherent interaction of laser radiation with multilevel atoms and molecules can lead to quantum interference in the electronic excitation pathways. A prominent example observed in atomic three-level-systems is the phenomenon of electromagnetically induced transparency (EIT), in which a control laser induces a narrow spectral transparency window for a weak probe laser beam. The concomitant rapid variation of the refractive index in this spectral window can give rise to dramatic reduction of the group velocity of a propagating pulse of probe light. Dynamic control of EIT via the control laser enables even a complete stop, that is, storage, of probe light pulses in the atomic medium. Here, we demonstrate optomechanically induced transparency (OMIT)--formally equivalent to EIT--in a cavity optomechanical system operating in the resolved sideband regime. A control laser tuned to the lower motional sideband of the cavity resonance induces a dipole-like interaction of optical and mechanical degrees of freedom. Under...

  4. Noise induced Hopf bifurcation

    OpenAIRE

    Shuda, I. A.; Borysov, S S; A.I. Olemskoi

    2008-01-01

    We consider effect of stochastic sources upon self-organization process being initiated with creation of the limit cycle induced by the Hopf bifurcation. General relations obtained are applied to the stochastic Lorenz system to show that departure from equilibrium steady state can destroy the limit cycle in dependence of relation between characteristic scales of temporal variation of principle variables. Noise induced resonance related to the limit cycle is found to appear if the fastest vari...

  5. Induced Charge Capacitive Deionization

    OpenAIRE

    Rubin, S.; Suss, M. E.; Biesheuvel, P. M.; Bercovici, M.

    2016-01-01

    We demonstrate the phenomenon of induced-charge capacitive deionization (ICCDI) that occurs around a porous and conducting particle immersed in an electrolyte, under the action of an external electrostatic field. The external electric field induces an electric dipole in the porous particle, leading to capacitive charging of its volume by both cations and anions at opposite poles. This regime is characterized both by a large RC charging time and a small electrochemical charge relaxation time, ...

  6. Exercise-Induced Bronchospasm

    OpenAIRE

    Molis, Marc A.; Molis, Whitney E.

    2010-01-01

    Context: Exercise-induced bronchospasm (EIB) is a phenomenon of airway narrowing that occurs during or after exercise or physical exertion. This condition has been reported in a range of sporting activities but is most common in participants of cold-weather sports (eg, Nordic skiing) and indoor sports (eg, ice-skating and swimming). Traditionally, the terms exercise induced-asthma (EIA) and EIB have been used interchangeably; however, more recent evidence suggests that these entities are sepa...

  7. Beam induced heating

    CERN Document Server

    Salvant, B; Arduini, G; Assmann, R; Baglin, V; Barnes, M J; Baudrenghien, P; Bracco, C; Bruce, R; Bertarelli, A; Carra, F; Cattenoz, G; Caspers, F; Claudet, S; Day, H; Esteban Mueller, J; Gentini, L; Goddar, B; Grudiev, A; Henrist, B; Jones, R; Lanza, G; Lari, L; Mastoridis, T; Métral, E; Mounet, N; Nougaret, J L; Piguiet, A M; Redaelli, S; Roncarolo, F; Rumolo, G; Sapinski, M; Shaposhinkova, E; Tavian, L; Timmins, M; Uythoven, J; Vidal, A; Wollmann, D

    2012-01-01

    In 2011, the rapid increase of the luminosity performance of LHC came at the expense of increased temperature and pressure readings on several near-beam LHC equipments. In some cases, this beam induced heating was suspected to cause beam dumps and even degradation of the equipment. This contribution aims at gathering the observations of beam induced heating due to beam coupling impedance, their current level of understanding and possible actions that could be implemented during the winter stop 2011-2012.

  8. Paroxetine-induced galactorrhea

    OpenAIRE

    Gulati, Prannay; Chavan, B.S.; Das, Subhash

    2014-01-01

    Drug-induced galactorrhea has been reported with agents such as antidopaminergic antiemetics, antipsychotics, etc., with few case reports of galactorrhea with selective serotonin reuptake inhibitors, including paroxetine, being reported in last few decades. Prolactin levels have been found to be either raised or normal in these cases. We here report a case of paroxetine induced galactorrhea in a 48-year-old female patient of obsessive compulsive disorder, having hyperprolactinemic and euprola...

  9. A single nucleotide polymorphism in the human bone morphogenetic protein-2 gene (109T>G) affects the Smad signaling pathway and the predisposition to ossification of the posterior longitudinal ligament of the spine

    Institute of Scientific and Technical Information of China (English)

    YAN Liang; CHANG Zhen; LIU Yang; LI Yi-bing; HE Bao-rong; HAO Ding-jun

    2013-01-01

    0.05).The expression of Smad4 protein transfected by pcDNA3.1-BMP2 (109G) and pcDNA3.1-BMP2 (109G,570T) was significantly higher than the other experimental groups (P <0.05).The increase in ALP activity has been detected in pcDNA3.1-BMP2 (109G) and pcDNA3.1-BMP2 (109G,570T) transfected cells up to 4 weeks after stable transfection.Activity of ALP was (30.56±0.46)nmol·min-1·mg-1 protein and (29.62±0.68) nmol·min-1·mg-1 protein,respectively.This was statistically different compared with the other experimental groups (P <0.05).Conclusions BMP-2 is the predisposing gene of OPLL.The "TG" genotype in the 109T>G and the "AT" genotype in the 570A>T polymorphisms are associated with the occurrence of OPLL.The 109T>G polymorphism in exon-2 of the BMP-2 gene is positively associated with the level of Smad4 protein expression and the activity of ALP.The Smad mediated signaling pathway plays an important role during the pathological process of OPLL induced by SNPs of BMP-2 gene.

  10. Multi-protein delivery by nanodiamonds promotes bone formation.

    Science.gov (United States)

    Moore, L; Gatica, M; Kim, H; Osawa, E; Ho, D

    2013-11-01

    Bone morphogenetic proteins (BMPs) are well-studied regulators of cartilage and bone development that have been Food and Drug Administration (FDA)-approved for the promotion of bone formation in certain procedures. BMPs are seeing more use in oral and maxillofacial surgeries because of recent FDA approval of InFUSE(®) for sinus augmentation and localized alveolar ridge augmentation. However, the utility of BMPs in medical and dental applications is limited by the delivery method. Currently, BMPs are delivered to the surgical site by the implantation of bulky collagen sponges. Here we evaluate the potential of detonation nanodiamonds (NDs) as a delivery vehicle for BMP-2 and basic fibroblast growth factor (bFGF). Nanodiamonds are biocompatible, 4- to 5-nm carbon nanoparticles that have previously been used to deliver a wide variety of molecules, including proteins and peptides. We find that both BMP-2 and bFGF are readily loaded onto NDs by physisorption, forming a stable colloidal solution, and are triggered to release in slightly acidic conditions. Simultaneous delivery of BMP-2 and bFGF by ND induces differentiation and proliferation in osteoblast progenitor cells. Overall, we find that NDs provide an effective injectable alternative for the delivery of BMP-2 and bFGF to promote bone formation. PMID:24045646

  11. Plasma Surface Modification for Immobilization of Bone Morphogenic Protein-2 on Polycaprolactone Scaffolds

    Science.gov (United States)

    Kim, Byung Hoon; Myung, Sung Woon; Jung, Sang Chul; Ko, Yeong Mu

    2013-11-01

    The immobilization of recombinant human bone formation protein-2 (rhBMP-2) on polycaprolactone (PCL) scaffolds was performed by plasma polymerization. RhBMP-2, which induces osteoblast differentiation in various cell types, is a growth factor that plays an important role in bone formation and repair. The surface of the PCL scaffold was functionalized with the carboxyl groups of plasma-polymerized acrylic acid (PPAA) thin films. Plasma polymerization was carried out at a discharge power of 60 W at an acrylic acid flow rate of 7 sccm for 5 min. The PPAA thin film exhibited moderate hydrophilic properties and possessed a high density of carboxyl groups. Carboxyl groups and rhBMP-2 on the PCL scaffolds surface were identified by attenuated total reflection Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy, respectively. The alkaline phosphatase activity assay showed that the rhBMP-2 immobilized PCL scaffold increased the level of MG-63 cell differentiation. Plasma surface modification for the preparation of biomaterials, such as biofunctionalized polymer scaffolds, can be used for the binding of bioactive molecules in tissue engineering.

  12. Delivery of bioactive lipids from composite microgel-microsphere injectable scaffolds enhances stem cell recruitment and skeletal repair.

    Science.gov (United States)

    Das, Anusuya; Barker, Daniel A; Wang, Tiffany; Lau, Cheryl M; Lin, Yong; Botchwey, Edward A

    2014-01-01

    In this study, a microgel composed of chitosan and inorganic phosphates was used to deliver poly(lactic-co-glycolic acid) (PLAGA) microspheres loaded with sphingolipid growth factor FTY720 to critical size cranial defects in Sprague Dawley rats. We show that sustained release of FTY720 from injected microspheres used alone or in combination with recombinant human bone morphogenic protein-2 (rhBMP2) improves defect vascularization and bone formation in the presence and absence of rhBMP2 as evaluated by quantitative microCT and histological measurements. Moreover, sustained delivery of FTY720 from PLAGA and local targeting of sphingosine 1-phosphate (S1P) receptors reduces CD45+ inflammatory cell infiltration, promotes endogenous recruitment of CD29+CD90+ bone progenitor cells and enhances the efficacy of rhBMP2 from chitosan microgels. Companion in vitro studies suggest that selective activation of sphingosine receptor subtype-3 (S1P3) via FTY720 treatment induces smad-1 phosphorylation in bone-marrow stromal cells. Additionally, FTY720 enhances stromal cell-derived factor-1 (SDF-1) mediated chemotaxis of CD90+CD11B-CD45- bone progenitor cells in vitro after stimulation with rhBMP2. We believe that use of such small molecule delivery formulations to recruit endogenous bone progenitors may be an attractive alternative to exogenous cell-based therapy.

  13. Delivery of bioactive lipids from composite microgel-microsphere injectable scaffolds enhances stem cell recruitment and skeletal repair.

    Directory of Open Access Journals (Sweden)

    Anusuya Das

    Full Text Available In this study, a microgel composed of chitosan and inorganic phosphates was used to deliver poly(lactic-co-glycolic acid (PLAGA microspheres loaded with sphingolipid growth factor FTY720 to critical size cranial defects in Sprague Dawley rats. We show that sustained release of FTY720 from injected microspheres used alone or in combination with recombinant human bone morphogenic protein-2 (rhBMP2 improves defect vascularization and bone formation in the presence and absence of rhBMP2 as evaluated by quantitative microCT and histological measurements. Moreover, sustained delivery of FTY720 from PLAGA and local targeting of sphingosine 1-phosphate (S1P receptors reduces CD45+ inflammatory cell infiltration, promotes endogenous recruitment of CD29+CD90+ bone progenitor cells and enhances the efficacy of rhBMP2 from chitosan microgels. Companion in vitro studies suggest that selective activation of sphingosine receptor subtype-3 (S1P3 via FTY720 treatment induces smad-1 phosphorylation in bone-marrow stromal cells. Additionally, FTY720 enhances stromal cell-derived factor-1 (SDF-1 mediated chemotaxis of CD90+CD11B-CD45- bone progenitor cells in vitro after stimulation with rhBMP2. We believe that use of such small molecule delivery formulations to recruit endogenous bone progenitors may be an attractive alternative to exogenous cell-based therapy.

  14. Induced Norm Control Toolbox

    DEFF Research Database (Denmark)

    Beran, Eric Bengt

    1996-01-01

    This paper describes the basic nature of the InducedNorm Control Toolbox (INCT). The toolbox is a set of Matlab-filesusing LMITOOL and the Semidefinite Programming package(SP). Thetoolbox is public domain. The INCT provides a series of analysisand synthesis tools for continuous time-invariant lin......This paper describes the basic nature of the InducedNorm Control Toolbox (INCT). The toolbox is a set of Matlab-filesusing LMITOOL and the Semidefinite Programming package(SP). Thetoolbox is public domain. The INCT provides a series of analysisand synthesis tools for continuous time......-invariant linear systems,all related to induced norms. A packing system has also beendeveloped to make the writing of code less cumbersome....

  15. Gravitationally induced quantum transitions

    CERN Document Server

    Landry, A

    2016-01-01

    In this letter, we calculate the probability for resonantly induced transitions in quantum states due to time dependent gravitational perturbations. Contrary to common wisdom, the probability of inducing transitions is not infinitesimally small. We consider a system of ultra cold neutrons (UCN), which are organized according to the energy levels of the Schr\\"odinger equation in the presence of the earth's gravitational field. Transitions between energy levels are induced by an oscillating driving force of frequency $\\omega$. The driving force is created by oscillating a macroscopic mass in the neighbourhood of the system of neutrons. The neutrons decay in 880 seconds while the probability of transitions increase as $t^2$. Hence the optimal strategy is to drive the system for 2 lifetimes. The transition amplitude then is of the order of $1.06\\times 10^{-5}$ hence with a million ultra cold neutrons, one should be able to observe transitions.

  16. Time Domain Induced Polarization

    DEFF Research Database (Denmark)

    Fiandaca, Gianluca; Auken, Esben; Christiansen, Anders Vest;

    2012-01-01

    of time-domaininduced polarization for wider purposes. For these reasons, a new forward code and inversion algorithm have been developed using the full-time decay of the induced polarization response, together with an accurate description of the transmitter waveform and of the receiver transfer function...... laterally constrained inversion algorithm that extracts the spectral content of the induced polarization phenomenon in terms of the Cole- Cole parameters. Synthetic examples and field examples from Denmark showed a significant improvement in the resolution of the parameters that control the induced...... polarization response when compared to traditional integral chargeability inversion. The quality of the inversion results has been assessed by a complete uncertainty analysis of the model parameters; furthermore, borehole information confirm the outcomes of the field interpretations. With this new accurate...

  17. Gravitationally induced quantum transitions

    Science.gov (United States)

    Landry, A.; Paranjape, M. B.

    2016-06-01

    In this paper, we calculate the probability for resonantly inducing transitions in quantum states due to time-dependent gravitational perturbations. Contrary to common wisdom, the probability of inducing transitions is not infinitesimally small. We consider a system of ultracold neutrons, which are organized according to the energy levels of the Schrödinger equation in the presence of the Earth's gravitational field. Transitions between energy levels are induced by an oscillating driving force of frequency ω . The driving force is created by oscillating a macroscopic mass in the neighborhood of the system of neutrons. The neutron lifetime is approximately 880 sec while the probability of transitions increases as t2. Hence, the optimal strategy is to drive the system for two lifetimes. The transition amplitude then is of the order of 1.06 ×10-5, and hence with a million ultracold neutrons, one should be able to observe transitions.

  18. Optically Induced Transparency

    CERN Document Server

    Zheng, Yuanlin; Shen, Zhenhua; Cao, Jianjun; Chen, Xianfeng; Liang, Xiaogan; Wan, Wenjie

    2015-01-01

    Light-matter-light interactions serve as the backbone technology of all-optical information processing for both on-chip and long-haul communication purposes. The representative example of electromagnetically induced transparency has its unique ability of optically controlling transparency windows with relative low light in atomic systems, though its practical applications are limited due to rigid experimental requirements. Here we demonstrate a new form of optically induced transparency in a micro-cavity by introducing four-wave mixing gain in order to couple nonlinearly two separated resonances of the micro-cavity in ambient environment. A signature Fano-like resonance is also observed owing to the nonlinear interference of two coupled resonances. Moreover, we show that the unidirectional gain of four-wave mixing can lead to non-reciprocal transmission at the transparency windows. Optically induced transparency may offer a unique platform for a compact, integrated solution to all-optical processing and quant...

  19. Rosuvastatin-induced pemphigoid.

    LENUS (Irish Health Repository)

    Murad, Aizuri A

    2012-01-01

    Statins are widely prescribed medications and very well tolerated. Rosuvastatin is another member of this drug used to treat dyslipidaemia. It is a competitive inhibitor of the enzyme 3-hydroxy-3-methylglutaryl coenzyme A reductase. Immunobullous disease is usually idiopathic but can be drug-induced. Both idiopathic and iatrogenic forms share common clinical and immunohistological features. The authors report a case of pemphigoid induced by rosuvastatin, a commonly prescribed medication. To our knowledge, there is limited report on rosuvastatin associated with pemphigoid in the literature.

  20. Investigation of the Co-Dependence of Morphology and Fluorescence Lifetime in a Metal-Organic Framework.

    Science.gov (United States)

    Schrimpf, Waldemar; Ossato, Giulia; Hirschle, Patrick; Wuttke, Stefan; Lamb, Don C

    2016-07-01

    Porous materials, due to their large surface-to-volume ratio, are important for a broad range of applications and are the subject of intense research. Most studies investigate the bulk properties of these materials, which are not sensitive to the effect of heterogeneities within the sample. Herein, a new strategy based on correlative fluorescence lifetime imaging and scanning electron microscopy is presented that allows the detection and localization of those heterogeneities, and connects them to morphological and structural features of the material. By applying this method to a dye-modified metal-organic framework (MOF), two independent fluorescence quenching mechanisms in the MOF scaffold are identified and quantified. The first mechanism is based on quenching via amino groups, while the second mechanism is influenced by morphology. Furthermore, a similar correlation between the inherent luminescence lifetime and the morphology of the unmodified MOF structure is demonstrated.

  1. Electron-impact dissociative double ionization of N2 and CO: Dependence of transition probability on impact energy

    Science.gov (United States)

    Pandey, A.; Kumar, P.; Banerjee, S. B.; Subramanian, K. P.; Bapat, B.

    2016-04-01

    We present an experimental and computational analysis of dissociative double ionization of N2 and CO molecules under electron impact. Experiments are performed at three energies, viz. 1, 3, and 5 keV, in order to observe the effect of impact energy on the dissociative ionization kinematics. We compare the kinetic energy release (KER) distributions of the charge symmetric dissociation channels of N22 + and CO2 + at these impact energies. An approximately linear trend between the transition energy and the expected KER values is inferred on the basis of the calculated potential energy curves of the dications. Experimentally, the normalized differential KER cross sections for these channels show an increasing trend in the low KER range and a decreasing trend in the high KER range as the electron-impact energy is increased. This observation indicates that the transition probability for excitation to different molecular ion states is not only a function of energy difference between the ground and excited states, but also a complicated function of the impact energy. In addition, nature of the observed trend in the differential KER cross sections differs significantly from their differential transition probability, which are calculated using inelastic collision model for fast-electron-impact case.

  2. Experimental study of the induced rat myoblasts into a tissue engineered bioartificial bone%经诱导的大鼠成肌细胞应用于组织工程化人工骨的实验研究

    Institute of Scientific and Technical Information of China (English)

    张玉强; 李游; 王岩峰; 王伟; 吕刚

    2011-01-01

    [Objective]To investigate the effectiveness of the induced rat myoblasts used as tissue engineered bioartificial bone for bridging tibiae defects. [Method]Thirty-two Sprague Dawley adult male rats weighing 200 -250 g were randomly divided into four groups of bone grafting,with 8 rats in each group. Group A; polyethylene tutes were seeded with syngeneic myoblasts induced 5 days with rhBMP -2 and sodium hyaluronate. Group B; polyethylene tutes were seeded with syngeneic myoblasts and sodium hyaluronate. Group C; polyethylene tutes were filled with sodium hyaluronate. Group D: polyethylene tutes were only filled with normal sodium. At 12 weeks,a series of examinations were performed,including morphology observation,radioactive ray,his-tological staining of bones,and labelling with tetracycline and calcein. [ Result] At 12 weeks after operation,groups A and B had significant bone tissues than groups C and D based on morphology. For radioactive ray,groups A and B had significantly absorption of bony callus and recanalization of cavum pulpi, groups C and D had a little bony callus and significant bone defect. From histology, groups A and B had more significant new bone trabecula than groups C or D. Flavo-green fluorescence was noted. [Conclusion]Induced rat myoblasts as seeding cells for bone tissue engineering can be used to repair bone defect.%[目的]探讨骨形态发生蛋白诱导的大鼠成肌细胞应用于组织工程化人工骨修复大鼠胫骨缺损的效果.[方法]32只体重在200~250 g的雄性SD大鼠随机分成4组,每组8只.A组:聚乙烯管内植入诱导2周的成肌细胞复合透明质酸钠.B组:聚乙烯管内植入成肌细胞复合透明质酸钠.C组:聚乙烯管内植入透明质酸钠.D组:聚乙烯管内注入生理盐水.术后12周,进行X线观察、大体观察、组织学观察(HE染色)以及四环素和钙黄绿素标记.[结果]术后12周时大体观察发现,A、B组骨缺损处可见大量类骨样组织填充,未触及反

  3. Biostimulation induces syntrophic interactions that impact C, S and N cycling in a sediment microbial community

    Energy Technology Data Exchange (ETDEWEB)

    Handley, KM [University of California, Berkeley; Verberkmoes, Nathan C [ORNL; Steefel, Carl I [Lawrence Berkeley National Laboratory (LBNL); Sharon, I [University of California, Berkeley; Williams, Ken [Lawrence Berkeley National Laboratory (LBNL); Miller, CS [University of California, Berkeley; Frischkorn, Kyle C [University of California, Berkeley; Chourey, Karuna [ORNL; Thomas, Brian [University of California, Berkeley; Shah, Manesh B [ORNL; Long, Phil [Pacific Northwest National Laboratory (PNNL); Hettich, Robert {Bob} L [ORNL; Banfield, Jillian F. [University of California, Berkeley

    2013-01-01

    Stimulation of subsurface microorganisms to induce reductive immobilization of metals is a promising approach for bioremediation, yet the overall microbial community response is typically poorly understood. Here we used community proteogenomics to test the hypothesis that excess input of acetate activates syntrophic interactions among autotrophs and heterotrophs. A flow-through sediment column was incubated in a groundwater well of an acetate-amended aquifer. Genomic sequences from the community recovered during microbial sulfate reduction were used to econstruct, de novo, near-complete genomes for Desulfobacter (Deltaproteobacteria) and relatives of Sulfurovum and Sulfurimonas (Epsilonproteobacteria), and Bacteroidetes. Partial genomes were obtained for Clostridiales (Firmicutes) and Desulfuromonadales-like Deltaproteobacteria. The majority of proteins identified by mass spectrometry corresponded to Desulfobacter-like species, and demonstrate the role of this organism in sulfate reduction (Dsr and APS), nitrogen-fixation (Nif) and acetate oxidation to CO2 during amendment. Results suggest less abundant Desulfuromonadales and Bacteroidetes also actively contributed to CO2 production via the TCA cycle. Proteomic data indicate that sulfide was partially re-oxidized by Epsilonproteobacteria through nitrate-dependent sulfide oxidation (using Nap, Nir, Nos, SQR and Sox), with CO2 fixed using the reverse TCA cycle. Modeling shows that this reaction was thermodynamically possible, and kinetically favorable relative to acetate-dependent denitrification. We conclude that high-levels of carbon amendment aimed to stimulate anaerobic heterotrophy led to carbon fixation in co-dependent chemoautotrophs. These results have implications for understanding complex ecosystem behavior, and show that high levels of organic carbon supplementation can expand the range of microbial functionalities accessible for ecosystem manipulation.

  4. Noise-induced linearisation

    OpenAIRE

    Dykman, Mark; Luchinsky, D. G.; Mannella, R.; McClintock, Peter V. E.; Short, H. E.; Stein, N. D.; Stocks, N. G.

    1994-01-01

    It is found that the response of a nonlinear dynamical system can be linearised, and its frequency dispersion diminished, by the addition of external noise of sufficient intensity. Taking as an example an overdamped bistable system driven by a low-frequency periodic field, this noise-induced linearisation is investigated through analogue electronic experiments. The wider implications are considered.

  5. Metformin induced acute pancreatitis

    OpenAIRE

    Alsubaie, Sadeem; Almalki, Mussa H.

    2013-01-01

    Acute pancreatitis frequently presents with abdomen pain but may presents with various skin manifestations as rash and rarely, pancreatic panniculitis. Metformin, one of the most effective and valuable oral hypoglycemic agents in the biguanide class was linked to acute pancreatitis in few cases. Here, we report a case of metformin induce acute pancreatitis in young healthy man with normal renal function.

  6. Drug-induced hyperkalemia.

    Science.gov (United States)

    Ben Salem, Chaker; Badreddine, Atef; Fathallah, Neila; Slim, Raoudha; Hmouda, Houssem

    2014-09-01

    Hyperkalemia is a common clinical condition that can be defined as a serum potassium concentration exceeding 5.0 mmol/L. Drug-induced hyperkalemia is the most important cause of increased potassium levels in everyday clinical practice. Drug-induced hyperkalemia may be asymptomatic. However, it may be dramatic and life threatening, posing diagnostic and management problems. A wide range of drugs can cause hyperkalemia by a variety of mechanisms. Drugs can interfere with potassium homoeostasis either by promoting transcellular potassium shift or by impairing renal potassium excretion. Drugs may also increase potassium supply. The reduction in renal potassium excretion due to inhibition of the renin-angiotensin-aldosterone system represents the most important mechanism by which drugs are known to cause hyperkalemia. Medications that alter transmembrane potassium movement include amino acids, beta-blockers, calcium channel blockers, suxamethonium, and mannitol. Drugs that impair renal potassium excretion are mainly represented by angiotensin-converting enzyme inhibitors, angiotensin-II receptor blockers, direct renin inhibitors, nonsteroidal anti-inflammatory drugs, calcineurin inhibitors, heparin and derivatives, aldosterone antagonists, potassium-sparing diuretics, trimethoprim, and pentamidine. Potassium-containing agents represent another group of medications causing hyperkalemia. Increased awareness of drugs that can induce hyperkalemia, and monitoring and prevention are key elements for reducing the number of hospital admissions, morbidity, and mortality related to drug-induced hyperkalemia.

  7. Heparin-induced thrombocytopenia.

    Science.gov (United States)

    2013-05-01

    Patients can develop thrombocytopenia during heparin therapy.The most frequent form, type I heparin-induced thrombocytopenia, does not require cessation of therapy. Type II heparin-induced thrombocytopenia is immune-mediated. It can cause venous or arterial thrombosis, which may be fatal or require amputation. Type II thrombocytopenia typically develops 5 to 10 days after initiation of treatment, sometimes earlier in patients previously exposed to heparins. The recommendations on platelet-count monitoring during heparin therapy are not based on high-level evidence. The main risk factors for type II thrombocytopenia must be taken into account: unfractionated heparin, previous heparin exposure, surgery, female patient. For patients considered at high risk for heparin-induced thrombocytopenia, platelet-count monitoring is usually recommended at least twice a week for at least 2 weeks. The treatment of immune-mediated heparin-induced thrombocytopenia is based on stopping heparin and replacing it with danaparoid or argatroban. In practice, the decision to initiate treatment with unfractionated or low-molecular-weight heparin is not a trivial one. In addition to the bleeding risk, the risk of type II thrombocytopenia in the short- term, or during subsequent heparin therapy, should be taken into account when assessing the harm-benefit balance. PMID:23819174

  8. Bowthruster-induced damage

    NARCIS (Netherlands)

    Schokking, L.A.; Janssen, P.C.; Verhagen, H.J.

    2003-01-01

    The stability of stones in propeller-induced jet wash is still difficult to predict. Especially the trend of bowthrusters increasing in size and power in sea going ships (especially ferries) over the last years may be a reason for concern when dealing with the protection of slopes and beds. But also

  9. Methacholine induced headache.

    Science.gov (United States)

    Carratala, C; Gea, J G; Aguar, M C; Grau, S; Espadaler-Medina, J M; Broquetas, J M

    1995-03-01

    A lung function technician developed episodes of headache, probably related to the use of methacholine. The headache disappeared with breathing 100% oxygen. Cholinergic agents are known to induce headaches but the mechanism remains unclear. Vascular factors could be implicated. PMID:7660351

  10. Cold-induced metabolism

    NARCIS (Netherlands)

    Lichtenbelt, W. van Marken; Daanen, H.A.M.

    2003-01-01

    Purpose of review Cold response can be insulative (drop in peripheral temperature) or metabolic (increase in energy expenditure). Nonshivering thermogenesis by sympathetic, norepinephrine-induced mitochondrial heat production in brown adipose tissue is a well known component of this metabolic respon

  11. Irradiation-Induced Nanostructures

    Energy Technology Data Exchange (ETDEWEB)

    Birtcher, R.C.; Ewing, R.C.; Matzke, Hj.; Meldrum, A.; Newcomer, P.P.; Wang, L.M.; Wang, S.X.; Weber, W.J.

    1999-08-09

    This paper summarizes the results of the studies of the irradiation-induced formation of nanostructures, where the injected interstitials from the source of irradiation are not major components of the nanophase. This phenomena has been observed by in situ transmission electron microscopy (TEM) in a number of intermetallic compounds and ceramics during high-energy electron or ion irradiations when the ions completely penetrate through the specimen. Beginning with single crystals, electron or ion irradiation in a certain temperature range may result in nanostructures composed of amorphous domains and nanocrystals with either the original composition and crystal structure or new nanophases formed by decomposition of the target material. The phenomenon has also been observed in natural materials which have suffered irradiation from the decay of constituent radioactive elements and in nuclear reactor fuels which have been irradiated by fission neutrons and other fission products. The mechanisms involved in the process of this nanophase formation are discussed in terms of the evolution of displacement cascades, radiation-induced defect accumulation, radiation-induced segregation and phase decomposition, as well as the competition between irradiation-induced amorphization and recrystallization.

  12. Radiation-induced pneumothorax

    Energy Technology Data Exchange (ETDEWEB)

    Epstein, D.M.; Littman, P.; Gefter, W.B.; Miller, W.T.; Raney, R.B. Jr.

    1983-01-01

    Pneumothorax is an uncommon complication of radiation therapy to the chest. The proposed pathogenesis is radiation-induced fibrosis promoting subpleural bleb formation that ruptures resulting in pneumothorax. We report on two young patients with primary sarcomas without pulmonary metastases who developed spontaneous pneumothorax after irradiation. Neither patient had antecedent radiographic evidence of pulmonary fibrosis.

  13. Radiation-induced pneumothorax

    International Nuclear Information System (INIS)

    Pneumothorax is an uncommon complication of radiation therapy to the chest. The proposed pathogenesis is radiation-induced fibrosis promoting subpleural bleb formation that ruptures resulting in pneumothorax. We report on two young patients with primary sarcomas without pulmonary metastases who developed spontaneous pneumothorax after irradiation. Neither patient had antecedent radiographic evidence of pulmonary fibrosis

  14. Advertising-Induced Embarrassment

    NARCIS (Netherlands)

    Puntoni, S.; Hooge, de I.E.; Verbeke, W.J.M.I.

    2015-01-01

    Abstract Consumer embarrassment is a concern for many advertisers. Yet little is known about ad-induced embarrassment. The authors investigate when and why consumers experience embarrassment as a result of exposure to socially sensitive advertisements. The theory distinguishes between viewing potent

  15. Pentazocine-induced agranulocytosis.

    OpenAIRE

    Sheehan, Meg; Hyland, Robert H; Norman, Conolly

    1984-01-01

    A 46-year-old man with pentazocine-induced agranulocytosis is described. In previously reported cases of a complete absence of mature neutrophils in the peripheral blood and bone marrow the patients had undergone marrow-depressing treatment with radiation and antineoplastic drugs. This case is unique in that the patient had complete agranulocytosis without predisposing factors.

  16. Induced Angular Momentum

    Science.gov (United States)

    Parker, G. W.

    1978-01-01

    Discusses, classically and quantum mechanically, the angular momentum induced in the bound motion of an electron by an external magnetic field. Calculates the current density and its magnetic moment, and then uses two methods to solve the first-order perturbation theory equation for the required eigenfunction. (Author/GA)

  17. Radiation Induced Fermion Resonance

    OpenAIRE

    Esposito, S.; M. W. Evans; Recami, E.

    1998-01-01

    The Dirac equation is solved for two novel terms which describe the interaction energy between the half integral spin of a fermion and the classical, circularly polarized, electromagnetic field. A simple experiment is suggested to test the new terms and the existence of radiation induced fermion resonance.

  18. Muon-induced fission

    International Nuclear Information System (INIS)

    A review of recent experimental results on negative-muon-induced fission, both of 238U and 232Th, is given. Some conclusions drawn by the author are concerned with muonic atoms of fission fragments and muonic atoms of the shape isomer of 238U. (author)

  19. Lupus induced by medicaments

    International Nuclear Information System (INIS)

    We describe a 55 years old female patient who consulted by fever syndrome, artralgias and the presence of high tittles positives antinuclear antibodies. She had arterial hypertension in treatment with captopril. We suspected the clinical diagnoses of drug-induced lupus; the withdraw of captopril was associated with the remission of the clinical and laboratory manifestations

  20. Geomagnetism and Induced Voltage

    Science.gov (United States)

    Abdul-Razzaq, W.; Biller, R. D.

    2010-01-01

    Introductory physics laboratories have seen an influx of "conceptual integrated science" over time in their classrooms with elements of other sciences such as chemistry, biology, Earth science, and astronomy. We describe a laboratory to introduce this development, as it attracts attention to the voltage induced in the human brain as it is…

  1. Mild induced hypothermia

    DEFF Research Database (Denmark)

    Johansen, Maria E; Jensen, Jens-Ulrik; Bestle, Morten H;

    2014-01-01

    trial; The Cooling And Surviving Septic shock (CASS) study. Patients suffering severe sepsis/septic shock are allocated to either mild induced hypothermia (cooling to 32-34°C for 24hours) or control (uncontrolled temperature). TRIAL REGISTRATION: NCT01455116. Thrombelastography (TEG) is performed three...

  2. Sulphasalazine induced renal failure.

    OpenAIRE

    Dwarakanath, A D; Michael, J.; Allan, R. N.

    1992-01-01

    Two men with longstanding ulcerative colitis who were treated with sulphasalazine for several years and who developed chronic renal failure are reported. Renal biopsy specimens showed histological changes consistent with drug induced chronic intestinal nephritis. Extensive investigation made other causes of chronic renal failure unlikely. One of these patients underwent renal transplantation, the other has impaired but stable renal function.

  3. Olanzapine induced hyperprolactinemia

    OpenAIRE

    Veena Nayak; Virupaksha Devaramane; Deepak Mallya; Panambur V Bhandary

    2013-01-01

    Olanzapine, a second generation antipsychotic is widely used for the treatment of schizophrenia and bipolar disorders. Though olanzapine is an efficacious antipsychotic it has been associated with many adverse effects like weight gain, hyperlipidemia, diabetes mellitus, etc necessitating its discontinuation. Here, we present two cases of hyperprolactinemia induced by olanzapine. [Int J Basic Clin Pharmacol 2013; 2(6.000): 836-837

  4. Uterine contraction induced by Tanzanian plants used to induce abortion

    DEFF Research Database (Denmark)

    Nikolajsen, Tine; Nielsen, Frank; Rasch, Vibeke;

    2011-01-01

    Women in Tanzania use plants to induce abortion. It is not known whether the plants have an effect.......Women in Tanzania use plants to induce abortion. It is not known whether the plants have an effect....

  5. Osteogenic potential of the human bone morphogenetic protein 2 gene activated nanobone putty

    Institute of Scientific and Technical Information of China (English)

    TIAN Xiao-bin; SUN Li; YANG Shu-hua; ZHANG Yu-kun; HU Ru-yin; FU De-hao

    2008-01-01

    Background Nanobone putty is an injectable and bioresorbable bone substitute. The neutral-pH putty resembles hard bone tissue, does not contain polymers or plasticizers, and is self-setting and nearly isothermic, properties which are helpful for the adhesion, proliferation, and function of bone cells. The aim of this study was to investigate the osteogenic potential of human bone morphogenetic protein 2(hBMP2)gene activated nanobone putty in inducing ectopic bone formation, and the effects of the hBMP2 gene activated nanobone putry on repairing bone defects. Methods Twenty four Kunming mice were randomly divided into two groups. The nanobone putty+hBMP2 plasmid was injected into the right thigh muscle pouches of the mice(experiment side). The nanobone putty+blank plasmid or nanobone putty was injected into the left thigh muscle pouches of the group 1(control side 1)or group 2(control side 2), respectively. The effects of ectopic bone formation were evaluated by radiography, histology, and molecular biology analysis at 2 and 4 weeks after operation. Bilateral 15 mm radial defects were made in forty-eight rabbits. These rabbits were randomly divided into three groups: Group A, nanobone putty+hBMP2 plasmid;Group B, putty+blank plasmid; Group C, nanobone putty only. Six rabbits with left radial defects served as blank controls. The effect of bone repairing was evaluated by radiography, histology, molecular biology, and biomechanical analysis at 4, 8, and 12 weeks after operation. Results The tissue from the experimental side of the mice expressed hBMP2. Obvious cartilage and island-distributed immature bone formation in implants of the experiment side were observed at 2 weeks after operation, and massive mature bone observed at 4 weeks. No bone formation was observed in the control side of the mice. The ALP activity in the experiment side of the mice was higher than that in the control side. The tissue of Group A rabbits expressed hBMP2 protein and higher ALP level

  6. Osthole-mediated cell differentiation through bone morphogenetic protein-2/p38 and extracellular signal-regulated kinase 1/2 pathway in human osteoblast cells.

    Science.gov (United States)

    Kuo, Po-Lin; Hsu, Ya-Ling; Chang, Cheng-Hsiung; Chang, Jiunn-Kae

    2005-09-01

    The survival of osteoblast cells is one of the determinants of the development of osteoporosis in patients. Osthole (7-methoxy-8-isopentenoxycoumarin) is a coumarin derivative present in many medicinal plants. By means of alkaline phosphatase (ALP) activity, osteocalcin, osteopontin, and type I collagen, enzyme-linked immunosorbent assay, we have shown that osthole exhibits a significant induction of differentiation in two human osteoblast-like cell lines, MG-63 and hFOB. Induction of differentiation by osthole was associated with increased bone morphogenetic protein (BMP)-2 production and the activations of SMAD1/5/8 and p38 and extracellular signal-regulated kinase (ERK) 1/2 kinases. Addition of purified BMP-2 protein did not increase the up-regulation of ALP activity and osteocalcin by osthole, whereas the BMP-2 antagonist noggin blocked both osthole and BMP-2-mediated ALP activity enhancement, indicating that BMP-2 production is required in osthole-mediated osteoblast maturation. Pretreatment of osteoblast cells with noggin abrogated p38 activation but only partially decreased ERK1/2 activation, suggesting that BMP-2 signaling is required in p38 activation and is partially involved in ERK1/2 activation in osthole-treated osteoblast cells. Cotreatment of p38 inhibitor SB203580 [4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)-1H-imidazole] or p38 small interfering RNA (siRNA) expression inhibited osthole-mediated activation of ALP but only slightly affected osteocalcin production. In contrast, the production of osteocalcin induced by osthole was inhibited by the mitogen-activated protein kinase kinase inhibitor PD98059 (2'-amino-3'-methoxyflavone) or by expression of an ERK2 siRNA. These data suggest that BMP-2/p38 pathway links to the early phase, whereas ERK1/2 pathway is associated with the later phase in osthole-mediated differentiation of osteoblast cells. In this study, we demonstrate that osthole is a promising agent for treating osteoporosis

  7. Wnt5a signaling is a substantial constituent in bone morphogenetic protein-2-mediated osteoblastogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Nemoto, Eiji, E-mail: e-nemoto@dent.tohoku.ac.jp [Department of Periodontology and Endodontology, Tohoku University Graduate School of Dentistry, Sendai 980-8575 (Japan); Ebe, Yukari; Kanaya, Sousuke [Department of Periodontology and Endodontology, Tohoku University Graduate School of Dentistry, Sendai 980-8575 (Japan); Tsuchiya, Masahiro [Department of Aging and Geriatric Dentistry, Tohoku University Graduate School of Dentistry, Sendai 980-8575 (Japan); Nakamura, Takashi [Department of Pediatric Dentistry, Tohoku University Graduate School of Dentistry, Sendai 980-8575 (Japan); Tamura, Masato [Department of Biochemistry and Molecular Biology, Hokkaido University Graduate School of Dentistry, Sapporo 060-8586 (Japan); Shimauchi, Hidetoshi [Department of Periodontology and Endodontology, Tohoku University Graduate School of Dentistry, Sendai 980-8575 (Japan)

    2012-06-15

    Highlights: Black-Right-Pointing-Pointer Wnt5a is identified in osteoblasts in tibial growth plate and bone marrow. Black-Right-Pointing-Pointer Osteoblastic differentiation is associated with increased expression of Wnt5a/Ror2. Black-Right-Pointing-Pointer Wnt5a/Ror2 signaling is important for BMP-2-mediated osteoblastic differentiation. Black-Right-Pointing-Pointer Wnt5a/Ror2 operates independently of BMP-Smad pathway. -- Abstract: Wnts are secreted glycoproteins that mediate developmental and post-developmental physiology by regulating cellular processes including proliferation, differentiation, and apoptosis through {beta}-catenin-dependent canonical and {beta}-catenin-independent noncanonical pathway. It has been reported that Wnt5a activates noncanonical Wnt signaling through receptor tyrosine kinase-like orphan receptor 2 (Ror2). Although it appears that Wnt5a/Ror2 signaling supports normal bone physiology, the biological significance of noncanonical Wnts in osteogenesis is essentially unknown. In this study, we identified expression of Wnt5a in osteoblasts in the ossification zone of the tibial growth plate as well as bone marrow of the rat tibia as assessed by immunohistochemistry. In addition, we show that osteoblastic differentiation mediated by BMP-2 is associated with increased expression of Wnt5a and Ror2 using cultured pre-osteoblasts, MC3T3-E1 cells. Silencing gene expression of Wnt5a and Ror2 in MC3T3-E1 cells results in suppression of BMP-2-mediated osteoblastic differentiation, suggesting that Wnt5a and Ror2 signaling are of substantial importance for BMP-2-mediated osteoblastic differentiation. BMP-2 stimulation induced phosphorylation of Smad1/5/8 in a similar fashion in both siWnt5a-treated cells and control cells, suggesting that Wnt5a was dispensable for the phosphorylation of Smads by BMP-2. Taken together, our results suggest that Wnt5a/Ror2 signaling appears to be involved in BMP-2-mediated osteoblast differentiation in a Smad independent

  8. Wnt5a signaling is a substantial constituent in bone morphogenetic protein-2-mediated osteoblastogenesis

    International Nuclear Information System (INIS)

    Highlights: ► Wnt5a is identified in osteoblasts in tibial growth plate and bone marrow. ► Osteoblastic differentiation is associated with increased expression of Wnt5a/Ror2. ► Wnt5a/Ror2 signaling is important for BMP-2-mediated osteoblastic differentiation. ► Wnt5a/Ror2 operates independently of BMP-Smad pathway. -- Abstract: Wnts are secreted glycoproteins that mediate developmental and post-developmental physiology by regulating cellular processes including proliferation, differentiation, and apoptosis through β-catenin-dependent canonical and β-catenin-independent noncanonical pathway. It has been reported that Wnt5a activates noncanonical Wnt signaling through receptor tyrosine kinase-like orphan receptor 2 (Ror2). Although it appears that Wnt5a/Ror2 signaling supports normal bone physiology, the biological significance of noncanonical Wnts in osteogenesis is essentially unknown. In this study, we identified expression of Wnt5a in osteoblasts in the ossification zone of the tibial growth plate as well as bone marrow of the rat tibia as assessed by immunohistochemistry. In addition, we show that osteoblastic differentiation mediated by BMP-2 is associated with increased expression of Wnt5a and Ror2 using cultured pre-osteoblasts, MC3T3-E1 cells. Silencing gene expression of Wnt5a and Ror2 in MC3T3-E1 cells results in suppression of BMP-2-mediated osteoblastic differentiation, suggesting that Wnt5a and Ror2 signaling are of substantial importance for BMP-2-mediated osteoblastic differentiation. BMP-2 stimulation induced phosphorylation of Smad1/5/8 in a similar fashion in both siWnt5a-treated cells and control cells, suggesting that Wnt5a was dispensable for the phosphorylation of Smads by BMP-2. Taken together, our results suggest that Wnt5a/Ror2 signaling appears to be involved in BMP-2-mediated osteoblast differentiation in a Smad independent pathway.

  9. Induced pluripotent stem cells

    Institute of Scientific and Technical Information of China (English)

    Siddhartha Bhowmik; LI Yong

    2011-01-01

    Induced pluripotent stem (iPS) cells are a recent development which has brought a promise of great therapeutic values. The previous technique of somatic cell nuclear transfer (SCNT) has been ineffective in humans. Recent discoveries show that human fibroblasts can be reprogrammed by a transient over expression of a small number of genes; they can undergo induced pluripotency. iPS were first produced in 2006. By 2008, work was underway to remove the potential oncogenes from their structure. In 2009, protein iPS (piPS) cells were discovered. Surface markers and reporter genes play an important role in stem cell research. Clinical applications include generation of self renewing stem cells, tissue replacement and many more. Stem cell therapy has the ability to dramatically change the treatment of human diseases.

  10. Contrast induced nephropathy

    DEFF Research Database (Denmark)

    Stacul, Fulvio; van der Molen, Aart J; Reimer, Peter;

    2011-01-01

    PURPOSE: The Contrast Media Safety Committee (CMSC) of the European Society of Urogenital Radiology (ESUR) has updated its 1999 guidelines on contrast medium-induced nephropathy (CIN). AREAS COVERED: Topics reviewed include the definition of CIN, the choice of contrast medium, the prophylactic...... measures used to reduce the incidence of CIN, and the management of patients receiving metformin. Key Points • Definition, risk factors and prevention of contrast medium induced nephropathy are reviewed. • CIN risk is lower with intravenous than intra-arterial iodinated contrast medium. • eGFR of 45 ml....../min/1.73 m (2) is CIN risk threshold for intravenous contrast medium. • Hydration with either saline or sodium bicarbonate reduces CIN incidence. • Patients with eGFR ≥ 60 ml/min/1.73 m (2) receiving contrast medium can continue metformin normally....

  11. Contrast induced nephropathy

    DEFF Research Database (Denmark)

    Stacul, Fulvio; van der Molen, Aart J; Reimer, Peter;

    2011-01-01

    PURPOSE: The Contrast Media Safety Committee (CMSC) of the European Society of Urogenital Radiology (ESUR) has updated its 1999 guidelines on contrast medium-induced nephropathy (CIN). AREAS COVERED: Topics reviewed include the definition of CIN, the choice of contrast medium, the prophylactic...... measures used to reduce the incidence of CIN, and the management of patients receiving metformin. Key Points • Definition, risk factors and prevention of contrast medium induced nephropathy are reviewed. • CIN risk is lower with intravenous than intra-arterial iodinated contrast medium. • eGFR of 45 ml....../min/1.73 m (2) is CIN risk threshold for intravenous contrast medium. • Hydration with either saline or sodium bicarbonate reduces CIN incidence. • Patients with eGFR = 60 ml/min/1.73 m (2) receiving contrast medium can continue metformin normally....

  12. Tulipalin A induced phytotoxicity.

    Science.gov (United States)

    McCluskey, James; Bourgeois, Marie; Harbison, Raymond

    2014-04-01

    Tulipalin A induced phytotoxicity is a persistent allergic contact dermatitides documented in floral workers exposed to Alstroemeria and its cultivars.[1] The causative allergen is tulipalin A, a toxic glycoside named for the tulip bulbs from which it was first isolated.[2] The condition is characterized by fissured acropulpitis, often accompanied by hyperpigmentation, onychorrhexis, and paronychia. More of the volar surface may be affected in sensitized florists. Dermatitis and paronychia are extremely common conditions and diagnostic errors may occur. A thorough patient history, in conjunction with confirmatory patch testing with a bulb sliver and tuliposide A exposure, can prevent misdiagnosis. We report a case of Tulipalin A induced phytotoxicity misdiagnosed as an unresolved tinea manuum infection in a patient evaluated for occupational exposure. PMID:25024947

  13. Ofloxacin induced hypersensitivity reaction

    Directory of Open Access Journals (Sweden)

    Hari Babu Ramineni

    2015-01-01

    Full Text Available Ofloxacin is a commonly used antimicrobial agent to combat various infections. The adverse profile of quinolones includes gastrointestinal symptoms, which are the most frequent, neuropsychiatric symptoms, hematologic abnormalities are less common. We report a rare case of ofloxacin induced hypersensitivity reaction in a 57 year old female patient with complaints of rashes over the axilla, upper limb and back, abdomen, thorax associated with exfoliation of skin all over the axilla associated with severe itching. Based on history and clinical examination patient was diagnosed as ofloxacin induced hypersensitivity reaction and was successfully treated with antihistamines and corticosteroids. Pharmacovigilance should be a part of patient care in order to reduce occurrence of adverse drug reaction and also encourage practitioners in reporting so as to gather more and more data regarding adverse drug reactions. [Int J Res Med Sci 2015; 3(1.000: 349-351

  14. Induced Charge Capacitive Deionization

    CERN Document Server

    Rubin, S; Biesheuvel, P M; Bercovici, M

    2016-01-01

    We demonstrate the phenomenon of induced-charge capacitive deionization (ICCDI) that occurs around a porous and conducting particle immersed in an electrolyte, under the action of an external electrostatic field. The external electric field induces an electric dipole in the porous particle, leading to capacitive charging of its volume by both cations and anions at opposite poles. This regime is characterized both by a large RC charging time and a small electrochemical charge relaxation time, which leads to rapid and significant deionization of ionic species from a volume which is on the scale of the particle. We show by theory and experiment that the transient response around a cylindrical particle results in spatially non-uniform charging and non-steady growth of depletion regions which emerge around the particle's poles. Potentially, ICCDI can be useful in applications where fast concentration changes of ionic species are required over large volumes.

  15. Curvature-induced dissipation

    CERN Document Server

    Debus, J -D; Succi, S; Herrmann, H J

    2015-01-01

    By inspecting the effect of curvature on a moving fluid, we find that local sources of curvature not only exert inertial forces on the flow, but also generate viscous stresses as a result of the departure of streamlines from the idealized geodesic motion. The curvature-induced viscous forces are shown to cause an indirect and yet appreciable energy dissipation. As a consequence, the flow converges to a stationary equilibrium state solely by virtue of curvature-induced dissipation. In addition, we show that flow through randomly-curved media satisfies a non-linear transport law, resembling Darcy-Forchheimer's law, due to the viscous forces generated by the spatial curvature. It is further shown that the permeability can be characterized in terms of the average metric perturbation.

  16. Induced galaxy formation

    CERN Document Server

    Dokuchaev, V; Rubin, S; Dokuchaev, Vyacheslav; Eroshenko, Yury; Rubin, Sergei

    2004-01-01

    We describe the model of protogalaxy formation around the cluster of primordial black holes with a minimum extension of standard cosmological model. Namely, it is supposed, that a mass fraction of the universe ~10^-3 is composed of the compact clusters of primordial (relict) black holes produced during the phase transitions in the early universe. These clusters are the centers of the dark matter (DM) condensations. As a result the protogalaxies with a mass 2x10^8Msun form at the redshift z=15. These induced protogalaxies contain the central black holes of mass ~10^5Msun and look like the dwarf spheroidal galaxies with a central density spike. Subsequent merging of the induced protogalaxies and ordinary DM haloes leads to the standard scenario of the large scale structure formation. Black holes merging gives the nowadays supermassive black holes and reproduces the observed correlations between their masses and velocity dispersions in the bulges.

  17. Noise-Induced Hearing Loss

    Science.gov (United States)

    ... Home » Health Info » Hearing, Ear Infections, and Deafness Noise-Induced Hearing Loss On this page: What is ... I find additional information about NIHL? What is noise-induced hearing loss? Every day, we experience sound ...

  18. OXYTOCIN INDUCED NEONATAL HYPERBILIRUBINEMIA

    Directory of Open Access Journals (Sweden)

    Smita S.

    2015-05-01

    Full Text Available INTRODUCTION: Hyperbilirubinemia is one of the most common causes of health problems, observed in 60% of term and 80% of preterm infants in the first week of life . Hyperbilirubinemia leads to neurotoxicity in severe condition. Some studies suggests that liberal use of oxytocin for inducing labour is one of the factor which lead to neonatal hyperbilirubinemia. OBJECTIVE: To compare the effect of oxytocin and neonatal bilirubin levels with spontaneous vaginal delivery . MATERIALS AND METHOD S : 100 full term parturients were selected for this study. The subjects were divided into two groups. 50 healthy babies of women who had oxytocin induced labour and 50 healthy babies of women with normal vaginal delivery following spontaneous onset of labour formed the control group. Neon atal serum bilirubin was measured on day 1, 3 and 5 after delivery. Bilirubin was measured by spectrophotometry. Data was analysed in ms excel sheet using spss 19.0v. Statistical analysis was done by using unpaired‘t’ test. RESULTS: There was significant i ncrease in bilirubin level in oxytocin induced group compared to control group on day 1 and 3. There was insignificant increase in bilirubin level in oxytocin induced group on day 5. However the level of serum bilirubin is within normal limits as bilirubin level normally rises on till 4 th day and decreases thereafter. CONCLUSION: Neonatal hyperbilirubinemia may be due to oxytocin administration by continues IV infusion which results in erythrocyte swell and rupture. Increase in bilirubin level in oxytocin i nduced group is within physiological limits

  19. Polarization induced doped transistor

    Energy Technology Data Exchange (ETDEWEB)

    Xing, Huili (Grace); Jena, Debdeep; Nomoto, Kazuki; Song, Bo; Zhu, Mingda; Hu, Zongyang

    2016-06-07

    A nitride-based field effect transistor (FET) comprises a compositionally graded and polarization induced doped p-layer underlying at least one gate contact and a compositionally graded and doped n-channel underlying a source contact. The n-channel is converted from the p-layer to the n-channel by ion implantation, a buffer underlies the doped p-layer and the n-channel, and a drain underlies the buffer.

  20. Inducement prizes and innovation

    OpenAIRE

    Brunt, Liam; Lerner, Josh; Nicholas, Tom

    2011-01-01

    We examine prizes as an inducement for innovation using a novel dataset of awards for inventiveness offered by the Royal Agricultural Society of England from 1839 to 1939. At annual shows the RASE held competitive trials and awarded medals and monetary prizes (exceeding one million pounds in current prices) to spur technological development. We find large effects of the prizes on contest entries, especially for the Society’s gold medal. Matching award and patent data, we also detect large eff...

  1. Tattoo-induced psoriasis

    OpenAIRE

    Orzan, OA; Popa, LG; Vexler, ES; Olaru, I; Voiculescu, VM; Bumbăcea, RS

    2014-01-01

    Koebner phenomenon represents the development of several inflammatory skin lesions (psoriasis, lichen planus, vitiligo, etc.) in uninvolved skin following various traumatic insults. The case of a 27-year-old male patient with scalp psoriasis who was referred to our clinic for generalized psoriatic lesions developed two weeks after tattooing his skin at the age of 18 was presented; the case illustrated the possibility of Koebner phenomenon induced by skin tattooing in patients with psoriasis.

  2. Radiation induced oral mucositis

    OpenAIRE

    P S Satheesh Kumar; Anita Balan; Arun Sankar; Tinky Bose

    2009-01-01

    Patients receiving radiotherapy or chemotherapy will receive some degree of oral mucositis The incidence of oral mucositis was especially high in patients: (i) With primary tumors in the oral cavity, oropharynx, or nasopharynx; (ii) who also received concomitant chemotherapy; (iii) who received a total dose over 5,000 cGy; and (iv) who were treated with altered fractionation radiation schedules. Radiation-induced oral mucositis affects the quality of life of the patients and the family concer...

  3. Tulipalin A induced phytotoxicity

    OpenAIRE

    McCluskey, James; Bourgeois, Marie; Harbison, Raymond

    2014-01-01

    Tulipalin A induced phytotoxicity is a persistent allergic contact dermatitides documented in floral workers exposed to Alstroemeria and its cultivars.[1] The causative allergen is tulipalin A, a toxic glycoside named for the tulip bulbs from which it was first isolated.[2] The condition is characterized by fissured acropulpitis, often accompanied by hyperpigmentation, onychorrhexis, and paronychia. More of the volar surface may be affected in sensitized florists. Dermatitis and paronychia ar...

  4. Doxycycline induced Esophagitis

    OpenAIRE

    Banu Karakus Yilmaz; Erdem Cevik

    2014-01-01

    Esophagitis is a hazardous condition such as acid reflux of esophageal mucosa, infection, systemic diseases, radiation, drugs and trauma. Drug- induced esophagial injury (DIEI) is a disease with the use of variety of drugs that caused serious damage and ulcer in the mucosa of the esophagus. The most commonly implicated drugs are non-steroidal anti-inflammatory drugs (NSAIDs), chloride and especially antibiotics. Thirty-six year-old female patient presented to the emergency department with...

  5. Magnetic Induced Axion Mass

    CERN Document Server

    Campanelli, L

    2006-01-01

    We study the effect of a uniform magnetic field on the dynamics of axions. In particular, we show that the Peccei-Quinn symmetry is explicitly broken by the presence of an external magnetic field. This breaking is induced by the non-conservation of the magnetic helicity and generates an electromagnetic contribution to the axion mass. We compute the magnetic axion mass in one loop approximation, with no restriction on the intensity of the magnetic field, and including thermal effects.

  6. Xerostomia induced by radiotherapy

    OpenAIRE

    Alimi, David

    2015-01-01

    David Alimi Department of Anesthesiology, University of Pittsburgh Medical Center, Pittsburgh, PA, USAWe read with great interest the excellent review on xerostomia induced by radiotherapy, by Pinna et al.1 The authors should be congratulated for a very detailed review of the physiopathology, clinical symptoms, and therapeutic management of an extremely difficult condition. Although we agree that the use of anticholinergic medication represents treatment, it requires the patient to have resi...

  7. Gold induced enterocolitis.

    OpenAIRE

    Jackson, C W; Haboubi, N Y; Whorwell, P.J.; Schofield, P. F.

    1986-01-01

    A case of gold associated enterocolitis is described. A review of all 27 previously reported cases revealed that the syndrome induced has common characteristics. The reaction occurs within three months of instituting gold therapy, is characterised by profuse diarrhoea and vomiting with abdominal pain, fever, and sometimes eosinophilia. Petechial changes are prominent on endoscopy and the endoscopic and histological features of the gut lesion do not resemble inflammatory bowel disease. The ove...

  8. Cisplatin Induced Nephrotoxicity

    Directory of Open Access Journals (Sweden)

    Seyed Seifollah Beladi Mousavi

    2014-02-01

    The standard approach to prevent cisplatin-induced nephrotoxicity is the administration of lower doses of cisplatin in combination with the administration of full intravenous isotonic saline before and after cisplatin administration. Although a number of pharmacologic agents including sodium thiosulfate, N-acetylcysteine, theophylline and glycine have been evaluated for prevention of nephrotoxicity, none have proved to have an established role, thus, additional clinical studies will be required to confirm their probable effects.

  9. Glycerol-induced hyperhydration

    Science.gov (United States)

    Riedesel, Marvin L.; Lyons, Timothy P.; Mcnamara, M. Colleen

    1991-01-01

    Maintenance of euhydration is essential for maximum work performance. Environments which induce hypohydration reduce plasma volume and cardiovascular performance progressively declines as does work capacity. Hyperhydration prior to exposure to dehydrating environments appears to be a potential countermeasure to the debilitating effects of hypohydration. The extravascular fluid space, being the largest fluid compartment in the body, is the most logical space by which significant hyperhydration can be accomplished. Volume and osmotic receptors in the vascular space result in physiological responses which counteract hyperhydration. Our hypothesis is that glycerol-induced hyperhydration (GIH) can accomplish extravascular fluid expansion because of the high solubility of glycerol in lipid and aqueous media. A hypertonic solution of glycerol is rapidly absorbed from the gastrointestinal tract, results in mild increases in plasma osmolality and is distributed to 65 percent of the body mass. A large volume of water ingested within minutes after glycerol intake results in increased total body water because of the osmotic action and distribution of glycerol. The resulting expanded extravascular fluid space can act as a reservoir to maintain plasma volume during exposure to dehydrating environments. The fluid shifts associated with exposure to microgravity result in increased urine production and is another example of an environment which induces hypohydration. Our goal is to demonstrate that GIH will facilitate maintenance of euhydration and cardiovascular performance during space flight and upon return to a 1 g environment.

  10. Ethanol-induced analgesia

    Energy Technology Data Exchange (ETDEWEB)

    Pohorecky, L.A.; Shah, P.

    1987-09-07

    The effect of ethanol (ET) on nociceptive sensitivity was evaluated using a new tail deflection response (TDR) method. The IP injection of ET (0.5 - 1.5 g/kg) produced raid dose-dependent analgesia. Near maximal effect (97% decrease in TDR) was produced with the 1.5 g/kg dose of ET ten minutes after injection. At ninety minutes post-injection there was still significant analgesia. Depression of ET-induced nociceptive sensitivity was partially reversed by a 1 mg/kg dose of naloxone. On the other hand, morphine (0.5 or 5.0 mg/kg IP) did not modify ET-induced analgesia, while 3.0 minutes of cold water swim (known to produce non-opioid mediated analgesia) potentiated ET-induced analgesic effect. The 0.5 g/kg dose of ET by itself did not depress motor activity in an open field test, but prevented partially the depression in motor activity produced by cold water swim (CWS). Thus, the potentiation by ET of the depression of the TDR produced by CWS cannot be ascribed to the depressant effects of ET on motor activity. 21 references, 4 figures, 1 table.

  11. Sildenafil induced priapism.

    Science.gov (United States)

    Aoyagi, T; Hayakawa, K; Miyaji, K; Ishikawa, H; Hata, M

    1999-11-01

    A 53 year-old Japanese man was referred to our hospital for persistent priapism, which had been induced by 200 mg (usual dose 25-50 mg) of sildenafil citrate (Viagra) three days earlier. He had a history of erectile dysfunction and had undergone penile injection therapy elsewhere; however, he had not used injection therapy this time. He obtained sildenafil personally without a doctor's prescription. He had not taken any other drugs that affect the metabolism of sildenafil, nor did he have any medical complications that might induce priapism. Since needle aspiration and irrigation were ineffective as first line therapy, surgical treatment was indicated to relieve the condition; a incision of tunica albuginea of both corpora cavernosa was made, and vigorous irrigation of saline washed out the blood clots. This is the first case report of priapism induced by sildenafil. Although this drug can be obtained through private commerce, it should be used under professional guidance as its abuse may lead to severe morbidity. PMID:11933312

  12. Dynamical gauge field induced

    CERN Document Server

    Kikkawa, K; Keiji Kikkawa; Humitaka Tamura

    1994-01-01

    Abstract: Some part of the local gauge symmetries in the low energy region, say, lower than GUT or the Planck energy can be an induced symmetry describable with the holonomy fields associated with a topologically non-trivial structure of partially compactified space. In the case where a six dimensional space is compactified by the Kaluza-Klein mechanism into a product of the four dimensional Minkowski space M_{4} and a two dimensional Riemann surface with the genus g, \\Sigma_{g}, we show that, in a limit where the compactification mass scale is sent to infinity, a model lagrangian with a U(1) gauge symmetry produces the dynamical gauge fields in M_{4} with a product of g U(1)'s symmetry, i.e., U(1)\\times \\cdots\\timesU(1). These fields are induced by a Berry phase mechanism, not by the Kaluza-Klein. The dynamical degrees of freedom of the induced fields are shown to come from the holonomies, or the solenoid potentials, associated with the cycles of \\Sigma_{g}. The production mechanism of kinetic energy terms f...

  13. Induced QCD I: Theory

    CERN Document Server

    Brandt, Bastian B; Wettig, Tilo

    2016-01-01

    We explore an alternative discretization of continuum SU(N_c) Yang-Mills theory on a Euclidean spacetime lattice, originally introduced by Budzcies and Zirnbauer. In this discretization the self-interactions of the gauge field are induced by a path integral over N_b auxiliary boson fields, which are coupled linearly to the gauge field. The main progress compared to earlier approaches is that N_b can be as small as N_c. In the present paper we (i) extend the proof that the continuum limit of the new discretization reproduces Yang-Mills theory in two dimensions from gauge group U(N_c) to SU(N_c), (ii) derive refined bounds on N_b for non-integer values, and (iii) perform a perturbative calculation to match the bare parameter of the induced gauge theory to the standard lattice coupling. In follow-up papers we will present numerical evidence in support of the conjecture that the induced gauge theory reproduces Yang-Mills theory also in three and four dimensions, and explore the possibility to integrate out the ga...

  14. Swimming pool-induced asthma.

    Science.gov (United States)

    Beretta, S; Vivaldo, T; Morelli, M; Carlucci, P; Zuccotti, G V

    2011-01-01

    A 13-year-old elite swimmer presented with wheezing after indoor swimming training. On the basis of her clinical history and the tests performed, exercise-induced asthma and mold-induced asthma were ruled out and a diagnosis of chlorine-induced asthma was made. PMID:21548454

  15. Duxorubicin-induced cardiotoxicity

    Directory of Open Access Journals (Sweden)

    Mukund Joshi

    2015-02-01

    Full Text Available The survival rate of cancer patients has greatly increased over the last 20 years. However, to achieve this result, a considerable price has been paid in terms of the side-effects associated with the intensive anticancer treatment. Cardiotoxicity of anticancer drugs is a serious problem. It is defined, by the National Cancer Institute, as the and ldquo;toxicity that affects the heart. and rdquo; This definition not only includes a direct effect of the drug on the heart, but also an indirect effect due to enhancement of hemodynamic flow alterations or due to thrombotic events. Cardiotoxicity can develop in a subacute, acute, or chronic manner. The risk for such effects depends upon: cumulative dose, rate of drug administration, mediastinal radiation, advanced age, younger age, female gender, pre-existing heart disease and hypertension. Anthracyclines, such as doxorubicin (DOX, cause serious cardiac side-effects. Acute tachyarrhythmias and acute heart failure (HF may occur after high doses, but these reactions are now rare due to changed dosage schemes (e.g. slower infusion with the aim to prevent this. However, the sub-acute or chronic cardiac effects of anthracyclines remain a clinical problem. Clinically, anthracycline induced cardiotoxicity manifests itself as left ventricular failure, which develops insidiously over months to years after completion of the anthracycline based chemotherapy and may result in congestive HF. The mechanism of anthracyclin induced cardiotoxicity is not totally unraveled. It is likely that the decline in myocardial function is related to apoptosis of cardiac myocytes that occurs apparently at random in the myocardium. Anthracyclin induced formation of reactive oxygen species (ROS in the presence of intracellular iron, impaired homeostasis of intracellular iron and calcium (that may facilitate the apoptosis induced by the ROS have been put forward as mechanisms. Cardiac protection can be achieved by limitation of the

  16. Differential effects of dexamethasone on the chondrogenesis of mesenchymal stromal cells: Influence of microenvironment, tissue origin and growth factor

    Directory of Open Access Journals (Sweden)

    N Shintani

    2011-11-01

    Full Text Available nchymal stromal cells (MSCs, which reside within various tissues, are utilized in the engineering of cartilage tissue. Dexamethasone (DEX – a synthetic glucocorticoid – is almost invariably applied to potentiate the growth-factor-induced chondrogenesis of MSCs in vitro, albeit that this effect has been experimentally demonstrated only for transforming-growth-factor-beta (TGF-β-stimulated bone-marrow-derived MSCs. Clinically, systemic glucocorticoid therapy is associated with untoward side effects (e.g., bone loss and increased susceptibility to infection. Hence, the use of these agents should be avoided or limited. We hypothesize that the influence of DEX on the chondrogenesis of MSCs depends upon their tissue origin and microenvironment [absence or presence of an extracellular matrix (ECM], as well as upon the nature of the growth factor. We investigated its effects upon the TGF-β1- and bone-morphogenetic-protein 2 (BMP-2-induced chondrogenesis of MSCs as a function of tissue source (bone marrow vs. synovium and microenvironment [cell aggregates (no ECM vs. explants (presence of a natural ECM]. In aggregates of bone-marrow-derived MSCs, DEX enhanced TGF-β1-induced chondrogenesis by an up-regulation of cartilaginous genes, but had little influence on the BMP-2-induced response. In aggregates of synovial MSCs, DEX exerted no remarkable effect on either TGF-β1- or BMP-2-induced chondrogenesis. In synovial explants, DEX inhibited BMP-2-induced chondrogenesis almost completely, but had little impact on the TGF-β1-induced response. Our data reveal that steroids are not indispensable for the chondrogenesis of MSCs in vitro. Their influence is context dependent (tissue source of the MSCs, their microenvironment and the nature of the growth-factor. This finding has important implications for MSC based approaches to cartilage repair.

  17. -induced continental warming

    Science.gov (United States)

    Kamae, Youichi; Watanabe, Masahiro; Kimoto, Masahide; Shiogama, Hideo

    2014-11-01

    In this the second of a two-part study, we examine the physical mechanisms responsible for the increasing contrast of the land-sea surface air temperature (SAT) in summertime over the Far East, as observed in recent decades and revealed in future climate projections obtained from a series of transient warming and sensitivity experiments conducted under the umbrella of the Coupled Model Intercomparison Project phase 5. On a global perspective, a strengthening of land-sea SAT contrast in the transient warming simulations of coupled atmosphere-ocean general circulation models is attributed to an increase in sea surface temperature (SST). However, in boreal summer, the strengthened contrast over the Far East is reproduced only by increasing atmospheric CO2 concentration. In response to SST increase alone, the tropospheric warming over the interior of the mid- to high-latitude continents including Eurasia are weaker than those over the surrounding oceans, leading to a weakening of the land-sea SAT contrast over the Far East. Thus, the increasing contrast and associated change in atmospheric circulation over East Asia is explained by CO2-induced continental warming. The degree of strengthening of the land-sea SAT contrast varies in different transient warming scenarios, but is reproduced through a combination of the CO2-induced positive and SST-induced negative contributions to the land-sea contrast. These results imply that changes of climate patterns over the land-ocean boundary regions are sensitive to future scenarios of CO2 concentration pathways including extreme cases.

  18. Sulphasalazine Induced Hypersensitivity Syndrome

    Directory of Open Access Journals (Sweden)

    Hatice Şanlı

    2013-05-01

    Full Text Available Drug-induced hypersensitivity syndrome (DIHS is one of the most dangerous drug reactions. Mortality and morbidity is increased by consequent systemic organ involvement. Maculopapular eruptions are the most common lesions accompanying DIHS, however, the morphology of skin lesions may vary. The most common cause of DIHS is the use of aromatic anticonvulsant drugs. However, one must not forget that other drugs may also cause DIHS. Early recognition of the condition is the most important step in the treatment. Herein, we present a case of DIHS triggered by sulphasalazine and associated with pustular eruption and maculopapular eruption.

  19. Cannabis induced asystole.

    Science.gov (United States)

    Brancheau, Daniel; Blanco, Jessica; Gholkar, Gunjan; Patel, Brijesh; Machado, Christian

    2016-01-01

    Cannabis or marijuana is the most used recreational, and until recently illegal, drug in the United States. Although cannabis has medicinal use, its consumption has been linked to motor vehicle accidents in dose dependent fashion. Marijuana and other cannabinoids produce a multitude of effects on the human body that may result in these motor vehicle accidents. Some of the effects that marijuana has been known to cause include altered sensorium, diminished reflexes, and increased vagal tone. We present a case of cannabis induced asystole from hypervagotonia.

  20. Catatonia induced by disulfiram

    Directory of Open Access Journals (Sweden)

    HK Goswami

    2015-07-01

    Full Text Available Catatonia is a clinical syndrome with varieties of psychomotor abnormalities of retardation and excitement. It can occur both in psychiatric and medical conditions. The aetiology of catatonia has not been fully described. Many researchers suggest that catatonia can occur due to deficiency of cortical gamma-aminobutyric acid (GABA which is an inhibitory neurotransmitter. Disulfiram is an agent that is being used in the treatment of alcohol dependence by its aversive effect. It has been seen that disulfiram is one of the causes of catatonia. This paper aimed to report a case of catatonia induced by disulfiram with no past history of any psychiatric or medical illness.

  1. Heparin induced thrombocytopenia: review.

    Science.gov (United States)

    Dasararaju, Radhika; Singh, Nirupama; Mehta, Amitkumar

    2013-08-01

    Heparin induced thrombocytopenia (HIT) is a serious, potentially life and limb threatening immune adverse reaction to heparin. IgG antibodies against platelet factor 4 and heparin multimer complexes activate platelets to create a prothrombotic state. ELISA based immunoassay to detect these antibodies is sensitive while serotonin release assay is highly specific but is not widely available. 4T score is a simple score to calculate pre-test probability of HIT. Score danaparoid are recommended in therapeutic dose to treat or prevent thrombotic events in HIT. Increased awareness of this condition among clinicians is important to ensure its early recognition and treatment to avoid serious complications. PMID:23991928

  2. [Neuroleptic induced deficit syndrome].

    Science.gov (United States)

    Szafrański, T

    1995-01-01

    Increasing interest in subjective aspects of therapy and rehabilitation focused the attention of psychiatrists, psychologists and psychopharmacologists on the mental side effects of neuroleptics. For the drug-related impairment of affective, cognitive and social function the name of neuroleptic-induced deficit syndrome (NIDS) is proposed. Patients with NIDS appear to be indifferent to the environmental stimuli, retarded and apathetic. They complain of feeling drugged and drowsy, weird, they suffer from lack of motivation, feel like "zombies". The paper presents description of NIDS and its differentiation from negative and depressive symptoms in schizophrenia and subjective perceiving of extrapyramidal syndromes. PMID:7652089

  3. Antioxidant-Induced Stress

    Directory of Open Access Journals (Sweden)

    Robert D. Kross

    2012-02-01

    Full Text Available Antioxidants are among the most popular health-protecting products, sold worldwide without prescription. Indeed, there are many reports showing the benefits of antioxidants but only a few questioning the possible harmful effects of these “drugs”. The normal balance between antioxidants and free radicals in the body is offset when either of these forces prevails. The available evidence on the harmful effects of antioxidants is analyzed in this review. In summary, a hypothesis is presented that “antioxidant-induced stress” results when antioxidants overwhelm the body’s free radicals.

  4. Emotionally induced hyperhidrosis.

    Science.gov (United States)

    Altman, Rachel S; Schwartz, Robert A

    2002-05-01

    Hyperhidrosis, a disorder that usually begins in childhood or adolescence, is defined as sweating in excess of what is required for normal thermoregulation. This condition may adversely affect one's quality of life by causing emotional disturbance and social embarrassment. Three forms of hyperhidrosis exist: emotionally induced, localized, and generalized. Hyperhidrosis may be either idiopathic or secondary to other diseases, metabolic disorders, febrile illnesses, or drugs. Diagnosis usually is made based on the patient's history and visible signs of excessive sweating. Various effective treatment options are available. PMID:12041810

  5. Trauma Induced Coagulopathy

    DEFF Research Database (Denmark)

    Genét, Gustav Folmer; Johansson, Per; Meyer, Martin Abild Stengaard;

    2013-01-01

    It remains debated whether traumatic brain injury (TBI) induces a different coagulopathy compared to non-TBI. This study investigated traditional coagulation tests, biomarkers of coagulopathy and endothelial damage in trauma patients with and without TBI. Blood from 80 adult trauma patients were...... sampled (median of 68 min (IQR 48-88) post-injury) upon admission to our trauma centre. Plasma/serum were retrospectively analysed for biomarkers reflecting sympathoadrenal activation (adrenaline, noradrenaline), coagulation activation/inhibition and fibrinolysis (protein C, activated protein C, tissue...

  6. Xerostomia induced by radiotherapy

    Directory of Open Access Journals (Sweden)

    Alimi D

    2015-08-01

    Full Text Available David Alimi Department of Anesthesiology, University of Pittsburgh Medical Center, Pittsburgh, PA, USAWe read with great interest the excellent review on xerostomia induced by radiotherapy, by Pinna et al.1 The authors should be congratulated for a very detailed review of the physiopathology, clinical symptoms, and therapeutic management of an extremely difficult condition. Although we agree that the use of anticholinergic medication represents treatment, it requires the patient to have residual salivary gland function. Unfortunately, it is well established that in most cases radiotherapy destroys most of the salivary gland and associated salivary secretions.     

  7. Nonlinearity Induced Critical Coupling

    CERN Document Server

    Reddy, K Nireekshan; Gupta, S Dutta

    2013-01-01

    We study a critically coupled system (Opt. Lett., \\textbf{32}, 1483 (2007)) with a Kerr-nonlinear spacer layer. Nonlinearity is shown to inhibit null-scattering in a critically coupled system at low powers. However, a system detuned from critical coupling can exhibit near-complete suppression of scattering by means of nonlinearity-induced changes in refractive index. Our studies reveal clearly an important aspect of critical coupling as a delicate balance in both the amplitude and the phase relations, while a nonlinear resonance in dispersive bistability concerns only the phase.

  8. Chemotherapy-induced polyneuropathy

    DEFF Research Database (Denmark)

    Zedan, Ahmed; Vilholm, Ole Jakob

    2014-01-01

    Chemotherapy-induced polyneuropathy (CIPN) is a common, but underestimated, clinical challenge. Incidence varies depending on many factors that are equally as important as the type of chemotherapeutic agent itself. Moreover, the assessment of CIPN is still uncertain, as several of the most...... frequently used scales do not rely on a formal neurological evaluation and depend on patients' reports and examiners' interpretations. Therefore, the aim of this MiniReview was to introduce the most common chemotherapies that cause neuropathy, and in addition to this, highlight the most significant...

  9. Man-Induced Vibrations

    DEFF Research Database (Denmark)

    Jönsson, Jeppe; Hansen, Lars Pilegaard

    1994-01-01

    work has been done on the measurement of the exact load functions and related reponse analysis. A recent work using a spectral description has been performed by Per-Erik Erikson and includes a good literature survey. Bachmann and Ammann give a good overview of vibrations caused by human activity. Other...... concerned with spectator-induced vertical vibrations on grandstands. The idea is to use impulse response analysis and base the load description on the load impulse. If the method is feasable, it could be used in connection with the formulation of requirements in building codes. During the last two decades...

  10. Ofloxacin-induced hallucinations

    Directory of Open Access Journals (Sweden)

    Urmila Chauhan

    2013-01-01

    Full Text Available Drug-induced hallucinations are not uncommon, and may be misdiagnosed as psychiatric illness leading to unnecessary treatment with antipsychotics. If a temporal association of use of a drug having the potential to cause hallucinations is present, mere withdrawal of the drug causes complete improvement in the symptoms. There are reports of various untoward central nervous system adverse events following administration of fluoroquinolones, including delirium, hallucinations and psychosis, even after a single dose. We describe a 5-year-old girl who suffered visual hallucinations following ofloxacin use.

  11. Inducing Constraint Grammars

    CERN Document Server

    Samuelsson, C; Voutilainen, A; Samuelsson, Christer; Tapanainen, Pasi; Voutilainen, Atro

    1996-01-01

    Constraint Grammar rules are induced from corpora. A simple scheme based on local information, i.e., on lexical biases and next-neighbour contexts, extended through the use of barriers, reached 87.3 percent precision (1.12 tags/word) at 98.2 percent recall. The results compare favourably with other methods that are used for similar tasks although they are by no means as good as the results achieved using the original hand-written rules developed over several years time.

  12. Electromagnetically Induced Entanglement.

    Science.gov (United States)

    Yang, Xihua; Xiao, Min

    2015-08-28

    Quantum entanglement provides an essential resource for quantum computation, quantum communication, and quantum network. How to conveniently and efficiently produce entanglement between bright light beams presents a challenging task to build realistic quantum information processing networks. Here, we present an efficient and convenient way to realize a novel quantum phenomenon, named electromagnetically induced entanglement, in the conventional Λ-type three-level atomic system driven by a strong pump field and a relatively weak probe field. Nearly perfect entanglement between the two fields can be achieved with a low coherence decay rate between the two lower levels, high pump-field intensity, and large optical depth of the atomic ensemble. The physical origin is quantum coherence between the lower doublet produced by the pump and probe fields, similar to the well-known electromagnetically induced transparency. This method would greatly facilitate the generation of nondegenerate narrow-band continuous-variable entanglement between bright light beams by using only coherent laser fields, and may find potential and broad applications in realistic quantum information processing.

  13. Drug-induced lupus.

    Science.gov (United States)

    Rubin, Robert L

    2005-04-15

    Autoantibodies and, less commonly, systemic rheumatic symptoms are associated with treatment with numerous medications and other types of ingested compounds. Distinct syndromes can be distinguished, based on clinical and laboratory features, as well as exposure history. Drug-induced lupus has been reported as a side-effect of long-term therapy with over 40 medications. Its clinical and laboratory features are similar to systemic lupus erythematosus, except that patients fully recover after the offending medication is discontinued. This syndrome differs from typical drug hypersensitivity reactions in that drug-specific T-cells or antibodies are not involved in induction of autoimmunity, it usually requires many months to years of drug exposure, is drug dose-dependent and generally does not result in immune sensitization to the drug. Circumstantial evidence strongly suggests that oxidative metabolites of the parent compound trigger autoimmunity. Several mechanisms for induction of autoimmunity will be discussed, including bystander activation of autoreactive lymphocytes due to drug-specific immunity or to non-specific activation of lymphocytes, direct cytotoxicity with release of autoantigens and disruption of central T-cell tolerance. The latter hypothesis will be supported by a mouse model in which a reactive metabolite of procainamide introduced into the thymus results in lupus-like autoantibody induction. These findings, as well as evidence for thymic function in drug-induced lupus patients, support the concept that abnormalities during T-cell selection in the thymus initiate autoimmunity.

  14. Drug-Induced Hematologic Syndromes

    Directory of Open Access Journals (Sweden)

    David M. Mintzer

    2009-01-01

    Full Text Available Objective. Drugs can induce almost the entire spectrum of hematologic disorders, affecting white cells, red cells, platelets, and the coagulation system. This paper aims to emphasize the broad range of drug-induced hematological syndromes and to highlight some of the newer drugs and syndromes. Methods. Medline literature on drug-induced hematologic syndromes was reviewed. Most reports and reviews focus on individual drugs or cytopenias. Results. Drug-induced syndromes include hemolytic anemias, methemoglobinemia, red cell aplasia, sideroblastic anemia, megaloblastic anemia, polycythemia, aplastic anemia, leukocytosis, neutropenia, eosinophilia, immune thrombocytopenia, microangiopathic syndromes, hypercoagulability, hypoprothrombinemia, circulating anticoagulants, myelodysplasia, and acute leukemia. Some of the classic drugs known to cause hematologic abnormalities have been replaced by newer drugs, including biologics, accompanied by their own syndromes and unintended side effects. Conclusions. Drugs can induce toxicities spanning many hematologic syndromes, mediated by a variety of mechanisms. Physicians need to be alert to the potential for iatrogenic drug-induced hematologic complications.

  15. Radiation induced microbial pesticide

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Ki Yup; Lee, Young Keun; Kim, Jae Sung; Kim, Jin Kyu; Lee, Sang Jae

    2000-01-01

    To control plant pathogenic fungi, 4 strains of bacteria (K1, K3, K4, YS1) were isolated from mushroom compost and hot spring. K4, K1, K3, YS1 strain showed wide antifungal spectrum and high antifungal activities against 13 kinds of fungi. Mutants of K1 and YS1 strains were induced by gamma-ray radiation and showed promising antifungal activities. These wild type and mutants showed resistant against more than 27 kinds of commercial pesticides among 30 kinds of commercial pesticides test particularly, YS1-1006 mutant strain showed resistant against hydrogen oxide. And mutants had increased antifungal activity against Botryoshaeria dothidea. These results suggested that radiation could be an useful method for the induction of functional mutants. (author)

  16. Trastuzumab-induced cardiomyopathy.

    Science.gov (United States)

    Guglin, Maya; Cutro, Raymond; Mishkin, Joseph D

    2008-06-01

    Trastuzumab is a recombinant humanized monoclonal antibody used for the treatment of advanced breast cancer. It improves survival and increases response to chemotherapy. The major side effect of trastuzumab is cardiotoxicity manifesting as a reduction in left ventricular systolic function, either asymptomatic or with signs and symptoms of heart failure. Although reversible in most cases, cardiotoxicity frequently results in the discontinuation of trastuzumab. The objective of this review is to summarize facts about trastuzumab-induced cardiotoxicity and to highlight the areas of future investigations. We searched PubMed for trials involving trastuzumab used as an adjuvant therapy for breast cancer, including the metastatic breast cancer setting, and focused on cardiotoxicity. PMID:18514938

  17. Radiation induced pesticidal microbes

    International Nuclear Information System (INIS)

    To isolate pesticidal microbes against plant pathogenic fungi, 4 strains of bacteria(K1. K3, K4, YS1) were isolated from mushroom compost and hot spring. K4, K1, K3, YS1 strain showed wide antifungal spectrum and high antifungal activities against 12 kinds of fungi. Specific proteins and the specific transcribed genes were found from the YS1 and its radiation-induced mutants. And knock-out mutants of antifungal activity were derived by transposon mutagenesis. From these knock-out mutants, the antifungal activity related genes and its modification by gamma-ray radiation are going to be studied. These results suggested that radiation could be an useful tool for the induction of functional mutants

  18. Radiation induced microbial pesticide

    International Nuclear Information System (INIS)

    To control plant pathogenic fungi, 4 strains of bacteria (K1, K3, K4, YS1) were isolated from mushroom compost and hot spring. K4, K1, K3, YS1 strain showed wide antifungal spectrum and high antifungal activities against 13 kinds of fungi. Mutants of K1 and YS1 strains were induced by gamma-ray radiation and showed promising antifungal activities. These wild type and mutants showed resistant against more than 27 kinds of commercial pesticides among 30 kinds of commercial pesticides test particularly, YS1-1006 mutant strain showed resistant against hydrogen oxide. And mutants had increased antifungal activity against Botryoshaeria dothidea. These results suggested that radiation could be an useful method for the induction of functional mutants. (author)

  19. Induced abortion in Indonesia.

    Science.gov (United States)

    Hull, T H; Sarwono, S W; Widyantoro, N

    1993-01-01

    Induced abortion is one of the most difficult sociomedical problems facing the Indonesian government. While well-known in traditional society, the practice was discouraged by all Indonesian religious groups, and forbidden by the Dutch colonial authorities. Although abortion was technically illegal under the criminal code, a judicial interpretation in the early 1970s permitted medical professionals to offer the procedure so long as they were discreet and careful. The numbers of medical abortions carried out in Indonesia rose dramatically, and there was evidence of matching declines in the incidence of morbidity and mortality caused by dangerous illegal procedures. Medical and community groups campaigned for a more liberal abortion law to protect legal practitioners and stamp out illegal traditional practices. Their efforts appeared to bear fruit in the draft Health Law, but when the law was passed by the legislature in late 1992, the issue was again clouded by contradictions and inconsistencies. PMID:8212094

  20. Tibolone induced Bullous pemphigoid.

    Directory of Open Access Journals (Sweden)

    Vishal. R. Tandon, Annil Mahajan* & Sudhaa Sharma**

    2008-01-01

    Full Text Available We present first ever report of Bullous pemphigoid induced by Tibolone, a STEAR (Selective tissueestrogenic activity regulator that has progestogenic, some androgenic as well as estrogenic effects prescribedas an alternative to estrogen replacement therapy for treatment of climacteric symptoms in one ofthe 51 year old postmenopausal women with one and half year duration since menopause with previoushistory of use of estrogen progesterone pills during her active sexual life. The mechanism for this ADR isnot well understood. But possible explanation could be progesterone activity of the drug leading to autoimmunityas reported previously. The present patient was managed by dechallenge of drug, local, oral corticosteroidsand injectable, methotrexate, along with folic acid and antibiotic coverage fearing anemia andsecondary infections.

  1. Migraine induced by hypoxia

    DEFF Research Database (Denmark)

    Arngrim, Nanna; Schytz, Henrik Winther; Britze, Josefine;

    2016-01-01

    Migraine with aura is prevalent in high-altitude populations suggesting an association between migraine aura and hypoxia. We investigated whether experimental hypoxia triggers migraine and aura attacks in patients suffering from migraine with aura. We also investigated the metabolic and vascular...... response to hypoxia. In a randomized double-blind crossover study design, 15 migraine with aura patients were exposed to 180 min of normobaric hypoxia (capillary oxygen saturation 70-75%) or sham on two separate days and 14 healthy controls were exposed to hypoxia. Glutamate and lactate concentrations...... in the visual cortex were measured by proton magnetic resonance spectroscopy. The circumference of cranial arteries was measured by 3 T high-resolution magnetic resonance angiography. Hypoxia induced migraine-like attacks in eight patients compared to one patient after sham (P = 0.039), aura in three...

  2. Gadolinium-Induced Fibrosis.

    Science.gov (United States)

    Todd, Derrick J; Kay, Jonathan

    2016-01-01

    Gadolinium-based contrast agents (GBCAs), once believed to be safe for patients with renal disease, have been strongly associated with nephrogenic systemic fibrosis (NSF), a severe systemic fibrosing disorder that predominantly afflicts individuals with advanced renal dysfunction. We provide a historical perspective on the appearance and disappearance of NSF, including its initial recognition as a discrete clinical entity, its association with GBCA exposure, and the data supporting a causative relationship between GBCA exposure and NSF. On the basis of this body of evidence, we propose that the name gadolinium-induced fibrosis (GIF) more accurately reflects the totality of knowledge regarding this disease. Use of high-risk GBCAs, such as formulated gadodiamide, should be avoided in patients with renal disease. Restriction of GBCA use in this population has almost completely eradicated new cases of this debilitating condition. Emerging antifibrotic therapies may be useful for patients who suffer from GIF.

  3. [Radiation-induced cancers].

    Science.gov (United States)

    Dutrillaux, B

    1998-01-01

    The induction of malignant diseases is one of the most concerning late effects of ionising radiation. A large amount of information has been collected form atomic bomb survivors, patients after therapeutic irradiation, occupational follow-up and accidentally exposed populations. Major uncertainties persist in the (very) low dose range i.e., population and workers radioprotection. A review of the biological mechanisms leading to cancer strongly suggests that the vast majority of radiation-induced malignancies arise as a consequence of recessive mutations of tumour-suppressor genes. These mutations can be unveiled by ageing, this process being possibly furthered by constitutional or acquired genomic instability. The individual risk is likely to be very low, probably because of the usual dose level. However, the magnitude of medical exposure and the reliance of our societies on nuclear industry are so high that irreproachable decision-making processes and standards for practice are inescapable. PMID:9868399

  4. Radiation induced pesticidal microbes

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Ki Yup; Lee, Y. K.; Kim, J. S.; Kim, J. K.; Lee, S. J.; Lim, D. S

    2001-01-01

    To isolate pesticidal microbes against plant pathogenic fungi, 4 strains of bacteria(K1. K3, K4, YS1) were isolated from mushroom compost and hot spring. K4, K1, K3, YS1 strain showed wide antifungal spectrum and high antifungal activities against 12 kinds of fungi. Specific proteins and the specific transcribed genes were found from the YS1 and its radiation-induced mutants. And knock-out mutants of antifungal activity were derived by transposon mutagenesis. From these knock-out mutants, the antifungal activity related genes and its modification by gamma-ray radiation are going to be studied. These results suggested that radiation could be an useful tool for the induction of functional mutants.

  5. Radiation induced oral mucositis

    Directory of Open Access Journals (Sweden)

    P S Satheesh Kumar

    2009-01-01

    Full Text Available Patients receiving radiotherapy or chemotherapy will receive some degree of oral mucositis The incidence of oral mucositis was especially high in patients: (i With primary tumors in the oral cavity, oropharynx, or nasopharynx; (ii who also received concomitant chemotherapy; (iii who received a total dose over 5,000 cGy; and (iv who were treated with altered fractionation radiation schedules. Radiation-induced oral mucositis affects the quality of life of the patients and the family concerned. The present day management of oral mucositis is mostly palliative and or supportive care. The newer guidelines are suggesting Palifermin, which is the first active mucositis drug as well as Amifostine, for radiation protection and cryotherapy. The current management should focus more on palliative measures, such as pain management, nutritional support, and maintenance, of good oral hygiene

  6. Vincristine induced cranial polyneuropathy.

    Science.gov (United States)

    Bay, Ali; Yilmaz, Cahide; Yilmaz, Nebi; Oner, Ahmet Faik

    2006-06-01

    We describe a 5-year-old girl showed recovery of vincristine induced cranial polyneuropathy with pyridoxine and pyridostigmine treatment. A 5-year-old girl was diagnosed preB cell Acute Lymphoblastic Leukemia (ALL). She received chemotherapy according to the previously described modified St. Jude total therapy studies XIII. Five days after the fourth dose of vincristine, she presented with bilateral ptosis. Neurological examination revealed bilateral ptosis, and complete external opthalmoplegia with normal pupillary and corneal reflexes. She received 3.8 mg cumulative dose of vincristin before development of ptosis. A neuroprotective and neuroregenerative treatment attempt with pyridoxine and pyridostigmine was initiated. The bilateral ptosis markedly improved after 7 days of pyridoxine and pyridostigmine treatment and completely resolved after two weeks. The both agents were given for 3 weeks and were well tolerated without any side effects. During the follow up period we did not observe residue or recurrence of the ptosis.

  7. Discreteness induced extinction

    Science.gov (United States)

    dos Santos, Renato Vieira; da Silva, Linaena Méricy

    2015-11-01

    Two simple models based on ecological problems are discussed from the point of view of non-equilibrium statistical mechanics. It is shown how discrepant may be the results of the models that include spatial distribution with discrete interactions when compared with the continuous analogous models. In the continuous case we have, under certain circumstances, the population explosion. When we take into account the finiteness of the population, we get the opposite result, extinction. We will analyze how these results depend on the dimension d of the space and describe the phenomenon of the "Discreteness Inducing Extinction" (DIE). The results are interpreted in the context of the "paradox of sex", an old problem of evolutionary biology.

  8. Uncertainty-induced quantum nonlocality

    Science.gov (United States)

    Wu, Shao-xiong; Zhang, Jun; Yu, Chang-shui; Song, He-shan

    2014-01-01

    Based on the skew information, we present a quantity, uncertainty-induced quantum nonlocality (UIN) to measure the quantum correlation. It can be considered as the updated version of the original measurement-induced nonlocality (MIN) preserving the good computability but eliminating the non-contractivity problem. For 2×d-dimensional state, it is shown that UIN can be given by a closed form. In addition, we also investigate the maximal uncertainty-induced nonlocality.

  9. Alcohol-Induced Blackout

    Directory of Open Access Journals (Sweden)

    Dai Jin Kim

    2009-11-01

    Full Text Available For a long time, alcohol was thought to exert a general depressant effect on the central nervous system (CNS. However, currently the consensus is that specific regions of the brain are selectively vulnerable to the acute effects of alcohol. An alcohol-induced blackout is the classic example; the subject is temporarily unable to form new long-term memories while relatively maintaining other skills such as talking or even driving. A recent study showed that alcohol can cause retrograde memory impairment, that is, blackouts due to retrieval impairments as well as those due to deficits in encoding. Alcoholic blackouts may be complete (en bloc or partial (fragmentary depending on severity of memory impairment. In fragmentary blackouts, cueing often aids recall. Memory impairment during acute intoxication involves dysfunction of episodic memory, a type of memory encoded with spatial and social context. Recent studies have shown that there are multiple memory systems supported by discrete brain regions, and the acute effects of alcohol on learning and memory may result from alteration of the hippocampus and related structures on a cellular level. A rapid increase in blood alcohol concentration (BAC is most consistently associated with the likelihood of a blackout. However, not all subjects experience blackouts, implying that genetic factors play a role in determining CNS vulnerability to the effects of alcohol. This factor may predispose an individual to alcoholism, as altered memory function during intoxication may affect an individual‟s alcohol expectancy; one may perceive positive aspects of intoxication while unintentionally ignoring the negative aspects. Extensive research on memory and learning as well as findings related to the acute effects of alcohol on the brain may elucidate the mechanisms and impact associated with the alcohol- induced blackout.

  10. Congruence properties of induced representations

    DEFF Research Database (Denmark)

    Mayer, Dieter; Momeni, Arash; Venkov, Alexei

    In this paper we study representations of the projective modular group induced from the Hecke congruence group of level 4 with Selberg's character. We show that the well known congruence properties of Selberg's character are equivalent to the congruence properties of the induced representations....... Concerning this congruence property, it turns out that working with the induced representations is easier than with Selberg's character itself. We also show that the kernels of the induced representations determine an infinite sequence of noncongruence groups, whose noncongruence property can not be detected...

  11. Radio-induced brain lesions

    Directory of Open Access Journals (Sweden)

    Gorgan Mircea Radu

    2014-03-01

    Full Text Available Introduction : Radiotherapy, an important tool in multimodal oncologic treatment, can cause radio-induced brain lesion development after a long period of time following irradiation.

  12. Radiation induced nano structures

    International Nuclear Information System (INIS)

    Full text: Nanometer-size silicon clusters have been attracting much attention due to their technological importance, in particular, as promising building blocks for nano electronic and nano photonic systems. Particularly, silicon wires are of great of interest since they have potential for use in one-dimensional quantum wire high-speed field effect transistors and light-emitting devices with extremely low power consumption. Carbon and metal nano structures are studied very intensely due to wide possible applications. Radiation material sciences have been dealing with sub-micron objects for a long time. Under interaction of high energy particles and ionizing radiation with solids by elastic and inelastic mechanisms, at first point defects are created, then they form clusters, column defects, disordered regions (amorphous colloids) and finally precipitates of another crystal phase in the matrix. Such irradiation induced evolution of structure defects and phase transformations was observed by X-diffraction techniques in dielectric crystals of quartz and corundum, which exist in and crystal modifications. If there is no polymorphism, like in alkali halide crystals, then due to radiolysis halogen atoms are evaporated from the surface that results in non-stoichiometry or accumulated in the pores formed by metal vacancies in the sub-surface layer. Nano-pores are created by intensive high energy particles irradiation at first chaotically and then they are ordered and in part filled by inert gas. It is well-known mechanism of radiation induced swelling and embrittlement of metals and alloys, which is undesirable for construction materials for nuclear reactors. Possible solution of this problem may come from nano-structured materials, where there is neither swelling nor embrittlement at gas absorption due to very low density of the structure, while strength keeps high. This review considers experimental observations of radiation induced nano-inclusions in insulating

  13. Sparfloxacin induced toxic epidermal necrolysis

    Directory of Open Access Journals (Sweden)

    Ramesh M

    2003-05-01

    Full Text Available Toxic epidermal necrolysis (TEN is a life-threatening cutaneous adverse drug reaction. TEN is known to occur with the fluoroquinolone class of antibiotics, but only four cases of sparfloxacin induced TEN have been reported to the WHO database. This is another case report of sparfloxacin induced TEN.

  14. Gold-induced lung disease.

    OpenAIRE

    Heyd, J.; Simmeran, A.

    1983-01-01

    A 70-year-old female with seronegative rheumatoid arthritis developed interstitial pneumonitis while on chrysotherapy. The reversibility of lung disease and favourable response to steroid treatment support the diagnosis of gold-induced lung disease and distinguish this entity from other forms of interstitial lung disease associated with rheumatoid arthritis. The relevant literature related to gold-induced lung disease is briefly reviewed.

  15. Drug-induced pulmonary disease

    Science.gov (United States)

    ... medlineplus.gov/ency/article/000104.htm Drug-induced pulmonary disease To use the sharing features on this page, ... take longer to improve. Some drug-induced lung diseases, such as pulmonary fibrosis, may never go away. Possible Complications Complications ...

  16. Traffic forecasts ignoring induced demand

    DEFF Research Database (Denmark)

    Næss, Petter; Nicolaisen, Morten Skou; Strand, Arvid

    2012-01-01

    Although the phenomenon of induced traffic has been theorized for more than 60 years and is now widely accepted among transport researchers, the traffic-generating effects of road capacity expansion are still often neglected in transport modelling. Such omission can lead to serious bias...... performance of a proposed road project in Copenhagen with and without short-term induced traffic included in the transport model. The available transport model was not able to include long-term induced traffic resulting from changes in land use and in the level of service of public transport. Even though...... the model calculations included only a part of the induced traffic, the difference in cost-benefit results compared to the model excluding all induced traffic was substantial. The results show lower travel time savings, more adverse environmental impacts and a considerably lower benefitcost ratio when...

  17. BMP signaling pathway is required for commitment of C3H10T1/2 pluripotent stem cells to the adipocyte lineage

    OpenAIRE

    Huang, Haiyan; Song, Tan-Jing; Li, Xi; Hu, Lingling; He, Qun; Liu, Mei; Lane, M. Daniel; Tang, Qi-Qun

    2009-01-01

    Obesity is accompanied by an increase in both adipocyte number and size. The increase in adipocyte number is the result of recruitment to the adipocyte lineage of pluripotent stem cells present in the vascular stroma of adipose tissue. These pluripotent cells have the potential to undergo commitment and then differentiate into adipocytes, as well as myocytes, osteocytes, and chondrocytes. In this article, we show that both bone morphogenetic protein (BMP)2 and BMP4 can induce commitment of C3...

  18. Histone deacetylase inhibitors epigenetically promote reparative events in primary dental pulp cells

    Energy Technology Data Exchange (ETDEWEB)

    Duncan, Henry F., E-mail: Hal.Duncan@dental.tcd.ie [Division of Restorative Dentistry and Periodontology, Dublin Dental University Hospital, Trinity College Dublin, Lincoln Place, Dublin 2 (Ireland); Smith, Anthony J. [Oral Biology, School of Dentistry, College of Medical and Dental Sciences, University of Birmingham, Birmingham (United Kingdom); Fleming, Garry J.P. [Material Science Unit, Division of Oral Biosciences, Dublin Dental University Hospital, Trinity College Dublin, Dublin (Ireland); Cooper, Paul R. [Oral Biology, School of Dentistry, College of Medical and Dental Sciences, University of Birmingham, Birmingham (United Kingdom)

    2013-06-10

    Application of histone deacetylase inhibitors (HDACi) to cells epigenetically alters their chromatin structure and induces transcriptional and cellular reparative events. This study investigated the application of two HDACi, valproic acid (VPA) and trichostatin A (TSA) on the induction of repair-associated responses in primary dental pulp cell (DPC) cultures. Flow cytometry demonstrated that TSA (100 nM, 400 nM) significantly increased cell viability. Neither HDACi was cytotoxic, although cell growth analysis revealed significant anti-proliferative effects at higher concentrations for VPA (>0.5 mM) and TSA (>50 nM). While high-content-analysis demonstrated that HDACi did not significantly induce caspase-3 or p21 activity, p53-expression was increased by VPA (3 mM, 5 mM) at 48 h. HDACi-exposure induced mineralization per cell dose-dependently to a plateau level (VPA-0.125 mM and TSA-25 nM) with accompanying increases in mineralization/dentinogenic-associated gene expression at 5 days (DMP-1, BMP-2/-4, Nestin) and 10 days (DSPP, BMP-2/-4). Both HDACis, at a range of concentrations, significantly stimulated osteopontin and BMP-2 protein expression at 10 and 14 days further supporting the ability of HDACi to promote differentiation. HDACi exert different effects on primary compared with transformed DPCs and promote mineralization and differentiation events without cytotoxic effects. These novel data now highlight the potential in restorative dentistry for applying low concentrations of HDACi in vital pulp treatment. -- Highlights: • Valproic acid and trichostatin A promoted mineralization in primary pulp cells. • Cell viability, apoptosis, caspase-3, p21 unaltered; p53 increased by valproic acid. • Trichostatin A increased cell viability at 24 h at selected concentrations. • Altered cell toxicity and differentiation between primary and transformed cells. • HDACi-induced the differentiation marker proteins osteopontin and BMP-2.

  19. Methaemoglobinemia Induced by MDMA?

    Directory of Open Access Journals (Sweden)

    L. L. W. Verhaert

    2011-01-01

    Full Text Available Case. A 45-year-old man with a blank medical history presented at the emergency room with dizziness and cyanosis. Physical examination showed cyanosis with a peripheral saturation (SpO2 of 85%, he did not respond to supplemental oxygen. Arterial blood gas analysis showed a striking chocolate brown colour. Based on these data, we determined the arterial methaemoglobin concentration. This was 32%. We gave 100% oxygen and observed the patient in a medium care unit. The next day, patient could be discharged in good condition. Further inquiry about exhibitions and extensive history revealed that the patient used MDMA (3,4- methylenedioxymethamphetamine, the active ingredient of ecstasy. Conclusion. Acquired methaemoglobinemia is a condition that occurs infrequently, but is potentially life threatening. Different nutrients, medications, and chemicals can induce methaemoglobinemia by oxidation of haemoglobin. The clinical presentation of a patient with methaemoglobinemia is due to the impossibility of O2 binding and transport, resulting in tissue hypoxia. Important is to think about methaemoglobin in a patient who presents with cyanosis, a peripheral saturation of 85% that fails to respond properly to the administration of O2. Because methaemoglobin can be reduced physiologically, it is usually sufficient to remove the causative agent, to give O2, and to observe the patient.

  20. Temozolomide-Induced Myelodysplasia

    Directory of Open Access Journals (Sweden)

    Ethan A. Natelson

    2010-01-01

    Full Text Available A patient who had received temozolomide (TMZ as a single agent in treatment of malignant glioma developed therapy-induced myelodysplasia (T-MDS. TMZ is an orally active imidazotetrazine which methylates guanine residues in DNA, ultimately causing single and double-strand DNA breaks leading to apoptotic cell death. TMZ does not chemically cross-link DNA and is considered a nonclassical alkylating agent, similar in structure and activity to dacarbazine. Observations on this patient, and on similarly treated others, suggest that the cumulative dose threshold (CDT for TMZ that predisposes to T-MDS and which may potentially lead to acute myeloid leukemia (T-AML is around 18000 to 20000 mg/sq m. Although the incidence of T-MDS and the predisposing CDT of TMZ may differ from that of other potentially leukemogenic compounds currently and formerly used as chemotherapeutic agents, all alkylating agents, including TMZ, should be considered potentially leukemogenic when administered long term.

  1. Carbimazole-induced agranulocytosis

    Directory of Open Access Journals (Sweden)

    Anisha Mohan

    2015-01-01

    Full Text Available A 47 year old lady with hyperthyroidism for past 1½ years was initially on Carbimazole 20 mg orally then changed to 30 mg (during Hysterectomy but was taking 10 mg for last 1 year. She had intermittent fever with severe B/L bifrontal headache since 3 weeks. Routine investigations showed anaemia, neutropenia, leucopenia and CRP elevation. Peripheral smear showed normocytic normochromic anaemia with Rouleaux formation, leucopenia with 2% atypical cells and mild thrombocytosis. Widal test, RA factor (Rheumatoid factor test, Ig M (Immunoglobulin M dengue, Ig M Lepto, TORCH infections (Toxoplasmosis, Other (Syphilis, varicella-zoster, parvovirus B19, Cytomegalovirus and Herpes infections, ANA (Antinuclear antibody screen cANCA (Cytoplasmic antineutrophil cytoplasmic antibodies and pANCA (Perinuclear Anti-Neutrophil Cytoplasmic Antibodies tests were negative. Bone marrow aspiration showed normo to hypercellular marrow with 15% atypical cells and plasma cells. Multiple myeloma workup was done. Carbimazole was withheld. Conclusion: Drug induced agranulocytosis occurs with in 1-2 months of taking the antithyroid medication but onset delayed by 1½ year. De-challenge resulted normalization of blood parameters.

  2. [Heparin-induced thrombocytopenia].

    Science.gov (United States)

    Thiele, T; Althaus, K; Greinacher, A

    2010-09-01

    Heparin-induced thrombocytopenia (HIT) is an adverse drug reaction that carries an increased risk of thromboembolic complications. HIT is caused by platelet-activating antibodies directed against a complex of platelet factor 4 (PF4) and heparin. HIT typically manifests in the second week after initiation of heparin therapy with a platelet count reduction of more than 50% of the highest level after the start of heparin administration as well as thromboembolic events. The clinical probability can be calculated by the 4 T's score. The laboratory diagnosis of HIT is based on confirmation of PF4/heparin antibodies or on functional tests that provide evidence of heparin-dependent platelet-activating antibodies. A low 4 T's score and negative HIT test virtually rule out the presence of HIT. Patients with acute HIT require anticoagulation with a compatible anticoagulant in a therapeutic dose. The drugs currently available for this include the direct thrombin inhibitors argatroban, lepirudin, bivalirudin, and desirudin and the indirect factor Xa inhibitors danaparoid and fondaparinux. PMID:20694716

  3. Chloroquine-induced pruritus

    Directory of Open Access Journals (Sweden)

    Aghahowa S

    2010-01-01

    Full Text Available Chloroquine-induced pruritus remains one of the most common side-effects in the use of chloroquine in the prophylaxis and treatment of uncomplicated malaria before the advent of artemisinin-based combination therapies. It has been reported to vary from a tolerable to intolerable intensity among susceptible individuals resulting in disruption of treatment and development of resistance to the drug thus leading to therapeutic failures as reported. This scourge is quite challenging due to the complex physiologic mechanism that has not been fully elucidated. Factors observed to be responsible in the induction of pruritus such as age, race, heredity, density of parasitaemia; impurities in formulations, plasmodial specie, dosage form and metabolites have been discussed in this review. Efforts to ameliorate this burden have necessitated the use of drugs of diverse pharmacological classes such as antihistamines, corticosteroids and multivitamins either alone or as a combination. This review is to look into the use of chloroquine retrospectively, and consider its re-introduction due to its safety. Efficacy can be attained if the pruritic effect is resolved.

  4. Neutron induced electron radiography

    International Nuclear Information System (INIS)

    In the present paper a new radiography technique, the 'Neutron Induced Electron Radiography' - NIER, to inspect low thickness samples on the order of micra, has been developed. This technique makes use of low energy electrons as penetrating radiation generated from metallic gadolinium screens when irradiated by thermal neutrons. The conditions to obtain the best image for the conventional X-ray film Kodak-AA were determined by using a digital system to quantify the darkening level of the film. The irradiations have been performed at a radiography equipment installed at the beam-hole no. 8 of the 5 MW IEA-R1 nuclear research reactor of IPEN-CNEN/SP. The irradiation time to obtain the best radiography was 100 seconds and for such condition the technique was able to discern 1 μm in 24 μm of aluminum at a resolution of 32 μm. By visual comparison the images obtained by the NIER shown a higher quality when compared with the ones from other usual techniques the make use of electrons a penetrating radiation and films for image registration. Furthermore the use of the digital system has provided a smaller time for data acquisition and data analysis as well as an improvement in the image visualization. (author)

  5. Exercise-induced anaphylaxis.

    Science.gov (United States)

    Sheffer, A L; Austen, K F

    1980-08-01

    Sixteen patients were seen because of possibly life-threatening exercise-associated symptoms similar to anaphylactic reactions. Asthma attacks, cholinergic urticaria and angioedema, and cardiac arrythmias are recognized as exertion-related phenomena in predisposed patients but are distinct from the syndrome described here. A syndrome characterized by the exertion-related onset of cutaneous pruritus and warmth, the development of generalized urticaria, and the appearance of such additional manifestations as collapse in 12 patients, gastrointestinal tract symptoms in five patients, and upper respiratory distress in 10 patients has been designated exercise-induced anaphylaxis, because of the striking similarity of this symptom complex to the anaphylactic syndrome elicited by ingestion or injection of a foreign antigenic substance. There is a family history of atopic desease for 11 patients and cold urticaria for two others and a personal history of atopy in six. The size of the wheals, the failure to develop an attack with a warm bath or shower or a fever, and the prominence of syncope rule against the diagnosis of conventional cholinergic urticaria. There is no history or evidence of an encounter with an environmental source of antigen during the exercise period. PMID:7400473

  6. Discreteness inducing coexistence

    Science.gov (United States)

    dos Santos, Renato Vieira

    2013-12-01

    Consider two species that diffuse through space. Consider further that they differ only in initial densities and, possibly, in diffusion constants. Otherwise they are identical. What happens if they compete with each other in the same environment? What is the influence of the discrete nature of the interactions on the final destination? And what are the influence of diffusion and additive fluctuations corresponding to random migration and immigration of individuals? This paper aims to answer these questions for a particular competition model that incorporates intra and interspecific competition between the species. Based on mean field theory, the model has a stationary state dependent on the initial density conditions. We investigate how this initial density dependence is affected by the presence of demographic multiplicative noise and additive noise in space and time. There are three main conclusions: (1) Additive noise favors denser populations at the expense of the less dense, ratifying the competitive exclusion principle. (2) Demographic noise, on the other hand, favors less dense populations at the expense of the denser ones, inducing equal densities at the quasi-stationary state, violating the aforementioned principle. (3) The slower species always suffers the more deleterious effects of statistical fluctuations in a homogeneous medium.

  7. Inducible HSP70 Protects Radiation-Induced Salivary Gland Damage

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Hae-June; Lee, Yoon-Jin; Kwon, Hee-Choong; Lee, Su-Jae; Bae, Sang-Woo; Lee, Yun-Sil [Korea Institute of Radiological Medical Sciences, Seoul (Korea, Republic of); Kim, Sung-Ho [Chonnam National University, Gwangju (Korea, Republic of)

    2006-07-01

    Irradiation (IR) delivered to the head and neck is a common treatment for malignancies. Salivary glands in the irradiation field are severely damaged, and consequently this resulted in marked salivary hypofunction. While the exact mechanism of salivary gland damage remains enigmatic, fluid secreting acinar cells are lost, and saliva output is dramatically reduced. Previously we have reported that inducible heat shock protein 70 (HSP70i) induced radioresistance in vitro. Moreover, HSP70i localized to salivary glands by gene transfer has great potential for the treatment of salivary gland. Herein, we investigated whether HSP70 can use as radio protective molecules for radiation-induced salivary gland damage in vivo.

  8. Heparin-induced thrombocytopenia

    Directory of Open Access Journals (Sweden)

    Shaikh Nissar

    2011-01-01

    Full Text Available In the last 7 decades heparin has remained the most commonly used anticoagulant. Its use is increasing, mainly due to the increase in the number of vascular interventions and aging population. The most feared complication of heparin use is heparin-induced thrombocytopenia (HIT. HIT is a clinicopathologic hypercoagulable, procoagulant prothrombotic condition in patients on heparin therapy, and decrease in platelet count by 50% or to less than 100,000, from 5 to 14 days of therapy. This prothrombotic hypercoagulable state in HIT patient is due to the combined effect of various factors, such as platelet activation, mainly the formation of PF4/heparin/IgG complex, stimulation of the intrinsic factor, and loss of anticoagulant effect of heparin. Diagnosis of HIT is done by clinical condition, heparin use, and timing of thrombocytopenia, and it is confirmed by either serotonin release assay or ELISA assay. Complications of HIT are venous/arterial thrombosis, skin gangrene, and acute platelet activation syndrome. Stopping heparin is the basic initial treatment, and Direct Thrombin Inhibitors (DTI are medication of choice in these patients. A few routine but essential procedures performed by using heparin are hemodialysis, Percutaneous Coronary Intervention, and Cardiopulmonary Bypass; but it cannot be used if a patient develops HIT. HIT patients with unstable angina, thromboembolism, or indwelling devices, such as valve replacement or intraaortic balloon pump, will require alternative anticoagulation therapy. HIT can be prevented significantly by keeping heparin therapy shorter, avoiding bovine heparin, using low-molecular weight heparin, and stopping heparin use for flush and heparin lock.

  9. Immune Vasculitis Induced Atherosclerosis

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    The relationship between immune vasculitis and atherosclerosis was studied. The experimental model of weanling rabbits for immune vasculitis was reproduced by intravenous injection of 10 % bovine serum albumin. There were 6 groups: group A, 25 weanling rabbits with immune vasculitis subject to coronary arteriography; group B, 10 normal mature rabbits subject to coronary arteriography; group C, 10 weanling rabbits subject to coronary arteriography; group D, 8 weanling rabbits with vasculitis and cholesterol diet; group E, 8 weanling rabbits receiving single cholesterol diet; group F: 8 weanling rabbits receiving basic diet. Four weeks later, coronary arteriography was performed in groups A, B and C. The rabbits in groups D, E and F were sacrificed for the study of pathological changes in the coronary artery after 12 weeks. The results showed that the dilatation of coronary artery occurred in 6 rabbits of group A, but in groups B and C, no dilatation of coronary artery appeared. In comparison with group E, more severe atherosclerosis occurred in group D, showing the thickened plaque, fibrous sclerosis and atherosclerotic lesion. Percentage of plaques covering aortic intima, incidence of atherosclerosis of small coronary arteries and degree of stenosis of coronary arteries were significantly higher in group D than in group E (P<0.01). No atherosclerosis changes were found in group F. It was concluded that in the acute phase, the serum immune vasculitis can induce the dilatation of coronary artery of some weanling rabbits, and aggravate the formation of atherosclerosis in rabbits fed with cholesterol diet. Immune vasculitis is a new risk factor of atherosclerosis and ischemic heart disease.

  10. Molecular mechanisms of induced mutagenesis

    International Nuclear Information System (INIS)

    Genetic analysis has revealed that radiation and many chemical mutagens induce in bacteria an error-prone DNA repair process which is responsible for their mutagenic effect. The biochemical mechanism of this inducible error-prone repair has been studied by analysis of the first round of DNA synthesis on ultraviolet light-irradiated phiX174 DNA in both intact and ultraviolet light-irradiated host cells. Intracellular phiX174 DNA was extracted, subjected to isopycnic CsCl density-gradient analysis, hydroxylapatite chromatography and digestion by single-strand-specific endonuclease S1. Ultraviolet light-induced photolesions in viral DNA cause a permanent blockage of DNA synthesis in intact Escherichia coli cells. However, when host cells were irradiated and incubated to induce fully the error-prone repair system, a significant fraction of irradiated phiX174 DNA molecules can be fully replicated. Thus, inducible error-prone repair in E.coli is manifested by an increased capacity for DNA synthesis on damaged phiX174 DNA. Chloramphenicol (100 μ g/ml), which is an inhibitor of the inducible error-prone DNA repair, is also an inhibitor of this particular inducible DNA synthesis. (author)

  11. Bone morphogenetic protein-2: a potential regulator in scleral remodeling

    OpenAIRE

    Hu, Jianmin; Cui, Dongmei; Yang, Xiao; Wang, Shaowei; Hu, Shoulong; Li, Chuanxu; Zeng, Junwen

    2008-01-01

    Purpose Bone morphogenetic protein 2 (BMP-2) is a member of the main subgroup of bone morphogenetic proteins within the transforming growth factor-β superfamily. BMP-2 is involved in numerous cellular functions including development, cell proliferation, apoptosis, and extracellular matrix synthesis. We examined BMP-2 expression in human scleral fibroblasts (HSF) and assessed the effects of recombinant human BMP-2 (rhBMP-2) on HSF proliferation, matrix metalloproteinase-2 (MMP-2), and tissue i...

  12. Noise-induced coherent switch

    Institute of Scientific and Technical Information of China (English)

    YUAN ZhanJiang; ZHANG Jiadun; ZHOU TianShou

    2008-01-01

    Taking the famous genetic toggle switch as an example, we numerically investigated the effect of noise on bistability. We found that extrinsic noise resulting from stochastic fluctuations in synthesis and degradation rates and from the environmental fluctuation in gene regulatory processes can induce coherent switch, and that there is an optimal noise intensity such that the noise not only can induce this switch, but also can amplify a weak input signal. In addition, we found that the intrinsic noise introduced through the Poisson τ-leap algorithm cannot induce such a switch.

  13. Noise-induced coherent switch

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Taking the famous genetic toggle switch as an example,we numerically investigated the effect of noise on bistability.We found that extrinsic noise resulting from stochastic fluctuations in synthesis and degradation rates and from the environmental fluctuation in gene regulatory processes can induce coherent switch,and that there is an optimal noise intensity such that the noise not only can induce this switch,but also can amplify a weak input signal.In addition,we found that the intrinsic noise introduced through the Poisson τ-leap algorithm cannot induce such a switch.

  14. Seizures induced by playing music.

    Science.gov (United States)

    Sutherling, W W; Hershman, L M; Miller, J Q; Lee, S I

    1980-09-01

    A 67-year-old organist and minister with diabetes mellitus had stereotyped focal seizures of the left lower face, jaw, and neck. Attacks occurred spontaneously or were induced when he played a specific hymn on the organ. The seizures were not induced by reading, singing, hearing, or playing the hymn silently. The patient had interictal weakness of the left lower face and left side of the tongue. Focal seizures were recorded on an electroencephalogram (EEG) at the right temporofrontal area. This patient illustrates partial seizures induced by playing music. PMID:6775246

  15. Cisplatin-Induced Eosinophilic Pneumonia

    Directory of Open Access Journals (Sweden)

    Hideharu Ideguchi

    2014-01-01

    Full Text Available A 67-year-old man suffering from esophageal cancer was admitted to our hospital complaining of dyspnea and hypoxemia. He had been treated with cisplatin, docetaxel, and fluorouracil combined with radiotherapy. Chest computed tomography revealed bilateral ground-glass opacity, and bronchoalveolar lavage fluid showed increased eosinophils. Two episodes of transient eosinophilia in peripheral blood were observed after serial administration of anticancer drugs before the admission, and drug-induced lymphocyte stimulation test to cisplatin was positive. Thus cisplatin-induced eosinophilic pneumonia was suspected, and corticosteroid was effectively administered. To our knowledge, this is the first reported case of cisplatin-induced eosinophilic pneumonia.

  16. Drug-induced cholestasis.

    Science.gov (United States)

    Zimmerman, H J; Lewis, J H

    1987-01-01

    Intrahepatic cholestasis, defined as arrested bile flow, mimics extrahepatic obstruction in its biochemical, clinical and morphological features. It may be due to hepatocyte lesions of which there are three types, termed canalicular, hepatocanalicular and hepatocellular, respectively; or it may be due to ductal lesions at the level of the cholangiole or portal or septal ducts. Defective bile flow due to hepatic lesions reflects abnormal modification of the ductular bile. Defective formation of canalicular bile may involve bile acid-dependent or independent flow. It appears to result most importantly from defective secretion of bile acid-dependent flow secondary to defective uptake from sinusoidal blood, defective transcellular transport and defective secretion; or from regurgitation of secreted bile via leaky tight junctions. An independent defect in bile acid-independent flow is less clear. Defective flow of bile along the canaliculus may reflect increased viscosity and impaired canalicular contractility secondary to injury of the pericanalicular microfibrillar network. Impaired flow beyond the canaliculus may result from ductal injury. Sites of lesions that contribute to cholestasis include the sinusoidal and canalicular plasma membrane, the pericanalicular network and the tight junction and, less certainly, microtubules and microfilaments and Golgi apparatus. A number of drugs that lead to cholestasis have been found to lead to injury at one or more of these sites. Other agents (alpha-naphthylisothiocyanate, methylenedianiline, contaminated rapeseed oil, paraquat) lead to ductal injury resulting in cholestasis. Reports of inspissated casts in ductules (benoxaprofen jaundice) and injury to the major excretory tree (5-fluorouridine after hepatic artery infusion) have led to other forms of ductal cholestasis. Most instances of drug-induced cholestasis present as acute, transient illness, although important chronic forms also occur. The clinical features include the

  17. Induced-charge Electrokinetic Phenomena

    CERN Document Server

    Bazant, M Z; Bazant, Martin Z.; Squires, Todd M.

    2003-01-01

    Motivated by the recent discovery of AC electro-osmosis near micro-electrodes, we predict a broad class of nonlinear electrokinetic phenomena involving induced interfacial charge. By considering various polarizable objects (metals or dielectrics) in DC and AC applied fields, we develop a simple physical picture of `induced-charge electro-osmosis' (ICEO), the fluid slip at a surface due to an electric field acting on the diffuse charge it induces. We also discuss `induced-charge electrophoresis' (ICEP), the analogous motion of a freely-suspended polarizable particle. Both differ significantly from their classical linear counterparts. We present a mathematical theory of ICEO flows in the weakly nonlinear limit of thin double layers. As an example, we calculate the time-dependent ICEO slip around a metallic sphere with a thin dielectric coating in a suddenly-applied DC field. We briefly discuss possible applications of ICEO to microfluidics and of ICEP to colloidal manipulation.

  18. Tachycardia-induced Cardiomyopathy (Tachycardiomyopathy

    Directory of Open Access Journals (Sweden)

    Hassan A. Mohamed

    2007-01-01

    Full Text Available The term tachycardia-induced cardiomyopathy or tachycardiomyopathy refers to impairment in left ventricular function secondary to chronic tachycardia, which is partially or completely reversible once the tachyarrhythmia is controlled. Tachycardia-induced cardiomyopathy has been shown to occur both in experimental models and in patients with incessant tachyarrhythmia.Data from several studies and from case reports have shown that rate control by means of cardioversion, negative chronotropic agents, and surgical or catheter-based atrioventricular node ablation, resulted in significant improvement of systolic function.The diagnosis of tachycardia-induced cardiomyopathy is usually made following observation of marked improvement in systolic function after normalization of heart rate. Clinicians should be aware that patients with unexplained systolic dysfunction may have tachycardia-induced cardiomyopathy, and that controlling the arrhythmia may result in improvement of systolic function.

  19. Drug-Induced Urinary Calculi

    Science.gov (United States)

    Matlaga, Brian R; Shah, Ojas D; Assimos, Dean G

    2003-01-01

    Urinary calculi may be induced by a number of medications used to treat a variety of conditions. These medications may lead to metabolic abnormalities that facilitate the formation of stones. Drugs that induce metabolic calculi include loop diuretics; carbonic anhydrase inhibitors; and laxatives, when abused. Correcting the metabolic abnormality may eliminate or dramatically attenuate stone activity. Urinary calculi can also be induced by medications when the drugs crystallize and become the primary component of the stones. In this case, urinary supersaturation of the agent may promote formation of the calculi. Drugs that induce calculi via this process include magnesium trisilicate; ciprofloxacin; sulfa medications; triamterene; indinavir; and ephedrine, alone or in combination with guaifenesin. When this situation occurs, discontinuation of the medication is usually necessary. PMID:16985842

  20. The Surgically Induced Stress Response

    OpenAIRE

    Finnerty, Celeste C.; Mabvuure, Nigel Tapiwa; Ali, Arham; Kozar, Rosemary A.; Herndon, David N

    2013-01-01

    The stress response to surgery, critical illness, trauma, and burns encompasses derangements of metabolic and physiological processes which induce perturbations in the inflammatory, acute phase, hormonal, and genomic responses. Hypermetabolism and hypercatabolism result, leading to muscle wasting, impaired immune function and wound healing, organ failure, and death. The surgery-induced stress response is largely similar to that triggered by traumatic injuries; the duration of the stress respo...

  1. Static behaviour of induced seismicity

    OpenAIRE

    Mignan, Arnaud

    2016-01-01

    The standard paradigm to describe seismicity induced by fluid injection is to apply non-linear diffusion dynamics in a poroelastic medium. I show that the spatio-temporal behaviour and rate evolution of induced seismicity can, instead, be expressed by geometric operations on a static stress field produced by volume change at depth. I obtain laws similar in form to the ones derived from poroelasticity while requiring a lower description length. Although fluid flow is known to...

  2. Static behaviour of induced seismicity

    OpenAIRE

    Mignan, A

    2015-01-01

    The standard paradigm to describe seismicity induced by fluid injection is to apply nonlinear diffusion dynamics in a poroelastic medium. I show that the spatiotemporal behaviour and rate evolution of induced seismicity can, instead, be expressed by geometric operations on a static stress field produced by volume change at depth. I obtain laws similar in form to the ones derived from poroelasticity while requiring a lower description length. Although fluid ...

  3. Static behaviour of induced seismicity

    OpenAIRE

    Mignan, Arnaud

    2015-01-01

    The standard paradigm to describe seismicity induced by fluid injection is to apply nonlinear diffusion dynamics in a poroelastic medium. I show that the spatiotemporal behaviour and rate evolution of induced seismicity can, instead, be expressed by geometric operations on a static stress field produced by volume change at depth. I obtain laws similar in form to the ones derived from poroelasticity while requiring a lower description length. Although fluid flow is known to occur in the ground...

  4. Inducible chemical defences in animals

    OpenAIRE

    Heyttyey, Attila; Tóth, Zoltán; Buskirk, Josh

    2014-01-01

    Phenotypic plasticity is extremely widespread in the behaviour, morphology and life-history of animals. However, inducible changes in the production of defensive chemicals are described mostly in plants and surprisingly little is known about similar plasticity in chemical defences of animals. Inducible chemical defences may be common in animals because many are known to produce toxins, the synthesis of toxins is likely to be costly, and there are a few known cases of animals adjusting their t...

  5. Radiation induced diarrhoea - literature review

    International Nuclear Information System (INIS)

    Radiation-induced diarrhoea is an acute side effect of radiotherapy treatment to the pelvic area, experienced by nearly all patients. This paper will explore the patho-physiological rationale of diarrhoea, the causes of radiation-induced diarrhoea, the factors that influence the severity and occurrence, and the treatment of diarrhoea in relation to the radiotherapy setting, by analysing the current literature and will conclude by outlining future directions in this field. Copyright (2004) Australian Institute of Radiography

  6. Mutations induced in plant breeding

    Energy Technology Data Exchange (ETDEWEB)

    Barriga B, P. (Universidad Austral de Chile, Valdivia. Inst. de Produccion y Sanidad Vegetal)

    1984-10-01

    The most significant aspects of the use of ionizing radiations in plant breeding are reviewed. Aspects such as basic principles of mutation, expression and selection in obtention of mutants, methods for using induced mutations and sucess achieved with this methodology in plant breeding are reviewed. Results obtained in a program of induced mutation on wheat for high content of protein and lysine at the Universidad Austral de Chile are presented.

  7. Anisotropy-induced Fano resonance

    OpenAIRE

    Qiu, Cheng-Wei; Novitsky, Andrey; Gao, Lei; Dong, Jian-Wen; Luk'yanchuk, Boris

    2012-01-01

    An optical Fano resonance, which is caused by birefringence control rather than frequency selection, is discovered. Such birefringence-induced Fano resonance comes with fast-switching radiation. The resonance condition $\\varepsilon_t< 1/\\varepsilon_r$ is revealed and a tiny perturbation in birefringence is found to result in a giant switch in the principal light pole induced near surface plasmon resonance. The loss and size effects upon the Fano resonance have been studied Fano resonance is s...

  8. Induced mutations in sesame breeding

    International Nuclear Information System (INIS)

    The scope of induced mutations in sesame (Sesamum indicum L.) breeding is reviewed. So far in Egypt, India, Iraq, Rep. of Korea, and Sri Lanka, 14 officially released varieties have been developed through induced mutations: 12 directly and 2 through cross breeding (one using the 'dt45' induced mutant from Israel). For another variety released in China there are no details. The induced mutations approach was adopted primarily in order to obtain genetic variability that was not available in the germplasm collection. The mutagens commonly applied have been gamma rays, EMS and sodium azide. Sesame seeds can withstand high mutagen doses, and there are genotypic differences in sensitivity between varieties. The mutants induced in the above named countries and others include better yield, improved seed retention, determinate habit, modified plant architecture and size, more uniform and shorter maturation period, earliness, resistance to diseases, genic male sterility, seed coat color, higher oil content and modified fatty acids composition. Some of the induced mutants have already given rise to improved varieties, the breeding value of other mutants is now being assessed and still others can serve as useful markers in genetic studies and breeding programmes. (author)

  9. Connectivity Map-based discovery of parbendazole reveals targetable human osteogenic pathway.

    Science.gov (United States)

    Brum, Andrea M; van de Peppel, Jeroen; van der Leije, Cindy S; Schreuders-Koedam, Marijke; Eijken, Marco; van der Eerden, Bram C J; van Leeuwen, Johannes P T M

    2015-10-13

    Osteoporosis is a common skeletal disorder characterized by low bone mass leading to increased bone fragility and fracture susceptibility. In this study, we have identified pathways that stimulate differentiation of bone forming osteoblasts from human mesenchymal stromal cells (hMSCs). Gene expression profiling was performed in hMSCs differentiated toward osteoblasts (at 6 h). Significantly regulated genes were analyzed in silico, and the Connectivity Map (CMap) was used to identify candidate bone stimulatory compounds. The signature of parbendazole matches the expression changes observed for osteogenic hMSCs. Parbendazole stimulates osteoblast differentiation as indicated by increased alkaline phosphatase activity, mineralization, and up-regulation of bone marker genes (alkaline phosphatase/ALPL, osteopontin/SPP1, and bone sialoprotein II/IBSP) in a subset of the hMSC population resistant to the apoptotic effects of parbendazole. These osteogenic effects are independent of glucocorticoids because parbendazole does not up-regulate glucocorticoid receptor (GR) target genes and is not inhibited by the GR antagonist mifepristone. Parbendazole causes profound cytoskeletal changes including degradation of microtubules and increased focal adhesions. Stabilization of microtubules by pretreatment with Taxol inhibits osteoblast differentiation. Parbendazole up-regulates bone morphogenetic protein 2 (BMP-2) gene expression and activity. Cotreatment with the BMP-2 antagonist DMH1 limits, but does not block, parbendazole-induced mineralization. Using the CMap we have identified a previously unidentified lineage-specific, bone anabolic compound, parbendazole, which induces osteogenic differentiation through a combination of cytoskeletal changes and increased BMP-2 activity. PMID:26420877

  10. Sociocultural determinants of induced abortion

    International Nuclear Information System (INIS)

    Objective: To determine the frequency of induced abortion and identity the role of sociocultural factors contributing to termination of pregnancy and associated morbidity and mortality in hospital setting. Subjects and Methods: The patients who were admitted for induced abortion were interviewed in privacy. On condition of anonymity they were asked about the age, parity, family setup and relationships, with particular emphasis on sociocultural reasons and factors contributing to induction of abortion. Details of status of abortionist and methods used for termination of pregnancy, the resulting complications and their severity were recorded. Results: Out of total admissions, 57(2.35%) gave history of induced abortion. All women belonged to low socioeconomic class and 59.6% of them were illiterate. Forty-three (75.5%) of these women had never practiced concentration. Twenty-four (42%) were grandmultiparae and did not want more children. In 29 women (50.9%) the decision for abortion had been supported by the husband. In 25 (43.8%) abortion was carried out by Daiyan (traditional midwives). Serious complications like uterine perforation with or without bowel injury were encouraged in 25 (43.8%) of these women. During the study period illegally induced abortion accounted for 6 (10.5%) maternal deaths. Conclusion: Prevalence of poverty, illiteracy, grand multiparity and non-practice of contraception are strong determinants of induced abortion. (author)

  11. Flash photography-induced maculopathy

    Directory of Open Access Journals (Sweden)

    Veugelen, Tim

    2011-01-01

    Full Text Available Objective: To report a flash photography-induced maculopathy. Methods: A professional photographer blinded himself accidentally and he consulted 3 days after the event with a scotoma in his dominant left eye. A unilateral acute light-induced maculopathy with hemorrhage was observed. The lesion was studied with colour photography, fluorescein and indocyanin angiography, autofluorescence imaging and repeated optical coherence tomography (OCT imaging. Results: At age 43, this professional photographer was blinded by the flash light of his camera and subsequently realized he had a scotoma in his dominant eye. Three days after the event visual acuity (VA was 20/70 and an acute light-induced maculopathy was noted. Another three days later, VA was 20/50 and the lesions were less prominent. After one month, the photographer still had problems making sharp pictures, VA was 20/25 and a macular scar was observed. During further follow-up, he regained full vision and experienced no professional problems. Conclusions: This case illustrates that the light of flash photography can accidentally hit an eye and induce a light-induced maculopathy.

  12. Drug-induced cutaneous vasculitides.

    Science.gov (United States)

    Antiga, E; Verdelli, A; Bonciani, D; Bonciolini, V; Quintarelli, L; Volpi, W; Fabbri, P; Caproni, M

    2015-04-01

    Cutaneous vasculitides (CV) can be idiopathic or secondary to several triggers, including drugs, which account for up to 30% of all the cases of CV. Several drugs can induce CV, including some medications commonly used in dermatology, including minocycline, and several new drugs, such as anti-TNF agents. Different pathomecanisms are involved in the development of drug-induced CV, including the formation and deposition of immune complexes, the induction of neutrophil apoptosis, the formation of neoantigens between the drugs and proteins from the host, the shift of the immune response, and others. Although the diagnosis is difficult, because the clinical picture of drug-induced CV is in general indistinguishable from that of other forms of CV, it is important to recognize such entities in order to correctly manage the patient. Anamnesis, diagnostic algorithms to assess the likelihood of the association between a drug and a cutaneous reaction, skin biopsy and laboratory testing (including the search for antineutrophil cytoplasmic antibodies) are useful tools to make a diagnosis of drug-induced CV. About the therapy, while in idiopathic vasculitides the treatment is usually more aggressive and long-lasting, very often requiring a maintenance therapy with immunosuppressive drugs, in drug-induced CV the discontinuation of the suspected drug alone is usually enough to achieve complete remission, making the prognosis usually very good.

  13. Static behaviour of induced seismicity

    Directory of Open Access Journals (Sweden)

    A. Mignan

    2015-12-01

    Full Text Available The standard paradigm to describe seismicity induced by fluid injection is to apply nonlinear diffusion dynamics in a poroelastic medium. I show that the spatiotemporal behaviour and rate evolution of induced seismicity can, instead, be expressed by geometric operations on a static stress field produced by volume change at depth. I obtain laws similar in form to the ones derived from poroelasticity while requiring a lower description length. Although fluid flow is known to occur in the ground, it is not pertinent to the behaviour of induced seismicity. The proposed model is equivalent to the static stress model for tectonic foreshocks generated by the Non-Critical Precursory Accelerating Seismicity Theory. This study hence verifies the explanatory power of this theory outside of its original scope.

  14. Late onset clozapine induced agranulocytosis

    Directory of Open Access Journals (Sweden)

    Rajmohan Velayudhan

    2014-01-01

    Full Text Available Agranulocytosis is defined as an absolute neutrophil count less than 100/mm 3 in association with infectious disease. The risk of agranulocytosis is 0.38% of all clozapine treated cases and there is a relatively lesser incidence in Indian population. The risk of clozapine-induced agranulocytosis and neutropenia is highest in the first 6 months and higher in the initial 18 months after the onset of treatment. There have been very few reports of neutropenia and agranulocytosis after this period. There have so far been no reports of late onset clozapine induced agranulocytosis has been reported from India. A case of late onset clozapine induced agranulocytosis with possible mechanism of the same is reported.

  15. The surgically induced stress response.

    Science.gov (United States)

    Finnerty, Celeste C; Mabvuure, Nigel Tapiwa; Ali, Arham; Kozar, Rosemary A; Herndon, David N

    2013-09-01

    The stress response to surgery, critical illness, trauma, and burns encompasses derangements of metabolic and physiological processes that induce perturbations in the inflammatory, acute phase, hormonal, and genomic responses. Hypermetabolism and hypercatabolism result, leading to muscle wasting, impaired immune function and wound healing, organ failure, and death. The surgery-induced stress response is largely similar to that triggered by traumatic injuries; the duration of the stress response, however, varies according to the severity of injury (surgical or traumatic). This spectrum of injuries and insults ranges from small lacerations to severe insults such as large poly-traumatic and burn injuries. Burn injuries provide an extreme model of trauma induced stress responses that can be used to study the long-term effects of a prolonged stress response. Although the stress response to acute trauma evolved to confer improved chances of survival following injury, in modern surgical practice the stress response can be detrimental. PMID:24009246

  16. Static behaviour of induced seismicity

    CERN Document Server

    Mignan, Arnaud

    2015-01-01

    The standard paradigm to describe seismicity induced by fluid injection is to apply nonlinear diffusion dynamics in a poroelastic medium. I show that the spatiotemporal behaviour and rate evolution of induced seismicity can, instead, be expressed by geometric operations on a static stress field produced by volume change at depth. I obtain laws similar in form to the ones derived from poroelasticity while requiring a lower description length. Although fluid flow is known to occur in the ground, it is not pertinent to the behaviour of induced seismicity. The proposed model is equivalent to the static stress model for tectonic foreshocks generated by the Non- Critical Precursory Accelerating Seismicity Theory. This study hence verifies the explanatory power of this theory outside of its original scope.

  17. Surface-induced evaporative cooling

    Institute of Scientific and Technical Information of China (English)

    Ke Min; Yan Bo; Cheng Feng; Wang Yu-Zhu

    2009-01-01

    The effects of surface-induced evaporative cooling on an atom chip are investigated. The evolutions of temperature, number and phase-space density of the atom cloud are measured when the atom cloud is brought close to the surface. Rapid decrease of the temperature and number of the atoms is found when the atom-surface distance is < 100 μm. A gain of about a factor of five on the phase-space density is obtained. It is found that the efficiency of the surface-induced evaporative cooling depends on the atom-surface distance and the shape of the evaporative trap. When the atoms are moved very close to the surface, severe heating is observed, which dominates when the holding time is > 8 ms. It is important that the surface-induced evaporative cooling offers novel possibilities for the realization of a continuous condensation, where a spatially varying evaporative cooling is required.

  18. Metal-induced crystallization fundamentals and applications

    CERN Document Server

    Wang, Zumin; Mittemeijer, Eric J

    2014-01-01

    Introduction to Metal-Induced CrystallizationAtomic Mechanisms and Interface Thermodynamics of Metal-Induced Crystallization of Amorphous Semiconductors at Low TemperaturesThermodynamics and Kinetics of Layer Exchange upon Low-Temperature Annealing Amorphous Si/Polycrystalline Al Layered StructuresMetal-Induced Crystallization by Homogeneous Insertion of Metallic Species in Amorphous SemiconductorsAluminum-Induced Crystallization: Applications in Photovoltaic TechnologiesApplications of Metal-Induced Crystallization for Advanced Flat-Panel DisplaysLaser-Assisted Meta

  19. Validating induced seismicity forecast models - Induced Seismicity Test Bench

    CERN Document Server

    Kiraly-Proag, Eszter; Gischig, Valentin; Wiemer, Stefan; Karvounis, Dimitrios; Doetsch, Joseph

    2016-01-01

    Induced earthquakes often accompany fluid injection, and the seismic hazard they pose threatens various underground engineering projects. Models to monitor and control induced seismic hazard with traffic light systems should be probabilistic, forward-looking, and updated as new data arrive. In this study, we propose an Induced Seismicity Test Bench to test and rank such models; this test bench can be used for model development, model selection, and ensemble model building. We apply the test bench to data from the Basel 2006 and Soultz-sous-For\\^ets 2004 geothermal stimulation projects, and we assess forecasts from two models: Shapiro and Smoothed Seismicity (SaSS) and Hydraulics and Seismics (HySei). These models incorporate a different mix of physics-based elements and stochastic representation of the induced sequences. Our results show that neither model is fully superior to the other. Generally, HySei forecasts the seismicity rate better after shut-in, but is only mediocre at forecasting the spatial distri...

  20. Pump cavitation and inducer design

    International Nuclear Information System (INIS)

    Details of past work on sodium pump development and cavitation studies executed mainly for SNR 300 were reported earlier. Among the requirements for large sodium pumps are long life (200000 hours up to 300000 hours) and small size of impeller and pump, fully meeting the process and design criteria. These criteria are the required 'Q, H, r characteristics' in combination with a low NPSH value and the avoidance of cavitation damage to the pump. The pump designer has to develop a sound hydraulic combination consisting of suction arrangement, impeller design and diffuser. On the other hand the designer is free to choose an optimal pump speed. The pump speed in its turn influences the rotor dynamic pump design and the pump drive. The introduction of the inducer as an integral part of the pump design is based on following advantages: no tip cavitation; (possible) cavitation bubbles move to the open centre due to centrifugal forces on the fluid; the head of the inducer improves the inlet conditions of the impeller. The aim of an inducer is the increase in the suction specific speed (SA value) of a pump whereby the inducer functions as a pressure source improving the impeller inlet conditions. With inducer-impeller combinations values up to SA=15000 are realistic. With the use of an inducer the overall pump sizes can be reduced with Ca. 30%. Pumps commonly available have SA values up to a maximum of ca. 10000. A development programme was executed for SNR 300 in order to reach an increase of the suction specific speed of the impeller from SA 8200 to SA 11000. Further studies to optimize pumps design for the follow up line introduced the 'inducer acting as a pre-impeller' development. This programme was executed in the period 1979-1981. At the FDO premises a scale 1 2.8 inducer impeller combination with a suction specific speed SA=15000 was developed, constructed and tested at the water test rig. This water test rig is equipped with a perspex pipe allowing also visualisation

  1. Anesthetic-Induced Developmental Neurotoxicity

    Institute of Scientific and Technical Information of China (English)

    Jia-RenLiu; Qian Liu; Jing Li; Sulpicio G. Soriano

    2011-01-01

    1 IntroductionMillions of newborn and infants receive anesthetic,sedative and analgesic drugs for surgery and painful procedures on a daily basis.Recent laboratory reports clearly demonstrate that anesthetic and sedative drugs induced both neuroapoptosis and neurocognitive deficits in laboratory models.This issue is of paramount interest to pediatric anesthesiologists and intensivists because it questions the safety of anesthetics used for fetal and neonatal anesthesia[1-2].In an attempt to summarize the rapidly expanding laboratorybased literature on anesthetic-induced developmental neurotoxicity (AIDN),this review will examine published reports on the characterization,mechanisms and alleviation of this phenomenon.

  2. Ceftriaxone-induced toxic hepatitis

    Institute of Scientific and Technical Information of China (English)

    Erdal Peker; Eren Cagan; Murat Dogan

    2009-01-01

    Toxic hepatitis or drug-induced liver injury encompasses a spectrum of clinical disease ranging from mild biochemical abnormalities to acute liver failure. The advantages of a long half-life, wide spectrum, high tissue penetration rate, and a good safety profile,make ceftriaxone, a third-generation cephalosporin,a frequent choice in the treatment of childhood infections. Previous studies have reported a few cases of high aspartate aminotransferase and alanine aminotransferase levels, along with three cases ofhepatitis caused by ceftriaxone. Here, we report a case of drug-induced toxic hepatitis in a patient who was treated with ceftriaxone for acute tons