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Sample records for classic bone morphogenetic

  1. The classic: Bone morphogenetic protein.

    Science.gov (United States)

    Urist, Marshall R; Strates, Basil S

    2009-12-01

    This Classic Article is a reprint of the original work by Marshall R. Urist and Basil S. Strates, Bone Morphogenetic Protein. An accompanying biographical sketch of Marshall R. Urist, MD is available at DOI 10.1007/s11999-009-1067-4; a second Classic Article is available at DOI 10.1007/s11999-009-1069-2; and a third Classic Article is available at DOI 10.1007/s11999-009-1070-9. The Classic Article is copyright 1971 by Sage Publications Inc. Journals and is reprinted with permission from Urist MR, Strates BS. Bone morphogenetic protein. J Dent Res. 1971;50:1392-1406.

  2. The classic: Bone morphogenetic protein.

    Science.gov (United States)

    Urist, Marshall R; Strates, Basil S

    2009-12-01

    This Classic Article is a reprint of the original work by Marshall R. Urist and Basil S. Strates, Bone Morphogenetic Protein. An accompanying biographical sketch of Marshall R. Urist, MD is available at DOI 10.1007/s11999-009-1067-4; a second Classic Article is available at DOI 10.1007/s11999-009-1069-2; and a third Classic Article is available at DOI 10.1007/s11999-009-1070-9. The Classic Article is copyright 1971 by Sage Publications Inc. Journals and is reprinted with permission from Urist MR, Strates BS. Bone morphogenetic protein. J Dent Res. 1971;50:1392-1406. PMID:19727989

  3. Bone morphogenetic proteins: Periodontal regeneration

    Directory of Open Access Journals (Sweden)

    Subramaniam M Rao

    2013-01-01

    Full Text Available Periodontitis is an infectious inflammatory disease that results in attachment loss and bone loss. Regeneration of the periodontal tissues entails de novo formation of cementum, periodontal ligament, and alveolar bone. Several different approaches are currently being explored to achieve complete, reliable, and reproducible regeneration of periodontal tissues. The therapeutic management of new bone formation is one of the key issues in successful periodontal regeneration. Bone morphogenetic proteins form a unique group of proteins within the transforming growth factor superfamily of genes and have a vital role in the regulation in the bone induction and maintenance. The activity of bone morphogenetic proteins was first identified in the 1960s, but the proteins responsible for bone induction were unknown until the purification and cloning of human bone morphogenetic proteins in the 1980s, because of their osteoinductive potential. Bone morphogenetic proteins have gained a lot of interest as therapeutic agents for treating periodontal defects. A systematic search for data related to the use of bone morphogenetic proteins for the regeneration of periodontal defects was performed to recognize studies on animals and human (PUBMED, MEDLINE, COCHRANE, and Google search. All the studies included showed noticeable regeneration of periodontal tissues with the use of BMP.

  4. Cross-talk between bone morphogenetic proteins and inflammatory pathways.

    Science.gov (United States)

    van der Kraan, Peter M; Davidson, Esmeralda N Blaney

    2015-11-23

    Pro-inflammatory cytokines and bone morphogenetic proteins are generally studied separately and considered to be elements of different worlds, immunology and developmental biology. Varas and colleagues report that these factors show cross-talk in rheumatoid arthritis synoviocytes. They show that pro-inflammatory cytokines not only stimulate the production of bone morphogenetic proteins but that these endogenously produced bone morphogenetic proteins interfere with the effects of pro-inflammatory cytokines on synoviocytes.

  5. 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

  6. Bone Regeneration Using Bone Morphogenetic Proteins and Various Biomaterial Carriers

    Directory of Open Access Journals (Sweden)

    Zeeshan Sheikh

    2015-04-01

    Full Text Available Trauma and disease frequently result in fractures or critical sized bone defects and their management at times necessitates bone grafting. The process of bone healing or regeneration involves intricate network of molecules including bone morphogenetic proteins (BMPs. BMPs belong to a larger superfamily of proteins and are very promising and intensively studied for in the enhancement of bone healing. More than 20 types of BMPs have been identified but only a subset of BMPs can induce de novo bone formation. Many research groups have shown that BMPs can induce differentiation of mesenchymal stem cells and stem cells into osteogenic cells which are capable of producing bone. This review introduces BMPs and discusses current advances in preclinical and clinical application of utilizing various biomaterial carriers for local delivery of BMPs to enhance bone regeneration.

  7. Multifunctional Bone Morphogenetic Protein System in Endocrinology

    Directory of Open Access Journals (Sweden)

    Otsuka,Fumio

    2013-04-01

    Full Text Available New biological activities of bone morphogenetic proteins (BMPs in the endocrine system have recently been revealed. The BMP system is composed of approximately 30 ligands and preferential combinations of type I and type II receptors. The BMP system not only induces bone formation but also plays unique tissue-specific roles in various organs. For instance, the ovarian BMP system is a physiological inhibitor of luteinization in growing ovarian follicles. In the ovary, the expression of oocyte-derived BMP-15 is critical for female reproduction. In the pituitary, BMP-4 is a key player for initial development of the anterior pituitary, while it is also functionally involved in some differentiated pituitary tumors, including prolactinoma and Cushingʼs disease. In the adrenal glands, BMP-6 and BMP-4 modulate aldosterone and catecholamine production, respectively, which contributes to a functional interaction between the cortex and medulla. In the present review, recent advances in BMP biology in the field of endocrinology are described and the possibility for clinical application of BMP activity is discussed.

  8. 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...

  9. Hepatoregenerative role of bone morphogenetic protein-9

    Science.gov (United States)

    Sosa, Ivan; Cvijanovic, Olga; Celic, Tanja; Cuculic, Drazen; Crncevic-Orlic, Zeljka; Vukelic, Lucian; Cvek, Sanja Zoricic; Dudaric, Luka; Bosnar, Alan; Bobinac, Dragica

    2011-01-01

    Summary Bone morphogenetic protein-9 (BMP-9) is a member of the transforming growth factor beta (TGF-β) superfamily of cytokines, which regulate cell growth and differentiation during embryogenesis. Apart of that, the hypoglycemic potential of BMP-9 is of great interest. It has been confirmed that BMP-9, like insulin, improves glycemia in diabetic mice and regulates directional glucose metabolism in hepatocytes; therefore it is proposed to be a candidate hepatic insulin-sensitizing substance (HISS). In liver fibrosis, due to the portocaval shunt, insulin bypasses the organ and the liver undergoes atrophy. Parenteral administration of insulin reverses atrophy by stimulating mitogenic activity of the hepatocytes. Because BMP-9 has a signaling pathway similar to other BMPs and insulin, it is to be expected that BMP-9 has a certain regenerative role in the liver, supporting the above-mentioned is evidence of BMP-9 expression in Dissè’s spaces and BMP-7’s mitogenic activity in mucosal cells. However, further studies are needed to confirm the possible regenerative role of BMP-9. PMID:22129908

  10. Evaluation of heterotopic bone formation induced by squalane and bone morphogenetic protein composite.

    Science.gov (United States)

    Kawakami, T; Kawai, T; Takei, N; Kise, T; Eda, S; Urist, M R

    1997-04-01

    Bone morphogenetic protein is an important molecule whose bioactivity depends on the carrier. Squalane is used in the formulation of various kinds of cosmetics because it is easily emulsified and has the property of spreading well. Thus, squalane might be effective as a bone morphogenetic protein delivery system. As a test for this possibility, gelatin capsules containing squalane and bone morphogenetic protein (bovine derived partially purified) composite were implanted under the hind-quarter perimuscular membrane of ddY mice. Control capsules containing only bone morphogenetic protein were used for controls. The implants were radiographically and histologically examined at 1 to 4 weeks after the operation. According to the radiographic analysis, squalane and bone morphogenetic protein composite and bone morphogenetic protein only control specimens formed widespread heterotopic bone tissues. The amount of heterotopic bone formation in the composite experimental specimens was approximately 40% greater than that in the controls. Histologic examination of experimental and control specimens revealed varying amounts of perichondral ossification by 2 weeks. By 3 and 4 weeks, the bone deposits were colonized by hematopoietic bone marrow. Squalane was effective for the slow local release of bone morphogenetic protein. Furthermore, the squalane and bone morphogenetic protein composite was a reliable osteoinductive biomaterial.

  11. Nuclear variants of bone morphogenetic proteins

    Directory of Open Access Journals (Sweden)

    Meinhart Christopher A

    2010-03-01

    Full Text Available Abstract Background Bone morphogenetic proteins (BMPs contribute to many different aspects of development including mesoderm formation, heart development, neurogenesis, skeletal development, and axis formation. They have previously been recognized only as secreted growth factors, but the present study detected Bmp2, Bmp4, and Gdf5/CDMP1 in the nuclei of cultured cells using immunocytochemistry and immunoblotting of nuclear extracts. Results In all three proteins, a bipartite nuclear localization signal (NLS was found to overlap the site at which the proproteins are cleaved to release the mature growth factors from the propeptides. Mutational analyses indicated that the nuclear variants of these three proteins are produced by initiating translation from downstream alternative start codons. The resulting proteins lack N-terminal signal peptides and are therefore translated in the cytoplasm rather than the endoplasmic reticulum, thus avoiding proteolytic processing in the secretory pathway. Instead, the uncleaved proteins (designated nBmp2, nBmp4, and nGdf5 containing the intact NLSs are translocated to the nucleus. Immunostaining of endogenous nBmp2 in cultured cells demonstrated that the amount of nBmp2 as well as its nuclear/cytoplasmic distribution differs between cells that are in M-phase versus other phases of the cell cycle. Conclusions The observation that nBmp2 localization varies throughout the cell cycle, as well as the conservation of a nuclear localization mechanism among three different BMP family members, suggests that these novel nuclear variants of BMP family proteins play an important functional role in the cell.

  12. Squalane as a possible carrier of bone morphogenetic protein.

    Science.gov (United States)

    Kawakami, T; Uji, H; Antoh, M; Hasegawa, H; Kise, T; Eda, S

    1993-07-01

    Gelatin capsules containing squalane partially purified bone morphogenetic protein (BMP) complex were placed on the perimuscular membrane of rats. Two kinds of control, gelatin capsules containing only BMP and those bearing squalane only, were used. The embedded areas were histopathologically examined at 3 and 6 wk after the operation. The observations revealed that the squalane/BMP complex elicited wide heterotopic bone formation with bone marrow tissue, suggesting that squalane is a possible carrier of BMP for clinical applications.

  13. Bone graft substitutes and bone morphogenetic proteins for osteoporotic fractures: What is the evidence?

    NARCIS (Netherlands)

    E.M.M. van Lieshout (Esther); V. Alt (Volker)

    2016-01-01

    textabstractDespite improvements in implants and surgical techniques, osteoporotic fractures remain challenging to treat. Among other major risk factors, decreased expression of morphogenetic proteins has been identified for impaired fracture healing in osteoporosis. Bone grafts or bone graft substi

  14. Cross-talk between bone morphogenetic proteins and inflammatory pathways

    NARCIS (Netherlands)

    Kraan, P.M. van der; Davidson, E.N.

    2015-01-01

    Pro-inflammatory cytokines and bone morphogenetic proteins are generally studied separately and considered to be elements of different worlds, immunology and developmental biology. Varas and colleagues report that these factors show cross-talk in rheumatoid arthritis synoviocytes. They show that pro

  15. Bone Morphogenetic Protein 4 Mediates Human Embryonic Germ Cell Derivation

    OpenAIRE

    Hiller, Marc; Liu, Cyndi; Blumenthal, Paul D; John D Gearhart; Kerr, Candace L.

    2010-01-01

    Human primordial germ cells (PGCs) have proven to be a source of pluripotent stem cells called embryonic germ cells (EGCs). Unlike embryonic stem cells, virtually little is known regarding the factors that regulate EGC survival and maintenance. In mice, the growth factor bone morphogenetic protein 4 (BMP4) has been shown to be required for maintaining mouse embryonic stem cells, and disruptions in this gene lead to defects in mouse PGC specification. Here, we sought to determine whether recom...

  16. The history and histology of bone morphogenetic protein.

    Science.gov (United States)

    Murray, Samuel S; Brochmann Murray, Elsa J; Wang, Jeffrey C; Duarte, Maria Eugenia Leite

    2016-07-01

    Bone morphogenetic proteins are a group of structurally related proteins within the TGF-β superfamily of proteins with a diverse repertoire of functions in embryonic and adult organisms. As is apparent from the name, the members first characterized participate in bone growth, development, and remodeling. The "morphogenic" activity per se is defined as the induction of a recapitulation of endochondral bone formation by appropriate stem cells. The regenerative capacity of bone has been recognized since ancient times. The mechanism, applications, and conceptual basis of bone transplantation, bone implantation, ectopic bone formation, and exogenously induced bone formation have been studied by many investigators for more than a century. This review examines the efforts to characterize this activity in the European and American literature over approximately the last century. Because of the inherently complex nature of the process induced by these molecules (inflammation, stem cell proliferation, cartilage differentiation, replacement of cartilage with bone) it is important to evaluate previous investigations through a histological perspective. The cellular basis of the contemporary bioassay for BMP activity is illustrated and discussed from the histological point of view. PMID:26907674

  17. Bone Morphogenetic Protein-2-Induced Signaling and Osteogenesis Is Regulated by Cell Shape, RhoA/ROCK, and Cytoskeletal Tension

    OpenAIRE

    Wang, Yang-Kao; Yu, Xiang; Cohen, Daniel M.; Wozniak, Michele A.; Yang, Michael T.; Gao, Lin; Eyckmans, Jeroen; Chen, Christopher S.

    2011-01-01

    Osteogenic differentiation of human mesenchymal stem cells (hMSCs) is classically thought to be mediated by different cytokines such as the bone morphogenetic proteins (BMPs). Here, we report that cell adhesion to extracellular matrix (ECM), and its effects on cell shape and cytoskeletal mechanics, regulates BMP-induced signaling and osteogenic differentiation of hMSCs. Using micropatterned substrates to progressively restrict cell spreading and flattening against ECM, we demonstrated that BM...

  18. Bone morphogenetic proteins: from structure to clinical use

    Directory of Open Access Journals (Sweden)

    Granjeiro J.M.

    2005-01-01

    Full Text Available Bone morphogenetic proteins (BMPs are multi-functional growth factors belonging to the transforming growth factor ß superfamily. Family members are expressed during limb development, endochondral ossification, early fracture, and cartilage repair. The activity of BMPs was first identified in the 1960s but the proteins responsible for bone induction were unknown until the purification and cloning of human BMPs in the 1980s. To date, about 15 BMP family members have been identified and characterized. The signal triggered by BMPs is transduced through serine/threonine kinase receptors, type I and II subtypes. Three type I receptors have been shown to bind BMP ligands, namely: type IA and IB BMP receptors and type IA activin receptors. BMPs seem to be involved in the regulation of cell proliferation, survival, differentiation and apoptosis, but their hallmark is their ability to induce bone, cartilage, ligament, and tendon formation at both heterotopic and orthotopic sites. This suggests that, in the future, they may play a major role in the treatment of bone diseases. Several animal studies have illustrated the potential of BMPs to enhance spinal fusion, repair critical-size defects, accelerate union, and heal articular cartilage lesions. Difficulties in producing and purifying BMPs from bone tissue have prompted the attempts made by several laboratories, including ours, to express these proteins in the recombinant form in heterologous systems. This review focuses on BMP structure, molecular mechanisms of action and significance and potential applications in medical, dental and veterinary practice for the treatment of cartilage and bone-related diseases.

  19. Harmine promotes osteoblast differentiation through bone morphogenetic protein signaling

    Energy Technology Data Exchange (ETDEWEB)

    Yonezawa, Takayuki [Department of Nutriproteomics, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan); Research Institute for Biological Functions, Chubu University, 1200 Matsumoto, Kasugai, Aichi 487-8501 (Japan); Lee, Ji-Won [Research Institute for Biological Functions, Chubu University, 1200 Matsumoto, Kasugai, Aichi 487-8501 (Japan); Hibino, Ayaka; Asai, Midori [Department of Biological Chemistry, College of Bioscience and Biotechnology, Chubu University, 1200 Matsumoto, Kasugai, Aichi 487-8501 (Japan); Hojo, Hironori [Center for Disease Biology and Integrative Medicine, Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan); Cha, Byung-Yoon [Research Institute for Biological Functions, Chubu University, 1200 Matsumoto, Kasugai, Aichi 487-8501 (Japan); Teruya, Toshiaki [Research Institute for Biological Functions, Chubu University, 1200 Matsumoto, Kasugai, Aichi 487-8501 (Japan); Faculty of Education, University of the Ryukyus, 1 Senbaru, Nishihara, Okinawa 903-0213 (Japan); Nagai, Kazuo [Research Institute for Biological Functions, Chubu University, 1200 Matsumoto, Kasugai, Aichi 487-8501 (Japan); Department of Biological Chemistry, College of Bioscience and Biotechnology, Chubu University, 1200 Matsumoto, Kasugai, Aichi 487-8501 (Japan); Chung, Ung-Il [Center for Disease Biology and Integrative Medicine, Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan); Yagasaki, Kazumi [Department of Nutriproteomics, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan); Division of Applied Biological Chemistry, Institute of Agriculture, Tokyo Noko University, 3-5-8 Saiwai, Fuchu, Tokyo 183-8509 (Japan); and others

    2011-06-03

    Highlights: {yields} Harmine promotes the activity and mRNA expression of ALP. {yields} Harmine enhances the expressions of osteocalcin mRNA and protein. {yields} Harmine induces osteoblastic mineralization. {yields} Harmine upregulates the mRNA expressions of BMPs, Runx2 and Osterix. {yields} BMP signaling pathways are involved in the actions of harmine. -- Abstract: Bone mass is regulated by osteoblast-mediated bone formation and osteoclast-mediated bone resorption. We previously reported that harmine, a {beta}-carboline alkaloid, inhibits osteoclast differentiation and bone resorption in vitro and in vivo. In this study, we investigated the effects of harmine on osteoblast proliferation, differentiation and mineralization. Harmine promoted alkaline phosphatase (ALP) activity in MC3T3-E1 cells without affecting their proliferation. Harmine also increased the mRNA expressions of the osteoblast marker genes ALP and Osteocalcin. Furthermore, the mineralization of MC3T3-E1 cells was enhanced by treatment with harmine. Harmine also induced osteoblast differentiation in primary calvarial osteoblasts and mesenchymal stem cell line C3H10T1/2 cells. Structure-activity relationship studies using harmine-related {beta}-carboline alkaloids revealed that the C3-C4 double bond and 7-hydroxy or 7-methoxy group of harmine were important for its osteogenic activity. The bone morphogenetic protein (BMP) antagonist noggin and its receptor kinase inhibitors dorsomorphin and LDN-193189 attenuated harmine-promoted ALP activity. In addition, harmine increased the mRNA expressions of Bmp-2, Bmp-4, Bmp-6, Bmp-7 and its target gene Id1. Harmine also enhanced the mRNA expressions of Runx2 and Osterix, which are key transcription factors in osteoblast differentiation. Furthermore, BMP-responsive and Runx2-responsive reporters were activated by harmine treatment. Taken together, these results indicate that harmine enhances osteoblast differentiation probably by inducing the expressions of

  20. Enhanced release of bone morphogenetic proteins from demineralized bone matrix by gamma irradiation

    International Nuclear Information System (INIS)

    Gamma irradiation is a useful method for sterilizing demineralized bone matrix (DBM), but its effect on the osteoinductivity of DBM is still controversial. In this study, the osteoinductive activity of gamma-irradiated DBM was examined using a mouse myoblastic cell line (C2C12). DBM was extracted from adult bovine bone and was irradiated at a dose of 25 kGy using a 60cobalt gamma-irradiator. Cell proliferation with DBM was not affected by gamma-irradiation, but alkaline phosphatase and osteocalcin productions were significantly increased in C2C12 cell groups treated with gamma-irradiated DBM. It was reasoned that bone morphogenetic proteins were more efficiently released from gamma-irradiated DBM than from the non-irradiated control. This result suggests the effectiveness of radiation sterilization of bone implants - Highlights: • Demineralized bone matrix (DBM) was gamma-irradiated for sterilization. • Irradiated DBM had higher alkaline phosphatase and osteocalcin production. • It was reasoned the more released bone morphogenetic proteins by irradiation. • This result supports the application of radiation sterilization for bone implants

  1. Bone morphogenetic protein-2: a potential regulator in scleral remodeling

    Science.gov (United States)

    Hu, Jianmin; Cui, Dongmei; Yang, Xiao; Wang, Shaowei; Hu, Shoulong; Li, Chuanxu

    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 inhibitor of metalloproteinase-2 (TIMP-2). Methods We used confocal fluorescence microscopy (CFM) to study BMP-2 distribution in HSF cells and frozen human scleral sections. The influence of rhBMP-2 on cell proliferation at different concentrations (0 ng/ml, 1 ng/ml, 10 ng/ml, and 100 ng/ml) was evaluated by the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. The effects of rhBMP-2 on the cell cycle were investigated with flow cytometric analysis. Reverse transcription polymerase chain reaction (RT–PCR) and enzyme-linked immunosorbent assay (ELISA) were used to examine MMP-2 and TIMP-2 mRNAs and secreted proteins in HSF that were incubated with rhBMP-2. Results BMP-2 protein expression from human sclera was confirmed by CFM. Cell proliferation was significantly increased with 100 ng/ml rhBMP-2 in a time-dependent manner (p<0.05). The HSF cell cycle moved to the S and S+G2M phases after rhBMP-2 stimulation at 100 ng/ml compared to normal cells (p<0.05). TIMP-2 mRNA levels were significantly increased in HSF incubated for 24 h with 100 ng/ml rhBMP-2 (p<0.01). A 48 h incubation with 10 ng/ml or 100 ng/ml rhBMP-2 resulted in significantly increased TIMP-2 mRNA and protein expression and significantly decreased MMP-2 mRNA expression (p<0.01) while MMP-2 protein expression significantly decreased at 100 ng/ml rhBMP-2 (p<0.01). Conclusions Human sclera fibroblasts expressed BMP-2, which promoted cell proliferation, and elicited changes in MMP-2 and TIMP-2

  2. Use of bone morphogenetic proteins in mesenchymal stem cell stimulation of cartilage and bone repair

    OpenAIRE

    Scarfì, Sonia

    2016-01-01

    The extracellular matrix-associated bone morphogenetic proteins (BMPs) govern a plethora of biological processes. The BMPs are members of the transforming growth factor-β protein superfamily, and they actively participate to kidney development, digit and limb formation, angiogenesis, tissue fibrosis and tumor development. Since their discovery, they have attracted attention for their fascinating perspectives in the regenerative medicine and tissue engineering fields. BMPs have been employed i...

  3. Bone morphogenetic protein 4 mediates human embryonic germ cell derivation.

    Science.gov (United States)

    Hiller, Marc; Liu, Cyndi; Blumenthal, Paul D; Gearhart, John D; Kerr, Candace L

    2011-02-01

    Human primordial germ cells (PGCs) have proven to be a source of pluripotent stem cells called embryonic germ cells (EGCs). Unlike embryonic stem cells, virtually little is known regarding the factors that regulate EGC survival and maintenance. In mice, the growth factor bone morphogenetic protein 4 (BMP4) has been shown to be required for maintaining mouse embryonic stem cells, and disruptions in this gene lead to defects in mouse PGC specification. Here, we sought to determine whether recombinant human BMP4 could influence EGC derivation and/or human PGC survival. We found that the addition of recombinant BMP4 increased the number of human PGCs after 1 week of culture in a dose-responsive manner. The efficiency of EGC derivation and maintenance in culture was also enhanced by the presence of recombinant BMP4 based on alkaline phosphatase and OCT4 staining. In addition, an antagonist of the BMP4 pathway, Noggin, decreased PGC proliferation and led to an increase in cystic embryoid body formation. Quantitative real-time (qRT)-polymerase chain reaction analyses and immunostaining confirmed that the constituents of the BMP4 pathway were upregulated in EGCs versus PGCs. Downstream activators of the BMP4 pathway such as ID1 and phosphorylated SMADs 1 and 5 were also expressed, suggesting a role of this growth factor in EGC pluripotency. PMID:20486775

  4. Bone morphogenetic protein signalling in heritable versus idiopathic pulmonary hypertension

    Science.gov (United States)

    Dewachter, Laurence; Adnot, Serge; Guignabert, Christophe; Tu, Ly; Marcos, Elisabeth; Fadel, Elie; Humbert, Marc; Dartevelle, Philippe; Simonneau, Gérald; Naeije, Robert; Eddahibi, Saadia

    2009-01-01

    Mutations in gene encoding for bone morphogenetic protein type 2 receptor (BMPR-2) have been reported in pulmonary arterial hypertension (PAH), but their functional relevance remains incompletely understood. BMP receptors expression was evaluated in human lungs and in cultured pulmonary artery smooth muscle cells (PASMCs) isolated from 19 idiopathic PAH patients and 9 heritable PAH patients with demonstrated BMPR-2 mutations. BMP4-treated PASMCs were assessed for Smad and p38MAPK signaling associated to mitosis and apoptosis. Lung tissue and PASMCs from heritable PAH patients presented with decreased BMPR-2 expression and variable increases in BMPR-1A and BMPR-1B expressions, while a less important decreased BMPR-2 expression was observed in PASMCs from idiopathic PAH patients. Heritable PAH PASMCs showed no increased phosphorylation of Smad1/5/8 in the presence of BMP4, which actually activated the p38MAPK pathway. Individual responses varied from one mutation to another. PASMCs from PAH patients presented with an in vitro proliferative pattern, which could be inhibited by BMP4 in idiopathic PAH, not in heritable PAH. PASMCs from idiopathic PAH and more so from heritable presented an inhibition of BMP4-induced apoptosis. Most heterogenous BMPR-2 mutations are associated with defective Smad signaling compensed for by an activation of p38MAPK signaling, accounting for PASMC proliferation and deficient apoptosis. PMID:19324947

  5. Simvastatin enhances bone morphogenetic protein receptor type II expression

    International Nuclear Information System (INIS)

    Statins confer therapeutic benefits in systemic and pulmonary vascular diseases. Bone morphogenetic protein (BMP) receptors serve essential signaling functions in cardiovascular development and skeletal morphogenesis. Mutations in BMP receptor type II (BMPR2) are associated with human familial and idiopathic pulmonary arterial hypertension, and pathologic neointimal proliferation of vascular endothelial and smooth muscle cells within small pulmonary arteries. In severe experimental pulmonary hypertension, simvastatin reversed disease and conferred a 100% survival advantage. Here, modulation of BMPR2 gene expression by simvastatin is characterized in human embryonic kidney (HEK) 293T, pulmonary artery smooth muscle, and lung microvascular endothelial cells (HLMVECs). A 1.4 kb BMPR2 promoter containing Egr-1 binding sites confers reporter gene activation in 293T cells which is partially inhibited by simvastatin. Simvastatin enhances steady-state BMPR2 mRNA and protein expression in HLMVEC, through posttranscriptional mRNA stabilization. Simvastatin induction of BMPR2 expression may improve BMP-BMPR2 signaling thereby enhancing endothelial differentiation and function

  6. Delivery of bone morphogenetic protein-2 and substance P using graphene oxide for bone regeneration

    Directory of Open Access Journals (Sweden)

    La WG

    2014-05-01

    Full Text Available Wan-Geun La,1 Min Jin,1 Saibom Park,1,2 Hee-Hun Yoon,1 Gun-Jae Jeong,1 Suk Ho Bhang,1 Hoyoung Park,1,2 Kookheon Char,1,2 Byung-Soo Kim1,31School of Chemical and Biological Engineering, Seoul National University, Seoul, Republic of Korea; 2The National Creative Research Initiative Center for Intelligent Hybrids, Seoul National University, Seoul, Republic of Korea; 3Institute of Bioengineering, Institute of Chemical Processes, Engineering Research Institute, Seoul National University, Seoul, Republic of KoreaAbstract: In this study, we demonstrate that graphene oxide (GO can be used for the delivery of bone morphogenetic protein-2 (BMP-2 and substance P (SP, and that this delivery promotes bone formation on titanium (Ti implants that are coated with GO. GO coating on Ti substrate enabled a sustained release of BMP-2. BMP-2 delivery using GO-coated Ti exhibited a higher alkaline phosphatase activity in bone-forming cells in vitro compared with bare Ti. SP, which is known to recruit mesenchymal stem cells (MSCs, was co-delivered using Ti or GO-coated Ti to further promote bone formation. SP induced the migration of MSCs in vitro. The dual delivery of BMP-2 and SP using GO-coated Ti showed the greatest new bone formation on Ti implanted in the mouse calvaria compared with other groups. This approach may be useful to improve osteointegration of Ti in dental or orthopedic implants.Keywords: bone morphogenetic protein-2, bone regeneration, graphene oxides, stem cell recruitment, substance P

  7. A novel, truncated human bone morphogenetic protein-2:construction, expression ,functions and clinical potential

    Institute of Scientific and Technical Information of China (English)

    XU Fang

    2001-01-01

    @@ Introduction As a member of the bone morphogenetic protein (BMP) family, BMP-2 plays important roles not only in bone regeneration and bone repair but also in cell proliferation, apoptosis, differentiation and morphogenesis. The BMP-2 remarkable ability to stimulate new bone growth results in the development of a novel therapy strategy for bone mass defect due to accidents or diseases. Because the BMP-2 itself, in conjunction with a suitable matrix, is sufficient to stimulate genesis of new bone, the genetically engineered BMP-2 has good applied prospects.

  8. Salicylic Acid-Based Polymers for Guided Bone Regeneration Using Bone Morphogenetic Protein-2.

    Science.gov (United States)

    Subramanian, Sangeeta; Mitchell, Ashley; Yu, Weiling; Snyder, Sabrina; Uhrich, Kathryn; O'Connor, J Patrick

    2015-07-01

    Bone morphogenetic protein-2 (BMP-2) is used clinically to promote spinal fusion, treat complex tibia fractures, and to promote bone formation in craniomaxillofacial surgery. Excessive bone formation at sites where BMP-2 has been applied is an established complication and one that could be corrected by guided tissue regeneration methods. In this study, anti-inflammatory polymers containing salicylic acid [salicylic acid-based poly(anhydride-ester), SAPAE] were electrospun with polycaprolactone (PCL) to create thin flexible matrices for use as guided bone regeneration membranes. SAPAE polymers hydrolyze to release salicylic acid, which is a nonsteroidal anti-inflammatory drug. PCL was used to enhance the mechanical integrity of the matrices. Two different SAPAE-containing membranes were produced and compared: fast-degrading (FD-SAPAE) and slow-degrading (SD-SAPAE) membranes that release salicylic acid at a faster and slower rate, respectively. Rat femur defects were treated with BMP-2 and wrapped with FD-SAPAE, SD-SAPAE, or PCL membrane or were left unwrapped. The effects of different membranes on bone formation within and outside of the femur defects were measured by histomorphometry and microcomputed tomography. Bone formation within the defect was not affected by membrane wrapping at BMP-2 doses of 12 μg or more. In contrast, the FD-SAPAE membrane significantly reduced bone formation outside the defect compared with all other treatments. The rapid release of salicylic acid from the FD-SAPAE membrane suggests that localized salicylic acid treatment during the first few days of BMP-2 treatment can limit ectopic bone formation. The data support development of SAPAE polymer membranes for guided bone regeneration applications as well as barriers to excessive bone formation.

  9. 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

  10. Comparative experiment of four different materials as carriers of Bone morphogenetic protein to repair long bone defect

    Institute of Scientific and Technical Information of China (English)

    WEI Kuan-hai; PEI Guo-xian; YANG Run-gong

    2001-01-01

    @@ OBJECTIVE To investigate the effects of four different materials as carriers of bone morphogenetic protein (BMP) to repair long bone defect. METHODS 12 mm radius bone defects were made. They were divided into 4 groups in random and repaired respectively with the vascular muscle flap combined with FS/BMP (group A), vascular muscle flap/BMP (group B), bloodless muscle flap/BMP (group C) and autolyzed antigen-extracted allogeneic bone (AAA)/BMP (group D).Their abilities of bone forming to repair bone defects were observed.

  11. Successful treatment of a humeral capitulum osteonecrosis with bone morphogenetic protein-7 combined with autologous bone grafting

    OpenAIRE

    Marsell, Richard; Hailer, Nils P

    2014-01-01

    We present the case of a 27-year-old female with subcortical osteonecrosis of the humeral capitulum. Percutaneous retrograde drilling of the lesion and application of recombinant human bone morphogenetic protein (BMP)-7 were combined with autologous bone grafting. At follow-up the patient was almost pain-free, had normalized her range of motion, and radiography showed consolidation of the lesion without any heterotopic bone formation. By timing surgery prior to subchondral collapse, biomechan...

  12. The bone morphogenetic protein pathway is active in human colon adenomas and inactivated in colorectal cancer

    NARCIS (Netherlands)

    Kodach, Liudmila L.; Bleurning, Sylvia A.; Musler, Alex R.; Peppelenbosch, Maikel R.; Hommes, Daniel W.; van den Brink, Gijs R.; van Noesel, Carel J. M.; Offerhaus, G. Johan A.; Hardwick, James C. H.

    2008-01-01

    BACKGROUND. Transforming growth factor beta (TGF beta) is important in colorectal cancer (CRQ progression. Bone morphogenetic proteins (BMPs), a subgroup within the TGF beta superfamily, recently also have been implicated in CRC, but their precise role in CRC has yet to be investigated. METHODS. The

  13. Bone morphogenetic protein signaling suppresses tumorigenesis at gastric epithelial transition zones in mice

    NARCIS (Netherlands)

    Bleuming, Sylvia A.; He, Xi C.; Kodach, Liudmila L.; Hardwick, James C.; Koopman, Frieda A.; ten Kate, Fiebo J.; van Deventer, Sander J. H.; Hommes, Daniel W.; Peppelenbosch, Maikel P.; Offerhaus, G. Johan; Li, Linheng; van den Brink, Gijs R.

    2007-01-01

    Bone morphogenetic protein (BMP) signaling is known to suppress oncogenesis in the small and large intestine of mice and humans. We examined the role of Bmpr1a signaling in the stomach. On conditional inactivation of Bmpr1a, mice developed neoplastic lesions specifically in the squamocolumnar and ga

  14. Estrogens increase expression of bone morphogenetic protein 8b in brown adipose tissue of mice

    NARCIS (Netherlands)

    A. Grefhorst (Aldo); J.C. van den Beukel (Johanna); A.F. van Houten (A.); J. Steenbergen (Jacobie); J.A. Visser (Jenny); A.P.N. Themmen (Axel)

    2015-01-01

    textabstractBackground: In mammals, white adipose tissue (WAT) stores fat and brown adipose tissue (BAT) dissipates fat to produce heat. Several studies showed that females have more active BAT. Members of the bone morphogenetic protein (BMP) and fibroblast growth factor (FGF) families are expressed

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

    NARCIS (Netherlands)

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

    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 we

  16. Bone graft substitutes and bone morphogenetic proteins for osteoporotic fractures: what is the evidence?

    Science.gov (United States)

    Van Lieshout, Esther M M; Alt, Volker

    2016-01-01

    Despite improvements in implants and surgical techniques, osteoporotic fractures remain challenging to treat. Among other major risk factors, decreased expression of morphogenetic proteins has been identified for impaired fracture healing in osteoporosis. Bone grafts or bone graft substitutes are often used for stabilizing the implant and for providing a scaffold for ingrowth of new bone. Both synthetic and naturally occurring biomaterials are available. Products generally contain hydroxyapatite, tricalcium phosphate, dicalcium phosphate, calcium phosphate cement, calcium sulfate (plaster of Paris), or combinations of the above. Products have been used for the treatment of osteoporotic fractures of the proximal humerus, distal radius, vertebra, hip, and tibia plateau. Although there is generally consensus that screw augmentation increased the biomechanical properties and implant stability, the results of using these products for void filling are not unequivocal. In osteoporotic patients, Bone Morphogenetic Proteins (BMPs) have the potential impact to improve fracture healing by augmenting the impaired molecular and cellular mechanisms. However, the clinical evidence on the use of BMPs in patients with osteoporotic fractures is poor as there are no published clinical trials, case series or case studies. Even pre-clinical literature on in vitro and in vivo data is weak as most articles focus on the beneficial role for BMPs for restoration of the underlying pathophysiological factors of osteoporosis but do not look at the specific effects on osteoporotic fracture healing. Limited data on animal experiments suggest stimulation of fracture healing in ovariectomized rats by the use of BMPs. In conclusion, there is only limited data on the clinical relevance and optimal indications for the use of bone graft substitute materials and BMPs on the treatment of osteoporotic fractures despite the clinical benefits of these materials in other clinical indications. Given the

  17. Calcium Phosphate Scaffolds Combined with Bone Morphogenetic Proteins or Mesenchymal Stem Cells in Bone Tissue Engineering

    Directory of Open Access Journals (Sweden)

    Han Sun

    2015-01-01

    Full Text Available Objective: The purpose of this study was to review the current status of calcium phosphate (CaP scaffolds combined with bone morphogenetic proteins (BMPs or mesenchymal stem cells (MSCs in the field of bone tissue engineering (BTE. Date Sources: Data cited in this review were obtained primarily from PubMed and Medline in publications from 1979 to 2014, with highly regarded older publications also included. The terms BTE, CaP, BMPs, and MSC were used for the literature search. Study Selection: Reviews focused on relevant aspects and original articles reporting in vitro and/or in vivo results concerning the efficiency of CaP/BMPs or CaP/MSCs composites were retrieved, reviewed, analyzed, and summarized. Results: An ideal BTE product contains three elements: Scaffold, growth factors, and stem cells. CaP-based scaffolds are popular because of their outstanding biocompatibility, bioactivity, and osteoconductivity. However, they lack stiffness and osteoinductivity. To solve this problem, composite scaffolds of CaP with BMPs have been developed. New bone formation by CaP/BMP composites can reach levels similar to those of autografts. CaP scaffolds are compatible with MSCs and CaP/MSC composites exhibit excellent osteogenesis and stiffness. In addition, a CaP/MSC/BMP scaffold can repair bone defects more effectively than an autograft. Conclusions: Novel BTE products possess remarkable osteoconduction and osteoinduction capacities, and exhibit balanced degradation with osteogenesis. Further work should yield safe, viable, and efficient materials for the repair of bone lesions.

  18. Calcium Phosphate Scaffolds Combined with Bone Morphogenetic Proteins or Mesenchymal Stem Cells in Bone Tissue Engineering

    Institute of Scientific and Technical Information of China (English)

    Han Sun; Hui-Lin Yang

    2015-01-01

    Objective:The purpose of this study was to review the current status of calcium phosphate (CaP) scaffolds combined with bone morphogenetic proteins (BMPs) or mesenchymal stem cells (MSCs) in the field of bone tissue engineering (BTE).Date Sources:Data cited in this review were obtained primarily from PubMed and Medline in publications from 1979 to 2014,with highly regarded older publications also included.The terms BTE,CaP,BMPs,and MSC were used for the literature search.Study Selection:Reviews focused on relevant aspects and original articles reporting in vitro and/or in vivo results concerning the efficiency of CaP/BMPs or CaP/MSCs composites were retrieved,reviewed,analyzed,and summarized.Results:An ideal BTE product contains three elements:Scaffold,growth factors,and stem cells.CaP-based scaffolds are popular because of their outstanding biocompatibility,bioactivity,and osteoconductivity.However,they lack stiffness and osteoinductivity.To solve this problem,composite scaffolds of CaP with BMPs have been developed.New bone formation by CaP/BMP composites can reach levels similar to those of autografts.CaP scaffolds are compatible with MSCs and CaP/MSC composites exhibit excellent osteogenesis and stiffness.In addition,a CaP/MSC/BMP scaffold can repair bone defects more effectively than an autograft.Conclusions:Novel BTE products possess remarkable osteoconduction and osteoinduction capacities,and exhibit balanced degradation with osteogenesis.Further work should yield safe,viable,and efficient materials for the repair of bone lesions.

  19. 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...

  20. Binding of integrin α1 to bone morphogenetic protein receptor IA suggests a novel role of integrin α1β1 in bone morphogenetic protein 2 signalling.

    Science.gov (United States)

    Zu, Yan; Liang, Xudong; Du, Jing; Zhou, Shuai; Yang, Chun

    2015-11-01

    Here, we observed that integrin α1β1 and bone morphogenetic protein receptor (BMPR) IA formed a complex and co-localised in several cell types. However, the molecular interaction between these two molecules was not studied in detail to date and the role of the interaction in BMPR signalling remains unknown; thus, these were investigated here. In a steered molecular dynamics (SMD) simulation, the observed development of the rupture force related to the displacement between the A-domain of integrin α1 and the extracellular domain of BMPR IA indicated a strong molecular interaction within the integrin-BMPR complex. Analysis of the intermolecular forces revealed that hydrogen bonds, rather than salt bridges, are the major contributors to these intermolecular interactions. By using Enzyme-linked immunosorbent assay (ELISA) and co-immunoprecipitation (co-IP) experiments with site-directed mutants, we found that residues 85-89 in BMPR IA play the most important role for BMPR IA binding to integrin α1β1. These residues are the same as those responsible for bone morphogenetic protein 2 (BMP-2)/BMPR IA binding. In our experiments, we also found that the interference of integrin α1β1 up regulated the level of phosphorylated Smad1, 5, 8, which is the downstream of BMP/BMPR signalling. Therefore, our results suggest that integrin α1β1/BMPR IA may block BMP-2/BMPR IA complex information and interfere with the BMP-2 signalling pathway in cells.

  1. Epidemiologic trends in the utilization, demographics, and cost of bone morphogenetic protein in spinal fusions

    OpenAIRE

    Louie, Philip K.; Hassanzadeh, Hamid; Singh, Kern

    2014-01-01

    Bone morphogenetic protein (BMP) utilization as an adjunct for spinal arthrodesis has gained considerable momentum among spine surgeons. Despite carrying Food and Drug Administration approval for only single level anterior lumbar interbody fusion from L4-S1, the majority of BMP administration is in “off label” settings. Over the last decade, BMP utilization has increased in all facets of spine surgery with the only exception being the anterior cervical spine, in which a downward trend resulte...

  2. Estrogens increase expression of bone morphogenetic protein 8b in brown adipose tissue of mice

    OpenAIRE

    Grefhorst, Aldo; van den Beukel, Johanna C; van Houten, E Leonie AF; Steenbergen, Jacobie; Visser, Jenny A.; Themmen, Axel PN

    2015-01-01

    Background In mammals, white adipose tissue (WAT) stores fat and brown adipose tissue (BAT) dissipates fat to produce heat. Several studies showed that females have more active BAT. Members of the bone morphogenetic protein (BMP) and fibroblast growth factor (FGF) families are expressed in BAT and are involved in BAT activity. We hypothesized that differential expression of BMPs and FGFs might contribute to sex differences in BAT activity. Methods We investigated the expression of BMPs and FG...

  3. A fucoidan from Nemacystus decipiens disrupts angiogenesis through targeting bone morphogenetic protein 4.

    Science.gov (United States)

    Wang, Wucheng; Chen, Huanjun; Zhang, Lei; Qin, Yi; Cong, Qifei; Wang, Peipei; Ding, Kan

    2016-06-25

    A sulfated and acetylated fucoidan, named NDH01, was extracted from seaweed Nemacystus decipiens. NDH01 was composed of mannose, glucuronic acid, fucose, sulfate group and acetyl group in the molar ratio of 3.0: 14.4: 82.6: 34.3: 13.9. The backbone of NDH01 was fucose-free core, composed of α-d-1,2-Manp and β-d-1,4-GlcpA disaccharide repeat unit. The branches were attached at the C3, C4 and C6 of α-d-1,2-Manp. The sidechain was composed of α-l-1,3,4-Fucp, α-l-1,4-Fucp, α-l-1,3-Fucp and α-l-1,4-GlcpA. The sulfate group was linked to C4 of α-l-1,3,4-Fucp, whereas, acetyl group was branched on C2 of α-l-1,2,3-Fucp. NDH01 could disrupt tube formation and inhibit the migration as well as cell growth of human microvascular endothelial cells. Besides, phosphorylation of Smad/1/5/8, Erk and FAK was significantly inhibited by NDH01. Further studies uncovered that NDH01 blocked Smad1/5/8 signaling via interacting with bone morphogenetic protein 4 and downregulating bone morphogenetic protein 4 expression. The results suggested that NDH01 might be an angiogenesis inhibitor through targeting bone morphogenetic protein 4. PMID:27083822

  4. No effect of bone morphogenetic protein-7 (OP-1) on the incorporation of impacted bone grafts in a realistic acetabular model.

    NARCIS (Netherlands)

    Buma, P.; Arts, J.J.C.; Gardeniers, J.W.M.; Verdonschot, N.J.J.; Schreurs, B.W.

    2008-01-01

    Bone morphogenetic proteins (BMPs) accelerate bone repair in experimental and clinical conditions. Impacted Morsellized Cancellous Bone grafts (MCB) are successfully used to reconstruct bone defects after failed hip implants. The main question in this study was if BMP-7 (OP-1) mixed with MCB could a

  5. Demineralized dentin matrix combined with recombinant human bone morphogenetic protein-2 in rabbit calvarial defects

    OpenAIRE

    Um, In-Woong; Hwang, Suk-Hyun; Kim, Young-Kyun; Kim, Moon-Young; Jun, Sang-Ho; Ryu, Jae-Jun; Jang, Hyon-Seok

    2016-01-01

    Objectives The aim of this study was to compare the osteogenic effects of demineralized dentin matrix (DDM) combined with recombinant human bone morphogenetic protein-2 (rhBMP-2) in rabbit calvarial defects with DDM and anorganic bovine bone (ABB) combined with rhBMP-2. Materials and Methods Four round defects with 8-mm diameters were created in each rabbit calvaria. Each defect was treated with one of the following: 1) DDM, 2) ABB/rhBMP-2, or 3) DDM/rhBMP-2. The rhBMP-2 was combined with DDM...

  6. Influence of bone morphogenetic protein type IA receptor conditional knockout in lens on expression of bone morphogenetic protein 4 in lens

    Institute of Scientific and Technical Information of China (English)

    Qi; Zhao; Jiang-Yue; Zhao; Jin-Song; Zhang

    2015-01-01

    AIM: To investigate the influence of bone morphogenetic protein type IA receptor [BMPR-IA(ALK3)] conditional knockout in lens on expression of bone morphogenetic protein 4(BMP4) in lens during the development of the vertebrate eye.METHODS: Cre-positive mice were mated with Crenegative mice to generate 50% Cre-positive(conditional knockout, CKO) 4 embryos, 8 eyes and 50% Cre-negative offspring(wild type, WT) 4 embryos, 8 eyes. The embryos were fixed in 4% paraformaldehyde, embedded in paraffin, and sectioned to a thickness of 4 μm.Removal of paraffin wax and dehydrating for sections,and then the procedure of in situ hybridization was processed, BMP4 MK1784-m(BOSTER) was used, and observed the expression of BMP4 in the lens in experimental group and control group. We selected SPSS11.0 software for statistical analysis, P<0.05 showed that the difference was statistically significant.· RESULTS: Four embryos of each genotype were examined, totally we had 8 embryos, 16 eyes. We got the uniform outcomes in all the embryos. We found ALK3 was required during lens growing, but was not essential for the formation of lens. We observed that the expression of BMP4 in the lens was significantly reduced in all 8 ALK3 CKO lens, BMP4 expression was normal in all the 8 WT lens, P <0.01. This phenomenon became increasingly visible in accordance with embryo development. The most apparent alteration was present at stage E15.5.CONCLUSION: ALK3 is essential for lens growth. The influence of ALK3 on the expression of BMP4 is present during the development of mice lens.

  7. Bone morphogenetic protein in complex cervical spine surgery: A safe biologic adjunct?

    OpenAIRE

    Lebl, Darren R.

    2013-01-01

    The advent of recombinant DNA technology has substantially increased the intra-operative utilization of biologic augmentation in spine surgery over the past several years after the Food and Drug Administration approval of the bone morphogenetic protein (BMP) class of molecules for indications in the lumbar spine. Much less is known about the potential benefits and risks of the “off-label” use of BMP in the cervical spine. The history and relevant literature pertaining to the use of the “off-l...

  8. Bone Morphogenetic Protein 4 Signalling in Neural Stem and Progenitor Cells during Development and after Injury

    Directory of Open Access Journals (Sweden)

    Alistair E. Cole

    2016-01-01

    Full Text Available Substantial progress has been made in identifying the extracellular signalling pathways that regulate neural stem and precursor cell biology in the central nervous system (CNS. The bone morphogenetic proteins (BMPs, in particular BMP4, are key players regulating neuronal and glial cell development from neural precursor cells in the embryonic, postnatal, and injured CNS. Here we review recent studies on BMP4 signalling in the generation of neurons, astrocytes, and oligodendroglial cells in the CNS. We also discuss putative mechanisms that BMP4 may utilise to influence glial cell development following CNS injury and highlight some questions for further research.

  9. Bone Morphogenetic Proteins in Craniofacial Surgery: Current Techniques, Clinical Experiences, and the Future of Personalized Stem Cell Therapy

    Directory of Open Access Journals (Sweden)

    Kristofer E. Chenard

    2012-01-01

    Full Text Available Critical-size osseous defects cannot heal without surgical intervention and can pose a significant challenge to craniofacial reconstruction. Autologous bone grafting is the gold standard for repair but is limited by a donor site morbidity and a potentially inadequate supply of autologous bone. Alternatives to autologous bone grafting include the use of alloplastic and allogenic materials, mesenchymal stem cells, and bone morphogenetic proteins. Bone morphogenetic proteins (BMPs are essential mediators of bone formation involved in the regulation of differentiation of osteoprogenitor cells into osteoblasts. Here we focus on the use of BMPs in experimental models of craniofacial surgery and clinical applications of BMPs in the reconstruction of the cranial vault, palate, and mandible and suggest a model for the use of BMPs in personalized stem cell therapies.

  10. Point-counter-point debate: the association between recombinant human bone morphogenetic protein utilization and complications in spine surgery

    OpenAIRE

    Siemionow, Kris; Sundberg, Eric; Tyrakowski, Marcin; Nandyala, Sreeharsha V.; Singh, Kern

    2014-01-01

    Bone morphogenetic proteins (BMPs) have been utilized in spine surgery for over 10 years as a bone graft substitute. Potential BMP-related adverse effects including retrograde ejaculation and heterotopic neuroforaminal bone formation have been described. Additionally, some studies have suggested an association between BMP and cancer. Inconsistencies exist in the published spine literature with regards to the incidence and association of complications with BMP utilization. In a point-counterpo...

  11. Cross talk between insulin and bone morphogenetic protein signaling systems in brown adipogenesis

    DEFF Research Database (Denmark)

    Zhang, Hongbin; Schulz, Tim J; Espinoza, Daniel O;

    2010-01-01

    Both insulin and bone morphogenetic protein (BMP) signaling systems are important for adipocyte differentiation. Analysis of gene expression in BMP7-treated fibroblasts revealed a coordinated change in insulin signaling components by BMP7. To further investigate the cross talk between insulin and...... BMP7's suppressive effect on pref-1 transcription. Together, these data suggest cross talk between the insulin and BMP signaling systems by which BMP7 can rescue brown adipogenesis in cells with insulin resistance.......Both insulin and bone morphogenetic protein (BMP) signaling systems are important for adipocyte differentiation. Analysis of gene expression in BMP7-treated fibroblasts revealed a coordinated change in insulin signaling components by BMP7. To further investigate the cross talk between insulin and...... BMP signaling systems in brown adipogenesis, we examined the effect of BMP7 in insulin receptor substrate 1 (IRS-1)-deficient brown preadipocytes, which exhibit a severe defect in differentiation. Treatment of these cells with BMP7 for 3 days prior to adipogenic induction restored differentiation and...

  12. Brown fat determination and development from muscle precursor cells by novel action of bone morphogenetic protein 6.

    Directory of Open Access Journals (Sweden)

    Ankur Sharma

    Full Text Available Brown adipose tissue (BAT plays a pivotal role in promoting energy expenditure by the virtue of uncoupling protein-1 (UCP-1 that differentiates BAT from its energy storing white adipose tissue (WAT counterpart. The clinical implication of "classical" BAT (originates from Myf5 positive myoblastic lineage or the "beige" fat (originates through trans-differentiation of WAT activation in improving metabolic parameters is now becoming apparent. However, the inducers and endogenous molecular determinants that govern the lineage commitment and differentiation of classical BAT remain obscure. We report here that in the absence of any forced gene expression, stimulation with bone morphogenetic protein 6 (BMP6 induces brown fat differentiation from skeletal muscle precursor cells of murine and human origins. Through a comprehensive transcriptional profiling approach, we have discovered that two days of BMP6 stimulation in C2C12 myoblast cells is sufficient to induce genes characteristic of brown preadipocytes. This developmental switch is modulated in part by newly identified regulators, Optineurin (Optn and Cyclooxygenase-2 (Cox2. Furthermore, pathway analyses using the Causal Reasoning Engine (CRE identified additional potential causal drivers of this BMP6 induced commitment switch. Subsequent analyses to decipher key pathway that facilitates terminal differentiation of these BMP6 primed cells identified a key role for Insulin Like Growth Factor-1 Receptor (IGF-1R. Collectively these data highlight a therapeutically innovative role for BMP6 by providing a means to enhance the amount of myogenic lineage derived brown fat.

  13. Deletion of the sequence encoding the tail domain of the bone morphogenetic protein type 2 receptor reveals a bone morphogenetic protein 7-specific gain of function.

    Science.gov (United States)

    Leyton, Patricio A; Beppu, Hideyuki; Pappas, Alexandra; Martyn, Trejeeve M; Derwall, Matthias; Baron, David M; Galdos, Rita; Bloch, Donald B; Bloch, Kenneth D

    2013-01-01

    The bone morphogenetic protein (BMP) type II receptor (BMPR2) has a long cytoplasmic tail domain whose function is incompletely elucidated. Mutations in the tail domain of BMPR2 are found in familial cases of pulmonary arterial hypertension. To investigate the role of the tail domain of BMPR2 in BMP signaling, we generated a mouse carrying a Bmpr2 allele encoding a non-sense mediated decay-resistant mutant receptor lacking the tail domain of Bmpr2. We found that homozygous mutant mice died during gastrulation, whereas heterozygous mice grew normally without developing pulmonary arterial hypertension. Using pulmonary artery smooth muscle cells (PaSMC) from heterozygous mice, we determined that the mutant receptor was expressed and retained its ability to transduce BMP signaling. Heterozygous PaSMCs exhibited a BMP7‑specific gain of function, which was transduced via the mutant receptor. Using siRNA knockdown and cells from conditional knockout mice to selectively deplete BMP receptors, we observed that the tail domain of Bmpr2 inhibits Alk2‑mediated BMP7 signaling. These findings suggest that the tail domain of Bmpr2 is essential for normal embryogenesis and inhibits Alk2‑mediated BMP7 signaling in PaSMCs.

  14. Recombinant human bone morphogenetic protein-2 in debridement and impacted bone graft for the treatment of femoral head osteonecrosis.

    Directory of Open Access Journals (Sweden)

    Wei Sun

    Full Text Available The purpose of this study was to compare the clinical outcomes of impacted bone graft with or without recombinant human bone morphogenetic protein-2 (rhBMP-2 for osteonecrosis of the femoral head (ONFH. We examined the effect of bone-grafting through a window at the femoral head-neck junction, known as the "light bulb" approach, for the treatment of ONFH with a combination of artificial bone (Novobone mixed with or without rhBMP-2. A total of 42 patients (72 hips were followed-up from 5 to 7.67 years (average of 6.1 years. The patients with and without BMP were the first group (IBG+rhBMP-2 and the second group (IBG, respectively. The clinical effectiveness was evaluated by Harris hip score (HHS. The radiographic follow-up was evaluated by pre-and postoperative X-ray and CT scan. Excellent, good, and fair functions were obtained in 36, 12, and 7 hips, respectively. The survival rate was 81.8% and 71.8% in the first and second group, respectively. However, the survival rate was 90.3% in ARCO stage IIb, c, and only 34.6% in ARCO stage IIIa (P<0.05. It was concluded that good and excellent mid-term follow-up could be achieved in selected patients with ONFH treated with impacted bone graft operation. The rhBMP-2 might improve the clinical efficacy and quality of bone repair.

  15. Autoradiographic studies of the intensity of morphogenetic processes in the bone skeleton under modeling microgravity

    Science.gov (United States)

    Rodionova, N. V.; Zolotova-Haidamaka, N. V.; Nithevich, T. P.

    electron microscopic investigations. The study has been performed of the dynamics and intensity of the nuclei labeling of the osteoclasts both in the control and experiment. The data obtained show that a continuous support unloading influences the morphogenetic processes in long bones, lowering a bone mass increase and necessitating readaptation during subsequent renewal of support functions.

  16. Changes of the intensity of morphogenetic process in the bone skeleton under lowering of gravitational loading

    Science.gov (United States)

    Vasilievna Rodionova, Natalia; Zolotova-Haidamaka, Nadezhda

    confirmed by our previous electron microscopic investigations. The study has been performed of the dynamics and intensity of the nuclei labeling of the osteoclasts both in the control and experiment. Our findings obtained show that a continuous support unloading influences the morphogenetic processes in long bones, lowering a bone mass increase and necessitating readaptation during subsequent renewal of support functions.

  17. 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

  18. 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.

  19. A new biocompatible delivery scaffold containing heparin and bone morphogenetic protein 2.

    Science.gov (United States)

    Thanyaphoo, Suphannee; Kaewsrichan, Jasadee

    2016-09-01

    Silicon-substituted calcium phosphate (Si-CaP) was developed in our laboratory as a biomaterial for delivery in bone tissue engineering. It was fabricated as a 3D-construct of scaffolds using chitosan-trisodium polyphosphate (TPP) cross-linked networks. In this study, heparin was covalently bonded to the residual -NH2 groups of chitosan on the scaffold applying carbodiimide chemistry. Bonded heparin was not leached away from scaffold surfaces upon vigorous washing or extended storage. Recombinant human bone morphogenetic protein 2 (rhBMP-2) was bound to conjugated scaffolds by ionic interactions between the negatively charged SO42- clusters of heparin and positively charged amino acids of rhBMP-2. The resulting scaffolds were inspected for bone regenerative capacity by subcutaneous implanting in rats. Histological observation and mineralization assay were performed after 4 weeks of implantation. Results from both in vitro and in vivo experiments suggest the potential of the developed scaffolds for bone tissue engineering applications in the future. PMID:27383886

  20. Bone morphogenetic protein Smads signaling in mesenchymal stem cells affected by osteoinductive calcium phosphate ceramics.

    Science.gov (United States)

    Tang, Zhurong; Wang, Zhe; Qing, Fangzhu; Ni, Yilu; Fan, Yujiang; Tan, Yanfei; Zhang, Xingdong

    2015-03-01

    Porous calcium phosphate ceramics (CaP ceramics) could induce ectopic bone formation which was regulated by various signal molecules. In this work, bone marrow mesenchymal stem cells (MSCs) were cultured on the surface of osteoinductive hydroxyapatite (HA) and biphasic calcium phosphate (BCP) ceramics in comparison with control (culture plate) for up to 14 days to detect the signal molecules which might be affected by the CaP ceramics. Without adding osteogenic factors, MSCs cultured on HA and BCP both expressed higher Runx2, Osterix, collagen type I, osteopontin, bone sialoprotein, and osteocalcin at various stages compared with control, thus confirmed the osteoblastic differentiation of MSCs. Later study demonstrated the messenger RNA level of bone morphogenetic protein 2 (BMP2) and BMP4 were also significantly enhanced by HA and BCP. Furthermore, Smad1, 4, 5, and Dlx5, the main molecules in the BMP/Smads signaling pathway, were upregulated by HA and BCP. Moreover, the higher expression of Smads and BMP2, 4 in BCP over HA, corresponded to the better performance of BCP in stimulating in vitro osteoblastic differentiation of MSCs. This was in accordance with the better osteoinductivity of BCP over HA in vivo. Altogether, these results implied that the CaP ceramics may initiate the osteoblastic differentiation of MSCs by influencing the expression of molecules in BMP/Smads pathway.

  1. A new biocompatible delivery scaffold containing heparin and bone morphogenetic protein 2

    Directory of Open Access Journals (Sweden)

    Thanyaphoo Suphannee

    2016-09-01

    Full Text Available Silicon-substituted calcium phosphate (Si-CaP was developed in our laboratory as a biomaterial for delivery in bone tissue engineering. It was fabricated as a 3D-construct of scaffolds using chitosan-trisodium polyphosphate (TPP cross-linked networks. In this study, heparin was covalently bonded to the residual -NH2 groups of chitosan on the scaffold applying carbodiimide chemistry. Bonded heparin was not leached away from scaffold surfaces upon vigorous washing or extended storage. Recombinant human bone morphogenetic protein 2 (rhBMP-2 was bound to conjugated scaffolds by ionic interactions between the negatively charged SO42- clusters of heparin and positively charged amino acids of rhBMP-2. The resulting scaffolds were inspected for bone regenerative capacity by subcutaneous implanting in rats. Histological observation and mineralization assay were performed after 4 weeks of implantation. Results from both in vitro and in vivo experiments suggest the potential of the developed scaffolds for bone tissue engineering applications in the future.

  2. The Use of Bone Morphogenetic Protein in Pediatric Cervical Spine Fusion Surgery: Case Reports and Review of the Literature

    OpenAIRE

    Molinari, Robert W.; Molinari, Christine

    2015-01-01

    Study Design Case report. Objective There is a paucity of literature describing the use of bone graft substitutes to achieve fusion in the pediatric cervical spine. The outcomes and complications involving the off-label use of bone morphogenetic protein (BMP)-2 in the pediatric cervical spine are not clearly defined. The purpose of this article is to report successful fusion without complications in two pediatric patients who had instrumented occipitocervical fusion using low-dose BMP-2. Meth...

  3. The application of bone morphogenetic proteins to periodontal and peri-implant tissue regeneration: A literature review

    OpenAIRE

    Sasikumar, Karuppanan P.; Sugumari Elavarasu; Jayaprakash S Gadagi

    2012-01-01

    Progress in understanding the role of bone morphogenetic proteins (BMPs) in craniofacial and tooth development and the demonstration of stem cells in periodontal ligament have set the stage for periodontal regenerative therapy and tissue engineering. Furthermore, recent approval by the Food and Drug Administration of recombinant human BMPs for accelerating bone fusion in slow-healing fractures indicates that this protein family may prove useful in designing regenerative treatments in periodon...

  4. Bone Tissue Engineering Using High Permeability Poly-epsilon-caprolactone Scaffolds Conjugated with Bone Morphogenetic Protein-2

    Science.gov (United States)

    Mitsak, Anna Guyer

    Bone is the second most commonly transplanted tissue in the United States. Limitations of current bone defect treatment options include morbidity at the autograft harvest site, mechanical failure, and poorly controlled growth factor delivery. Combining synthetic scaffolds with biologics may address these issues and reduce dependency on autografts. The ideal scaffolding system should promote tissue in-growth and nutrient diffusion, control delivery of biologics and maintain mechanical integrity during bone formation. This dissertation evaluates how scaffold permeability, conjugated bone morphogenetic protein-2 (BMP-2) and differentiation medium affect osteogenesis in vitro and bone growth in vivo.. "High" and "low" permeability polycaprolactone (PCL) scaffolds with regular architectures were manufactured using solid free form fabrication. Bone growth in vivo was evaluated in an ectopic mouse model. High permeability scaffolds promoted better 8 week bone growth, supported tissue penetration into the scaffold core, and demonstrated increased mechanical properties due to newly formed bone. Next, the effects of differentiation medium and conjugated BMP-2 on osteogenesis were compared. Conjugation may improve BMP-2 loading efficiency, help localize bone growth and control release. High permeability scaffolds were conjugated with BMP-2 using the crosslinker, sulfo-SMCC. When adipose-derived and bone marrow stromal cells were seeded onto constructs (with or without BMP-2), BMSC expressed more differentiation markers, and differentiation medium affected differentiation more than BMP-2. In vivo, scaffolds with ADSC pre-differentiated in osteogenic medium (with and without BMP-2) and scaffolds with only BMP-2 grew the most bone. Bone volume did not differ among these groups, but constructs with ADSC had evenly distributed, scaffold-guided bone growth. Analysis of two additional BMP-2 attachment methods (heparin and adsorption) showed highest conjugation efficiency for the

  5. SPECIFIC BINDING OF HUMAN BONE MORPHOGENETIC PROTEIN (2A) WITH MOUSE OSTEOBLASTIC CELLS

    Institute of Scientific and Technical Information of China (English)

    刘新平; 陈苏民; 陈南春; 高磊; 赵忠良

    1996-01-01

    Human bone morphogenetic protein 2A (hBMP2A) cDNA terminal 567 nucleotides were cloned and expressed in a phage display vector pCSM2I. Hulnata BMP2A C-terminal peptide displayed on the surface of the phage can bind specifically to the sttrface of mouse osteoblastie cell (MC3T3) membrane. ELISA assay showed a positive signal of the binding by using antibody against M13 phage gene 8 protein. After labeling with 3HTdR,the counts of the binding groups were 3 to 10 times higher than the control groups. It suggests that the'surface of MC3T3 cells exist the recepzor for hBMP2A.

  6. Water-dispersed bone morphogenetic protein nanospheres prepared by co-precipitation method

    Institute of Scientific and Technical Information of China (English)

    江兵兵; 高长有; 胡玲; 沈家骢

    2004-01-01

    A modified complex coacervation-co-precipitation method was used to prepare bone morphogenetic protein(BMP)-loaded nanospheres. Three natural polymers were used as packing materials to obtain nanoscale delivery device for BMP,in the presence of phosphatidylcholine functioning as stabilizer. Positively charged polysaccharide, N,N-diethylaminoethyl dex-tran (DEAE-dextran) tended to form stable, uniform and smaller size particles carrying BMP. Negatively charged bovine serumalbumin (BSA) induced precipitation of the produced BMP particles due to its weak interaction with BMP molecules, although itproduced nanosized BMP spheres. While collagen, a weakly positively charged protein shaped larger particles due to the stronginteraction among themselves. A mechanism of co-precipitation process was also deduced to depict the formation of stablenanospheres.

  7. Water-dispersed bone morphogenetic protein nanospheres prepared by co-precipitation method

    Institute of Scientific and Technical Information of China (English)

    江兵兵; 高长有; 胡玲; 沈家骢

    2004-01-01

    A modified complex coacervation-co-precipitation method was used to prepare bone morphogenetic protein (BMP)-loaded nanospheres. Three natural polymers were used as packing materials to obtain nanoscale delivery device for BMP,in the presence of phosphatidylcholine functioning as stabilizer. Positively charged polysaccharide, N,N-diethylaminoethyl dex-tran (DEAE-dextran) tended to form stable, uniform and smaller size particles carrying BMP. Negatively charged bovine serum albumin (BSA) induced precipitation of the produced BMP particles due to its weak interaction with BMP molecules, although it produced nanosized BMP spheres. While collagen, a weakly positively charged protein shaped larger particles due to the strong interaction among themselves. A mechanism of co-precipitation process was also deduced to depict the formation of stable nanospheres.

  8. 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.

  9. USP15 targets ALK3/BMPR1A for deubiquitylation to enhance bone morphogenetic protein signalling.

    Science.gov (United States)

    Herhaus, Lina; Al-Salihi, Mazin A; Dingwell, Kevin S; Cummins, Timothy D; Wasmus, Lize; Vogt, Janis; Ewan, Richard; Bruce, David; Macartney, Thomas; Weidlich, Simone; Smith, James C; Sapkota, Gopal P

    2014-05-01

    Protein kinase ALK3/BMPR1A mediates bone morphogenetic protein (BMP) signalling through phosphorylation and activation of SMADs 1/5/8. SMAD6, a transcriptional target of BMP, negatively regulates the BMP pathway by recruiting E3 ubiquitin ligases and targeting ALK3 for ubiquitin-mediated degradation. Here, we identify a deubiquitylating enzyme USP15 as an interactor of SMAD6 and ALK3. We show that USP15 enhances BMP-induced phosphorylation of SMAD1 by interacting with and deubiquitylating ALK3. RNAi-mediated depletion of USP15 increases ALK3 K48-linked polyubiquitylation, and reduces both BMP-induced SMAD1 phosphorylation and transcription of BMP target genes. We also show that loss of USP15 expression from mouse myoblast cells inhibits BMP-induced osteoblast differentiation. Furthermore, USP15 modulates BMP-induced phosphorylation of SMAD1 and transcription during Xenopus embryogenesis. PMID:24850914

  10. 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...

  11. Recombinant Human Bone Morphogenetic Protein-2 in Development and Progression of Oral Squamous Cell Carcinoma.

    Science.gov (United States)

    Zaid, Khaled Waleed; Chantiri, Mansour; Bassit, Ghassan

    2016-01-01

    Bone morphogenetic proteins (BMPs), belonging to the transforming growth factor-β superfamily, regulate many cellular activities including cell migration, differentiation, adhesion, proliferation and apoptosis. Use of recombinant human bone morphogenic protein?2 (rhBMP?2) in oral and maxillofacial surgery has seen a tremendous increase. Due to its role in many cellular pathways, the influence of this protein on carcinogenesis in different organs has been intensively studied over the past decade. BMPs also have been detected to have a role in the development and progression of many tumors, particularly disease-specific bone metastasis. In oral squamous cell carcinoma - the tumor type accounting for more than 90% of head and neck malignancies- aberrations of both BMP expression and associated signaling pathways have a certain relation with the development and progression of the disease by regulating a range of biological functions in the altered cells. In the current review, we discuss the influence of BMPs -especially rhBMP-2- in the development and progression of oral squamous cell carcinoma. PMID:27039814

  12. Effects of Osseointegration by Bone Morphogenetic Protein-2 on Titanium Implants In Vitro and In Vivo.

    Science.gov (United States)

    Teng, Fu-Yuan; Chen, Wen-Cheng; Wang, Yin-Lai; Hung, Chun-Cheng; Tseng, Chun-Chieh

    2016-01-01

    This study designed a biomimetic implant for reducing healing time and achieving early osseointegration to create an active surface. Bone morphogenetic protein-2 (BMP-2) is a strong regulator protein in osteogenic pathways. Due to hardly maintaining BMP-2 biological function and specificity, BMP-2 efficient delivery on implant surfaces is the main challenge for the clinic application. In this study, a novel method for synthesizing functionalized silane film for superior modification with BMP-2 on titanium surfaces is proposed. Three groups were compared with and without BMP-2 on modified titanium surfaces in vitro and in vivo: mechanical grinding; electrochemical modification through potentiostatic anodization (ECH); and sandblasting, alkali heating, and etching (SMART). Cell tests indicated that the ECH and SMART groups with BMP-2 markedly promoted D1 cell activity and differentiation compared with the groups without BMP-2. Moreover, the SMART group with a BMP-2 surface markedly promoted early alkaline phosphatase expression in the D1 cells compared with the other surface groups. Compared with these groups in vivo, SMART silaning with BMP-2 showed superior bone quality and created contact areas between implant and surrounding bones. The SMART group with BMP-2 could promote cell mineralization in vitro and osseointegration in vivo, indicating potential clinical use. PMID:26977141

  13. Effects of Osseointegration by Bone Morphogenetic Protein-2 on Titanium Implants In Vitro and In Vivo

    Directory of Open Access Journals (Sweden)

    Fu-Yuan Teng

    2016-01-01

    Full Text Available This study designed a biomimetic implant for reducing healing time and achieving early osseointegration to create an active surface. Bone morphogenetic protein-2 (BMP-2 is a strong regulator protein in osteogenic pathways. Due to hardly maintaining BMP-2 biological function and specificity, BMP-2 efficient delivery on implant surfaces is the main challenge for the clinic application. In this study, a novel method for synthesizing functionalized silane film for superior modification with BMP-2 on titanium surfaces is proposed. Three groups were compared with and without BMP-2 on modified titanium surfaces in vitro and in vivo: mechanical grinding; electrochemical modification through potentiostatic anodization (ECH; and sandblasting, alkali heating, and etching (SMART. Cell tests indicated that the ECH and SMART groups with BMP-2 markedly promoted D1 cell activity and differentiation compared with the groups without BMP-2. Moreover, the SMART group with a BMP-2 surface markedly promoted early alkaline phosphatase expression in the D1 cells compared with the other surface groups. Compared with these groups in vivo, SMART silaning with BMP-2 showed superior bone quality and created contact areas between implant and surrounding bones. The SMART group with BMP-2 could promote cell mineralization in vitro and osseointegration in vivo, indicating potential clinical use.

  14. Recombinant human bone morphogenetic protein-2 suspended in fibrin glue enhances bone formation during distraction osteogenesis in rabbits

    Science.gov (United States)

    Li, Yunfeng; Li, Rui; Hu, Jing; Song, Donghui; Jiang, Xiaowen

    2016-01-01

    Introduction Bone morphogenetic protein-2 (BMP-2) has high potential for bone formation, but its in vivo effects are unpredictable due to the short life time. This study was designed to evaluate the effects of recombinant human (rh) BMP-2 suspended in fibrin on bone formation during distraction osteogenesis (DO) in rabbits. Material and methods The in vitro release kinetics of rhBMP-2 suspended in fibrin was tested using an enzyme-linked immunosorbent assay. Unilateral tibial lengthening for 10 mm was achieved in 48 rabbits. At the completion of osteodistraction, vehicle, fibrin, rhBMP-2 or rhBMP-2 suspended in fibrin (rhBMP-2 + fibrin) was injected into the center of the lengthened gap, with 12 animals in each group. Eight weeks later, the distracted callus was examined by histology, micro-CT and biomechanical testing. Radiographs of the distracted tibiae were taken at both 4 and 8 weeks after drug treatment. Results It was found that fibrin prolonged the life span of rhBMP-2 in vitro with sustained release during 17 days. The rhBMP-2 + fibrin treated animals showed the best results in bone mineral density, bone volume fraction, cortical bone thickness by micro-CT evaluation and mechanical properties by the three-point bending test when compared to the other groups (p < 0.05). In histological images, rhBMP-2 + fibrin treatment showed increased callus formation and better gap bridging compared to the other groups. Conclusions The results of this study suggest that fibrin holds promise to be a good carrier of rhBMP-2, and rhBMP-2 suspended in fibrin showed a stronger promoting effect on bone formation during DO in rabbits. PMID:27279839

  15. Osteoinductivity assay of the variability of repeated extractions of bone morphogenetic proteins from bovine bone at different times

    Institute of Scientific and Technical Information of China (English)

    HU Zhen-ming 胡侦明; Sean AF Peel; Cameron ML Clokie

    2004-01-01

    Objective:To observe the activity of repeated extracts of bone matrix and the production of purified bone morphogenetic proteins (BMPs).Methods: BMPs were extracted 1- 4 times from fresh bovine cortical bone by the modified Urist's method, with each collected precipitate separated and lyophilized as partially purified BMPs. Another fresh bovine bone was extracted three times and the precipitates were mixed and lyophilized. Meanwhile, the alkaline phosphatase (ALP)activity was measured by an in vitro assay employing cultured C2C12 mouse myoblast cells through the osteoinductivity of bovine BMPs extracted four times at days 1, 4, 7, and 14, and the correlation between BMPs quantities and costing during extraction processes was analyzed.Results:The purified and the cost showed a positive correlation(r=0.969).To separate and lyophilize each collected precipitate as partially purified BMPs raised the cost,and mixed precipitates also cost much.ALPactivities of 1st and mixed extractions of BMPs were shown to be highly osteoinductive and keep a significantly high level(P<0.05-0.01)4 days after culturing compared with the 2nd,3rd and 4th extractions,especially the control group.However,the more times the extraction ws done,the less activity of BMPs was shown and more costing was.The x-ray and histological analysis also showed that the 1st extraction of BMPs induced more ossicles and new bone formation.Conclusions:The results indicated that BMPs enhanced the abilities of osteoinductiviyt in C2C12 culture in vitro.The first extraction of BMPsfrom bone is fitfull,4th extractions are unnecessary for they cost more and waste more time,say nothing of mixed extractions.

  16. Construction of Adeno-associated Virus System for Human Bone Morphogenetic Protein 7 Gene

    Institute of Scientific and Technical Information of China (English)

    Ke SONG; Nianjing RAO; Meiling CHEN; Yingguang CAO

    2008-01-01

    To construct the recombinant adeno-associated virus (rAAV) vector with human bone morphogenetic protein 7 (BMP7) and observe the BMP7 mRNA expression in vitro, BMP7 CDS se- quence was cloned into expression plasmid pAAV-MCS of AAV Helper Free System. The recombi- nant plasmid was identified with enzyme digestion and sequencing. The recombinant plasmid, pAAV-RC, pHelper were co-transfected into AAV-293 cells according to the calcium phosphate-based protocol. The viral stock was collected by 4 rounds of freeze/thaw. After purified and concentrated,the recombinant virus titer was determined by dot-blot assay. HEK293 cells were transfected with the recombinant virus at different MOI, and the expression of BMP7 mRNA was detected by RT-PCR. The results showed rAAV-BMP7 was constructed and packaged successfully. The physical particle titer was 2.5×1011 vector genomes/mL. There was different expression level of BMP7 mRNA after transfecton. These data suggested that recombinant AAV mediated a stable expression of hBMP7 mRNA in 293 cells. The AAV production method may pave the way of an effective strategy for the jaw bone defection around dental implants.

  17. Enhanced in vivo osteogenesis by nanocarrier-fused bone morphogenetic protein-4

    Directory of Open Access Journals (Sweden)

    Shiozaki Y

    2013-04-01

    Full Text Available Yasuyuki Shiozaki,1,2 Takashi Kitajima,4 Tetsuro Mazaki,1,2 Aki Yoshida,1 Masato Tanaka,1 Akihiro Umezawa,5 Mariko Nakamura,6 Yasuhiro Yoshida,3 Yoshihiro Ito,4 Toshifumi Ozaki,1 Akihiro Matsukawa2 1Department of Orthopedic Surgery, Okayama University, Okayama, Okayama, Japan; 2Department of Pathology and Experimental Medicine, Okayama University, Okayama, Okayama, Japan; 3Department of Biomaterials, Graduate School of Medical, Dentistry, and Pharmaceutical Sciences, Okayama University, Okayama, Okayama, Japan; 4Nano Medical Engineering Laboratory, RIKEN, Wako, Saitama, Japan; 5National Research Institute for Child Health and Development, Okura, Tokyo, Japan; 6Department of Health and Welfare Program, Kibi International University Junior College, Takahashi, Okayama, Japan Purpose: Bone defects and nonunions are major clinical skeletal problems. Growth factors are commonly used to promote bone regeneration; however, the clinical impact is limited because the factors do not last long at a given site. The introduction of tissue engineering aimed to deter the diffusion of these factors is a promising therapeutic strategy. The purpose of the present study was to evaluate the in vivo osteogenic capability of an engineered bone morphogenetic protein-4 (BMP4 fusion protein. Methods: BMP4 was fused with a nanosized carrier, collagen-binding domain (CBD, derived from fibronectin. The stability of the CBD-BMP4 fusion protein was examined in vitro and in vivo. Osteogenic effects of CBD-BMP4 were evaluated by computer tomography after intramedullary injection without a collagen–sponge scaffold. Recombinant BMP-4, CBD, or vehicle were used as controls. Expressions of bone-related genes and growth factors were compared among the groups. Osteogenesis induced by CBD-BMP4, BMP4, and CBD was also assessed in a bone-defect model. Results: In vitro, CBD-BMP4 was retained in a collagen gel for at least 7 days while BMP4 alone was released within 3 hours. In vivo

  18. 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...

  19. Bone morphogenetic protein 6 polymorphisms are associated with radiographic progression in ankylosing spondylitis.

    Directory of Open Access Journals (Sweden)

    Young Bin Joo

    Full Text Available Nearly 25 genetic loci associated with susceptibility to ankylosing spondylitis (AS have been identified by several large studies. However, there have been limited studies to identify the genes associated with radiographic severity of the disease. Thus we investigated which genes involved in bone formation pathways might be associated with radiographic severity in AS.A total of 417 Korean AS patients were classified into two groups based on the radiographic severity as defined by the modified Stoke' Ankylosing Spondylitis Spinal Score (mSASSS system. Severe AS was defined by the presence of syndesmophytes and/or fusion in the lumbar or cervical spine (n = 195. Mild AS was defined by the absence of any syndesmophyte or fusion (n = 170. A total of 251 single nucleotide polymorphisms (SNPs within 52 genes related to bone formation were selected and genotyped. Odds ratios (OR and 95% confidence interval (95% CI were analysed by multivariate logistic regression controlling for age at onset of symptoms, sex, disease duration, and smoking status as covariates.We identified new loci of bone morphogenetic protein 6 (BMP6 associated with radiographic severity in patients with AS that passed false discovery rate threshold. Two SNPs in BMP6 were significantly associated with radiologic severity [rs270378 (OR 1.97, p = 6.74 × 10(-4 and rs1235192 [OR 1.92, p = 1.17 × 10(-3] adjusted by covariates.This is the first study to demonstrate that BMP6 is associated with radiographic severity in AS, supporting the role wingless-type like/BMP pathway on radiographic progression in AS.

  20. RETINOIC ACID DOWN-REGULATES BONE MORPHOGENETIC PROTEIN 7 EXPRESSION IN RAT WITH CLEFT PALATE

    Institute of Scientific and Technical Information of China (English)

    Lei Guo; Yu-yan Zhao; Shi-liang Zhang; Kui Liu; Xiao-yu Gao

    2008-01-01

    Objective To evaluate the effects of retinoic acid (RA) on expression of bone morphogenetic protein 7 (BMP-7)in rat fetus with cleft palate, and the effects of RA on proliferation and apoptosis of osteoblasts. Methods All-trans RA (ATRA) was used to induce congenital cleft palate in Wistar rat. BMP-7 mRNA expres-sion in maxillary bone tissue of fetal rats was measured by Northern blotting analysis. Flow cytometry and MTT assay were used to measure the apoptosis and proliferation of ATRA-treated MC-3T3-E1 cells. BMP-7 mRNA and protein ex-pressions in ATRA-treated MC-3T3-E1 cells were detected by RT-PCR and Western blotting analysis.Results ATRA could induce cleft palate of rat fetus. The incidence rate of cleft palate induced by 100 mg/kg AT-RA (45.5%) was significantly higher than 50 mg/kg ATRA (12.5%, P<0.05). BMP-7 mRNA expression de-creased in maxillary bone tissue of rat fetus with cleft palate. MC-3T3-E1 cells proliferation treated with 1 × 10-6 mol/L ATRA decreased by 60%, the cell apoptosis increased by 2 times. BMP-7 mR.NA and protein levels in MC-3T3-E1cells treated with 1 × 10-6 mol/L ATRA decreased by 60% and 80%, respectively, compared with ATRA-untreated ceils (P<0.05).Conclusions BMP-7 may play an important role in embryonic palate development RA may possess the ability to down-regulate cell proliferation through regulation of BMP-7 gene expression.

  1. Potential bone-inducing activity in vitro of recombinant human bone morphogenetic protein-7 from a CHO expression system

    Institute of Scientific and Technical Information of China (English)

    LI Xiao-yan; SHI Wei-wei; WANG Hao; LI Bo-hua; YANG Yang; TAN Min; XUE Jing-ya; GUO Ya-jun

    2005-01-01

    Objective: To express the recombinant human bone morphogenetic protein-7 (rhBMP-7) in Chinese hamster ovary(CHO) cells, and to establish the in vitro biological activity assay of rhBMP-7.Methods: Human BMP-7 cDNA was subcloned into p114 mammalian expression vector and transfected to CHO cells by using the Lipofectamine2000 transfection method. CHO cell supernatants were harvested and analyzed to identify the molecule mass of secreted rhBMP-7 and examine its biological activity in vitro to stimulate the synthesis of alkaline phophatase(ALP), a characteristic of osteoblast phenotypes. Results:rhBMP-7 was produced stably in CHO cells, as a processed mature disulfide-linked homodimer, with an apparent molecular mass of 36 000. Examination of the rhBMP-7 biological activity showed that rhBMP-7 specifically stimulated the production of ALP(4-fold increase at 100 ng of rhBMP-7/ml). Conclusion: The rhBMP-7 from CHO expression system has significant biological activity in induction of osteoblast phenotype, which demonstrates rhBMP-7 has the potential bone regeneration activity.

  2. Recombinant human bone morphogenetic protein-7 expressed from CHO cells possessing the activity of bone-induced in vitro

    Institute of Scientific and Technical Information of China (English)

    LI Xiaoyan; WANG Hao; YANG Yang; TAN Min; XUE Jingya; NI Haidong; GUO Yajun

    2006-01-01

    Objective To express the recombinant human bone morphogenetic protein-7 (rhBMP-7) in Chinese hamster ovary (CHO) cells and to establish the in vitro biological activity assay of rhBMP-7. Methods Human BMP-7 cDNA was subcloned into pcDNA3.1 mammalian expression vector and transfected to CHO cells by using the lipofectin transfection method. BMP-7 expression cell culture supernatants were harvested and purified for target protein. To analyze the bioactivity of the secreted rhBMP-7, a novel in vitro assay was established by measuring its alkaline phosphatase (ALP) stimulating of osteoblast cell line, W-20-17. Results BMP-7 stably expressing cell clone was selected, which secreted mature disulfide-linked homodimer form of hBMP-7 and had an apparent molecular weight of 36kDa. rhBMP-7 with >95% purity was obtained using 3 step chromatography method. Bioactivity assay showed that the purified protein specifically stimulated W-20-17 cell producing ALP, with a 4-fold increase of ALP activity at 100ng/ml or more, and the EC50 of 15.6ng/ml. Conclusion Purified rhBMP-7 from this CHO expression system has significant biological activity in induction of osteoblast phenotype, which demonstrates potential bone regeneration activity.

  3. Icariine stimulates proliferation and differentiation of human osteoblasts by increasing production of bone morphogenetic protein 2

    Institute of Scientific and Technical Information of China (English)

    YIN Xiao-xue; CHEN Zhong-qiang; LIU Zhong-jun; MA Qing-jun; DANG Geng-ting

    2007-01-01

    Background lcariine is a flavonoid isolated from a traditional Chinese medicine Epimedium pubescens and is the main active compound of it. Recently, Epimedium pubescens was found to have a therapeutic effect on osteoporosis. But the mechanism is unclear. The aim of the study was to research the effect of lcariine on the proliferation and differentiation of human osteoblasts.Methods Human osteoblasts were obtained byinducing human marrow mesenchymal stem cells (hMSCs) directionally and were cultured in the presence of various concentrations of lcariine. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test was used to observe the effect of lcariine on cell proliferation. The activity of alkaline phosphatase (ALP) and the amount of calcified nodules were assayed to observe the effect on cell differentiation.The expression of bone morphogenetic protein 2 (BMP-2) mRNA was detected by reverse transcriptase-polymerase chain reaction (RT-PCR).Results Icariine (20 μg/ml) increased significantly the proliferation of human osteoblasts. And, lcariine (10 μg/ml and 20μg/ml) increased the activity of ALP and the amount of calcified nodules of human osteoblasts significantly (P<0.05).BMP-2 mRNA synthesis was elevated significantly in response to lcariine (20 μg/ml).Conclusions lcariine has a direct stimulatory effect on the proliferation and differentiation of cultured human osteoblastcells in vitro, which may be mediated by increasing production of BMP-2 in osteoblasts.

  4. Caenorhabditis elegans SMA-10/LRIG is a conserved transmembrane protein that enhances bone morphogenetic protein signaling.

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    Tina L Gumienny

    2010-05-01

    Full Text Available Bone morphogenetic protein (BMP pathways control an array of developmental and homeostatic events, and must themselves be exquisitely controlled. Here, we identify Caenorhabditis elegans SMA-10 as a positive extracellular regulator of BMP-like receptor signaling. SMA-10 acts genetically in a BMP-like (Sma/Mab pathway between the ligand DBL-1 and its receptors SMA-6 and DAF-4. We cloned sma-10 and show that it has fifteen leucine-rich repeats and three immunoglobulin-like domains, hallmarks of an LRIG subfamily of transmembrane proteins. SMA-10 is required in the hypodermis, where the core Sma/Mab signaling components function. We demonstrate functional conservation of LRIGs by rescuing sma-10(lf animals with the Drosophila ortholog lambik, showing that SMA-10 physically binds the DBL-1 receptors SMA-6 and DAF-4 and enhances signaling in vitro. This interaction is evolutionarily conserved, evidenced by LRIG1 binding to vertebrate receptors. We propose a new role for LRIG family members: the positive regulation of BMP signaling by binding both Type I and Type II receptors.

  5. Bone Morphogenetic Proteins stimulate mammary fibroblasts to promote mammary carcinoma cell invasion.

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    Philip Owens

    Full Text Available Bone Morphogenetic Proteins (BMPs are secreted cytokines that are part of the Transforming Growth Factor β (TGFβ superfamily. BMPs have been shown to be highly expressed in human breast cancers, and loss of BMP signaling in mammary carcinomas has been shown to accelerate metastases. Interestingly, other work has indicated that stimulation of dermal fibroblasts with BMP can enhance secretion of pro-tumorigenic factors. Furthermore, treatment of carcinoma-associated fibroblasts (CAFs derived from a mouse prostate carcinoma with BMP4 was shown to stimulate angiogenesis. We sought to determine the effect of BMP treatment on mammary fibroblasts. A large number of secreted pro-inflammatory cytokines and matrix-metallo proteases (MMPs were found to be upregulated in response to BMP4 treatment. Fibroblasts that were stimulated with BMP4 were found to enhance mammary carcinoma cell invasion, and these effects were inhibited by a BMP receptor kinase antagonist. Treatment with BMP in turn elevated pro-tumorigenic secreted factors such as IL-6 and MMP-3. These experiments demonstrate that BMP may stimulate tumor progression within the tumor microenvironment.

  6. Regulation of oligodendrocyte progenitor cell maturation by PPARδ: effects on bone morphogenetic proteins

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    Jill C Richardson

    2010-01-01

    Full Text Available In EAE (experimental autoimmune encephalomyelitis, agonists of PPARs (peroxisome proliferator-activated receptors provide clinical benefit and reduce damage. In contrast with PPARγ, agonists of PPARδ are more effective when given at later stages of EAE and increase myelin gene expression, suggesting effects on OL (oligodendrocyte maturation. In the present study we examined effects of the PPARδ agonist GW0742 on OPCs (OL progenitor cells, and tested whether the effects involve modulation of BMPs (bone morphogenetic proteins. We show that effects of GW0742 are mediated through PPARδ since no amelioration of EAE clinical scores was observed in PPARδ-null mice. In OPCs derived from E13 mice (where E is embryonic day, GW0742, but not the PPARγ agonist pioglitazone, increased the number of myelin-producing OLs. This was due to activation of PPARδ since process formation was reduced in PPARδ-null compared with wild-type OPCs. In both OPCs and enriched astrocyte cultures, GW0742 increased noggin protein expression; however, noggin mRNA was only increased in astrocytes. In contrast, GW0742 reduced BMP2 and BMP4 mRNA levels in OPCs, with lesser effects in astrocytes. These findings demonstrate that PPARδ plays a role in OPC maturation, mediated, in part, by regulation of BMP and BMP antagonists.

  7. Inhibitory Effect of Bone Morphogenetic Protein 4 in Retinal Pigment Epithelial-Mesenchymal Transition

    Science.gov (United States)

    Yao, Haipei; Li, Hui; Yang, Shuai; Li, Min; Zhao, Chun; Zhang, Jingfa; Xu, Guotong; Wang, Fang

    2016-09-01

    Proliferative vitreoretinopathy (PVR), a serious vision-threatening complication of retinal detachment (RD), is characterized by the formation of contractile fibrotic membranes, in which epithelial-mesenchymal transition (EMT) of the retinal pigment epithelium (RPE) is a major event. Recent studies suggest an important role of bone morphogenetic protein 4 (BMP4) in the suppression of fibrosis. In this study, we aimed to investigate the role of BMP4 in the pathological process of PVR, particularly in the EMT of RPE cells. We found that BMP4 and its receptors were co-labelled with cytokeratin and α-SMA positive cells within the PVR membrane. Moreover, the mRNA and protein expression levels of BMP4 were decreased whereas BMP4 receptors ALK2, ALK3 and ALK6 were increased during TGF-β-induced EMT in primary RPE cells. Exogenous BMP4 inhibited TGF-β-induced epithelial marker down-regulation, as well as mesenchymal marker up-regulation at both the mRNA and protein levels in RPE cells. In addition, BMP4 treatment attenuated the TGF-β-induced gel contraction, cell migration and Smad2/3 phosphorylation. However, knockdown of endogenous BMP4 stimulated changes in EMT markers. Our results confirm the hypothesis that BMP4 might inhibit TGF-β-mediated EMT in RPE cells via the Smad2/3 pathway and suppress contraction. This might represent a potential treatment for PVR.

  8. Imaging bone morphogenetic protein 7 induced cell cycle arrest in experimental gliomas.

    Science.gov (United States)

    Klose, Anke; Waerzeggers, Yannic; Monfared, Parisa; Vukicevic, Slobodan; Kaijzel, Eric L; Winkeler, Alexandra; Wickenhauser, Claudia; Löwik, Clemens W G M; Jacobs, Andreas H

    2011-03-01

    Bone morphogenetic protein 7 (BMP-7) belongs to the superfamily of transforming growth factor β-like cytokines, which can act either as tumor suppressors or as tumor promoters depending on cell type and differentiation. Our investigations focused on analyzing the effects of BMP-7 during glioma cell proliferation in vitro and in vivo. BMP-7 treatment decreased the proliferation of Gli36ΔEGFR-LITG glioma cells up to 50%through a cell cycle arrest in the G(1) phase but not by induction of apoptosis. This effect was mediated by the modulation of the expression and phosphorylation of cyclin-dependent kinase 2, cyclin-dependent kinase inhibitor p21, and downstream retinoblastoma protein. Furthermore, in vivo optical imaging of luciferase activity of Gli36ΔEGFR-LITG cells implanted intracranially into nude mice in the presence or absence of BMP-7 treatment corroborated the antiproliferative effects of this cytokine. This report clearly underlines the tumor-suppressive role of BMP-7 in glioma-derived cells. Taken together, our results indicate that manipulating the BMP/transforming growth factor β signaling cascade may serve as a new strategy for imaging-guided molecular-targeted therapy of malignant gliomas.

  9. Imaging Bone Morphogenetic Protein 7 Induced Cell Cycle Arrest in Experimental Gliomas

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    Anke Klose

    2011-03-01

    Full Text Available Bone morphogenetic protein 7 (BMP-7 belongs to the superfamily of transforming growth factor β-like cytokines, which can act either as tumor suppressors or as tumor promoters depending on cell type and differentiation. Our investigations focused on analyzing the effects of BMP-7 during glioma cell proliferation in vitro and in vivo. BMP-7 treatment decreased the proliferation of Gli36ΔEGFR-LITG glioma cells up to 50%through a cell cycle arrest in the G1 phase but not by induction of apoptosis. This effect was mediated by the modulation of the expression and phosphorylation of cyclin-dependent kinase 2, cyclin-dependent kinase inhibitor p21, and downstream retinoblastoma protein. Furthermore, in vivo optical imaging of luciferase activity of Gli36ΔEGFR-LITG cells implanted intracranially into nude mice in the presence or absence of BMP-7 treatment corroborated the antiproliferative effects of this cytokine. This report clearly underlines the tumor-suppressive role of BMP-7 in glioma-derived cells. Taken together, our results indicate that manipulating the BMP/transforming growth factor β signaling cascade may serve as a new strategy for imaging-guided molecular-targeted therapy of malignant gliomas.

  10. The bone morphogenetic protein axis is a positive regulator of skeletal muscle mass

    Science.gov (United States)

    Chen, Justin L.; Qian, Hongwei; Liu, Yingying; Bernardo, Bianca C.; Beyer, Claudia; Watt, Kevin I.; Thomson, Rachel E.; Connor, Timothy; Turner, Bradley J.; McMullen, Julie R.; Larsson, Lars; McGee, Sean L.; Harrison, Craig A.

    2013-01-01

    Although the canonical transforming growth factor β signaling pathway represses skeletal muscle growth and promotes muscle wasting, a role in muscle for the parallel bone morphogenetic protein (BMP) signaling pathway has not been defined. We report, for the first time, that the BMP pathway is a positive regulator of muscle mass. Increasing the expression of BMP7 or the activity of BMP receptors in muscles induced hypertrophy that was dependent on Smad1/5-mediated activation of mTOR signaling. In agreement, we observed that BMP signaling is augmented in models of muscle growth. Importantly, stimulation of BMP signaling is essential for conservation of muscle mass after disruption of the neuromuscular junction. Inhibiting the phosphorylation of Smad1/5 exacerbated denervation-induced muscle atrophy via an HDAC4-myogenin–dependent process, whereas increased BMP–Smad1/5 activity protected muscles from denervation-induced wasting. Our studies highlight a novel role for the BMP signaling pathway in promoting muscle growth and inhibiting muscle wasting, which may have significant implications for the development of therapeutics for neuromuscular disorders. PMID:24145169

  11. Recombinant Bone Morphogenetic Protein 2 Stimulates the Remodeling Chitosan-Based Porous Scaffold Into Hyaline-like Cartilage: Study in Heterotopic Implantation

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    Nurshat M. Gaifullin

    2013-09-01

    Full Text Available To study the morphology of remodeling the chitosan-based three-dimensional porous scaffold, containing bone morphogenetic protein-2 (BMP-2 for chondroinduction, the experiments with heterotopic implantation using 28 Wistar rats were carried out. Scaffolds with growth factor (n=12 or without it (n=12, against intact control (n=4 were implanted subcutaneously. Classical methods of histology and morphometry as well as immune histochemical markers (CD-68, CD-31, MMP-9, TIMP-1, and osteonectin expression, one used to investigate zone of remodeling in euthanized animals at 4 and 8 weeks after implantation. The BMP-2 application provides more intensive and rapid new cartilage formation from the scaffold matter. The additional chondroinductive effect proved more intensive settlement and proliferation of chondral cells in the regenerate, expression of chondral phenotype with the building the hyaline-like matrix, and the supporting necessary balance between the matrix metalloproteinases and their tissue inhibitors.

  12. Mode of heparin attachment to nanocrystalline hydroxyapatite affects its interaction with bone morphogenetic protein-2.

    Science.gov (United States)

    Goonasekera, Chandhi S; Jack, Kevin S; Bhakta, Gajadhar; Rai, Bina; Luong-Van, Emma; Nurcombe, Victor; Cool, Simon M; Cooper-White, Justin J; Grøndahl, Lisbeth

    2015-12-16

    Heparin has a high affinity for bone morphogenetic protein-2 (BMP-2), which is a key growth factor in bone regeneration. The aim of this study was to investigate how the rate of release of BMP-2 was affected when adsorbed to nanosized hydroxyapatite (HAP) particles functionalized with heparin by different methods. Heparin was attached to the surface of HAP, either via adsorption or covalent coupling, via a 3-aminopropyltriethoxysilane (APTES) layer. The chemical composition of the particles was evaluated using X-ray photoelectron spectroscopy and elemental microanalysis, revealing that the heparin grafting densities achieved were dependent on the curing temperature used in the fabrication of APTES-modified HAP. Comparable amounts of heparin were attached via both covalent coupling and adsorption to the APTES-modified particles, but characterization of the particle surfaces by zeta potential and Brunauer-Emmett-Teller measurements indicated that the conformation of the heparin on the surface was dependent on the method of attachment, which in turn affected the stability of heparin on the surface. The release of BMP-2 from the particles after 7 days in phosphate-buffered saline found that 31% of the loaded BMP-2 was released from the APTES-modified particles with heparin covalently attached, compared to 16% from the APTES-modified particles with the heparin adsorbed. Moreover, when heparin was adsorbed onto pure HAP, it was found that the BMP-2 released after 7 days was 5% (similar to that from unmodified HAP). This illustrates that by altering the mode of attachment of heparin to HAP the release profile and total release of BMP-2 can be manipulated. Importantly, the BMP-2 released from all the heparin particle types was found by the SMAD 1/5/8 phosphorylation assay to be biologically active.

  13. Basic science and spine literature document bone morphogenetic protein increases cancer risk

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    Nancy E Epstein

    2014-01-01

    Full Text Available Background: Increasingly, clinical articles document that bone morphogenetic protein (BMP/INFUSE: Medtronic, Memphis, TN, USA and its derivatives utilized in spinal surgery increase the risk of developing cancer. However, there is also a large body of basic science articles that also document that various types of BMP and other members of the TGF-Beta (transforming growth factor beta family promote the growth of different types of cancers. Methods: This review looks at many clinical articles citing BMP/INFUSE′s role, largely "off-label", in contributing to complications encountered during spinal surgery. Next, however, specific attention is given to the clinical and basic science literature regarding how BMP and its derivatives (e.g. members of the TGF-beta family may also impact the development of breast and other cancers. Results: Utilizing BMP/INFUSE in spine surgery increased the risk of cancers/new malignancy as documented in several studies. For example, Carragee et al. found that for single-level instrumented posterolateral fusions (PLF using high-dose rhBMP-2 (239 patients vs. autograft (control group; n = 224, the risks of new cancers at 2 and 5 years postoperatively were increased. In laboratory studies, BMP′s along with other members of the TGF-Beta family also modulated/contributed to the proliferation/differentiation of breast cancer (e.g. bone formation/turnover, breast cancer-related solid tumors, and metastases, lung, adrenal, and colon cancer. Conclusions: BMP/INFUSE when utilized clinically in spinal fusion surgery appears to promote cancer at higher rates than observed in the overall population. Furthermore, BMP and TGF-beta are correlated with increased cancer growth both in the clinic and the laboratory.

  14. Bone morphogenetic protein-2 gene controls tooth root development in coordination with formation of the periodontium

    Institute of Scientific and Technical Information of China (English)

    Audrey Rakian; Wu-Chen Yang; Jelica Gluhak-Heinrich; Yong Cui; Marie A Harris; Demitri Villarreal; Jerry Q Feng; Mary MacDougall; Stephen E Harris

    2013-01-01

    Formation of the periodontium begins following onset of tooth-root formation in a coordinated manner after birth. Dental follicle progenitor cells are thought to form the cementum, alveolar bone and Sharpey’s fibers of the periodontal ligament (PDL). However, little is known about the regulatory morphogens that control differentiation and function of these progenitor cells, as well as the progenitor cells involved in crown and root formation. We investigated the role of bone morphogenetic protein-2 (Bmp2) in these processes by the conditional removal of the Bmp2 gene using the Sp7-Cre-EGFP mouse model. Sp7-Cre-EGFP first becomes active at E18 in the first molar, with robust Cre activity at postnatal day 0 (P0), followed by Cre activity in the second molar, which occurs after P0. There is robust Cre activity in the periodontium and third molars by 2 weeks of age. When the Bmp2 gene is removed from Sp71 (Osterix1) cells, major defects are noted in root, cellular cementum and periodontium formation. First, there are major cell autonomous defects in root-odontoblast terminal differentiation. Second, there are major alterations in formation of the PDLs and cellular cementum, correlated with decreased nuclear factor IC (Nfic), periostin and a-SMA1 cells. Third, there is a failure to produce vascular endothelial growth factor A (VEGF-A) in the periodontium and the pulp leading to decreased formation of the microvascular and associated candidate stem cells in the Bmp2-cKOSp7-Cre-EGFP. Fourth, ameloblast function and enamel formation are indirectly altered in the Bmp2-cKOSp7-Cre-EGFP. These data demonstrate that the Bmp2 gene has complex roles in postnatal tooth development and periodontium formation.

  15. Bone Marrow Mesenchymal Stem Cells Expressing Baculovirus-Engineered Bone Morphogenetic Protein-7 Enhance Rabbit Posterolateral Fusion.

    Science.gov (United States)

    Liao, Jen-Chung

    2016-01-01

    Previous studies have suggested that bone marrow-derived mesenchymal stem cells (BMDMSCs) genetically modified with baculoviral bone morphogenetic protein-2 (Bac-BMP-2) vectors could achieve successful fusion in a femur defect model or in a spinal fusion model. In this study, BMDMSCs expressing BMP-7 (Bac-BMP-7-BMDMSCs) were generated. We hypothesized that Bac-BMP-7-BMDMSCs could secrete more BMP-7 than untransduced BMDMSCs in vitro and achieve spinal posterolateral fusion in a rabbit model. Eighteen rabbits underwent posterolateral fusion at L4-5. Group I (n = 6) was implanted with collagen-β-tricalcium phosphate (TCP)-hydroxyapatite (HA), Group II (n = 6) was implanted with collagen-β-TCP-HA plus BMDMSCs, and Group III (n = 6) was implanted with collagen-β-TCP-HA plus Bac-BMP-7-BMDMSCs. In vitro production of BMP-7 was quantified with an enzyme-linked immunosorbent assay (ELISA). Spinal fusion was examined using computed tomography (CT), manual palpation, and histological analysis. ELISA demonstrated that Bac-BMP-7-BMDMSCs produced four-fold to five-fold more BMP-7 than did BMDMSCs. In the CT results, 6 fused segments were observed in Group I (50%, 6/12), 8 in Group II (67%, 8/12), and 12 in Group III (100%, 12/12). The fusion rate, determined by manual palpation, was 0% (0/6) in Group I, 0% (0/6) in Group II, and 83% (5/6) in Group III. Histology showed that Group III had more new bone and matured marrow formation. In conclusion, BMDMSCs genetically transduced with the Bac-BMP-7 vector could express more BMP-7 than untransduced BMDMSCs. These Bac-BMP-7-BMDMSCs on collagen-β-TCP-HA scaffolds were able to induce successful spinal fusion in rabbits. PMID:27399674

  16. Bone Marrow Mesenchymal Stem Cells Expressing Baculovirus-Engineered Bone Morphogenetic Protein-7 Enhance Rabbit Posterolateral Fusion

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    Jen-Chung Liao

    2016-07-01

    Full Text Available Previous studies have suggested that bone marrow-derived mesenchymal stem cells (BMDMSCs genetically modified with baculoviral bone morphogenetic protein-2 (Bac-BMP-2 vectors could achieve successful fusion in a femur defect model or in a spinal fusion model. In this study, BMDMSCs expressing BMP-7 (Bac-BMP-7-BMDMSCs were generated. We hypothesized that Bac-BMP-7-BMDMSCs could secrete more BMP-7 than untransduced BMDMSCs in vitro and achieve spinal posterolateral fusion in a rabbit model. Eighteen rabbits underwent posterolateral fusion at L4-5. Group I (n = 6 was implanted with collagen-β-tricalcium phosphate (TCP-hydroxyapatite (HA, Group II (n = 6 was implanted with collagen-β-TCP-HA plus BMDMSCs, and Group III (n = 6 was implanted with collagen-β-TCP-HA plus Bac-BMP-7-BMDMSCs. In vitro production of BMP-7 was quantified with an enzyme-linked immunosorbent assay (ELISA. Spinal fusion was examined using computed tomography (CT, manual palpation, and histological analysis. ELISA demonstrated that Bac-BMP-7-BMDMSCs produced four-fold to five-fold more BMP-7 than did BMDMSCs. In the CT results, 6 fused segments were observed in Group I (50%, 6/12, 8 in Group II (67%, 8/12, and 12 in Group III (100%, 12/12. The fusion rate, determined by manual palpation, was 0% (0/6 in Group I, 0% (0/6 in Group II, and 83% (5/6 in Group III. Histology showed that Group III had more new bone and matured marrow formation. In conclusion, BMDMSCs genetically transduced with the Bac-BMP-7 vector could express more BMP-7 than untransduced BMDMSCs. These Bac-BMP-7-BMDMSCs on collagen-β-TCP-HA scaffolds were able to induce successful spinal fusion in rabbits.

  17. Sustained release of bone morphogenetic protein 2 via coacervate improves the osteogenic potential of muscle-derived stem cells.

    Science.gov (United States)

    Li, Hongshuai; Johnson, Noah Ray; Usas, Arvydas; Lu, Aiping; Poddar, Minakshi; Wang, Yadong; Huard, Johnny

    2013-09-01

    Muscle-derived stem cells (MDSCs) isolated from mouse skeletal muscle by a modified preplate technique exhibit long-term proliferation, high self-renewal, and multipotent differentiation capabilities in vitro. MDSCs retrovirally transduced to express bone morphogenetic proteins (BMPs) can differentiate into osteocytes and chondrocytes and enhance bone and articular cartilage repair in vivo, a feature that is not observed with nontransduced MDSCs. These results emphasize that MDSCs require prolonged exposure to BMPs to undergo osteogenic and chondrogenic differentiation. A sustained BMP protein delivery approach provides a viable and potentially more clinically translatable alternative to genetic manipulation of the cells. A unique growth factor delivery platform comprised of native heparin and a synthetic polycation, poly(ethylene argininylaspartate diglyceride) (PEAD), was used to bind, protect, and sustain the release of bone morphogenetic protein-2 (BMP2) in a temporally and spatially controlled manner. Prolonged exposure to BMP2 released by the PEAD:heparin delivery system promoted the differentiation of MDSCs to an osteogenic lineage in vitro and induced the formation of viable bone at an ectopic site in vivo. This new strategy represents an alternative approach for bone repair mediated by MDSCs while bypassing the need for gene therapy.

  18. Use of bone morphogenetic proteins in mesenchymal stemcell stimulation of cartilage and bone repair

    Institute of Scientific and Technical Information of China (English)

    2016-01-01

    The extracellular matrix-associated bone morphogeneticproteins (BMPs) govern a plethora of biological processes.The BMPs are members of the transforming growthfactor-β protein superfamily, and they actively participateto kidney development, digit and limb formation,angiogenesis, tissue fibrosis and tumor development.Since their discovery, they have attracted attentionfor their fascinating perspectives in the regenerativemedicine and tissue engineering fields. BMPs havebeen employed in many preclinical and clinical studiesexploring their chondrogenic or osteoinductive potentialin several animal model defects and in human diseases.During years of research in particular two BMPs, BMP2and BMP7 have gained the podium for their use inthe treatment of various cartilage and bone defects.In particular they have been recently approved foremployment in non-union fractures as adjunct therapies.On the other hand, thanks to their potentialities inbiomedical applications, there is a growing interest instudying the biology of mesenchymal stem cell (MSC),the rules underneath their differentiation abilities, andto test their true abilities in tissue engineering. In fact,the specific differentiation of MSCs into targeted celltypelineages for transplantation is a primary goal of theregenerative medicine. This review provides an overviewon the current knowledge of BMP roles and signaling inMSC biology and differentiation capacities. In particularthe article focuses on the potential clinical use of BMPsand MSCs concomitantly, in cartilage and bone tissuerepair.

  19. Nanofibrous yet injectable polycaprolactone-collagen bone tissue scaffold with osteoprogenitor cells and controlled release of bone morphogenetic protein-2

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    Subramanian, Gayathri; Bialorucki, Callan [Department of Bioengineering, College of Engineering, University of Toledo, Toledo, OH 43606 (United States); Yildirim-Ayan, Eda, E-mail: eda.yildirimayan@utoledo.edu [Department of Bioengineering, College of Engineering, University of Toledo, Toledo, OH 43606 (United States); Department of Orthopaedic Surgery, University of Toledo Medical Center, Toledo, OH 43614 (United States)

    2015-06-01

    In this work, we developed a nanofibrous, yet injectable orthobiologic tissue scaffold that is capable of hosting osteoprogenitor cells and controlling kinetic release profile of the encapsulated pro-osteogenic factor without diminishing its bioactivity over 21 days. This innovative injectable scaffold was synthesized by incorporating electrospun and subsequently O{sub 2} plasma-functionalized polycaprolactone (PCL) nanofibers within the collagen type-I solution along with MC3T3-E1 cells (pre-osteoblasts) and bone morphogenetic protein-2 (BMP2). Through changing the PCL nanofiber concentration within the injectable scaffolds, we were able to tailor the mechanical strength, protein retention capacity, bioactivity preservation, and osteoinductive potential of the scaffolds. The nanofibrous internal structure of the scaffold allowed us to use a low dose of BMP2 (200 ng/ml) to achieve osteoblastic differentiation in in vitro culture. The osteogenesis capacity of the injectable scaffolds were evaluated though measuring MC3T3-E1 cell proliferation, ALP activity, matrix mineralization, and early- and late-osteoblast specific gene expression profiles over 21 days. The results demonstrated that the nanofibrous injectable scaffold provides not only an osteoinductive environment for osteoprogenitor cells to differentiate, but also a suitable biomechanical and biochemical environment to act as a reservoir for osteogenic factors with controlled release profile. - Highlights: • Injectable nanofibrous scaffold with osteoprogenitor cells and BMP2 was synthesized. • PCL nanofiber concentration within collagen scaffold affected the BMP2 retention and bioactivity. • Optimal PCL concentration was identified for mechanical stability, injectability, and osteogenic activity. • Scaffolds exhibited long-term osteoinductive capacity for bone repair and regeneration.

  20. Repair of radius defect with bone-morphogenetic-protein loaded hydroxyapatite/collagen-poly(L-lactic acid) composite

    Institute of Scientific and Technical Information of China (English)

    胡蕴玉; 张超; 吕荣; 徐建强; 李丹

    2003-01-01

    Objective: To explore the method to repair bone defect with bone-morphogenetic-protein loaded hydroxyapatite/collagen-poly(L-lactic acid) composite. Methods: 18 adult beagle dogs were randomly divided into 3 groups. In Group A, bone-morphogenetic-protein (BMP) loaded hydroxyapatite/collagen-poly(L-lactic acid) (HAC-PLA) scaffold was implanted in a 2 cm diaphyseal defect in the radius. In Group B, unloaded pure HAC-PLA scaffold was implanted in the defects. No material was implanted in Group C (control group). The dogs were sacrificed 6 months postoperatively. Features of biocompatibility, biodegradability and osteoinduction were evaluated with histological, radiological examinations and bone mineral density (BMD) measurements.Results: In Group A, the radius defect healed after the treatment with BMP loaded HAC-PLA. BMD at the site of the defect was higher than that of the contralateral radius. Fibrous union developed in the animals of the control group. Conclusions: BMP not only promotes osteogenesis but also accelerates degradation of the biomaterials. Optimized design parameters of a three-dimensional porous biomaterial would give full scope to the role of BMP as an osteoinductive growth factor.

  1. Bone morphogenetic protein 15 in the pro-mature complex form enhances bovine oocyte developmental competence.

    Directory of Open Access Journals (Sweden)

    Jaqueline Sudiman

    Full Text Available Developmental competence of in vitro matured (IVM oocytes needs to be improved and this can potentially be achieved by adding recombinant bone morphogenetic protein 15 (BMP15 or growth differentiation factor (GDF9 to IVM. The aim of this study was to determine the effect of a purified pro-mature complex form of recombinant human BMP15 versus the commercially available bioactive forms of BMP15 and GDF9 (both isolated mature regions during IVM on bovine embryo development and metabolic activity. Bovine cumulus oocyte complexes (COCs were matured in vitro in control medium or treated with 100 ng/ml pro-mature BMP15, mature BMP15 or mature GDF9 +/- FSH. Metabolic measures of glucose uptake and lactate production from COCs and autofluorescence of NAD(PH, FAD and GSH were measured in oocytes after IVM. Following in vitro fertilisation and embryo culture, day 8 blastocysts were stained for cell numbers. COCs matured in medium +/- FSH containing pro-mature BMP15 displayed significantly improved blastocyst development (57.7±3.9%, 43.5±4.2% compared to controls (43.3±2.4%, 28.9±3.7% and to mature GDF9+FSH (36.1±3.0%. The mature form of BMP15 produced intermediate levels of blastocyst development; not significantly different to control or pro-mature BMP15 levels. Pro-mature BMP15 increased intra-oocyte NAD(PH, and reduced glutathione (GSH levels were increased by both forms of BMP15 in the absence of FSH. Exogenous BMP15 in its pro-mature form during IVM provides a functional source of oocyte-secreted factors to improve bovine blastocyst development. This form of BMP15 may prove useful for improving cattle and human artificial reproductive technologies.

  2. Hypermethylation leads to bone morphogenetic protein 6 downregulation in hepatocellular carcinoma.

    Directory of Open Access Journals (Sweden)

    Yinghua He

    Full Text Available BACKGROUND: In the liver, bone morphogenetic protein 6 (BMP-6 maintains balanced iron metabolism. However, the mechanism that underlies greater BMP-6 expression in hepatocellular carcinoma (HCC tissue than adjacent non-cancerous tissue is unclear. This study sought to investigate the epigenetic mechanisms of BMP-6 expression by analysing the relationship between the DNA methylation status of BMP-6 and the expression of BMP-6. METHODS: Methylation-specific polymerase chain reaction (PCR, bisulphite sequencing PCR, the MethyLight assay, and quantitative real-time PCR were performed to examine BMP-6 methylation and mRNA expression levels. Immunohistochemistry (IHC was performed on tissue arrays to evaluate the BMP-6 protein level. RESULTS: BMP-6 mRNA expression was approximately 84.09% lower in HCC tissues than in adjacent non-cancerous tissues, and this low level of expression was associated with a poor prognosis. Moreover, the hypermethylation observed in HCC cell lines and HCC tissues was correlated with the BMP-6 mRNA expression level, and this correlation was validated following treatment with 5-aza-CdR, a demethylation agent. In addition, BMP-6 DNA methylation was upregulated by 68.42% in 114 clinical HCC tissue samples compared to adjacent normal tissues, whereas the BMP-6 staining intensity was downregulated by 77.03% in 75 clinical HCC tissue samples in comparison to adjacent normal tissues. Furthermore, elevated expression of BMP-6 in HCC cell lines inhibited cell colony formation. CONCLUSIONS: Our results suggest that BMP-6 CpG island hypermethylation leads to decreased BMP-6 expression in HCC tissues.

  3. Identification of bone morphogenetic protein 9 (BMP9) as a novel profibrotic factor in vitro.

    Science.gov (United States)

    Muñoz-Félix, José M; Cuesta, Cristina; Perretta-Tejedor, Nuria; Subileau, Mariela; López-Hernández, Francisco J; López-Novoa, José M; Martínez-Salgado, Carlos

    2016-09-01

    Upregulated synthesis of extracellular matrix (ECM) proteins by myofibroblasts is a common phenomenon in the development of fibrosis. Although the role of TGF-β in fibrosis development has been extensively studied, the involvement of other members of this superfamily of cytokines, the bone morphogenetic proteins (BMPs) in organ fibrosis has given contradictory results. BMP9 is the main ligand for activin receptor-like kinase-1 (ALK1) TGF-β1 type I receptor and its effect on fibrosis development is unknown. Our purpose was to study the effect of BMP9 in ECM protein synthesis in fibroblasts, as well as the involved receptors and signaling pathways. In cultured mice fibroblasts, BMP9 induces an increase in collagen, fibronectin and connective tissue growth factor expression, associated with Smad1/5/8, Smad2/3 and Erk1/2 activation. ALK5 inhibition with SB431542 or ALK1/2/3/6 with dorsomorphin-1, inhibition of Smad3 activation with SIS3, and inhibition of the MAPK/Erk1/2 with U0126, demonstrates the involvement of these pathways in BMP9-induced ECM synthesis in MEFs. Whereas BMP9 induced Smad1/5/8 phosphorylation through ALK1, it also induces Smad2/3 phosphorylation through ALK5 but only in the presence of ALK1. Summarizing, this is the first study that accurately identifies BMP9 as a profibrotic factor in fibroblasts that promotes ECM protein expression through ALK1 and ALK5 receptors. PMID:27208502

  4. Inhibitory Smads and bone morphogenetic protein (BMP) modulate anterior photoreceptor cell number during planarian eye regeneration.

    Science.gov (United States)

    González-Sastre, Alejandro; Molina, Ma Dolores; Saló, Emili

    2012-01-01

    Planarians represent an excellent model to study the processes of body axis and organ re-specification during regeneration. Previous studies have revealed a conserved role for the bone morphogenetic protein (BMP) pathway and its intracellular mediators Smad1/5/8 and Smad4 in planarian dorsoventral (DV) axis re-establishment. In an attempt to gain further insight into the role of this signalling pathway in planarians, we have isolated and functionally characte-rized the inhibitory Smads (I-Smads) in Schmidtea mediterranea. Two I-Smad homologues have been identified: Smed-smad6/7-1 and Smed-smad6/7-2. Expression of smad6/7-1 was detected in the parenchyma, while smad6/7-2 was found to be ex-pressed in the central nervous system and the eyes. Neither single smad6/7-1 and smad6/7-2 nor double smad6/7-1,-2 silencing gave rise to any apparent disruption of the DV axis. However, both regenerating and intact smad6/7-2 (RNAi) planarians showed defects in eye morphogenesis and displayed small, rounded eyes that lacked the anterior subpopulation of photoreceptor cells. The number of pigment cells was also reduced in these animals at later stages of regeneration. In contrast, after low doses of Smed-bmp(RNAi), planarians regenerated larger eyes in which the anterior subpopulation of photoreceptor cells was expanded. Our results suggest that Smed-smad6/7-2 and Smed-bmp control the re-specification and maintenance of anterior photoreceptor cell number in S. mediterranea. PMID:22451003

  5. Bone morphogenetic protein 15 may promote follicle selection in the hen.

    Science.gov (United States)

    Stephens, C S; Johnson, P A

    2016-09-01

    In the hen, optimal ovulation rate depends on selection of a single follicle into the pre-ovulatory hierarchy. Follicle selection is associated with increased oocyte growth and changes in gene expression in granulosa cells surrounding the oocyte, in preparation for ovulation. This study investigated the expression, function and regulation of bone morphogenetic protein-15 (BMP15) during follicle development in the hen. BMP15 mRNA expression was analyzed in the ooplasm and granulosa cells of 3mm follicles and was confirmed to be primarily in the ooplasm. BMP15 was detected by immunoblotting in 6 and 8mm follicles near the time of follicle selection. Expression of mRNA for BMP15 receptors (BMPR1B and BMPR2) in granulosa cells increased with follicle size, indicating that BMP15 may play an important role around follicle selection. The function of BMP15 was examined by culturing granulosa cells from 3-5mm and 6-8mm follicles with recombinant human BMP15 (rhBMP15). BMP15 increased expression of follicle stimulating hormone receptor (FSHR) mRNA and decreased anti-Müllerian hormone (AMH) mRNA and occludin (OCLN), factors associated with follicle maturation and growth in the hen. Hormonal regulation of BMP15 was assessed by whole follicle culture with estradiol (E2) which increased BMP15 mRNA expression. The distinct expression pattern of BMP15 and its receptors, coupled with the effects of BMP15 to increase FSHR mRNA and decrease AMH mRNA and OCLN mRNA and protein expression suggest that the oocyte may have a role in follicle selection in the chicken. PMID:27340039

  6. Bone morphogenetic protein 7 induces cementogenic differentiation of human periodontal ligament-derived mesenchymal stem cells.

    Science.gov (United States)

    Torii, D; Tsutsui, T W; Watanabe, N; Konishi, K

    2016-01-01

    Bone morphogenetic protein 7 (BMP-7) is a multifunctional differentiation factor that belongs to the transforming growth factor superfamily. BMP-7 induces gene expression of protein tyrosine phosphatase-like, member A/cementum attachment protein (PTPLA/CAP) and cementum protein 1 (CEMP1), both of which are markers of cementoblasts and cementocytes. In the previous study, we reported that BMP-7 treatment enhanced PTPLA/CAP and CEMP1 expression in both normal and immortal human periodontal ligament (PDL) cells. To elucidate the molecular mechanisms of the gene expression of these molecules, in this study, we identified a functional transcription activator binding region in the promoter region of PTPLA/CAP and CEMP1 that is responsive to BMP signals. Here, we report that some short motifs termed GC-rich Smad-binding elements (GC-SBEs) that are located in the human PTPLA/CAP promoter and CEMP1 promoter are BMP-7 responsive as analyzed with luciferase promoter assays. On the other hand, we found that transcription of Sp7/Osterix and PTPLA/CAP was up-regulated after 1 week of BMP-7 treatment on purified normal human PDL cells as a result of gene expression microarray analysis. Furthermore, transcription of Sp7/Osterix, runt-related transcription factor 2 (RUNX2), and alkaline phosphatase (ALP) was up-regulated after 2 weeks of BMP-7 treatment, whereas gene expression of osteo/odontogenic markers such as integrin-binding sialoprotein (IBSP), collagen, type I, alpha 1 (COL1A1), dentin matrix acidic phosphoprotein 1 (DMP1), and dentin sialophosphoprotein (DSPP) was not up-regulated in purified normal or immortal human PDL cells as a result of qRT-PCR. The results suggest that BMP-7 mediates cementogenesis via GC-SBEs in human PDL cells and that its molecular mechanism is different from that for osteo/odontogenesis. PMID:25464857

  7. 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.

  8. Effectiveness and safety of recombinant human bone morphogenetic protein-2 for adults with lumbar spine pseudarthrosis following spinal fusion surgery

    Science.gov (United States)

    Balaji, V.; Kaila, R.; Wilson, L.

    2016-01-01

    Objectives We performed a systematic review of the literature to determine the safety and efficacy of bone morphogenetic protein (BMP) compared with bone graft when used specifically for revision spinal fusion surgery secondary to pseudarthrosis. Methods The MEDLINE, EMBASE and Cochrane Library databases were searched using defined search terms. The primary outcome measure was spinal fusion, assessed as success or failure in accordance with radiograph, MRI or CT scan review at 24-month follow-up. The secondary outcome measure was time to fusion. Results A total of six studies (three prospective and three retrospective) reporting on the use of BMP2 met the inclusion criteria (203 patients). Of these, four provided a comparison of BMP2 and bone graft whereas the other two solely investigated the use of BMP2. The primary outcome was seen in 92.3% (108/117) of patients following surgery with BMP2. Although none of the studies showed superiority of BMP2 to bone graft for fusion, its use was associated with a statistically quicker time to achieving fusion. BMP2 did not appear to increase the risk of complication. Conclusion The use of BMP2 is both safe and effective within the revision setting, ideally in cases where bone graft is unavailable or undesirable. Further research is required to define its optimum role. Cite this article: Mr P. Bodalia. Effectiveness and safety of recombinant human bone morphogenetic protein-2 for adults with lumbar spine pseudarthrosis following spinal fusion surgery: A systematic review. Bone Joint Res 2016;5:145–152. DOI: 10.1302/2046-3758.54.2000418. PMID:27121215

  9. Regulation of Pancreatic Alpha Cell Function and Proliferation by Bone Morphogenetic Protein 4 (BMP4) in vitro

    DEFF Research Database (Denmark)

    Nielsen, Sofie Sylvest; Christensen, Gitte Lund; Holst, Jens Juul;

    2016-01-01

    Increased expression of Bone Morphogenetic Proteins (BMPs) in several tissues is associated with inflammation and Type II Diabetes Mellitus. BMP2 and BMP4 mRNA expression is increased in pancreatic islets from db/db mice and beta cell proliferation and function are inhibited by BMP4. The effect...... incubation with BMP4 in mouse islets, but not in human islets. The percentage of proliferating alpha cells was reduced from 7.3 to 0.2 % in mouse islets incubated with BMP4. Alpha cell proliferation in human islets ranged from 0 to 11.8 %, and BMP4 was found to inhibit proliferation of alpha cells from all...

  10. Enhanced healing of rabbit segmental radius defects with surface-coated calcium phosphate cement/bone morphogenetic protein-2 scaffolds

    International Nuclear Information System (INIS)

    Large osseous defects remain a difficult clinical problem in orthopedic surgery owing to the limited effective therapeutic options, and bone morphogenetic protein-2 (BMP-2) is useful for its potent osteoinductive properties in bone regeneration. Here we build a strategy to achieve prolonged duration time and help inducting new bone formation by using water-soluble polymers as a protective film. In this study, calcium phosphate cement (CPC) scaffolds were prepared as the matrix and combined with sodium carboxymethyl cellulose (CMC-Na), hydroxypropylmethyl cellulose (HPMC), and polyvinyl alcohol (PVA) respectively to protect from the digestion of rhBMP-2. After being implanted in the mouse thigh muscles, the surface-modified composite scaffolds evidently induced ectopic bone formation. In addition, we further evaluated the in vivo effects of surface-modified scaffolds in a rabbit radius critical defect by radiography, three dimensional micro-computed tomographic (μCT) imaging, synchrotron radiation-based micro-computed tomographic (SRμCT) imaging, histological analysis, and biomechanical measurement. The HPMC-modified CPC scaffold was regarded as the best combination for segmental bone regeneration in rabbit radius. - Highlights: • A simple surface-coating method was used to fabricate composite scaffolds. • Growth factor was protected from rapid depletion via superficial coating. • Significant promotion of bone regeneration was achieved. • HPMC-modification displayed optimal effect of bone regeneration

  11. Enhanced healing of rabbit segmental radius defects with surface-coated calcium phosphate cement/bone morphogenetic protein-2 scaffolds

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Yi; Hou, Juan; Yin, ManLi [Engineering Research Center for Biomedical Materials of Ministry of Education, East China University of Science and Technology, Shanghai 200237 (China); Wang, Jing, E-mail: biomatwj@163.com [Engineering Research Center for Biomedical Materials of Ministry of Education, East China University of Science and Technology, Shanghai 200237 (China); Liu, ChangSheng, E-mail: csliu@sh163.net [Engineering Research Center for Biomedical Materials of Ministry of Education, East China University of Science and Technology, Shanghai 200237 (China); The State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237 (China); Key Laboratory for Ultrafine Materials of Ministry of Education, East China University of Science and Technology, Shanghai 200237 (China)

    2014-11-01

    Large osseous defects remain a difficult clinical problem in orthopedic surgery owing to the limited effective therapeutic options, and bone morphogenetic protein-2 (BMP-2) is useful for its potent osteoinductive properties in bone regeneration. Here we build a strategy to achieve prolonged duration time and help inducting new bone formation by using water-soluble polymers as a protective film. In this study, calcium phosphate cement (CPC) scaffolds were prepared as the matrix and combined with sodium carboxymethyl cellulose (CMC-Na), hydroxypropylmethyl cellulose (HPMC), and polyvinyl alcohol (PVA) respectively to protect from the digestion of rhBMP-2. After being implanted in the mouse thigh muscles, the surface-modified composite scaffolds evidently induced ectopic bone formation. In addition, we further evaluated the in vivo effects of surface-modified scaffolds in a rabbit radius critical defect by radiography, three dimensional micro-computed tomographic (μCT) imaging, synchrotron radiation-based micro-computed tomographic (SRμCT) imaging, histological analysis, and biomechanical measurement. The HPMC-modified CPC scaffold was regarded as the best combination for segmental bone regeneration in rabbit radius. - Highlights: • A simple surface-coating method was used to fabricate composite scaffolds. • Growth factor was protected from rapid depletion via superficial coating. • Significant promotion of bone regeneration was achieved. • HPMC-modification displayed optimal effect of bone regeneration.

  12. 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.

  13. Bone Morphogenetic Protein (BMP-7 expression is decreased in human hypertensive nephrosclerosis

    Directory of Open Access Journals (Sweden)

    Cohen Clemens D

    2010-11-01

    Full Text Available Abstract Background Bone Morphogenetic Protein (BMP-7 is protective in different animal models of acute and chronic kidney disease. Its role in human kidneys, and in particular hypertensive nephrosclerosis, has thus far not been described. Methods BMP-7 mRNA was quantified using real-time PCR and localised by immunostaining in tissue samples from normal and nephrosclerotic human kidneys. The impact of angiotensin (AT-II and the AT-II receptor antagonist telmisartan on BMP-7 mRNA levels and phosphorylated Smad 1/5/8 (pSmad 1/5/8 expression was quantified in proximal tubular cells (HK-2. Functional characteristics of BMP-7 were evaluated by testing its influence on TGF-β induced epithelial-to-mesenchymal transition (EMT, expression of TGF-β receptor type I (TGF-βRI and phosphorylated Smad 2 (pSmad 2 as well as on TNF-α induced apoptosis of proximal tubular cells. Results BMP-7 was predominantly found in the epithelia of the distal tubule and the collecting duct and was less abundant in proximal tubular cells. In sclerotic kidneys, BMP-7 was significantly decreased as demonstrated by real-time PCR and immunostaining. AT-II stimulation in HK-2 cells led to a significant decrease of BMP-7 and pSmad 1/5/8, which was partially ameliorated upon co-incubation with telmisartan. Only high concentrations of BMP-7 (100 ng/ml were able to reverse TNF-α-induced apoptosis and TGF-β-induced EMT in human proximal tubule cells possibly due to a decreased expression of TGF-βRI. In addition, BMP-7 was able to reverse TGF-β-induced phosphorylation of Smad 2. Conclusions The findings suggest a protective role for BMP-7 by counteracting the TGF-β and TNF-α-induced negative effects. The reduced expression of BMP-7 in patients with hypertensive nephrosclerosis may imply loss of protection and regenerative potential necessary to counter the disease.

  14. Preparation of recombinant human bone morphogenetic protein-2 loaded dextran-based microspheres and their characteristics

    Institute of Scientific and Technical Information of China (English)

    Fa-ming CHEN; Zhi-fen WU; Qin-tao WANG; Hong WU; Yong-jie ZHANG; Xin NIE; Yan JIN

    2005-01-01

    Aim: To prepare new pharmaceutical forms with sustained delivery properties of recombinant human bone morphogenetic protein-2 (rhBMP2) for tissue engineering and guided tissue regeneration (GTR) use. Methods: rhBMP2-1oaded dextranbased hydrogel microspheres (rhBMP2-MPs), which aimed to keep rhBMP2 bioactivity and to achieve long-term sustained release of rhBMP2, were prepared by double-phase emulsified condensation polymerization. The physical, chemical performances and biological characteristics of those microspheres were studied both in vitro and in vivo. Results: The microspheres' average diameter was 30.33±4.32 μm with 75.4% ranging from 20 μm to 40 μm and the drug loading and encapsulation efficiency were 7.82% and 82.25%, respectively. The rhBMP2-releasing profiles in vitro showed that rhBMP2 release could be maintained more than 10 d. The rhBMP2-MPs, with good swelling and biodegradation behavior,could be kept for 6 months at below 4 ℃ without significant characteristic change or bioactivity loss. Cytology studies showed that rhBMP2-MPs could promote the proliferation of periodontal ligament cells (PDLCs) approximately 10 d, while the bioactivity of concentrated rhBMP2 solution could keep no more than 3 d.Scanning electron microscope showed that rhBMP2-MPs could be enchased into the porous structure of calcium phosphate ceremic (CPC) and the eugonic growth of PDLCs in CPC/rhBMP2-MPs scaffolds. Animal experiments indicated that using CPC/rhBMP2-MPs scaffolds could gain more periodontal tissue regeneration than using rhBMP2 compound firsthand with CPC (CPC/rhBMP2). Conclusion:By encapsulating rhBMP2 into dextran-based microspheres, a small quantity of rhBMP2 could achieve equivalent effects to the concentrated rhBMP2 solution and at the same time, could prolong rhBMP2 retention both in vitro and in vivo.

  15. Compound soft regenerated skull material for repairing dog skull defects using bone morphogenetic protein as an inductor and nanohydroxyapatite as a scaffold

    Institute of Scientific and Technical Information of China (English)

    Zhidong Shi; Mingwang Liu; Zhongzong Qin; Qinmei Wang; Ying Guo; Haiyong He; Zhonghe Yu

    2008-01-01

    BACKGROUND: In previous studies of skull defects and regeneration, bone morphogenetic protein as an inductor and nanohydroxyapatite as a scaffold have been cocultured with osteoblasts.OBJECTIVE: To verify the characteristics of the new skull regenerated material after compound soft regenerated skull material implantatiom.DESIGN, TIME AND SETTING: The self-control and inter-group control animal experiment was perfurmed at the Sun Yat-sen University, China from February to July 2007.MATERIALS: Twenty-tour healthy adult dogs of both genders weighing 15-20 kg were used in this study. Nanohydroxyapatite as a scaffold was cocultured with osteoblasts. Using demineralized canine bone matrix as a carrier, recombinant human bone morphogenetic protein-2 was employed to prepare compound soft regenerated skull material. Self-designed compound soft regenerated skull material was implanted in models of skull defects.METHODS: Animals were randomly assigned into two groups, Group A (n = 16) and Group B (n = 8).Bilateral 2.5-cm-diameter full-thickness parietal skull defects were made in all animals. In Group A, the right side was reconstructed with calcium alginate gel, osteoblasts, and nanomcter bone meal composite;the left side was reconstructed with calcium alginate gel, osteoblasts, nanometer bone meal and recombinant human bone morphogenetic protein-2 composite. In Group B, the right side was kept as a simple skull detect, and the left side was reconstructed with calcium alginate gel, osteoblasts, nanometer bone meal and recombinant human bone morphogenetic protein-2 composite.MAIN OUTCOME MEASURES: Bone regeneration and histopathological changes at the site of the skull defect were observed with an optical microscope and a scanning electron microscope after surgery.The ability to form bone was measured by alizarin red S staining. In vitro cultured osteoblasts were observed for morphology.RESULTS: One month following surgery, newly formed bone trabeculae mostly covered the

  16. The Use of Platelet Rich Plasma, Bone Morphogenetic Protein-2 and Different Scaffolds in Oral and Maxillofacial Surgery - Literature Review in Comparison with Own Clinical Experience

    OpenAIRE

    Karl-Heinz Schuckert; Stefan Jopp; Magdalena Osadnik

    2011-01-01

    ABSTRACT Objectives The purpose of this article was to review and critically assess the use of platelet rich plasma, recombinant human bone morphogenetic protein-2 and different scaffolds (i.e. tricalciumphosphate, polycaprolactone, demineralized bone matrix and anorganic bovine bone mineral) in oral and maxillofacial surgery comparing the relevant literature and own clinical experience. Material and Methods A literature review was conducted using MEDLINE, MEDPILOT and COCHRANE DATABASE OF SY...

  17. Synergistic actions of olomoucine and bone morphogenetic protein-4 in axonal repair after acute spinal cord contusion

    Institute of Scientific and Technical Information of China (English)

    Liang Chen; Jianjun Li; Liang Wu; Mingliang Yang; Feng Gao; Li Yuan

    2014-01-01

    To determine whether olomoucine acts synergistically with bone morphogenetic protein-4 in the treatment of spinal cord injury, we established a rat model of acute spinal cord contusion by impacting the spinal cord at the T8 vertebra. We injected a suspension of astrocytes derived from glial-restricted precursor cells exposed to bone morphogenetic protein-4 (GDAsBMP) into the spinal cord around the site of the injury, and/or olomoucine intraperitoneally. Olomoucine effectively inhibited astrocyte proliferation and the formation of scar tissue at the injury site, but did not prevent proliferation of GDAsBMP or inhibit their effects in reducing the spinal cord lesion cavity. Furthermore, while GDAsBMP and olomoucine independently resulted in small improve-ments in locomotor function in injured rats, combined administration of both treatments had a signiifcantly greater effect on the restoration of motor function. These data indicate that the combined use of olomoucine and GDAsBMP creates a better environment for nerve regeneration than the use of either treatment alone, and contributes to spinal cord repair after injury.

  18. The Use of Platelet Rich Plasma, Bone Morphogenetic Protein-2 and Different Scaffolds in Oral and Maxillofacial Surgery - Literature Review in Comparison with Own Clinical Experience

    Directory of Open Access Journals (Sweden)

    Karl-Heinz Schuckert

    2011-01-01

    Full Text Available Objectives: The purpose of this article was to review and critically assess the use of platelet rich plasma, recombinant human bone morphogenetic protein-2 and different scaffolds (i.e. tricalciumphosphate, polycaprolactone, demineralized bone matrix and anorganic bovine bone mineral in oral and maxillofacial surgery comparing the relevant literature and own clinical experience.Material and Methods: A literature review was conducted using MEDLINE, MEDPILOT and COCHRANE DATABASE OF SYSTEMATIC REVIEWS. It concentrated on manuscripts and overviews published in the last five years (2006-2010. The key terms employed were platelet rich plasma, bone morphogenetic proteins and their combinations with the above mentioned scaffolds. The results of clinical studies and animal trials were especially emphasized. The statements from the literature were compared with authors’ own clinical data.Results: New publications and overviews demonstrate the advantages of platelet rich plasma in bone regeneration. The results from the literature review were discussed and compared with the publications detailing authors’ own experiences.Conclusions: A favourable outcome concerning newly grown bone was achieved combining platelet rich plasma in addition to optimal matrices with or without recombinant human bone morphogenetic protein-2, depending on the clinical case. As a consequence, the paradigm shift from transplantation of autogenous bone to bone tissue engineering appears promising.

  19. The Use of Bone Morphogenetic Protein in Pediatric Cervical Spine Fusion Surgery: Case Reports and Review of the Literature.

    Science.gov (United States)

    Molinari, Robert W; Molinari, Christine

    2016-02-01

    Study Design Case report. Objective There is a paucity of literature describing the use of bone graft substitutes to achieve fusion in the pediatric cervical spine. The outcomes and complications involving the off-label use of bone morphogenetic protein (BMP)-2 in the pediatric cervical spine are not clearly defined. The purpose of this article is to report successful fusion without complications in two pediatric patients who had instrumented occipitocervical fusion using low-dose BMP-2. Methods A retrospective review of the medical records was performed, and the patients were followed for 5 years. Two patients under 10 years of age with upper cervical instability were treated with occipitocervical instrumented fusion using rigid occipitocervical fixation techniques along with conventionally available low-dose BMP-2. A Medline and PubMed literature search was conducted using the terms "bone morphogenetic protein," "BMP," "rh-BMP2," "bone graft substitutes," and "pediatric cervical spine." Results Solid occipitocervical fusion was achieved in both pediatric patients. There were no reported perioperative or follow-up complications. At 5-year follow-up, radiographs in both patients showed successful occipital cervical fusion without evidence of instrumentation failure or changes in the occipitocervical alignment. To date, there are few published reports on this topic. Complications and the appropriate dosage application in the pediatric posterior cervical spine remain unknown. Conclusions We describe two pediatric patients with upper cervical instability who achieved successful occipital cervical fusion without complication using off-label BMP-2. This report underscores the potential for BMP-2 to achieve successful arthrodesis of the posterior occipitocervical junction in pediatric patients. Use should be judicious as complications and long-term outcomes of pediatric BMP-2 use remain undefined in the existing literature. PMID:26835215

  20. Prolonged propagation of rat neural stem cells relies on inhibiting autocrine/paracrine bone morphogenetic protein and platelet derived growth factor signals

    Institute of Scientific and Technical Information of China (English)

    Yirui Sun; Liangfu Zhou; Xing Wu; Hua Liu; Qiang Yuan; Ying Mao; Jin Hu

    2011-01-01

    Continuous expansion of rat neural stem cell lines has not been achieved due to proliferation arrest and spontaneous differentiation in vitro. In the current study, neural precursor cells derived from the subventricular zone of adult rats spontaneously underwent astroglial and oligodendroglial differentiation after limited propagation. This differentiation was largely induced by autocrine or paracrine bone morphogenetic protein and platelet derived growth factor signals. The results showed that, by inhibiting bone morphogenetic protein and platelet derived growth factor signals, adult rat neural precursor cells could be extensively cultured in vitro as tripotent stem cell lines. In addition to adult rat neural stem cells, we found that bone morphogenetic protein antagonists can promote the proliferation of human neural stem cells. Therefore, the present findings illustrated the role of autocrine or paracrine bone morphogenetic protein and platelet derived growth factor signaling in determining neural stem cell self-renewal and differentiation. By antagonizing both signals, the long-term propagation of rat neural stem cell lines can be achieved.

  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. Bone morphogenetic protein-9 suppresses growth of myeloma cells by signaling through ALK2 but is inhibited by endoglin

    International Nuclear Information System (INIS)

    Multiple myeloma is a malignancy of plasma cells predominantly located in the bone marrow. A number of bone morphogenetic proteins (BMPs) induce apoptosis in myeloma cells in vitro, and with this study we add BMP-9 to the list. BMP-9 has been found in human serum at concentrations that inhibit cancer cell growth in vitro. We here show that the level of BMP-9 in serum was elevated in myeloma patients (median 176 pg/ml, range 8–809) compared with healthy controls (median 110 pg/ml, range 8–359). BMP-9 was also present in the bone marrow and was able to induce apoptosis in 4 out of 11 primary myeloma cell samples by signaling through ALK2. BMP-9-induced apoptosis in myeloma cells was associated with c-MYC downregulation. The effects of BMP-9 were counteracted by membrane-bound (CD105) or soluble endoglin present in the bone marrow microenvironment, suggesting a mechanism for how myeloma cells can evade the tumor suppressing activity of BMP-9 in multiple myeloma

  3. 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.

  4. Healing patterns of critical size bony defects in rats after grafting with bone substitutes soaked in recombinant human bone morphogenetic protein-2: histological and histometric evaluation.

    Science.gov (United States)

    Mokbel, N; Naaman, N; Nohra, J; Badawi, N

    2013-09-01

    The aim of the study was to evaluate the effect of different bone substitutes soaked in recombinant human bone morphogenetic protein-2 (rhBMP-2) on the healing of critical size defects in calvarial bone. Defects were created in 24 Sprague Dawley rats. The rhBMP-2 was diluted to obtain a final concentration of 0.2mg/ml. Rats were divided into four groups and treated as follows: in the first group the defect was filled with anorganic bovine bone mineral (ABBM) and rhBMP-2, the second group was treated with freeze-dried bone allograft (FDBA) and rhBMP-2, and the third group was treated with autogenous bone (AUTO). In the control group the defects were left untreated. Animals were killed after 8weeks and calcified histological sections prepared. Histometric measurements showed that mean (SD) bone formation was 4.00 (1.69)mm(2) in the ABBM group, 2.56 (1.06)mm(2) in the FDBA group, and 2.30 (0.34)mm(2) in the AUTO group. The difference between the ABBM group and the other 3 groups was significant (p<0.0001) with a mean bone formation of 0.82 (0.25)mm(2) in the control group. There was no significant difference between the FDBA and the AUTO groups (p=0.96). Within the limits of this study we concluded that the addition of rhBMP-2 to bone substitutes was efficacious in regenerating bone in critical size bone defects in calveria in rats. PMID:22939894

  5. Reinforcing effect of calcium sulfate cement bovine bone morphogenetic protein on vertebral in the rabbit model of osteoporosis

    Institute of Scientific and Technical Information of China (English)

    Jie Zhang; Yu-Ming Chen; Chen Sheng-Guo; Kaken Habaerxi; Shawuti Alimujiang; Yu Chen; Ming-Zhen Peng; Rong Yue; Yu-Lian Wu; De-Quan Wang

    2014-01-01

    Objective:To observe reinforcing effect of calcium sulfate cement(CSC) bovine bone morphogenetic protein(bBMP) on vertebral in the rabbit model of osteoporosis.Methods:A total of48NewZealand white rabbits were randomly divided into groupⅠ(blank control group), group Ⅱ(CSC injection group), group Ⅲ(CSC/bBMP injection group) and control group.White rabbit osteoporosis model was established rapidly by using castration method+methylprednisolone candidate.After modeling, groups Ⅱ, Ⅲ were given corresponding vertebral body injection material, and4 animals were sacrificed respectively at24 h,6 weeks,12 weeks after vertebral plasty.Tissue pathological status, vertebral mineral density and vertebral body bone mechanical strength were observed.Results:Vertebral body structure form was normal in the groups Ⅱand Ⅲ.Trabecular bone coarsens, connection and repair were observed in micro fracture and bone defects, bone trabecular connectivity was superior to group Ⅰ significantly; vertebral body compression strength in the groupⅠ was on the decline, vertebral compression strength in the groups Ⅱand Ⅲ was on the rise, the largest vertebra.PostoperativeBMC andBMD in groups Ⅱand Ⅲ were incresed, andsignificantly higher than group Ⅰ after6 weeks(P<0.05),BMC and BMD in group Ⅲ after12 weeks were higher than the other three groups.Conclusion:Compound bBMPCSC has good bone induction.It can improve the three-dimensional construction effect for osteoporosis vertebral trabecula, and can significantly improve the vertebral strength, as a vertebral packing material with good application prospect.

  6. Facilitated receptor-recognition and enhanced bioactivity of bone morphogenetic protein-2 on magnesium-substituted hydroxyapatite surface

    Science.gov (United States)

    Huang, Baolin; Yuan, Yuan; Li, Tong; Ding, Sai; Zhang, Wenjing; Gu, Yuantong; Liu, Changsheng

    2016-04-01

    Biomaterial surface functionalized with bone morphogenetic protein-2 (BMP-2) is a promising approach to fabricating successful orthopedic implants/scaffolds. However, the bioactivity of BMP-2 on material surfaces is still far from satisfactory and the mechanism of related protein-surface interaction remains elusive. Based on the most widely used bone-implants/scaffolds material, hydroxyapatite (HAP), we developed a matrix of magnesium-substituted HAP (Mg-HAP, 2.2 at% substitution) to address these issues. Further, we investigated the adsorption dynamics, BMPRs-recruitment, and bioactivity of recombinant human BMP-2 (rhBMP-2) on the HAP and Mg-HAP surfaces. To elucidate the mechanism, molecular dynamic simulations were performed to calculate the preferred orientations, conformation changes, and cysteine-knot stabilities of adsorbed BMP-2 molecules. The results showed that rhBMP-2 on the Mg-HAP surface exhibited greater bioactivity, evidenced by more facilitated BMPRs-recognition and higher ALP activity than on the HAP surface. Moreover, molecular simulations indicated that BMP-2 favoured distinct side-on orientations on the HAP and Mg-HAP surfaces. Intriguingly, BMP-2 on the Mg-HAP surface largely preserved the active protein structure evidenced by more stable cysteine-knots than on the HAP surface. These findings explicitly clarify the mechanism of BMP-2-HAP/Mg-HAP interactions and highlight the promising application of Mg-HAP/BMP-2 matrixes in bone regeneration implants/scaffolds.

  7. 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.

  8. 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.

  9. Depot injectable biodegradable nanoparticles loaded with recombinant human bone morphogenetic protein-2: preparation, characterization, and in vivo evaluation

    Directory of Open Access Journals (Sweden)

    Hassan AH

    2015-07-01

    Full Text Available Ali Habiballah Hassan,1 Khaled Mohamed Hosny,2,3 Zuahir A Murshid,1 Adel Alhadlaq,4 Ahmed Alyamani,5 Ghada Naguib6 1Department of Orthodontics, Faculty of Dentistry, 2Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia; 3Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Beni Suef University, Beni Suef, Egypt; 4Department of Pediatric Dentistry and Orthodontics, College of Dentistry, King Saud University, Riyadh, 5Department of Oral Surgery, 6Department of Restorative Dentistry, Faculty of Dentistry, King Abdulaziz University, Jeddah, Saudi Arabia Objective: The aim of this study is to utilize the biocompatibility characteristics of biodegradable polymers, viz, poly lactide-co-glycolide (PLGA and polycaprolactone (PCL, to prepare sustained-release injectable nanoparticles (NPs of bone morphogenetic protein-2 (BMP-2 for the repair of alveolar bone defects in rabbits. The influence of formulation parameters on the functional characteristics of the prepared NPs was studied to develop a new noninvasive injectable recombinant human BMP-2 (rhBMP-2 containing grafting material for the repair of alveolar bone clefts.Materials and methods: BMP-2 NPs were prepared using a water-in-oil-in-water double-emulsion solvent evaporation/extraction method. The influence of molar ratio of PLGA to PCL on a suitable particle size, encapsulation efficiency, and sustained drug release was studied. Critical size alveolar defects were created in the maxilla of 24 New Zealand rabbits divided into three groups, one of them treated with 5 µg/kg of rhBMP-2 NP formulations.Results: The results found that NPs formula prepared using blend of PLGA and PCL in 4:2 (w/w ratio showed the best sustained-release pattern with lower initial burst, and showed up to 62.7% yield, 64.5% encapsulation efficiency, 127 nm size, and more than 90% in vitro release. So, this formula was selected for

  10. Implanting hydroxyapatite-coated porous titanium with bone morphogenetic protein-2 and hyaluronic acid into distal femoral metaphysis of rabbits

    Institute of Scientific and Technical Information of China (English)

    PENG Lei; BIAN Wei-guo; LIANG Fang-hui; XU Hua-zi

    2008-01-01

    Objective: To assess the osseointegration capability of hydroxyapatite-coated porous titanium with bone morphogenetic protein-2 (BMP-2) and hyaluronic acid to repair defects in the distal femur metaphysis in rabbits. Methods: Porous titanium implants were made by sintering titanium powder at high temperature, which were coated with hydroxyapatite by alkali and heat treatment and with BMP-2 combined with bone regeneration materials. And hyaluronic acid was further used as delivery system to prolong the effect of BMP-2. The implants were inserted into the metaphysis of the distal femur of rabbits. The animals were killed at 6, 12 and 24 weeks to accomplish histological and biomechanical analyses. Results: According to the result of histological analysis, the osseointegration in BMP-2 group was better than that of the HA-coated porous titanium group. In push-out test, all the samples had bigger shear stress as time passed by. There was statistical difference between the two groups in 6 and 12 weeks but not in 24 weeks. Conclusion: Hydroxyapatite-coated porous titanium with BMP-2 and hyaluronic acid has a good effect in repairing defects of distal fumur in rabbits, which is a fine biotechnology for future clinical application.

  11. Bone Morphogenetic Protein 4,Bone Morphogenetic Protein 7 and Polycystic Ovary Syndrome%骨形态蛋白4和骨形态蛋白7与多囊卵巢综合征

    Institute of Scientific and Technical Information of China (English)

    黄晓; 金洁雯; 王勇

    2014-01-01

    多囊卵巢综合征(PCOS)是育龄妇女最常见的生殖内分泌紊乱疾病之一。以稀发排卵或不排卵、高雄激素血症以及形态学上的多囊卵巢为主要表现特征。迄今为止,其病因和病理机制尚不清楚。有研究显示,PCOS的形成与卵源性的某些转录因子有关,如转化生长因子β(TGF-β)。骨形态蛋白4(BMP4)和BMP7是TGF-β超家族的重要成员,在卵泡的形成、排卵、颗粒细胞的生长成熟和凋亡中发挥重要作用。因此了解BMP4和BMP7在女性生殖系统的调节作用,对研究PCOS的病因机制以及治疗有重要价值。%Polycystic ovary syndrome (PCOS) is one of the common endocrine disorder affecting women of reproductive age,and is characterized by oligo-or anovulation,hyperandrogenism and polycystic ovaries. Some findings show that the cause of PCOS has something to do with the abnormal regulation of transcription factors ,such as the Transforming Growth Factor-beta (TGF-β) superfamily. Bone Morphogenetic Protein 4 (BMP4) and Bone Morphogenetic Protein 7 (BMP7) are both important members in TGF-βsuperfamily, and play an significant role in the folliculogenesis、ovulation and the development and apotosis of granulosa cells in ovary. As a result,in order to know more about the pathogenesis and treatment of PCOS, it is necessary to make clear the regulation function of BMP4 and BMP7 in female reproductive system.

  12. Three-Dimensional Upper Lip and Nostril Sill Changes After Cleft Alveolus Reconstruction Using Autologous Bone Grafting Versus Recombinant Human Bone Morphogenetic Protein-2.

    Science.gov (United States)

    Raposo-Amaral, Cassio Eduardo; Denadai, Rafael; Alonso, Nivaldo

    2016-06-01

    Cleft alveolus in patients with unilateral complete cleft lip and palate has been alternatively reconstructed with recombinant human bone morphogenetic protein (rhBMP)-2. However, its effects on upper lip and nostril sill anatomy are not known. Thus, the objective of this investigation was to assess and compare upper lip and nostril sill changes after cleft alveolus reconstruction with autologous bone from the iliac crest region and rhBMP-2. Patients were randomly allocated into 2 groups. In group 1, autologous bone from the iliac crest region was used to fill the cleft alveolus (n = 4), and in group 2, rhBMP-2 was used to fill the cleft alveolus (n = 8). Preoperatively and at one after the surgery, computerized tomography (CT) was performed. Reformatted CT imaging was used to perform cephalometric linear measurements of the upper lip and nostril sill regions. Inter- and intragroup data of the pre and postoperative reformatted CT measurements of the upper lip and nostril sill regions did not show differences (P >0.05) in cutaneous upper lip height and projection, nostril sill elevation, and subnasale projection. There were no significant upper lip and nostril sill anatomical changes after cleft alveolus reconstruction using autologous bone grafting and rhBMP-2. PMID:27244210

  13. Use of recombinant human bone morphogenetic protein-2 as an adjunct for instrumented posterior arthrodesis in the occipital cervical region: An analysis of safety, efficacy, and dosing

    OpenAIRE

    D Kojo Hamilton; Smith, Justin S.; Reames, Davis L.; Williams, Brian J.; Shaffrey, Christopher I.

    2010-01-01

    Background: There have been few reports on the use of recombinant human bone morphogenetic protein (rhBMP)-2 in posterior spine. However, no study has investigated the dosing, safety, and efficacy of its use in the posterior atlantoaxial, and/or craniovertebral junction. Recent case report of the cytokine-mediated inflammatory reaction, following off label use of rhBMP-2 as an adjunct for cervical fusion, particularly in complex cases, has increased concern about complications associated with...

  14. Tribulus terrestris Alters the Expression of Growth Differentiation Factor 9 and Bone Morphogenetic Protein 15 in Rabbit Ovaries of Mothers and F1 Female Offspring

    OpenAIRE

    Desislava Abadjieva; Elena Kistanova

    2016-01-01

    Although previous research has demonstrated the key role of the oocyte-derived factors, bone morphogenetic protein (BMP) 15 and growth differentiation factor (GDF) 9, in follicular development and ovulation, there is a lack of knowledge on the impact of external factors, which females are exposed to during folliculogenesis, on their expression. The present study investigated the effect of the aphrodisiac Tribulus terrestris on the GDF9 and BMP15 expression in the oocytes and cumulus cells at ...

  15. Comparison of Cell Viability and Embryoid Body Size of Two Embryonic Stem Cell Lines After Different Exposure Times to Bone Morphogenetic Protein 4

    OpenAIRE

    Nehleh Zarei Fard; Tahereh Talaei-Khozani; Soghra Bahmanpour; Tahereh Esmaeilpour

    2015-01-01

    Background: Activation of bone morphogenetic protein 4 (BMP4) signaling pathway in embryonic stem (ES) cells plays an important role in controlling cell proliferation, differentiation, and apoptosis. Adverse effects of BMP4 occur in a time dependent manner; however, little is known about the effect of different time exposure of this growth factor on cell number in culture media. In this study, we investigated the role of two different exposure times to BMP4 in cell viability, embryoid body (E...

  16. Pretreatment with Bone Morphogenetic Protein-7 (BMP-7) Mimics Ischemia Preconditioning Following Intestinal Ischemia/Reperfusion Injury in The Intestine and Liver

    OpenAIRE

    Radhakrishnan, Ravi S.; Radhakrishnan, Geetha L.; Radhakrishnan, Hari R.; Xue, Hasen; Adams, Sasha D.; Moore-Olufemi, Stacey D.; Harting, Matthew T.; Cox, Charles S.; Kone, Bruce C.

    2008-01-01

    Intestinal ischemia/reperfusion (I/R) injury has been shown to cause intestinal mucosal injury and adversely affect function. Ischemic preconditioning (IPC) has been shown to protect against intestinal I/R injury by reducing polymorphonuclear leukocyte infiltration, intestinal mucosal injury, and liver injury, and preserve intestinal transit. Bone morphogenetic protein 7 (BMP-7) has been shown to protect against I/R injury in the kidney and brain. Recently, microarray analysis has been used t...

  17. Conversion of the Nipple to Hair-Bearing Epithelia by Lowering Bone Morphogenetic Protein Pathway Activity at the Dermal-Epidermal Interface

    OpenAIRE

    Mayer, Julie Ann; Foley, John; de la Cruz, Damon; Chuong, Cheng-ming; Widelitz, Randall

    2008-01-01

    Epithelial appendages, such as mammary glands and hair, arise as a result of epithelial-mesenchymal interactions. Bone morphogenetic proteins (BMPs) are important for hair follicle morphogenesis and cycling and are known to regulate a wide variety of developmental processes. For example, overexpression of BMPs inhibits hair follicle formation. We hypothesized that the down-regulation of the BMP signaling pathway in the basal epidermis expands regions that are competent to form hair follicles ...

  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. Enzymatically synthesized inorganic polymers as morphogenetically active bone scaffolds: application in regenerative medicine.

    Science.gov (United States)

    Wang, Xiaohong; Schröder, Heinz C; Müller, Werner E G

    2014-01-01

    In recent years a paradigm shift in understanding of human bone formation has occurred that starts to change current concepts in tissue engineering of bone and cartilage. New discoveries revealed that fundamental steps in biomineralization are enzyme driven, not only during hydroxyapatite deposition, but also during initial bioseed formation, involving the transient deposition and subsequent transformation of calcium carbonate to calcium phosphate mineral. The principal enzymes mediating these reactions, carbonic anhydrase and alkaline phosphatase, open novel targets for pharmacological intervention of bone diseases like osteoporosis, by applying compounds acting as potential activators of these enzymes. It is expected that these new findings will give an innovation boost for the development of scaffolds for bone repair and reconstruction, which began with the use of bioinert materials, followed by bioactive materials and now leading to functional regenerative tissue units. These new developments have become possible with the discovery of the morphogenic activity of bioinorganic polymers, biocalcit, bio-polyphosphate and biosilica that are formed by a biogenic, enzymatic mechanism, a driving force along with the development of novel rapid-prototyping three-dimensional (3D) printing methods and bioprinting (3D cell printing) techniques that may allow a fabrication of customized implants for patients suffering in bone diseases in the future. PMID:25376489

  20. Enzymatically synthesized inorganic polymers as morphogenetically active bone scaffolds: application in regenerative medicine.

    Science.gov (United States)

    Wang, Xiaohong; Schröder, Heinz C; Müller, Werner E G

    2014-01-01

    In recent years a paradigm shift in understanding of human bone formation has occurred that starts to change current concepts in tissue engineering of bone and cartilage. New discoveries revealed that fundamental steps in biomineralization are enzyme driven, not only during hydroxyapatite deposition, but also during initial bioseed formation, involving the transient deposition and subsequent transformation of calcium carbonate to calcium phosphate mineral. The principal enzymes mediating these reactions, carbonic anhydrase and alkaline phosphatase, open novel targets for pharmacological intervention of bone diseases like osteoporosis, by applying compounds acting as potential activators of these enzymes. It is expected that these new findings will give an innovation boost for the development of scaffolds for bone repair and reconstruction, which began with the use of bioinert materials, followed by bioactive materials and now leading to functional regenerative tissue units. These new developments have become possible with the discovery of the morphogenic activity of bioinorganic polymers, biocalcit, bio-polyphosphate and biosilica that are formed by a biogenic, enzymatic mechanism, a driving force along with the development of novel rapid-prototyping three-dimensional (3D) printing methods and bioprinting (3D cell printing) techniques that may allow a fabrication of customized implants for patients suffering in bone diseases in the future.

  1. EFFECTS OF TRANSFORMING GROWTH FACTOR β AND RECOMBINANT HUMAN BONE MORPHOGENETIC PROTEIN 2 ON HUMAN PERIODONTAL LIGAMENT FIBROBLASTS

    Institute of Scientific and Technical Information of China (English)

    司晓辉; 刘正

    2001-01-01

    Objective To evaluate the effects of transforming growth factor β(TGF-β) and recombinant human bone morphogenetic protein 2 (rhBMP2) on human periodontal ligament fibroblasts ( HPDLFs ). Methods HPDLFs were done primary culture to detect the distinct concentrations of TGF-β and rhBMP2 on its proliferation, alkaline phosphatase (ALP) activity, osteocalcin ( OC) synthesis and formation of the mineralized nodules, respectively. Results TGF-β(5~100ng /ml) significantly stimulated the proliferation of HPDLFs. The ALP activity of HPDLFs was evaluated evidently by 5ng /ml TGF-β. TGF-β(0.5~100ng /ml) had no effects on OC synthesis and formation of the mineralized nodules of HPDLFs. rhBMP2 (0.25~2mg/ ml) had no rernarkable effect on the proliferation of HPDLFs. The ALP activity, OC synthesis and formation of the mineralized nodules of HPDLFs were significantly stimulated by 0.5~2mg/ml rhBMP2. Conclusion The effects of TGF-β and rhBMP2 on HPDLFs are dose-dependent. TGF-β can stimulate HPDLFs to express the early marker of osteoblastic phenotype , and it lacks the ability to promote maturation of the osteogenic phenotype. rhBMP2 can not only stimulate the expression but also promote the maturation of osteoblastic phenotype of HPDLFs.

  2. Bone Morphogenetic Protein-7 Ameliorates Cerebral Ischemia and Reperfusion Injury via Inhibiting Oxidative Stress and Neuronal Apoptosis

    Directory of Open Access Journals (Sweden)

    Haitao Pei

    2013-11-01

    Full Text Available Previous studies have indicated that bone morphogenetic protein-7 (BMP-7 is neuroprotective against cerebral ischemia/reperfusion (IR injury. The present study was undertaken to determine the molecular mechanisms involved in this effect. Adult male Wistar rats were subjected to 2 h of transient middle cerebral artery occlusion (MCAO, followed by 24 h of reperfusion. BMP-7 (10−4 g/kg or vehicle was infused into rats at the onset of reperfusion via the tail vein. Neurological deficits, infarct volume, histopathological changes, oxidative stress-related biochemical parameters, neuronal apoptosis, and apoptosis-related proteins were assessed. BMP-7 significantly improved neurological and histological deficits, reduced the infarct volume, and decreased apoptotic cells after cerebral ischemia. BMP-7 also markedly enhanced the activities of antioxidant enzymes superoxide dismutase (SOD and glutathione peroxidase (GSH-PX, and reduced the level of malondialdehyde (MDA in IR rats. In addition, Western blot analysis indicated that BMP-7 prevented cytochrome c release, inhibited activation of caspase-3, caspase-9 and caspase-8. Our data suggested that BMP-7 has protective effects against cerebral IR injury in rats, and the neuroprotective effects may be attributed to attenuating oxidative stress and inhibiting neuronal apoptosis.

  3. Effect of transforming growth factor beta and bone morphogenetic proteins on rat hepatic stellate cell proliferation and trans-differentiation

    Institute of Scientific and Technical Information of China (English)

    Hong Shen; Guo-Jiang Huang; Yue-Wen Gong

    2003-01-01

    AIM: To explore different roles of TGF-β (transforming growth factor beta) and bone morphogenetic proteins (BMPs)in hepatic stellate cell proliferation and trans-differentiation.METHODS: Hepatic stellate cells were isolated from male Sprague-Dawley rats. Sub-cultured hepatic stellate cells were employed for cell proliferation assay with WST-1 reagent and Western blot analysis with antibody against smooth muscle alpha actin (SMA).RESULTS: The results indicated that TGF-β1 significantly inhibited cell proliferation at concentration as low as 0.1 ng/ml, but both BMP-2 and BMP-4 did not affect cell proliferation at concentration as high as 10 ng/ml. The effect on hepatic stellate cell trans-differentiation was similar between TGFβ1 and BMPs. However, BMPs was more potent at transdifferentiation of hepatic stellate cells than TGF-β1. In addition, we observed that TGF-β1 transient reduced the abundance of SMA in hepatic stellate cells.CONCLUSION: TGF-β may be more important in regulation of hepatic stellate cell proliferation while BMPs may be the major cytokines regulating hepatic stellate cell transdifferentiation.

  4. Bone morphogenetic protein 4 and retinoic acid trigger bovine VASA homolog expression in differentiating bovine induced pluripotent stem cells.

    Science.gov (United States)

    Malaver-Ortega, Luis F; Sumer, Huseyin; Jain, Kanika; Verma, Paul J

    2016-02-01

    Primordial germ cells (PGCs) are the earliest identifiable and completely committed progenitors of female and male gametes. They are obvious targets for genome editing because they assure the transmission of desirable or introduced traits to future generations. PGCs are established at the earliest stages of embryo development and are difficult to propagate in vitro--two characteristics that pose a problem for their practical application. One alternative method to enrich for PGCs in vitro is to differentiate them from pluripotent stem cells derived from adult tissues. Here, we establish a reporter system for germ cell identification in bovine pluripotent stem cells based on green fluorescent protein expression driven by the minimal essential promoter of the bovine Vasa homolog (BVH) gene, whose regulatory elements were identified by orthologous modelling of regulatory units. We then evaluated the potential of bovine induced pluripotent stem cell (biPSC) lines carrying the reporter construct to differentiate toward the germ cell lineage. Our results showed that biPSCs undergo differentiation as embryoid bodies, and a fraction of the differentiating cells expressed BVH. The rate of differentiation towards BVH-positive cells increased up to tenfold in the presence of bone morphogenetic protein 4 or retinoic acid. Finally, we determined that the expression of key PGC genes, such as BVH or SOX2, can be modified by pre-differentiation cell culture conditions, although this increase is not necessarily mirrored by an increase in the rate of differentiation. PMID:26660942

  5. Mutation in bone morphogenetic protein receptor-IB is associated with increased ovulation rate in Booroola Mérino ewes

    Science.gov (United States)

    Mulsant, Philippe; Lecerf, Frédéric; Fabre, Stéphane; Schibler, Laurent; Monget, Philippe; Lanneluc, Isabelle; Pisselet, Claudine; Riquet, Juliette; Monniaux, Danielle; Callebaut, Isabelle; Cribiu, Edmond; Thimonier, Jacques; Teyssier, Jacques; Bodin, Loys; Cognié, Yves; Chitour, Nour; Elsen, Jean-Michel

    2001-01-01

    Ewes from the Booroola strain of Australian Mérino sheep are characterized by high ovulation rate and litter size. This phenotype is due to the action of the FecBB allele of a major gene named FecB, as determined by statistical analysis of phenotypic data. By genetic analysis of 31 informative half-sib families from heterozygous sires, we showed that the FecB locus is situated in the region of ovine chromosome 6 corresponding to the human chromosome 4q22–23 that contains the bone morphogenetic protein receptor IB (BMPR-IB) gene encoding a member of the transforming growth factor-β (TGF-β) receptor family. A nonconservative substitution (Q249R) in the BMPR-IB coding sequence was found to be associated fully with the hyperprolificacy phenotype of Booroola ewes. In vitro, ovarian granulosa cells from FecBB/FecBB ewes were less responsive than granulosa cells from FecB+/FecB+ ewes to the inhibitory effect on steroidogenesis of GDF-5 and BMP-4, natural ligands of BMPR-IB. It is suggested that in FecBB/FecBB ewes, BMPR-IB would be inactivated partially, leading to an advanced differentiation of granulosa cells and an advanced maturation of ovulatory follicles. PMID:11320249

  6. 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.

  7. Different temporal patterns in the expressions of bone morphogenetic proteins and noggin during astroglial scar formation after ischemic stroke.

    Science.gov (United States)

    Shin, Jin A; Kang, Jihee Lee; Lee, Kyung-Eun; Park, Eun-Mi

    2012-05-01

    Bone morphogenetic proteins (BMPs) and their antagonists have roles in scar formation and regeneration after central nervous system injuries. However, temporal changes in their expression during astroglial scar formation in the ischemic brain are unknown. Here, we examined protein levels of BMP2, BMP7, and their antagonist noggin in the ischemic brain up to 4 weeks after experimental stroke in mice. BMP2 and BMP7 levels were increased from 1 to 4 weeks in the ischemic brain, and their expression was associated with astrogliosis. BMP7 expression was more intense and co-localized in reactive astrocytes in the ischemic subcortex at 1 week. Noggin expression began to increase after 2 weeks and was further increased at 4 weeks only in the ischemic subcortex, but the intensity was weak compared to the intensity of BMPs. Noggin was co-localized mainly in activated microglia. These findings show that expression of BMPs and noggin differed over time, in intensity and in types of cell, and suggest that BMPs and noggin have different roles in the processes of glial scar formation and neurorestoration in the ischemic brain.

  8. Recombinant human bone morphogenetic protein-2 promotes the proliferation of mesenchymal stem cells in vivo and in vitro

    Institute of Scientific and Technical Information of China (English)

    LIU Shui-bing; HU Pei-zhen; HOU Ying; LI Peng; CAO Wei; TIAN Qiong

    2009-01-01

    Background Bone morphogenetic protein (BMP) is a member of the superfamily of transforming growth factor-β.Recent studies show that it is an indispensable factor in hematopoiesis.To better characterize the effect of recombinant human BMP (rhBMP)-2 in hematopoiesis,we set out to determine whether rhBMP-2 could promote the proliferation of mesenchymal stem cells (MSCs) and increase the levels of hematopoietic cytokines in MSCs.Methods 2,3-bis (2-methoxy-4-nitro-5-sulfophenyl)-5-((phenylamino) carbonyl)-2H-tetrazolium hydroxide (XTT),real-time polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA) were used to deteMP-2 on the proliferation and hematopoietic cytokine levels of MSCs.In addition,MSCs marked with Hoechst33342 were transplanted into BALB/c mice by the intravenous route or intra-bone marrow transplantation,and cluster numbers were counted.Results The XTT test revealed that rhBMP-2 significantly induced proliferation of MSCs in doses ranging from 10 ng/ml to 0.1 mg/ml in a dose-dependent manner.The experiments in vivo showed that there were more clusters of donor cells in bone marrow,spleen,liver and lung of the BMP group than those in the control group after both intra-bone marrow transplantation (P<0.001,P <0.001,P <0.001,and P=0.001,respectively) and intravenous transplantation (P <0.001,P <0.001,and P <0.001 respectively).The results of real-time PCR and ELISA revealed that rhBMP-2 significantly increased mRNA expressions and protein levels of IL-6,IL-7,IL-11,G-CSF,M-CSF and SCF.Conclusions The treatment with rhBMP-2 promotes the proliferation of MSCs in vivo and in vitro and increases the levels of hematopoietic cytokines in MSCs,which may contribute to the improvement of hematopoietic function.

  9. Evolving New Skeletal Traits by cis-Regulatory Changes in Bone Morphogenetic Proteins.

    Science.gov (United States)

    Indjeian, Vahan B; Kingman, Garrett A; Jones, Felicity C; Guenther, Catherine A; Grimwood, Jane; Schmutz, Jeremy; Myers, Richard M; Kingsley, David M

    2016-01-14

    Changes in bone size and shape are defining features of many vertebrates. Here we use genetic crosses and comparative genomics to identify specific regulatory DNA alterations controlling skeletal evolution. Armor bone-size differences in sticklebacks map to a major effect locus overlapping BMP family member GDF6. Freshwater fish express more GDF6 due in part to a transposon insertion, and transgenic overexpression of GDF6 phenocopies evolutionary changes in armor-plate size. The human GDF6 locus also has undergone distinctive regulatory evolution, including complete loss of an enhancer that is otherwise highly conserved between chimps and other mammals. Functional tests show that the ancestral enhancer drives expression in hindlimbs but not forelimbs, in locations that have been specifically modified during the human transition to bipedalism. Both gain and loss of regulatory elements can localize BMP changes to specific anatomical locations, providing a flexible regulatory basis for evolving species-specific changes in skeletal form. PMID:26774823

  10. Osteogenic efficiency of in situ gelling poloxamine systems with and without bone morphogenetic protein-2

    Directory of Open Access Journals (Sweden)

    A Rey-Rico

    2011-04-01

    Full Text Available In situ gelling solutions for minimally invasive local application of bone growth factors are attracting increasing attention as efficient and patient-friendly alternative to bone grafts and solid scaffolds for repairing bone defects. Poloxamines, i.e., X-shaped poly(ethylene oxide-poly(propylene oxide block copolymers with an ethylenediamine core (Tetronic®, were evaluated both as an active osteogenic component and as a vehicle for rhBMP-2 injectable implants. After cytotoxicity screening of various poloxamine varieties, Tetronic 908, 1107, 1301 and 1307 solutions were chosen as the most cytocompatible and their sol-to-gel transitions were rheologically characterized. Viscoelastic gels, formed at 37 ºC, sustained protein release under physiological-like conditions. Formulations of rhBMP-2 led to differentiation of mesenchymal stem cells to osteoblasts, quantified as alkaline phosphatase activity with a maximum at day 7, and to mineralized nodules. Interestingly, poloxamine solely gels led to an initial proliferation of the mesenchymal stem cells (first week, followed by differentiation to osteoblasts (second to third week. Histochemical analysis revealed that Tetronic 908 is only osteoinductive; Tetronic 1107 is mostly osteoinductive, although its use leads to a minor differentiation to adipocytes; Tetronic 1307, solely or loaded with rhBMP-2, causes differentiation of both osteoblasts and adipocytes. Enhanced expression levels of CBFA-1 and collagen type I were observed for Tetronic 908, 1107 and 1307, both solely and combined with rhBMP-2. The intrinsic osteogenic activity of poloxamines (not observed for Pluronic F127 offers novel perspectives for bone regeneration using minimally invasive procedures (i.e., injectable scaffolds and overcoming the safety and the cost/effectiveness concerns associated with large scale clinical use of recombinant growth factors.

  11. Kartogenin, transforming growth factor-β1 and bone morphogenetic protein-7 coordinately enhance lubricin accumulation in bone-derived mesenchymal stem cells.

    Science.gov (United States)

    Liu, Chun; Ma, Xueqin; Li, Tao; Zhang, Qiqing

    2015-09-01

    Osteoarthritis, a common joint degeneration, can cause breakdown of articular cartilage with the presence of lubricin metabolic abnormalities. Lubricin is a multi-level chondroprotective mucinous glycoprotein in articular joints. Joint defect and infection is elevated and accompanied by accelerated cartilage lesions involving degradation and loss of lubricin. However, a novel, heterocyclic compound called kartogenin (KGN) was discovered to stimulate chondrogenic differentiation of bone-derived mesenchymal stem cells (BMSCs). And the synergistic effect of transforming growth factor-β1 (TGF-β1) and bone morphogenetic protein-7 (BMP-7) could provoke lubricin accumulation. This paper attempted to explore the connection between accumulation of lubricin and the effect of TGF-β1, BMP-7 and/or KGN. Hence, we investigated the expression and secretion of lubricin in BMSCs treated with different combinations of TGF-β1, BMP-7, and/or KGN. Using an in vitro BMSCs system, we observed the content of lubricin from BMSCs treated with TGF-β1, BMP-7, and KGN was the highest at both the protein level and the gene level. The accumulation of lubricin was enhanced coordinately by the increase of synthesis and decrease of degradation possibly via c-Myc and adamts5 pathway. These results further suggested that supplementation of the defect parts with lubricin by using growth factors and small molecules showed a promising potential on preventing joint deterioration in patients with acquired or genetic deficiency of lubricin in the future of regenerative medicine. PMID:25857705

  12. Kartogenin, transforming growth factor-β1 and bone morphogenetic protein-7 coordinately enhance lubricin accumulation in bone-derived mesenchymal stem cells.

    Science.gov (United States)

    Liu, Chun; Ma, Xueqin; Li, Tao; Zhang, Qiqing

    2015-09-01

    Osteoarthritis, a common joint degeneration, can cause breakdown of articular cartilage with the presence of lubricin metabolic abnormalities. Lubricin is a multi-level chondroprotective mucinous glycoprotein in articular joints. Joint defect and infection is elevated and accompanied by accelerated cartilage lesions involving degradation and loss of lubricin. However, a novel, heterocyclic compound called kartogenin (KGN) was discovered to stimulate chondrogenic differentiation of bone-derived mesenchymal stem cells (BMSCs). And the synergistic effect of transforming growth factor-β1 (TGF-β1) and bone morphogenetic protein-7 (BMP-7) could provoke lubricin accumulation. This paper attempted to explore the connection between accumulation of lubricin and the effect of TGF-β1, BMP-7 and/or KGN. Hence, we investigated the expression and secretion of lubricin in BMSCs treated with different combinations of TGF-β1, BMP-7, and/or KGN. Using an in vitro BMSCs system, we observed the content of lubricin from BMSCs treated with TGF-β1, BMP-7, and KGN was the highest at both the protein level and the gene level. The accumulation of lubricin was enhanced coordinately by the increase of synthesis and decrease of degradation possibly via c-Myc and adamts5 pathway. These results further suggested that supplementation of the defect parts with lubricin by using growth factors and small molecules showed a promising potential on preventing joint deterioration in patients with acquired or genetic deficiency of lubricin in the future of regenerative medicine.

  13. Management of subtrochanteric femur fractures with internal fixation and recombinant human bone morphogenetic protein-7 in a patient with osteopetrosis: a case report

    Directory of Open Access Journals (Sweden)

    Golden Robert D

    2010-05-01

    Full Text Available Abstract Introduction Osteopetrosis is a group of conditions characterized by defects in the osteoclastic function of the bone resulting in defective bone resorption. Clinically, the condition is characterized by a dense, sclerotic, deformed bone which, despite an increased density observable by radiography, often results in an increased propensity to fracture and delayed union. Case Presentation We report the case of a 27-year-old Asian man presenting with bilateral subtrochanteric femur fractures. He had a displaced right subtrochanteric femur fracture after a low-energy fall, which was treated surgically. The second fracture that our patient endured was diagnosed as a stress fracture ten weeks later when he complained of pain in the contralateral left thigh. By that time, the right-sided fracture exhibited no radiographic evidence of healing, and when the left-sided stress fracture was being treated surgically, bone grafting with recombinant human bone morphogenetic protein-7 was also performed on the right side. Conclusion While there are no data supporting the use of bone morphogenic proteins in the management of delayed healing in patients with osteopetrosis, no other reliable osteoinductive grafting options are available to treat this condition. Both fractures in our patient healed, but based on the serial radiographic assessment it is uncertain to what degree the recombinant human bone morphogenetic protein-7 may have contributed to the successful outcome. It may have also contributed to the formation of heterotopic bone around the fracture site. Further investigation of the effectiveness and indications of bone morphogenic protein use for the management of delayed fracture healing in patients with osteopetrosis is warranted.

  14. 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.

  15. Bone morphogenetic protein-1 and its related metalloproteinase%骨形态发生蛋白-1及其相关金属蛋白酶

    Institute of Scientific and Technical Information of China (English)

    陈冬瑛; 朱全胜; 丘钜世

    2004-01-01

    Bone morphogenetic protein-1(BMP-1) and its related molecules are members of metalloendoproteinase astacin family, including BMP-1, mTLD, mTLL-1 and mTLL-2. Even though all of them lack of the ability to induce bone or cartilage formation directly, they play key roles in numerable activities in ECM from embryo to adult, then affect the procedure and the result of osteogenesis and bone remodeling directly or indirectly. They are critical in maturation and deposition of some major collagen types, and in regulating the signaling of some growth factors in TGF-β superfamily by degradation of TGF-β inhibitor such as Chordin. The investigations about tissue distribution of BMP-1 and its related proteinases and also gene knock-out studies strongly indicate that they play key roles in osteogenesis and bone development.

  16. 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

  17. 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.

  18. Controlled spatial and conformational display of immobilised bone morphogenetic protein-2 and osteopontin signalling motifs regulates osteoblast adhesion and differentiation in vitro

    Directory of Open Access Journals (Sweden)

    McCaskie Andrew W

    2010-05-01

    Full Text Available Abstract Background The interfacial molecular mechanisms that regulate mammalian cell growth and differentiation have important implications for biotechnology (production of cells and cell products and medicine (tissue engineering, prosthetic implants, cancer and developmental biology. We demonstrate here that engineered protein motifs can be robustly displayed to mammalian cells in vitro in a highly controlled manner using a soluble protein scaffold designed to self assemble on a gold surface. Results A protein was engineered to contain a C-terminal cysteine that would allow chemisorption to gold, followed by 12 amino acids that form a water soluble coil that could switch to a hydrophobic helix in the presence of alkane thiols. Bioactive motifs from either bone morphogenetic protein-2 or osteopontin were added to this scaffold protein and when assembled on a gold surface assessed for their ability to influence cell function. Data demonstrate that osteoblast adhesion and short-term responsiveness to bone morphogenetic protein-2 is dependent on the surface density of a cell adhesive motif derived from osteopontin. Furthermore an immobilised cell interaction motif from bone morphogenetic protein supported bone formation in vitro over 28 days (in the complete absence of other osteogenic supplements. In addition, two-dimensional patterning of this ligand using a soft lithography approach resulted in the spatial control of osteogenesis. Conclusion These data describe an approach that allows the influence of immobilised protein ligands on cell behaviour to be dissected at the molecular level. This approach presents a durable surface that allows both short (hours or days and long term (weeks effects on cell activity to be assessed. This widely applicable approach can provide mechanistic insight into the contribution of immobilised ligands in the control of cell activity.

  19. Bone morphogenetic proteins regulate osteoprotegerin and its ligands in human vascular smooth muscle cells

    DEFF Research Database (Denmark)

    Knudsen, Kirsten Quyen Nguyen; Olesen, Ping; Ledet, Thomas;

    2007-01-01

    ) and TNF-related apoptosis-inducing ligand (TRAIL) in HVSMC. All three growth factors decreased OPG protein production significantly; these results were paralleled by reduced OPG mRNA expression. TRAIL mRNA levels were also decreased. RANKL mRNA expression declined when treated with TGF-beta1 but were......The bone-related protein osteoprotegerin (OPG) may be involved in the development of vascular calcifications, especially in diabetes, where it has been found in increased amounts in the arterial wall. Experimental studies suggest that members of the TGF-superfamily are involved in the...... transformation of human vascular smooth muscle cells (HVSMC) to osteoblast-like cells. In this study, we evaluated the effect of BMP-2, BMP-7 and transforming growth factor beta (TGF-beta1) on the secretion and mRNA expression of OPG and its ligands receptor activator of nuclear factor-kappabeta ligand (RANKL...

  20. 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.

  1. Smad5 determines murine amnion fate through the control of bone morphogenetic protein expression and signalling levels.

    Science.gov (United States)

    Bosman, Erika A; Lawson, Kirstie A; Debruyn, Joke; Beek, Lisette; Francis, Annick; Schoonjans, Luc; Huylebroeck, Danny; Zwijsen, An

    2006-09-01

    Smad5 is an intracellular mediator of bone morphogenetic protein (Bmp) signalling. It is essential for primordial germ cell (PGC) development, for the development of the allantois and for amnion closure, as demonstrated by loss of Bmp signalling. By contrast, the appearance of ectopic PGC-like cells and regionalized ectopic vasculogenesis and haematopoiesis in thickened Smad5(m1/m1) amnion are amnion defects that have not been associated with loss of Bmp signalling components. We show that defects in amnion and allantois can already be detected at embryonic day (E) 7.5 in Smad5 mutant mice. However, ectopic Oct4-positive (Oct4(+)) and alkaline phosphatase-positive (AP(+)) cells appear suddenly in thickened amnion at E8.5, and at a remote distance from the allantois and posterior primitive streak, suggesting a change of fate in situ. These ectopic Oct4(+), AP(+) cells appear to be Stella negative and hence cannot be called bona fide PGCs. We demonstrate a robust upregulation of Bmp2 and Bmp4 expression, as well as of Erk and Smad activity, in the Smad5 mutant amnion. The ectopic expression of several Bmp target genes in different domains and the regionalized presence of cells of several Bmp-sensitive lineages in the mutant amnion suggest that different levels of Bmp signalling may determine cell fate. Injection of rBMP4 in the exocoelom of wild-type embryos can induce thickening of amnion, mimicking the early amnion phenotype in Smad5 mutants. These results support a model in which loss of Smad5 results paradoxically in gain of Bmp function defects in the amnion. PMID:16887830

  2. Mutation analysis of exon1 of bone morphogenetic protein-15 gene in Iranian patients with polycystic ovarian syndrome

    Science.gov (United States)

    Mehdizadeh, Anahita; Sheikhha, Mohammad Hasan; Kalantar, Seyed Mehdi; Aali, Bibi Shahnaz; Ghanei, Azam

    2016-01-01

    Background: With the prevalence of 6-10%, polycystic ovarian syndrome (PCOS) is considered the most common endocrinological disorder affecting women in their reproductive age. It has been suggested that genetic factors participate in the development of PCOS. Follicular development has been considered as one of the impaired processes in PCOS. Bone morphogenetic protein-15 (BMP-15) gene is a candidate gene in follicular development and its variants may play role in pathogenesis of PCOS. Objective: To investigate whether BMP-15 gene mutations are present in Iranian women with PCOS. Materials and Methods: In this cross-sectional study 5 ml venous blood samples was taken from 70 PCOS women referring to Afzalipour Hospital, Kerman University of Medical Sciences, Kerman, Iran, between January to December 2014. Genomic DNA was extracted from the blood sample by salting out method. Then a set of PCR reactions for exon1 of BMP-15 gene was performed using specific primers followed by genotyping with direct sequencing. Results: Two different polymorphisms were found in the gene under study. In total 20 patients (28.6%) were heterozygote (C/G), and 2 patients (2.86%) were homozygous (G/G) for c.-9C>G in 5´UTR promoter region of BMP-15 gene (rs3810682). In addition, in the coding region of exon1, three patients (4.3%) were heterozygote (G/A) for c.A308G (rs41308602). Two PCOS patients (2.86%) appeared to have both c.-9C>G (C/G) and c.A308G (G/A) variants simultaneously. Conclusion: Our research detected two polymorphisms of BMP-15 gene among PCOS patients, indicating that even though it cannot be concluded that variants of BMP-15 gene are the principal cause of polycystic ovarian syndrome; they could be involved in pathogenic process in development of PCOS. PMID:27679828

  3. Endoglin-mediated suppression of prostate cancer invasion is regulated by activin and bone morphogenetic protein type II receptors.

    Directory of Open Access Journals (Sweden)

    Michael J Breen

    Full Text Available Mortality from prostate cancer (PCa is due to the formation of metastatic disease. Understanding how that process is regulated is therefore critical. We previously demonstrated that endoglin, a type III transforming growth factor β (TGFβ superfamily receptor, suppresses human PCa cell invasion and metastasis. Endoglin-mediated suppression of invasion was also shown by us to be dependent upon the type I TGFβ receptor, activin receptor-like kinase 2 (ALK2, and the downstream effector, Smad1. In this study we demonstrate for the first time that two type II TGFβ receptors are required for endoglin-mediated suppression of invasion: activin A receptor type IIA (ActRIIA and bone morphogenetic protein receptor type II (BMPRII. Downstream signaling through these receptors is predominantly mediated by Smad1. ActRIIA stimulates Smad1 activation in a kinase-dependent manner, and this is required for suppression of invasion. In contrast BMPRII regulates Smad1 in a biphasic manner, promoting Smad1 signaling through its kinase domain but suppressing it through its cytoplasmic tail. BMPRII's Smad1-regulatory effects are dependent upon its expression level. Further, its ability to suppress invasion is independent of either kinase function or tail domain. We demonstrate that ActRIIA and BMPRII physically interact, and that each also interacts with endoglin. The current findings demonstrate that both BMPRII and ActRIIA are necessary for endoglin-mediated suppression of human PCa cell invasion, that they have differential effects on Smad1 signaling, that they make separate contributions to regulation of invasion, and that they functionally and physically interact.

  4. 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.

  5. 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.

  6. Union Rate and Complications in Spine Fusion with Recombinant Human Bone Morphogenetic Protein-7: Systematic Review and Meta-Analysis.

    Science.gov (United States)

    Vavken, Julia; Vavken, Patrick; Mameghani, Alexander; Schaeren, Stefan

    2016-03-01

    Study Design Systematic review and meta-analysis. Objective The objective of this meta-analysis was to evaluate the current best evidence to assess effectiveness and safety of recombinant human bone morphogenetic protein-7 (rhBMP-7) as a biological stimulant in spine fusion. Methods Studies were included if they reported on outcomes after spine fusion with rhBMP-7. The data was synthesized using Mantel-Haenszel pooled risk ratios (RRs) with 95% confidence intervals (CIs). Main end points were union rate, overall complications, postoperative back and leg pain, revision rates, and new-onset cancer. Results Our search produced 796 studies, 6 of which were eligible for inclusion. These studies report on a total of 442 patients (328 experimental, 114 controls) with a mean age of 59 ± 11 years. Our analysis showed no statistically significant differences in union rates (RR 0.97, 95% CI 0.84 to 1.11, p = 0.247), overall complications (RR 0.92, 95% CI 0.71 to 1.20, p = 0.545), postoperative back and leg pain (RR 1.03, 95% CI 0.48 to 2.19, p = 0.941), or revision rate (RR 0.81, 95% CI 0.47 to 1.40, p = 0.449). There was a mathematical indicator of increased tumor rates, but with only one case, the clinical meaningfulness of this finding is questionable. Conclusion We were not able to find data in support of the use of rhBMP-7 for spine fusion. We found no evidence for increased complication or revision rates with rhBMP-7. On the other hand, we also found no evidence in support of improved union rates. PMID:26933613

  7. Inhibition of bone morphogenetic protein signal transduction prevents the medial vascular calcification associated with matrix Gla protein deficiency.

    Directory of Open Access Journals (Sweden)

    Rajeev Malhotra

    Full Text Available Matrix Gla protein (MGP is reported to inhibit bone morphogenetic protein (BMP signal transduction. MGP deficiency is associated with medial calcification of the arterial wall, in a process that involves both osteogenic transdifferentiation of vascular smooth muscle cells (VSMCs and mesenchymal transition of endothelial cells (EndMT. In this study, we investigated the contribution of BMP signal transduction to the medial calcification that develops in MGP-deficient mice.MGP-deficient mice (MGP(-/- were treated with one of two BMP signaling inhibitors, LDN-193189 or ALK3-Fc, beginning one day after birth. Aortic calcification was assessed in 28-day-old mice by measuring the uptake of a fluorescent bisphosphonate probe and by staining tissue sections with Alizarin red. Aortic calcification was 80% less in MGP(-/- mice treated with LDN-193189 or ALK3-Fc compared with vehicle-treated control animals (P<0.001 for both. LDN-193189-treated MGP(-/- mice survived longer than vehicle-treated MGP(-/- mice. Levels of phosphorylated Smad1/5 and Id1 mRNA (markers of BMP signaling did not differ in the aortas from MGP(-/- and wild-type mice. Markers of EndMT and osteogenesis were increased in MGP(-/- aortas, an effect that was prevented by LDN-193189. Calcification of isolated VSMCs was also inhibited by LDN-193189.Inhibition of BMP signaling leads to reduced vascular calcification and improved survival in MGP(-/- mice. The EndMT and osteogenic transdifferentiation associated with MGP deficiency is dependent upon BMP signaling. These results suggest that BMP signal transduction has critical roles in the development of vascular calcification in MGP-deficient mice.

  8. Attenuation of bone morphogenetic protein signaling during amphibian limb development results in the generation of stage-specific defects.

    Science.gov (United States)

    Jones, Tamsin E M; Day, Robert C; Beck, Caroline W

    2013-11-01

    The vertebrate limb is one of the most intensively studied organs in the field of developmental biology. Limb development in tetrapod vertebrates is highly conserved and dependent on the interaction of several important molecular pathways. The bone morphogenetic protein (BMP) signaling cascade is one of these pathways and has been shown to be crucial for several aspects of limb development. Here, we have used a Xenopus laevis transgenic line, in which expression of the inhibitor Noggin is under the control of the heat-shock promoter hsp70 to examine the effects of attenuation of BMP signaling at different stages of limb development. Remarkably different phenotypes were produced at different stages, illustrating the varied roles of BMP in development of the limb. Very early limb buds appeared to be refractory to the effects of BMP attenuation, developing normally in most cases. Ectopic limbs were produced by overexpression of Noggin corresponding to a brief window of limb development at about stage 49/50, as recently described by Christen et al. (2012). Attenuation of BMP signaling in stage 51 or 52 tadpoles lead to a reduction in the number of digits formed, resulting in hypodactyly or ectrodactyly, as well as occasional defects in the more proximal tibia-fibula. Finally, inhibition at stage 54 (paddle stage) led to the formation of dramatically shortened digits resulting from loss of distal phalanges. Transcriptome analysis has revealed the possibility that more Noggin-sensitive members of the BMP family could be involved in limb development than previously suspected. Our analysis demonstrates the usefulness of heat-shock-driven gene expression as an effective method for inhibiting a developmental pathway at different times during limb development. PMID:23981117

  9. Furin is the major processing enzyme of the cardiac-specific growth factor bone morphogenetic protein 10.

    Science.gov (United States)

    Susan-Resiga, Delia; Essalmani, Rachid; Hamelin, Josée; Asselin, Marie-Claude; Benjannet, Suzanne; Chamberland, Ann; Day, Robert; Szumska, Dorota; Constam, Daniel; Bhattacharya, Shoumo; Prat, Annik; Seidah, Nabil G

    2011-07-01

    Bone morphogenetic protein 10 (BMP10) is a member of the TGF-β superfamily and plays a critical role in heart development. In the postnatal heart, BMP10 is restricted to the right atrium. The inactive pro-BMP10 (∼60 kDa) is processed into active BMP10 (∼14 kDa) by an unknown protease. Proteolytic cleavage occurs at the RIRR(316)↓ site (human), suggesting the involvement of proprotein convertase(s) (PCs). In vitro digestion of a 12-mer peptide encompassing the predicted cleavage site with furin, PACE4, PC5/6, and PC7, showed that furin cleaves the best, whereas PC7 is inactive on this peptide. Ex vivo studies in COS-1 cells, a cell line lacking PC5/6, revealed efficient processing of pro-BMP10 by endogenous PCs other than PC5/6. The lack of processing of overexpressed pro-BMP10 in the furin- and PACE4-deficient cell line, CHO-FD11, and in furin-deficient LoVo cells, was restored by stable (CHO-FD11/Fur cells) or transient (LoVo cells) expression of furin. Use of cell-permeable and cell surface inhibitors suggested that endogenous PCs process pro-BMP10 mostly intracellularly, but also at the cell surface. Ex vivo experiments in mouse primary hepatocytes (wild type, PC5/6 knock-out, and furin knock-out) corroborated the above findings that pro-BMP10 is a substrate for endogenous furin. Western blot analyses of heart right atria extracts from wild type and PACE4 knock-out adult mice showed no significant difference in the processing of pro-BMP10, implying no in vivo role of PACE4. Overall, our in vitro, ex vivo, and in vivo data suggest that furin is the major convertase responsible for the generation of BMP10.

  10. Furin Is the Major Processing Enzyme of the Cardiac-specific Growth Factor Bone Morphogenetic Protein 10*

    Science.gov (United States)

    Susan-Resiga, Delia; Essalmani, Rachid; Hamelin, Josée; Asselin, Marie-Claude; Benjannet, Suzanne; Chamberland, Ann; Day, Robert; Szumska, Dorota; Constam, Daniel; Bhattacharya, Shoumo; Prat, Annik; Seidah, Nabil G.

    2011-01-01

    Bone morphogenetic protein 10 (BMP10) is a member of the TGF-β superfamily and plays a critical role in heart development. In the postnatal heart, BMP10 is restricted to the right atrium. The inactive pro-BMP10 (∼60 kDa) is processed into active BMP10 (∼14 kDa) by an unknown protease. Proteolytic cleavage occurs at the RIRR316↓ site (human), suggesting the involvement of proprotein convertase(s) (PCs). In vitro digestion of a 12-mer peptide encompassing the predicted cleavage site with furin, PACE4, PC5/6, and PC7, showed that furin cleaves the best, whereas PC7 is inactive on this peptide. Ex vivo studies in COS-1 cells, a cell line lacking PC5/6, revealed efficient processing of pro-BMP10 by endogenous PCs other than PC5/6. The lack of processing of overexpressed pro-BMP10 in the furin- and PACE4-deficient cell line, CHO-FD11, and in furin-deficient LoVo cells, was restored by stable (CHO-FD11/Fur cells) or transient (LoVo cells) expression of furin. Use of cell-permeable and cell surface inhibitors suggested that endogenous PCs process pro-BMP10 mostly intracellularly, but also at the cell surface. Ex vivo experiments in mouse primary hepatocytes (wild type, PC5/6 knock-out, and furin knock-out) corroborated the above findings that pro-BMP10 is a substrate for endogenous furin. Western blot analyses of heart right atria extracts from wild type and PACE4 knock-out adult mice showed no significant difference in the processing of pro-BMP10, implying no in vivo role of PACE4. Overall, our in vitro, ex vivo, and in vivo data suggest that furin is the major convertase responsible for the generation of BMP10. PMID:21550985

  11. 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

  12. Increased osteoinductivity and mineralization by minimal concentration of bone morphogenetic protein-2 loaded onto biphasic calcium phosphate in a rabbit sinus

    Science.gov (United States)

    2016-01-01

    Purpose The purpose of the present study was to evaluate the effectiveness of a minimal concentration of bone morphogenetic protein-2 (BMP-2) in terms of quantitative and qualitative analyses of newly formed bone in a rabbit maxillary sinus model. Methods In 7 rabbits, sinus windows were prepared bilaterally. Biphasic calcium phosphate (BCP) loaded with 0.05 mg/mL BMP-2 was grafted into one sinus (the BMP group) and saline-soaked BCP was placed into the other (the control group) in each animal. The animals were allowed an 8-week healing period before being sacrificed. Specimens including the augmented area and surrounding tissues were then removed and evaluated both radiographically and histologically. Results There was a difference in the mineralization of new bone between the groups. In the BMP group, the greater part of the new bone consisted of mature lamellar bone with an evident trabecular pattern, whereas the control group showed mostly woven bone, consisting only partially of lamellar bone. Histometrically, the area of new bone was significantly greater (4.55±1.35 mm2 vs. 2.99±0.86 mm2) in the BMP group than in the control group (Pmineralization in a rabbit sinus model using a BCP carrier. PMID:27800217

  13. 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.)

  14. A new growth factor controlled drug release system to promote healing of bone fractures: nanospheres of recombinant human bone morphogenetic-2 and polylactic acid.

    Science.gov (United States)

    Chen, Lin; Liu, Lei; Li, Cai; Tan, Yinghui; Zhang, Gang

    2011-04-01

    To prepare a new drug control release system, which can markedly promote the healing of bone fractures. Optimized water-in-oil-in-water multiple emulsion evaporation method, prepared nanospheres of recombinant human bone morphogenetic-2 and polylactic acid (rhBMP-2-PLA-Ns). Its physical character was determined by the enzyme linked immunosorbent assay method. Its bioactivity was measured with the microculture tetrazolium test immunohistochemical analyses, alizarin red staining and western blot analysis. rhBMP-2-PLA-Ns exhibited an even and uniform spherical appearance without adhesion, with a particle size distribution between 35 and 65 nm, and a mean size of 45 nm. The drug loading volume and encapsulation efficiency reached ([124.73 +/- 0.41] x 10(-3))% and (90.54 +/- 1.32)%, respectively. The drug release in vitro persisted for 14 days, with a mean concentration of 73.44 +/- 5.38 ng/ml, and corresponded to the Higuichi equation (r = 0.9962). The microculture tetrazolium test showed that 4 days later, the optical density value ranking was rhBMP-2-PLA-N group > rhBMP-2 group > blank control group. Fluorescence immunocytochemical analysis showed that 10 days later the fluorescent density of the rhBMP-2-PLA-N group was significantly higher than the other two groups. Western blot analysis confirmed that the amount of vascular endothelial growth factor in the rhBMP-2-PLA-N group was the greatest. This study showed that rhBMP-2-PLA-Ns have excellent biological activity, can promote proliferation, differentiation and mineralization of osteoblasts. The drug release time is suitable for fracture healing and is an ideal delivery system for fracture healing. PMID:21776677

  15. 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

    Full Text Available Chunyan Qiao,1,* Kai Zhang,2,* Han Jin,1 Leiying Miao,3 Ce Shi,1 Xia Liu,1 Anliang Yuan,1 Jinzhong Liu,1 Daowei Li,1 Changyu Zheng,4 Guirong Zhang,5 Xiangwei Li,1 Bai Yang,2 Hongchen Sun11Department of Pathology, School of Stomatology, Jilin University, Changchun, 2State Key Laboratory of Supramolecular Structure and Materials, College of Chemistry, Jilin University, Changchun, 3Institute and Hospital of Stomatology, Nanjing University Medical School, Nanjing, People's Republic of China; 4Molecular Physiology and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA; 5Department of Biochemistry, School of Basic Medicine, Jilin University, Changchun, People's Republic of China*These authors contributed equally to this workAbstract: Repair of large bone defects is a major challenge, requiring sustained stimulation to continually promote bone formation locally. Bone morphogenetic protein 2 (BMP-2 plays an important role in bone development. In an attempt to overcome this difficulty of bone repair, we created a delivery system to slowly release human BMP-2 cDNA plasmid locally, efficiently transfecting local target cells and secreting functional human BMP-2 protein. For transfection, we used polyethylenimine (PEI to create pBMP-2/PEI nanoparticles, and to ensure slow release we used poly(lactic-co-glycolic acid (PLGA to create microsphere encapsulated pBMP-2/PEI nanoparticles, PLGA@pBMP-2/PEI. We demonstrated that pBMP-2/PEI nanoparticles could slowly release from the PLGA@pBMP-2/PEI microspheres for a long period of time. The 3–15 µm diameter of the PLGA@pBMP-2/PEI further supported this slow release ability of the PLGA@pBMP-2/PEI. In vitro transfection assays demonstrated that pBMP-2/PEI released from PLGA@pBMP-2/PEI could efficiently transfect MC3T3-E1 cells, causing MC3T3-E1 cells to secrete human BMP-2 protein, increase calcium deposition and gene expressions of alkaline

  16. Expression of bone morphogenetic protein 7 in the cerebral cortex of rats after ischemic-hypoxic injury

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    BACKGROUND: Some researches demonstrate that exogenous bone morphogenetic protein 7 (BMP-7) can protect ischemic cerebral nerve tissue and promote recovery of motor energy function; however, there is lack of direct evidences of endogenous BMP-7 effect.OBJECTIVE: To observe the expression of endogenous BMP-7 in nerve tissue with ischemic-hypoxic injury and investigate the possible effects on damaged nerve tissue.DESIGN: Observational contrast animal study.SETTING: Department of Anatomy and Histoembryology, Peking University Health Science Center.MATERIALS: The experiment was carried out in the Nerve Researching Laboratory of Anatomy Department, Peking University Health Science Center from October 2006 to March 2007. A total of 25 adult male SD rats weighing 250 - 300 g and several newborn SD rats were selected from Experimental Animal Center, Peking University Health Science Center. Rabbit-anti-BMP-7 polyclonal antibody was provided by Wuhan Boster Company.METHODS: ① Adult rats were randomly divided into ischemia group (n =10), sham operation group (n =10) and normal group (n =5). Right external-internal carotid artery occlusion was used to infarct middle cerebral artery of adult rats in the ischemia group so as to copy focal cerebral infarction models. Line cork was inserted in crotch of internal and external carotid artery of adult rats in the sham operation group, while adult rats in the normal group were not given any treatments. ② Cerebral cortex of newborn rats was separated to obtain cell suspension. Cells which were cultured for 10 days were divided into control group and hypoxia/reoxygenation group. And then, cells in the hypoxia/reoxygenation group were cultured in hypoxic incubator for 4 hours and given reoxygenation for 24 hours.MAIN OUTCOME MEASURES: Immunohistochemical method was used to measure expression of BMP-7 in cerebral cortex at 24 hours after ischemia/reperfusion culture and in primary hypoxic culture.RESULTS: ① At 24 hours after

  17. Bone morphogenetic protein-15 in follicle fluid combined with age may differentiate between successful and unsuccessful poor ovarian responders

    Directory of Open Access Journals (Sweden)

    Wu Yan-Ting

    2012-12-01

    Full Text Available Abstract Background The counselling of poor ovarian responders about the probability of pregnancy remains a puzzle for gynaecologists. The aim of this study was to optimise the management of poor responders by investigating the role of the oocyte-derived factor bone morphogenetic protein-15 (BMP-15 combined with chronological age in the prediction of the outcome of in-vitro fertilisation-embryo transfer (IVF-ET in poor responders. Methods A retrospective study conducted in a university hospital. A total of 207 poor ovarian responders who reached the ovum pick-up stage undergoing IVF/intracytoplasmic sperm injection (ICSI with three or fewer follicles no less than 14 mm on the day of oocyte retrieval were recruited from July 1, 2008 to December 31, 2009. Another 215 coinstantaneous cycles with normal responses were selected as controls. The BMP-15 levels in the follicular fluid (FF of the 207 poor responders were analysed by western blot. Based on the FF BMP-15 level and age, poor responders were sub-divided into four groups. The main outcome measures were the FF BMP-15 level, implantation rate, pregnancy rate, and live birth rate. Results The implantation rate (24.2% vs. 15.3%, chemical pregnancy rate (40% vs. 23.7%, clinical pregnancy rate (36.5% vs. 20.4% and live birth rate (29.4% vs. 15.1% in the high BMP-15 group were significantly higher than those in the low BMP-15 group. Furthermore, poor responders aged less than or equal to 35 years with a higher FF BMP-15 level had the best implantation, pregnancy and live birth rates, which were comparable with those of normal responders. Conclusions Our study suggests a potential role of BMP-15 in the prediction of the IVF outcome. A high FF BMP-15 combined with an age less than or equal to 35 years may be used as a potential indicator for repeating IVF cycles in poor ovarian responders.

  18. [Effects of phosphatidylinositol-3 kinase/protein kinase b/bone morphogenetic protein-15 pathway on the follicular development in the mammalian ovary].

    Science.gov (United States)

    Wu, Yan-qing; Chen, Li-yun; Zhang, Zheng-hong; wang, Zheng-chao

    2013-04-01

    In mammals, ovarian follicle is made of an oocyte with its surrounding granulosa cells and theca cells. Follicular growth and development is a highly coordinated programmable process, which guarantees the normal oocyte maturation and makes it having the fertilizing capacity. The paracrine and autocrine between oocytes and granulosa cells are essential for the follicular development to provide a suitable microenvironment. Phosphatidylinositol-3 kinase /protein kinase B is one of these important regulatory signaling pathways during this developmental process, and bone morphogenetic protein-15 an oocyte-specific secreted signal molecule, which regulates the follicular development by paracrine in the mammalian ovary. The present article overviewed the role of phosphatidylinositol-3 kinase / protein kinase B signaling during the follicular development based on our previous investigation about protein kinase B /forkhead transcription factor forkhead family of transcription factors -3a, and then focused on the regulatory effects of bone morphogenetic protein-15, as a downstream signal molecule of phosphatidylinositol-3 kinase / forkhead family of transcription factors -3a pathway, on ovarian follicular development, which helped to further understand the molecular mechanism regulating the follicular development and to treat ovarian diseases like infertility.

  19. Revised Proposal for the Prevention of Low Bone Mass in Patients with Classic Galactosemia

    OpenAIRE

    van Erven, Britt; Römers, Myrna M. M.; Rubio-Gozalbo, M. Estela

    2014-01-01

    Decreased bone mass is frequently encountered in classic galactosemia, an inborn error of galactose metabolism. This decrease is most prominent in adults, but is already seen in prepubertal children with increased risk of osteoporosis and fractures later in life. Therefore, bone health in patients with classic galactosemia is increasingly monitored. Although the pathophysiological mechanism is still not fully understood, several factors could negatively affect bone metabolism in this disease....

  20. Development of a morphogenetically active scaffold for three-dimensional growth of bone cells: biosilica-alginate hydrogel for SaOS-2 cell cultivation.

    Science.gov (United States)

    Müller, Werner E G; Schröder, Heinz C; Feng, Qingling; Schlossmacher, Ute; Link, Thorben; Wang, Xiaohong

    2015-11-01

    Polymeric silica is formed from ortho-silicate during a sol-gel formation process, while biosilica is the product of an enzymatically driven bio-polycondensation reaction. Both polymers have recently been described as a template that induces an increased expression of the genes encoding bone morphogenetic protein 2 (BMP-2) and osteoprotegerin in osteoblast-related SaOS-2 cells; simultaneously or subsequently the cells respond with enhanced hydroxyapatite formation. In order to assess whether the biocompatible polymeric silica/biosilica can serve as a morphogenetically active matrix suitable for three-dimensional (3D) cell growth, or even for 3D cell bioprinting, SaOS-2 cells were embedded into a Na-alginate-based hydrogel. Four different gelatinous hydrogel matrices were used for suspending SaOS-2 cells: (a) the hydrogel alone; (b) the hydrogel with 400 μM ortho-silicate; (c) the hydrogel supplemented with 400 μM ortho-silicate and recombinant silicatein to allow biosilica synthesis to occur; and (d) the hydrogel with ortho-silicate and BSA. The SaOS-2 cells showed an increased growth if silica/biosilica components were present in the hydrogel. Likewise intensified was the formation of hydroxyapatite nodules in the silica-containing hydrogels. After an incubation period of 2 weeks, cells present in silica-containing hydrogels showed a significantly higher expression of the genes encoding the cytokine BMP-2, the major fibrillar structural protein collagen 1 and likewise of carbonic anhydrase. It is concluded that silica, and to a larger extent biosilica, retains its morphogenetic/osteogenic potential after addition to Na-alginate-based hydrogels. This property might qualify silica hydrogels to be also used as a matrix for 3D cell printing.

  1. Neuropeptide Y, substance P, and human bone morphogenetic protein 2 stimulate human osteoblast osteogenic activity by enhancing gap junction intercellular communication

    Energy Technology Data Exchange (ETDEWEB)

    Ma, W.H.; Liu, Y.J.; Wang, W.; Zhang, Y.Z. [The Third Hospital of Hebei Medical University, The Provincial Key Laboratory for Orthopedic Biomechanics of Hebei, Shijiazhuang, Hebei Province (China)

    2015-02-13

    Bone homeostasis seems to be controlled by delicate and subtle “cross talk” between the nervous system and “osteo-neuromediators” that control bone remodeling. The purpose of this study was to evaluate the effect of interactions between neuropeptides and human bone morphogenetic protein 2 (hBMP2) on human osteoblasts. We also investigated the effects of neuropeptides and hBMP2 on gap junction intercellular communication (GJIC). Osteoblasts were treated with neuropeptide Y (NPY), substance P (SP), or hBMP2 at three concentrations. At various intervals after treatment, cell viability was measured by the MTT assay. In addition, cellular alkaline phosphatase (ALP) activity and osteocalcin were determined by colorimetric assay and radioimmunoassay, respectively. The effects of NPY, SP and hBMP on GJIC were determined by laser scanning confocal microscopy. The viability of cells treated with neuropeptides and hBMP2 increased significantly in a time-dependent manner, but was inversely associated with the concentration of the treatments. ALP activity and osteocalcin were both reduced in osteoblasts exposed to the combination of neuropeptides and hBMP2. The GJIC of osteoblasts was significantly increased by the neuropeptides and hBMP2. These results suggest that osteoblast activity is increased by neuropeptides and hBMP2 through increased GJIC. Identification of the GJIC-mediated signal transduction capable of modulating the cellular activities of bone cells represents a novel approach to studying the biology of skeletal innervation.

  2. Antigen-free bovine cancellous bone loaded with recombinant human bone morphogenetic protein-2 for the repair of tibial bone defects in goat model.

    Science.gov (United States)

    Li, Donghai; Deng, Liqing; Yang, Zhouyuan; Xie, Xiaowei; Kang, Pengde; Tan, Zhen

    2016-04-01

    Antigen-free bovine cancellous bone has good performances of porous network structures and mechanics with antigen extracted. To develop a bioactive scaffold for enhancing bone repair and evaluate its biological property, rhBMP-2 loaded with antigen-free bovine cancellous bone was used to treat tibial bone defect. Twenty-four healthy adult goats were chosen to establish goat defects model and randomly divided into four groups. The goats were treated with rhBMP-2/antigen-free bovine cancellous bone scaffolds (group A), autogenous cancellous bone graft (group B), porous tricalciumphosphate scaffolds (group C) and nothing (group D). Animals were evaluated with radiological and histological methods at 4, 8 and 12 weeks after surgery. The gray value of radiographs was used to evaluate the healing of the defects, which revealed that the group A had a better outcome of defect healing compared with group C at 4, 8 and 12 weeks, respectively (p difference between groups A and B was without significance at each time (p > 0.05). The newly formed bone area was calculated from histological sections, and the results indicated that the amount of new bone in group A increased significantly compared with that in group C (p  0.05) at 4, 8 and 12 weeks, respectively. In addition, the expression of collagen I and vascular endothelial growth factor by real-time polymerase chain reaction at 12 weeks in group A was significantly higher than that in group C (p = 0.034, p = 0.032, respectively), but no significant differences were found when compared with that in group B (p = 0.36, p = 0.54, respectively). At the same time, group C presented better results than group D on bone defects healing. Therefore, the composites of antigen-free bovine cancellous bone loaded with rhBMP-2 have a good osteoinductive activity and capacity to promote the repair of bone defects. PMID:26801475

  3. In vivo local co-delivery of recombinant human bone morphogenetic protein-7 and pamidronate via poly-D, L-lactic acid

    Directory of Open Access Journals (Sweden)

    NYC Yu

    2010-12-01

    Full Text Available The effects of bone anabolic agents such as bone morphogenetic proteins (BMPs have the potential to be augmented by co-treatment with an anti-catabolic such as a bisphosphonate. We hypothesised that the effects of bisphosphonates on BMP-induced bone anabolism would be dose dependent, and we aimed to test this in a small animal model. Agents were delivered locally using a biodegradable poly-d, l-lactic-acid (PDLLA polymer delivery system. Recombinant human BMP-7 (25 µg was tested with a range of doses of the bisphosphonate pamidronate (0.02 mg, 0.2 mg and 2 mg local PAM; 0.3 mg/kg and 3 mg/kg thrice-weekly systemic PAM versus BMP-7 alone. Polymer pellets were surgically implanted in the hind limbs of female C57BL6/J mice (8-10 week and ectopic bone nodules were harvested at 3 and 8 weeks post-operatively. At 3 weeks, local low dose PAM (0.02 mg induced a 102% increase in rhBMP-7 induced bone volume (p<0.01 as measured by miroCT, and this was comparable to systemic PAM (0.3 mg/kg thrice-weekly. In contrast, local high dose PAM (2 mg resulted in a 97% decrease in bone volume (p<0.01. Radiography and histology indicated that the polymer vehicle was still largely present at 8 weeks indicating inefficient biodegradation. This is the first study to validate the utility of local co-delivery of BMP/bisphosphonate via biodegradable polymer and supports the continued refinement of more advanced bioresorbable delivery systems for clinical applications.

  4. 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.

  5. Evaluation of an injectable silk fibroin enhanced calcium phosphate cement loaded with human recombinant bone morphogenetic protein-2 in ovine lumbar interbody fusion.

    Science.gov (United States)

    Gu, Yong; Chen, Liang; Yang, Hui-Lin; Luo, Zong-Ping; Tang, Tian-Si

    2011-05-01

    The objective of this study was to investigate the efficacy of an injectable calcium phosphate cement/silk fibroin/human recombinant bone morphogenetic protein-2 composite (CPC/SF/rhBMP-2) in an ovine interbody fusion model. Twenty-four mature sheep underwent anterior lumbar interbody fusion at the levels of L1/2, L3/4, and L5/6 with random implantation of CPC/SF, CPC/rhBMP-2, CPC/SF/rhBMP-2, or autogenous iliac bone. After the sheep were sacrificed, the fusion segments were evaluated by manual palpation, CT scan, undestructive biomechanical testing, undecalcified histology, and histomorphology. The fusion rates of CPC/SF/rhBMP-2 were 55.56% and 77.78% at 6 and 12 months, respectively. The fusion was superior to all the biomaterial grafts in stiffness, and reached the same stiffness as the autograft at 12 months. The new bone formation was less than autograft at 6 months, but similar with that at 12 months. However, the ceramic residue volume of CPC/SF/rhBMP-2 was significantly decreased compared with CPC/SF and CPC/rhBMP-2 at both times. The results indicated that CPC/SF/rhBMP-2 composite had excellent osteoconduction and osteoinduction, and balanced degradation and osteogenesis.

  6. 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.

  7. 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.

  8. 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.

  9. 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

  10. Quantum flesh on classical bones: Semiclassical bridges across the quantum-classical divide

    Energy Technology Data Exchange (ETDEWEB)

    Bokulich, Alisa [Center for Philosophy and History of Science, Boston University, Boston, MA (United States)

    2014-07-01

    Traditionally quantum mechanics is viewed as having made a sharp break from classical mechanics, and the concepts and methods of these two theories are viewed as incommensurable with one another. A closer examination of the history of quantum mechanics, however, reveals that there is a strong sense in which quantum mechanics was built on the backbone of classical mechanics. As a result, there is a considerable structural continuity between these two theories, despite their important differences. These structural continuities provide a ground for semiclassical methods in which classical structures, such as trajectories, are used to investigate and model quantum phenomena. After briefly tracing the history of semiclassical approaches, I show how current research in semiclassical mechanics is revealing new bridges across the quantum-classical divide.

  11. 大鼠腭中缝牵张成骨中骨形态发生蛋白7的作用%Role of bone morphogenetic protein-7 in the distraction osteogenesis of rat mid-palatal suture

    Institute of Scientific and Technical Information of China (English)

    李威; 李鹍; 王培军; 韩晶莹

    2012-01-01

    BACKGROUND: Experiments have confirmed that bone morphogenetic protein-7 can induce bone and cartilage formation; it can also promote bone formation in the process of distraction osteogenesis. OBJECTIVE: To explore the role of bone morphogenetic protein-7 in the suture distraction osteogenesis of rat mid-palatal suture and to detect the changes of bone morphogenetic protein-7 under the mechanical expansion force. METHODS: Expansionary force was applied on rats using a self-made expansing arch spring for binoculus to construct maxillary expansion rat model. Rat mid-palatal sutures were randomly collected on 1, 3, 5, 7, 9, 12 and 14 days after model construction; real-time PCR was performed to detect the changing regularities of the target genes. RESULTS AND CONCLUSION: The expression of the bone morphogenetic protein-7 mRNA in the rat mid-palatal sutures increased gradually on 3, 9, 12 and 14 days after model construction (P < 0.05). These findings demonstrate that bone morphogenetic protein-7 mRNA expression is significantly increased in the distraction osteogenesis process of rat mid-palatal sutures under the stimulus of mechanical force.%背景:已有实验证实,骨形态发生蛋白7可诱导骨组织和软骨组织的形成,在牵张成骨的过程中促进骨组织形成.目的:测定骨形态发生蛋白7在腭中缝牵张成骨中的作用及机械扩张力作用下的变化.方法:采用自制双眼扩弓簧对大鼠施加扩张力,建立上颌骨扩张大鼠模型.分别于建模后第1,3,5,7,9,12,14天随机选取大鼠取腭中缝组织,实时定量PCR法测定目的基因的变化规律.结果与结论:建模后第3,9,12,14天大鼠腭中缝组织骨形态发生蛋白7 Mrna的表达逐渐升高(P < 0.05).结果证实,大鼠腭中缝牵张成骨时,骨形态发生蛋白7 Mrna在机械力刺激下表达明显上调.

  12. 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

  13. 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.

  14. Comparative study of osteogenic potential of a composite scaffold incorporating either endogenous bone morphogenetic protein-2 or exogenous phytomolecule icaritin: an in vitro efficacy study.

    Science.gov (United States)

    Chen, S-H; Wang, X-L; Xie, X-H; Zheng, L-Z; Yao, D; Wang, D-P; Leng, Y; Zhang, G; Qin, L

    2012-08-01

    A local delivery system with sustained and efficient release of therapeutic agents from an appropriate carrier is desirable for orthopedic applications. Novel composite scaffolds made of poly (lactic-co-glycolic acid) with tricalcium phosphate (PLGA/TCP) were fabricated by an advanced low-temperature rapid prototyping technique, which incorporated either endogenous bone morphogenetic protein-2 (BMP-2) (PLGA/TCP/BMP-2) or phytomolecule icaritin (ICT) (PLGA/TCP/ICT) at low, middle and high doses. PLGA/TCP served as control. In vitro degradation, osteogenesis and release tests showed statistical differences among PLGA/TCP/ICT, PLGA/TCP and PLGA/TCP/BMP-2 groups, where PLGA/TCP/ICT had the desired slow release of bioactive icaritin in a dose-dependent manner, whereas there was almost no BMP-2 release from the PLGA/TCP/BMP-2 scaffolds. PLGA/TCP/ICT significantly increased more ALP activity, upregulated mRNA expression of osteogenic genes and enhanced calcium deposition and mineralization in rabbit bone marrow stem cells cultured on scaffolds compared with the other two groups. These results indicate the desired degradation rate, osteogenic capability and release property in PLGA/TCP/ICT composite scaffold, as icaritin preserved its bioactivity and structure after incorporation, while PLGA/TCP/BMP-2 did not show an initially expected osteogenic potential, owing to loss of the original bioactivity of BMP-2 during its incorporation and fabrication procedure. The results suggest that PLGA/TCP composite scaffolds incorporating osteogenic ICT might be a promising approach for bone tissue bioengineering and regeneration. PMID:22543006

  15. Adeno-associated virus-mediated bone morphogenetic protein-7 gene transfer induces C2C12 cell differentiation into osteoblast lineage cells

    Institute of Scientific and Technical Information of China (English)

    Min YANG; Qing-jun MA; Geng-ting DANG; Kang-tao MA; Ping CHEN; Chun-yan ZHOU

    2005-01-01

    Aim: To investigate the effects of bone morphogenetic protein-7 (BMP7)-expressing recombinant adeno-associated virus (AAV) vector on the differentiation of C2C12 cells. Methods: AAV-BMP7 was packaged by infecting the stable cell clone BHK-21 (integrated with recombinant AAV vector plasmid pSNAV-BMP7)with recombinant herpes simplex virus type 1, which expresses AAV-2 Rep and Cap and possesses AAV packaging functions. Following infection with AAVBMP7 at multiplicities of infection of 1× 105 vector genomes per cell and subsequent culture, C2C12 cells were assessed qualitatively for BMP7 production, alkaline phosphatase activity, osteocalcin production and Cbfal and MyoD expression.Results: C2C 12 cells transduced with AAV-BMP7 could produce BMP7 protein until d 28. Alkaline phosphatase in the cultured C2C12 cell lysate was elevated.Secreted osteocalcin in the culture medium was detectable at d 12 and Cbfal mRNA expression level was upregulated, coinciding with downregulation of MyoD in a temporal manner. Conclusion: The present in vitro study demonstrated that AAV-BMP7 could infect and efficiently convert C2C12 cells from myoblasts into osteoblast lineage cells.

  16. 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.

  17. Role of Growth Differentiation Factor 9 and Bone Morphogenetic Protein 15 in Ovarian Function and Their Importance in Mammalian Female Fertility - A Review.

    Science.gov (United States)

    de Castro, Fernanda Cavallari; Cruz, Maria Helena Coelho; Leal, Claudia Lima Verde

    2016-08-01

    Growth factors play an important role during early ovarian development and folliculogenesis, since they regulate the migration of germ cells to the gonadal ridge. They also act on follicle recruitment, proliferation/atresia of granulosa cells and theca, steroidogenesis, oocyte maturation, ovulation and luteinization. Among the growth factors, the growth differentiation factor 9 (GDF9) and the bone morphogenetic protein 15 (BMP15), belong to the transforming growth factor beta (TGF-β) superfamily, have been implicated as essential for follicular development. The GDF9 and BMP15 participate in the evolution of the primordial follicle to primary follicle and play an important role in the later stages of follicular development and maturation, increasing the steroidogenic acute regulatory protein expression, plasminogen activator and luteinizing hormone receptor (LHR). These factors are also involved in the interconnections between the oocyte and surrounding cumulus cells, where they regulate absorption of amino acids, glycolysis and biosynthesis of cholesterol cumulus cells. Even though the mode of action has not been fully established, in vitro observations indicate that the factors GDF9 and BMP15 stimulate the growth of ovarian follicles and proliferation of cumulus cells through the induction of mitosis in cells and granulosa and theca expression of genes linked to follicular maturation. Thus, seeking greater understanding of the action of these growth factors on the development of oocytes, the role of GDF9 and BMP15 in ovarian function is summarized in this brief review. PMID:26954112

  18. Dual delivery of active antibactericidal agents and bone morphogenetic protein at sustainable high concentrations using biodegradable sheath-core-structured drug-eluting nanofibers

    Science.gov (United States)

    Hsu, Yung-Hen; Lin, Chang-Tun; Yu, Yi-Hsun; Chou, Ying-Chao; Liu, Shih-Jung; Chan, Err-Cheng

    2016-01-01

    In this study, we developed biodegradable sheath-core-structured drug-eluting nanofibers for sustainable delivery of antibiotics (vancomycin and ceftazidime) and recombinant human bone morphogenetic protein (rhBMP-2) via electrospinning. To prepare the biodegradable sheath-core nanofibers, we first prepared solutions of poly(d,l)-lactide-co-glycolide, vancomycin, and ceftazidime in 1,1,1,3,3,3-hexafluoro-2-propanol and rhBMP-2 in phosphate-buffered solution. The poly(d,l)-lactide-co-glycolide/antibiotics and rhBMP-2 solutions were then fed into two different capillary tubes controlled by two independent pumps for coaxial electrospinning. The electrospun nanofiber morphology was observed under a scanning electron microscope. We further characterized the in vitro antibiotic release from the nanofibers via high-performance liquid chromatography and that of rhBMP-2 via enzyme-linked immunosorbent assay and alkaline phosphatase activity. We showed that the biodegradable coaxially electrospun nanofibers could release high vancomycin/ceftazidime concentrations (well above the minimum inhibition concentration [MIC]90) and rhBMP-2 for >4 weeks. These experimental results demonstrate that novel biodegradable nanofibers can be constructed with various pharmaceuticals and proteins for long-term drug deliveries. PMID:27574423

  19. A new mutation in exon 2 of the bone morphogenetic protein 15 gene is associated with increase in prolificacy of Mehraban and Lori sheep.

    Science.gov (United States)

    Zamani, Pouya; Nadri, Sara; Saffaripour, Rezvan; Ahmadi, Ahmad; Dashti, Farshad; Abdoli, Ramin

    2015-06-01

    Some mutations in bone morphogenetic protein 15 (BMP15) gene have been known to be associated with prolificacy in various breeds of sheep. Polymorphism of BMP15 gene exon 2 was studied in 100 Mehraban and 100 Lori ewes, using PCR-SSCP and DNA sequencing methods. A new point mutation (G → A) was found at position 57 of the amplified 312-b fragment of BMP15 gene exon 2. The frequencies of the AG and GG genotypes were 69.4 and 30.6 % in Mehraban and 44.7 and 55.3 % in Lori ewes, respectively. No individual carrying the AA genotype was found in the studied population. The allelic frequencies for A and G alleles were 34.7 and 65.3 % in Mehraban and 22.4 and 77.6 % in Lori ewes, respectively. Average litter size in the AG genotype (1.56) was significantly (P < 0.01) higher than the GG ewes (1.08). The results of the present study indicated the potential of the observed SNP in exon 2 of BMP15 for further exploitation in marker-assisted selection to improve reproduction efficiency of Mehraban and Lori sheep.

  20. Dual delivery of active antibactericidal agents and bone morphogenetic protein at sustainable high concentrations using biodegradable sheath-core-structured drug-eluting nanofibers.

    Science.gov (United States)

    Hsu, Yung-Hen; Lin, Chang-Tun; Yu, Yi-Hsun; Chou, Ying-Chao; Liu, Shih-Jung; Chan, Err-Cheng

    2016-01-01

    In this study, we developed biodegradable sheath-core-structured drug-eluting nanofibers for sustainable delivery of antibiotics (vancomycin and ceftazidime) and recombinant human bone morphogenetic protein (rhBMP-2) via electrospinning. To prepare the biodegradable sheath-core nanofibers, we first prepared solutions of poly(d,l)-lactide-co-glycolide, vancomycin, and ceftazidime in 1,1,1,3,3,3-hexafluoro-2-propanol and rhBMP-2 in phosphate-buffered solution. The poly(d,l)-lactide-co-glycolide/antibiotics and rhBMP-2 solutions were then fed into two different capillary tubes controlled by two independent pumps for coaxial electrospinning. The electrospun nanofiber morphology was observed under a scanning electron microscope. We further characterized the in vitro antibiotic release from the nanofibers via high-performance liquid chromatography and that of rhBMP-2 via enzyme-linked immunosorbent assay and alkaline phosphatase activity. We showed that the biodegradable coaxially electrospun nanofibers could release high vancomycin/ceftazidime concentrations (well above the minimum inhibition concentration [MIC]90) and rhBMP-2 for >4 weeks. These experimental results demonstrate that novel biodegradable nanofibers can be constructed with various pharmaceuticals and proteins for long-term drug deliveries. PMID:27574423

  1. 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

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    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.

  2. 血管内皮生长因子和骨形态发生蛋白在骨组织工程中的作用%Vascular endothelial growth factor and bone morphogenetic protein in the bone tissue engineering

    Institute of Scientific and Technical Information of China (English)

    纪经涛; 胡永成; 夏群; 苗军; 陈晓鹏; 方程

    2015-01-01

    and progressive bone disorder are very common, and bone tissue engineering provides a new approach to bone defect repair. Growth factors related to bone tissue engineering bone have been reported a lot and have achieved some results. How to mimick the natural timing of different growth factors with different bioactivities has become the current hotspot in bone repair. OBJECTIVE: To review the new developments in vascular endothelial growth factor and bone morphogenetic protein in bone tissue engineering. METHODS: The first author searched CNKI (1990/2015) and Medline database (1990/2015) for related articles using the key words of “osteogenic factors, angiogenic factors, tissue engineering bone, bone repair, vascularization, vascular endothelial growth factor, bone morphogenetic protein, sequential release, seed cels, cytoskeleton” in Chinese and English, respectively. Mechanism of action and research direction about vascular endothelial growth factor and bone morphogenetic protein were summarized. RESULTS AND CONCLUSION:Totaly 313 papers were searched initialy, and finaly 87 papers were enroled in result analysis. The results show that different growth factors play different roles in bone repair. Vascularization and osteogenesis are the most important processes in bone repair. The osteogenic factors play an important role in maintaining bone structure and bone formation. The angiogenic factors can provide oxygen and nutrients for tissue growth, differentiation and functionalization. The combination of osteogenic and angiogenic factors has a better osteogenic effect than osteogenic or angiogenic factors used alone. However, the most important problem is how to control the exogenous osteogenesis and the release dosage of angiogenic factors in bone repair.

  3. Chondrogenesis of periodontal ligament stem cells by transforming growth factor-β3 and bone morphogenetic protein-6 in a normal healthy impacted third molar

    Institute of Scientific and Technical Information of China (English)

    Sunyoung Choi; Tae-Jun Cho; Soon-Keun Kwon; Gene Lee; Jaejin Cho

    2013-01-01

    The periodontal ligament-derived mesenchymal stem cell is regarded as a source of adult stem cells due to its multipotency. However, the proof of chondrogenic potential of the cells is scarce. Therefore, we investigated the chondrogenic differentiation capacity of periodontal ligament derived mesenchymal stem cells induced by transforming growth factor (TGF)-β3 and bone morphogenetic protein (BMP)-6. After isolation of periodontal ligament stem cells (PDLSCs) from human periodontal ligament, the cells were cultured in Dulbecco's modified Eagle's medium (DMEM) with 20% fetal bovine serum (FBS). A mechanical force initiated chondrogenic differentiation of the cells. For chondrogenic differentiation, 10 μg ·L-1 TGF-β3 or 100 μg ·L-1 BMP-6 and the combination treating group for synergistic effect of the growth factors. We analyzed the PDLSCs by fluorescence-activated cell sorting and chondrogenesis were evaluated by glycosaminoglycans assay, histology, immunohistochemistry and genetic analysis. PDLSCs showed mesenchymal stem cell properties proved by FACS analysis. Glycosaminoglycans contents were increased 217% by TGF-β3 and 220% by BMP-6. The synergetic effect of TGF-β3 and BMP-6 were shown up to 281% compared to control. The combination treatment increased Sox9, aggrecan and collagen II expression compared with not only controls, but also TGF-β3 or BMP-6 single treatment dramatically. The histological analysis also indicated the chondrogenic differentiation of PDLSCs in our conditions. The results of the present study demonstrate the potential of the dental stem cell as a valuable cell source for chondrogenesis, which may be applicable for regeneration of cartilage and bone fracture in the field of cell therapy.

  4. Single nucleotide polymorphism of bone morphogenetic protein 4 gene: A risk factor of non-syndromic cleft lip with or without palate

    Science.gov (United States)

    Savitha, Sathyaprasad; Sharma, S. M.; Veena, Shetty; Rekha, R.

    2015-01-01

    Background: The bone morphogenetic protein (BMP) signalling pathway is crucial in a number of developmental processes and is critical in the formation of variety of craniofacial elements including cranial neural crest, facial primordium, tooth, lip and palate. It is an important mediator in regulation of lip and palate fusion, cartilage and bone formation. Aim: To study the role of mutation of BMP4 genes in the aetiology of non-syndromic cleft lip with or without palate (NSCL ± P) and identify it directly from human analyses. Materials and Methods: A case-control study was done to evaluate whether BMP4T538C polymorphism, resulting in an amino acid change of Val=Ala (V152A) in the polypeptide, is associated with NSCL ± P in an Indian paediatric population. Genotypes of 100 patients with NSCL ± P and 100 controls (in whom absence of CL ± P was confirmed in three generations) were detected using a polymerase chain reaction-restriction fragment length polymorphism strategy. Logistic regression was performed to evaluate allele and genotype association with NSCLP. Results: Results showed significant association between homozygous CC genotype with CL ± P (odds ratio [OR]-5.59 and 95% confidence interval [CI] = 2.85-10.99). The 538C allele carriers showed an increased risk of NSCL ± P as compared with 538 T allele (OR - 4.2% CI = 2.75-6.41). Conclusion: This study suggests an association between SNP of BMP4 gene among carriers of the C allele and increased risk for NSCLP in an Indian Population. Further studies on this aspect can scale large heights in preventive strategies for NSCLP that may soon become a reality. PMID:26424979

  5. Single nucleotide polymorphism of bone morphogenetic protein 4 gene: A risk factor of non-syndromic cleft lip with or without palate

    Directory of Open Access Journals (Sweden)

    Sathyaprasad Savitha

    2015-01-01

    Full Text Available Background: The bone morphogenetic protein (BMP signalling pathway is crucial in a number of developmental processes and is critical in the formation of variety of craniofacial elements including cranial neural crest, facial primordium, tooth, lip and palate. It is an important mediator in regulation of lip and palate fusion, cartilage and bone formation. Aim: To study the role of mutation of BMP4 genes in the aetiology of non-syndromic cleft lip with or without palate (NSCL ± P and identify it directly from human analyses. Materials and Methods: A case-control study was done to evaluate whether BMP4T538C polymorphism, resulting in an amino acid change of Val=Ala (V152A in the polypeptide, is associated with NSCL ± P in an Indian paediatric population. Genotypes of 100 patients with NSCL ± P and 100 controls (in whom absence of CL ± P was confirmed in three generations were detected using a polymerase chain reaction-restriction fragment length polymorphism strategy. Logistic regression was performed to evaluate allele and genotype association with NSCLP. Results: Results showed significant association between homozygous CC genotype with CL ± P (odds ratio [OR]-5.59 and 95% confidence interval [CI] = 2.85-10.99. The 538C allele carriers showed an increased risk of NSCL ± P as compared with 538 T allele (OR - 4.2% CI = 2.75-6.41. Conclusion: This study suggests an association between SNP of BMP4 gene among carriers of the C allele and increased risk for NSCLP in an Indian Population. Further studies on this aspect can scale large heights in preventive strategies for NSCLP that may soon become a reality.

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

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    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.

  7. The Deep-Sea Natural Products, Biogenic Polyphosphate (Bio-PolyP and Biogenic Silica (Bio-Silica, as Biomimetic Scaffolds for Bone Tissue Engineering: Fabrication of a Morphogenetically-Active Polymer

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    Florian Draenert

    2013-03-01

    Full Text Available Bone defects in human, caused by fractures/nonunions or trauma, gain increasing impact and have become a medical challenge in the present-day aging population. Frequently, those fractures require surgical intervention which ideally relies on autografts or suboptimally on allografts. Therefore, it is pressing and likewise challenging to develop bone substitution materials to heal bone defects. During the differentiation of osteoblasts from their mesenchymal progenitor/stem cells and of osteoclasts from their hemopoietic precursor cells, a lineage-specific release of growth factors and a trans-lineage homeostatic cross-talk via signaling molecules take place. Hence, the major hurdle is to fabricate a template that is functioning in a way mimicking the morphogenetic, inductive role(s of the native extracellular matrix. In the last few years, two naturally occurring polymers that are produced by deep-sea sponges, the biogenic polyphosphate (bio-polyP and biogenic silica (bio-silica have also been identified as promoting morphogenetic on both osteoblasts and osteoclasts. These polymers elicit cytokines that affect bone mineralization (hydroxyapatite formation. In this manner, bio-silica and bio-polyP cause an increased release of BMP-2, the key mediator activating the anabolic arm of the hydroxyapatite forming cells, and of RANKL. In addition, bio-polyP inhibits the progression of the pre-osteoclasts to functionally active osteoclasts. Based on these findings, new bioinspired strategies for the fabrication of bone biomimetic templates have been developed applying 3D-printing techniques. Finally, a strategy is outlined by which these two morphogenetically active polymers might be used to develop a novel functionally active polymer.

  8. 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

  9. Repetitive recombinant human bone morphogenetic protein 2 injections improve the callus microarchitecture and mechanical stiffness in a sheep model of distraction osteogenesis

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    Marc-Frederic Pastor

    2012-03-01

    Full Text Available Evidence suggests that recombinant human bone morphogenetic protein 2 (rhBMP-2 increases the mechanical integrity of callus tissue during bone healing. This effect may be either explained by an increase of callus formation or a modification of the trabecular microarchitecture. Therefore the purpose of the study was to evaluate the potential benefit of rhBMP-2 on the trabecular microarchitecture and on multidirectional callus stiffness. Further we asked, whether microarchitecture changes correlate with optimized callus stiffness. In this study a tibial distraction osteogenesis (DO model in 12 sheep was used to determine, whether percutaneous injection of rhBMP-2 into the distraction zone influences the microarchitecture of the bone regenerate. After a latency period of 4 days, the tibiae were distracted at a rate of 1.25 mm/day over a period of 20 days, resulting in total lengthening of 25 mm. The operated limbs were randomly assigned to one treatment groups and one control group: (A triple injection of rhBMP-2 (4 mg rhBMP-2/injection and (B no injection. The tibiae were harvested after 74 days and scanned by μCT (90 μm/voxel. In addition, we conducted a multidirectional mechanical testing of the tibiae by using a material testing system to assess the multidirectional strength. The distraction zones were tested for torsional stiffness and bending stiffness antero-posterior (AP and medio-lateral (ML direction, compression strength and maximum axial torsion. Statistical analysis was performed using multivariate analysis of variance (ANOVA followed by student’s t-test and Regression analysis using power functions with a significance level of P<0.05. Triple injections of rhBMP-2 induced significant changes in the trabecular architecture of the regenerate compared with the control: increased trabecular number (Tb.N. (treatment group 1.73 mm/1 vs. control group 1.2 mm/1, increased cortical bone volume fraction (BV/TV (treatment group 0.68 vs

  10. Tribulus terrestris Alters the Expression of Growth Differentiation Factor 9 and Bone Morphogenetic Protein 15 in Rabbit Ovaries of Mothers and F1 Female Offspring.

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    Desislava Abadjieva

    Full Text Available Although previous research has demonstrated the key role of the oocyte-derived factors, bone morphogenetic protein (BMP 15 and growth differentiation factor (GDF 9, in follicular development and ovulation, there is a lack of knowledge on the impact of external factors, which females are exposed to during folliculogenesis, on their expression. The present study investigated the effect of the aphrodisiac Tribulus terrestris on the GDF9 and BMP15 expression in the oocytes and cumulus cells at mRNA and protein levels during folliculogenesis in two generations of female rabbits. The experiment was conducted with 28 New Zealand rabbits. Only the diet of the experimental mothers group was supplemented with a dry extract of T. terrestris for the 45 days prior to insemination. The expression of BMP15 and GDF9 genes in the oocytes and cumulus cells of mothers and F1 female offspring was analyzed using real-time polymerase chain reaction (RT-PCR. The localization of the GDF9 and BMP15 proteins in the ovary tissues was determined by immunohistochemical analysis. The BMP15 and GDF9 transcripts were detected in the oocytes and cumulus cells of rabbits from all groups. T. terrestris caused a decrease in the BMP15 mRNA level in the oocytes and an increase in the cumulus cells. The GDF9 mRNA level increased significantly in both oocytes and cumulus cells. The downregulated expression of BMP15 in the treated mothers' oocytes was inherited in the F1 female offspring born to treated mothers. BMP15 and GDF9 show a clearly expressed sensitivity to the bioactive compounds of T. terrestris.

  11. Tribulus terrestris Alters the Expression of Growth Differentiation Factor 9 and Bone Morphogenetic Protein 15 in Rabbit Ovaries of Mothers and F1 Female Offspring.

    Science.gov (United States)

    Abadjieva, Desislava; Kistanova, Elena

    2016-01-01

    Although previous research has demonstrated the key role of the oocyte-derived factors, bone morphogenetic protein (BMP) 15 and growth differentiation factor (GDF) 9, in follicular development and ovulation, there is a lack of knowledge on the impact of external factors, which females are exposed to during folliculogenesis, on their expression. The present study investigated the effect of the aphrodisiac Tribulus terrestris on the GDF9 and BMP15 expression in the oocytes and cumulus cells at mRNA and protein levels during folliculogenesis in two generations of female rabbits. The experiment was conducted with 28 New Zealand rabbits. Only the diet of the experimental mothers group was supplemented with a dry extract of T. terrestris for the 45 days prior to insemination. The expression of BMP15 and GDF9 genes in the oocytes and cumulus cells of mothers and F1 female offspring was analyzed using real-time polymerase chain reaction (RT-PCR). The localization of the GDF9 and BMP15 proteins in the ovary tissues was determined by immunohistochemical analysis. The BMP15 and GDF9 transcripts were detected in the oocytes and cumulus cells of rabbits from all groups. T. terrestris caused a decrease in the BMP15 mRNA level in the oocytes and an increase in the cumulus cells. The GDF9 mRNA level increased significantly in both oocytes and cumulus cells. The downregulated expression of BMP15 in the treated mothers' oocytes was inherited in the F1 female offspring born to treated mothers. BMP15 and GDF9 show a clearly expressed sensitivity to the bioactive compounds of T. terrestris. PMID:26928288

  12. Elevated extracellular calcium increases expression of bone morphogenetic protein-2 gene via a calcium channel and ERK pathway in human dental pulp cells

    International Nuclear Information System (INIS)

    Dental pulp cells, which have been shown to share phenotypical features with osteoblasts, are capable of differentiating into odontoblast-like cells and generating a dentin-like mineral structure. Elevated extracellular Ca2+Cao2+ has been implicated in osteogenesis by stimulating the proliferation and differentiation of osteoblasts; however, the role of Cao2+ signaling in odontogenesis remains unclear. We found that elevated Cao2+ increases bone morphogenetic protein (BMP)-2 gene expression in human dental pulp cells. The increase was modulated not only at a transcriptional level but also at a post-transcriptional level, because treatment with Ca2+ increased the stability of BMP-2 mRNA in the presence of actinomycin D, an inhibitor of transcription. A similar increase in BMP-2 mRNA level was observed in other human mesenchymal cells from oral tissue; periodontal ligament cells and gingival fibroblasts. However, the latter cells exhibited considerably lower expression of BMP-2 mRNA compared with dental pulp cells and periodontal ligament cells. The BMP-2 increase was markedly inhibited by pretreatment with an extracellular signal-regulated kinase (ERK) inhibitor, PD98059, and partially inhibited by the L-type Ca2+ channels inhibitor, nifedipine. However, pretreatment with nifedipine had no effect on ERK1/2 phosphorylation triggered by Ca2+, suggesting that the Ca2+ influx from Ca2+ channels may operate independently of ERK signaling. Dental pulp cells do not express the transcript of Ca2+-sensing receptors (CaSR) and only respond slightly to other cations such as Sr2+ and spermine, suggesting that dental pulp cells respond to Cao2+ to increase BMP-2 mRNA expression in a manner different from CaSR and rather specific for Cao2+ among cations.

  13. Comparison of Cell Viability and Embryoid Body Size of Two Embryonic Stem Cell Lines After Different Exposure Times to Bone Morphogenetic Protein 4

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    Nehleh Zarei Fard

    2015-03-01

    Full Text Available Background: Activation of bone morphogenetic protein 4 (BMP4 signaling pathway in embryonic stem (ES cells plays an important role in controlling cell proliferation, differentiation, and apoptosis. Adverse effects of BMP4 occur in a time dependent manner; however, little is known about the effect of different time exposure of this growth factor on cell number in culture media. In this study, we investigated the role of two different exposure times to BMP4 in cell viability, embryoid body (EB, size, and cavitation of ES cells. Methods: Embryonic stem cells (R1 and B1 lines were released from the feeder cell layers and were cultured using EBs protocol by using the hanging drop method and monolayer culture system. The cells were cultured for 5 days with 100 ng/mL BMP4 from the beginning (++BMP4 or after 48 h (+BMP4 of culture and their cell number were counted by trypan blue staining. The data were analyzed using non-parametric two-tailed Mann-Whitney test. P<0.05 was considered as significant. Results: In EB culture protocol, cell number significantly decreased in +BMP4 culture condition with greater cavity size compared to the ++BMP4 condition at day 5 (P=0.009. In contrast, in monolayer culture system, there was no significant difference in the cell number between all groups (P=0.91. Conclusion: The results suggest that short-term exposure of BMP4 is required to promote cavitation in EBs according to lower cell number in +BMP4 condition. Different cell lines showed different behavior in cavitation formation.

  14. Low melting point amphiphilic microspheres for delivery of bone morphogenetic protein-6 and transforming growth factor-β3 in a hydrogel matrix.

    Science.gov (United States)

    Sukarto, Abby; Amsden, Brian G

    2012-02-28

    Low melting-point poly(1,3-trimethylene carbonate-co-ε-caprolactone)-b-poly(ethylene glycol)-b-poly(1,3-trimethylene carbonate-co-ε-caprolactone), P(TMC-CL)(2)-PEG, was employed to fabricate microspheres for sustained growth factor delivery in a photocrosslinked N-methacrylate glycol chitosan hydrogel matrix. The P(TMC-CL)(2)-PEG had a melting range such that it was solid at 10°C, yet liquid with a low degree of crystallinity at 37°C. The in vitro degradation of P(TMC-CL)(2)-PEG microspheres was slow, regardless of the triblock copolymer molecular weight and so did not influence protein release. The size of protein loaded P(TMC-CL)(2)-PEG microspheres manufactured using a low-temperature electrospray technique was between 65 and 85μm. Initial formulation work was done with the model protein lysozyme, co-lyophilized with trehalose and encapsulated as approximately 2μm particles within P(TMC-CL)(2)-PEG microspheres. This work indicated a sustained release could be achieved with high trehalose content (90% w/w) in the particles. Under these conditions, the release rate of bone morphogenetic protein-6 was more sustained than that of the excipient bovine serum albumin (BSA) and closely followed that of lysozyme. On the other hand, transforming growth factor-β3 and the stabilizing agent BSA generated similar release profiles. This difference in release was proposed to be linked to the protein isoelectric point, with positively charged proteins possibly being more strongly adsorbed to the P(TMC-CL)(2)-PEG. Both growth factors were released in highly bioactive form, indicating the potential of the release approach. PMID:22037107

  15. Comparison of expression patterns of fibroblast growth factor 8, bone morphogenetic protein 4 and sonic hedgehog in jaw development of the house shrew, Suncus murinus.

    Science.gov (United States)

    Ogi, Hidenao; Tabata, Makoto J; Yamanaka, Atsushi; Yasui, Kinya; Uemura, Masanori

    2002-01-01

    To elucidate the mechanism underlying jaw development in mammals, we used a new laboratory animal, Suncus murinus (house shrew, an insectivore) as the subject for the investigation, because Suncus has all types of teeth (incisor, canine, premolar and molar) in its upper and lower jaws and is thought to be a good model animal having a general mammalian tooth pattern. At the start, by use of degenerate primers we cloned Suncus homologues of fibroblast growth factor 8 (sFgf8), bone morphogenetic protein 4 (sBmp4) and sonic hedgehog (sShh) genes from cDNA library derived from whole Suncus embryos at day 12 (E12). Thereafter, we examined the expression patterns of these genes in the jaw development of Suncus E11-16 embryos (for mouse E9.5-12 embryos). sFgf8 and sBmp4 were expressed in E11 but not in E15 and onward during orofacial development. sShh was expressed from E11 onward, and its expression was increased in the orofacial area. The expression pattern of sFgf8 in the maxillary and mandibular arches of E14 coincided with the area of the presumptive tooth arch. However, sShh and sBmp4 were expressed only in the outer area (= buccal/labial side) of presumptive tooth arch. Thus, these 3 genes showed specific expression pattern in jaw development of Suncus, and their distributions did not overlap each other except in a few regions. These findings suggest that sFgf8, sBmp4 and sShh have a specific function respectively during jaw development in Suncus murinus.

  16. Addition of bone morphogenetic protein type 2 to ascorbate and β-glycerophosphate supplementation did not enhance osteogenic differentiation of human adipose-derived stem cells

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    Ariadne Cristiane Cabral Cruz

    2012-12-01

    Full Text Available Bone morphogenetic protein type 2 (BMP-2 is a potent local factor, which promotes bone formation and has been used as an osteogenic supplement for mesenchymal stem cells. OBJECTIVES: This study evaluated the effect of a recombinant BMP-2 as well as the endogenous BMP-4 and BMP-7 in the osteogenic differentiation of adipose-derived stem cells (ASCs in medium supplemented with ascorbate and β-glycerophosphate. MATERIAL AND METHODS: Human ASCs were treated with osteogenic medium in the presence (ASCs+OM+BMP-2 or absence (ASCs+OM of BMP-2. The alkaline phosphatase (ALP activity was determined and the extracellular matrix mineralization was evaluated by Von Kossa staining and calcium quantification. The expressions of BMP-4, BMP-7, Smad1, Smad4, and phosphorylated Smad1/5/8 were analyzed by western blotting. Relative mRNA expressions of Smad1, BMP receptor type II (BMPR-II, osteonectin, and osteocalcin were evaluated by qPCR. Results: ASCs+OM demonstrated the highest expression of BMP-4 and BMP-7 at days 21 and 7, respectively, the highest levels of BMPR-II mRNA expression at day 28, and the highest levels of Smad1 mRNA at days 14 and 28. ASCs+OM+BMP-2 demonstrated the highest levels of Smad1 mRNA expression at days 1, 7, and 21, the highest expression of Smad1 at day 7, the highest expression of Smad4 at day 14, the highest ALP activity at days 14 and 21, and expression of phosphorylated Smad1/5/8 at day 7. ASCs+OM and ASCs+OM+BMP2 showed similar ALP activity at days 7 and 28, similar osteonectin and osteocalcin mRNA expression at all time periods, and similar calcium depositions at all time periods. CONCLUSIONS: We concluded that human ASCs expressed endogenous BMP-4 and BMP-7. Moreover, the supplementation of ASCs with BMP-2 did not increase the level of osteogenic markers in the initial (ALP activity, intermediate (osteonectin and osteocalcin, or final (calcium deposition phases, suggesting that the exogenous addition of BMP-2 did not improve

  17. Adenovirus-mediated human bone morphogenetic protein 2 gene transfects bone marrow mesenchymal stem cells%腺病毒介导的人骨形态发生蛋白2基因转染骨髓间充质干细胞*☆

    Institute of Scientific and Technical Information of China (English)

    尹承慧; 邱俊钦; 曾昭勋; 陈宗雄

    2013-01-01

      背景:骨髓间充质干细胞作为骨、软骨创伤缺损及退变修复的种子细胞越来越受到关注。目的:分析人骨形态发生蛋白2基因转染对白色封闭群大鼠(SD 大鼠)骨髓间充质干细胞的影响。方法:分离纯化 SD 大鼠骨髓间充质干细胞并体外扩增,通过腺病毒载体介导人骨形态发生蛋白2基因转染骨髓间充质干细胞,分别通过荧光显微镜观察荧光表达情况及蛋白质水平来测定转染后人骨形态发生蛋白2的表达,碱性磷酸酶定量测定鉴定成骨活性及 MTT 法评估人骨形态发生蛋白2转染对骨髓间充质干细胞的影响。结果与结论:从 SD 大鼠骨髓提取物中分离培养的细胞形态为梭形,呈铺路石状、漩涡状生长,经流式细胞仪检测及多项分化能力鉴定符合骨髓间充质干细胞的特征;经转染人骨形态发生蛋白2基因后,骨髓间充质干细胞表达人骨形态发生蛋白2、碱性磷酸酶;MTT 法检测转染人骨形态发生蛋白2基因后,骨髓间充质干细胞增殖能力明显增强(P <0.05)。说明人骨形态发生蛋白2基因转染骨髓间充质干细胞后可以持续、高效表达人骨形态发生蛋白2和碱性磷酸酶,在体外明显促进骨髓间充质干细胞的增殖。%BACKGROUND: Bone marrow mesenchymal stem cel s as the seed cel s for repair of bone and cartilage trauma and degeneration have been paid increasing attention. OBJECTIVE: To investigative the effects of human bone morphogenetic protein 2 gene transfection on Sprague-Dawley rat bone marrow mesenchymal stem cel s. METHODS: Sprague-Dawley rat bone marrow mesenchyal stem cel s were in vitro isolated, purified and amplified. Adenovirus-mediated human bone morphogenetic protein 2 was transfected into bone marrow mesenchymal stem cel s. CD90 and CD45 expression levels were tested by flow cytometry. The successful y packaged virus was transfected into bone marrow mesenchymal

  18. Acerogenin A, a natural compound isolated from Acer nikoense Maxim, stimulates osteoblast differentiation through bone morphogenetic protein action

    Energy Technology Data Exchange (ETDEWEB)

    Kihara, Tasuku [Section of Oral Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo (Japan); Section of Maxillofacial Surgery, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo (Japan); Global Center of Excellence (GCOE) Program, International Research Center for Molecular Science in Tooth and Bone Diseases, Tokyo Medical and Dental University, Tokyo (Japan); Ichikawa, Saki [Section of Oral Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo (Japan); Yonezawa, Takayuki; Lee, Ji-Won [Research Institute for Biological Functions, Chubu University, Kasugai, Aichi (Japan); Akihisa, Toshihiro [College of Science and Technology, Nihon University, Tokyo (Japan); Woo, Je Tae [Research Institute for Biological Functions, Chubu University, Kasugai, Aichi (Japan); Michi, Yasuyuki; Amagasa, Teruo [Section of Maxillofacial Surgery, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo (Japan); Yamaguchi, Akira, E-mail: akira.mpa@tmd.ac.jp [Section of Oral Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo (Japan); Global Center of Excellence (GCOE) Program, International Research Center for Molecular Science in Tooth and Bone Diseases, Tokyo Medical and Dental University, Tokyo (Japan)

    2011-03-11

    Research highlights: {yields} Acerogenin A stimulated osteoblast differentiation in osteogenic cells. {yields} Acerogenin A-induced osteoblast differentiation was inhibited by noggin. {yields} Acerogenin A increased Bmp-2, Bmp-4 and Bmp-7 mRNA expression in MC3T3-E1 cells. {yields} Acerogenin A is a candidate agent for stimulating bone formation. -- Abstract: We investigated the effects of acerogenin A, a natural compound isolated from Acer nikoense Maxim, on osteoblast differentiation by using osteoblastic cells. Acerogenin A stimulated the cell proliferation of MC3T3-E1 osteoblastic cells and RD-C6 osteoblastic cells (Runx2-deficient cell line). It also increased alkaline phosphatase activity in MC3T3-E1 and RD-C6 cells and calvarial osteoblastic cells isolated from the calvariae of newborn mice. Acerogenin A also increased the expression of mRNAs related to osteoblast differentiation, including Osteocalcin, Osterix and Runx2 in MC3T3-E1 cells and primary osteoblasts: it also stimulated Osteocalcin and Osterix mRNA expression in RD-C6 cells. The acerogenin A treatment for 3 days increased Bmp-2, Bmp-4, and Bmp-7 mRNA expression levels in MC3T3-E1 cells. Adding noggin, a BMP specific-antagonist, inhibited the acerogenin A-induced increase in the Osteocalcin, Osterix and Runx2 mRNA expression levels. These results indicated that acerogenin A stimulates osteoblast differentiation through BMP action, which is mediated by Runx2-dependent and Runx2-independent pathways.

  19. 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

  20. Effect of recombinant human bone morphogenetic protein-2 on a novel lung cancer spine metastasis model in rodents.

    Science.gov (United States)

    Sonn, Kevin A; Kannan, Abhishek S; Bellary, Sharath S; Yun, Chawon; Hashmi, Sohaib Z; Nelson, John T; Ghodasra, Jason H; Nickoli, Michael S; Parimi, Vamsi; Ghosh, Anjan; Shawen, Nicholas; Ashtekar, Amruta; Stock, Stuart R; Hsu, Erin L; Hsu, Wellington K

    2016-07-01

    Lung cancer is the second most prevalent cancer. Spinal metastases are found in 30-90% of patients with death attributed to cancer. Due to bony destruction caused by metastases, surgical intervention is often required to restore spinal alignment and stability. While some research suggests that BMP-2 may possess tumorigenic effects, other studies show possible inhibition of cancer growth. Thirty-six athymic rats underwent intraosseous injection of lung adenocarcinoma cells into the L5 vertebral body. Cells were pre-treated with vehicle control (Group A) or rhBMP-2 (Group B) prior to implantation. At 4 weeks post-implantation, in vivo bioluminescent imaging (BLI) was performed to confirm presence of tumor and quantify signal. Plain radiographs and microComputed Tomography (microCT) were employed to establish and quantitate osteolysis. Histological analysis characterized pathologic changes in the vertebral body. At 4 weeks post-implantation, BLI showed focal signal in the L5 vertebral body in 93% of Group A animals and 89% of Group B animals. Average tumor burden by BLI radiance was 7.43 × 10(3)  p/s/cm(2) /sr (Group A) and 1.11 × 10(4)  p/s/cm(2) /sr (Group B). Radiographs and microCT demonstrated osteolysis in 100% of animals showing focal BLI signal. MicroCT demonstrated significant bone loss in both groups compared to age-matched controls but no difference between study groups. Histological analysis confirmed tumor invasion in the L5 vertebral body. These findings provide a reliable in vivo model to study isolated spinal metastases from lung cancer. Statement of Clinical Significance: The data support the notion that exposure to rhBMP-2 does not promote the growth of A549 lung cancer spine lesions. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1274-1281, 2016. PMID:26694749

  1. 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.

  2. Use of recombinant human bone morphogenetic protein-2 as an adjunct for instrumented posterior arthrodesis in the occipital cervical region: An analysis of safety, efficacy, and dosing

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    D Kojo Hamilton

    2010-01-01

    Full Text Available Background: There have been few reports on the use of recombinant human bone morphogenetic protein (rhBMP-2 in posterior spine. However, no study has investigated the dosing, safety, and efficacy of its use in the posterior atlantoaxial, and/or craniovertebral junction. Recent case report of the cytokine-mediated inflammatory reaction, following off label use of rhBMP-2 as an adjunct for cervical fusion, particularly in complex cases, has increased concern about complications associated with the product. Objective: To assess the safety, efficacy, and dosing of rhBMP-2 as an adjunct for instrumented posterior atlantoaxial and/or craniovertebral junction arthrodesis. Materials and Methods: We included all patients treated by the senior author that included posterior atlantoaxial and/or craniovertebral junction instrumented fusion using rhBMP-2 from 2003 to 2008 with a minimum two year follow-up. Diagnosis, levels fused, rhBMP-2 dose, complications, and fusion were assessed. Results: Twenty three patients with a mean age of 60.9 years (range 4 - 89 years and an average follow-up of 45 months (range 27 to 84 months met inclusion criteria. The indications for surgery included, atlantoaxial instability (n = 16, basilar invagination (n = 6, and kyphoscoliosis (n = 1. The specific pathologic diagnosis included type 2 dens fracture (n = 7, complex C1 and C2 ring fracture (n = 2, chordoma (n = 2, degenerative/osteoporosis (n = 3, rheumatoid disease (n = 8, and pseudogout (n = 1. The average rhBMP-2 dose was 2.38 mg/level, with a total of 76 levels treated (average 3.3 levels, SD= 1.4 levels. There were no complications. During the most recent follow-up, all patients had achieved fusion. Conclusions: In a series of patients with complex pathology and/or rheumatoid arthritis, 100% fusion rate was achieved with adjunct use of rhBMP-2, with a safe and effective average rhBMP-2 dose of 2.38 mg per level.

  3. Alterations in bone morphogenetic protein 15, growth differentiation factor 9, and gene expression in granulosa cells in preovulatory follicles of dairy cows given porcine LH.

    Science.gov (United States)

    Behrouzi, Amir; Colazo, Marcos Germán; Ambrose, Divakar Justus

    2016-04-15

    In a previous work, using porcine LH (pLH) in lieu of GnRH for synchronizing ovulation in dairy cows improved pregnancy rates without increasing plasma progesterone concentrations after ovulation. The LH profile is known to remain elevated above basal concentrations (≥1 ng/mL) for up to 20 hours in pLH-treated cows compared to less than 6 hours in GnRH-treated cows. Because LH triggers a cascade of signaling networks in the preovulatory follicle to promote final maturation and support oocyte competence, we hypothesized that dissimilar LH profiles will differentially regulate the intrafollicular factors and expression of downstream genes associated with improved oocyte competence. Specific objectives were to determine differences in the abundance of oocyte-secreted factors in the preovulatory follicular fluid and target genes in granulosa cells associated with oocyte competence, in response to exogenous porcine LH or GnRH-induced endogenous bovine LH exposure, in dairy cows. Follicular contents were aspirated by a transvaginal ultrasound-guided procedure from the preovulatory follicle of cyclic, nonlactating Holstein cows 21 ± 1 hour after administration of either pLH (25-mg) or GnRH (100-μg). Mature forms of bone morphogenetic protein 15, growth differentiation factor 9, and transforming growth factorβ1 were approximately 2-fold more abundant in pLH-treated cows which were exposed to an extended, low LH profile, than in GnRH-treated cows that had a short, high LH profile. The relative abundance of messenger RNA for cyclooxygenase-2, LH receptor, and progesterone receptor in granulosa cells, was about two-, eight-, and two-fold higher, respectively, in cows subjected to pLH than GnRH treatment. We infer that the improved pregnancy rate after pLH-induced ovulation reported previously, occurred through greater activation of intrafollicular transforming growth factor-β1 superfamily members, as these proteins promote cumulus expansion and oocyte competence

  4. Production of Transgenic Pigs with an Introduced Missense Mutation of the Bone Morphogenetic Protein Receptor Type IB Gene Related to Prolificacy.

    Science.gov (United States)

    Zhao, Xueyan; Yang, Qiang; Zhao, Kewei; Jiang, Chao; Ren, Dongren; Xu, Pan; He, Xiaofang; Liao, Rongrong; Jiang, Kai; Ma, Junwu; Xiao, Shijun; Ren, Jun; Xing, Yuyun

    2016-07-01

    In the last few decades, transgenic animal technology has witnessed an increasingly wide application in animal breeding. Reproductive traits are economically important to the pig industry. It has been shown that the bone morphogenetic protein receptor type IB (BMPR1B) A746G polymorphism is responsible for the fertility in sheep. However, this causal mutation exits exclusively in sheep and goat. In this study, we attempted to create transgenic pigs by introducing this mutation with the aim to improve reproductive traits in pigs. We successfully constructed a vector containing porcine BMPR1B coding sequence (CDS) with the mutant G allele of A746G mutation. In total, we obtained 24 cloned male piglets using handmade cloning (HMC) technique, and 12 individuals survived till maturation. A set of polymerase chain reactions indicated that 11 of 12 matured boars were transgene-positive individuals, and that the transgenic vector was most likely disrupted during cloning. Of 11 positive pigs, one (No. 11) lost a part of the terminator region but had the intact promoter and the CDS regions. cDNA sequencing showed that the introduced allele (746G) was expressed in multiple tissues of transgene-positive offspring of No.11. Western blot analysis revealed that BMPR1B protein expression in multiple tissues of transgene-positive F1 piglets was 0.5 to 2-fold higher than that in the transgene-negative siblings. The No. 11 boar showed normal litter size performance as normal pigs from the same breed. Transgene-positive F1 boars produced by No. 11 had higher semen volume, sperm concentration and total sperm per ejaculate than the negative siblings, although the differences did not reached statistical significance. Transgene-positive F1 sows had similar litter size performance to the negative siblings, and more data are needed to adequately assess the litter size performance. In conclusion, we obtained 24 cloned transgenic pigs with the modified porcine BMPR1B CDS using HMC. c

  5. Elevated extracellular calcium increases expression of bone morphogenetic protein-2 gene via a calcium channel and ERK pathway in human dental pulp cells

    Energy Technology Data Exchange (ETDEWEB)

    Tada, Hiroyuki [Division of Periodontology and Endodontology, Tohoku University Graduate School of Dentistry, Sendai 980-8575 (Japan); Nemoto, Eiji, E-mail: e-nemoto@umin.ac.jp [Division of Periodontology and Endodontology, Tohoku University Graduate School of Dentistry, Sendai 980-8575 (Japan); Kanaya, Sousuke; Hamaji, Nozomu; Sato, Hisae; Shimauchi, Hidetoshi [Division of Periodontology and Endodontology, Tohoku University Graduate School of Dentistry, Sendai 980-8575 (Japan)

    2010-04-16

    Dental pulp cells, which have been shown to share phenotypical features with osteoblasts, are capable of differentiating into odontoblast-like cells and generating a dentin-like mineral structure. Elevated extracellular Ca{sup 2+}Ca{sub o}{sup 2+} has been implicated in osteogenesis by stimulating the proliferation and differentiation of osteoblasts; however, the role of Ca{sub o}{sup 2+} signaling in odontogenesis remains unclear. We found that elevated Ca{sub o}{sup 2+} increases bone morphogenetic protein (BMP)-2 gene expression in human dental pulp cells. The increase was modulated not only at a transcriptional level but also at a post-transcriptional level, because treatment with Ca{sup 2+} increased the stability of BMP-2 mRNA in the presence of actinomycin D, an inhibitor of transcription. A similar increase in BMP-2 mRNA level was observed in other human mesenchymal cells from oral tissue; periodontal ligament cells and gingival fibroblasts. However, the latter cells exhibited considerably lower expression of BMP-2 mRNA compared with dental pulp cells and periodontal ligament cells. The BMP-2 increase was markedly inhibited by pretreatment with an extracellular signal-regulated kinase (ERK) inhibitor, PD98059, and partially inhibited by the L-type Ca{sup 2+} channels inhibitor, nifedipine. However, pretreatment with nifedipine had no effect on ERK1/2 phosphorylation triggered by Ca{sup 2+}, suggesting that the Ca{sup 2+} influx from Ca{sup 2+} channels may operate independently of ERK signaling. Dental pulp cells do not express the transcript of Ca{sup 2+}-sensing receptors (CaSR) and only respond slightly to other cations such as Sr{sup 2+} and spermine, suggesting that dental pulp cells respond to Ca{sub o}{sup 2+} to increase BMP-2 mRNA expression in a manner different from CaSR and rather specific for Ca{sub o}{sup 2+} among cations.

  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. 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.

  8. Bone Morphogenetic Protein (BMP-4 and BMP-7 regulate differentially Transforming Growth Factor (TGF-β1 in normal human lung fibroblasts (NHLF

    Directory of Open Access Journals (Sweden)

    Lloyd Clare M

    2010-06-01

    Full Text Available Abstract Background Airway remodelling is thought to be under the control of a complex group of molecules belonging to the Transforming Growth Factor (TGF-superfamily. The Bone Morphogenetic Proteins (BMPs belong to this family and have been shown to regulate fibrosis in kidney and liver diseases. However, the role of BMPs in lung remodelling remains unclear. BMPs may regulate tissue remodelling in asthma by controlling TGF-β-induced profibrotic functions in lung fibroblasts. Methods Cell cultures were exposed to TGF-β1 alone or in the presence of BMP-4 or BMP-7; control cultures were exposed to medium only. Cell proliferation was assessed by quantification of the incorporation of [3H]-thymidine. The expression of the mRNA encoding collagen type I and IV, tenascin C and fibronectin in normal human lung fibroblasts (NHLF was determined by real-time quantitative PCR and the main results were confirmed by ELISA. Cell differentiation was determined by the analysis of the expression of α-smooth muscle actin (α-SMA by western blot and immunohistochemistry. The effect on matrix metalloproteinase (MMP activity was assessed by zymography. Results We have demonstrated TGF-β1 induced upregulation of mRNAs encoding the extracellular matrix proteins, tenascin C, fibronectin and collagen type I and IV when compared to unstimulated NHLF, and confirmed these results at the protein level. BMP-4, but not BMP-7, reduced TGF-β1-induced extracellular matrix protein production. TGF-β1 induced an increase in the activity of the pro-form of MMP-2 which was inhibited by BMP-7 but not BMP-4. Both BMP-4 and BMP-7 downregulated TGF-β1-induced MMP-13 release compared to untreated and TGF-β1-treated cells. TGF-β1 also induced a myofibroblast-like transformation which was partially inhibited by BMP-7 but not BMP-4. Conclusions Our study suggests that some regulatory properties of BMP-7 may be tissue or cell type specific and unveil a potential regulatory role for

  9. 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

  10. Hepatocyte growth factor activator inhibitor-1 is induced by bone morphogenetic proteins and regulates proliferation and cell fate of neural progenitor cells.

    Directory of Open Access Journals (Sweden)

    Raili Koivuniemi

    Full Text Available BACKGROUND: Neural progenitor cells (NPCs in the developing neuroepithelium are regulated by intrinsic and extrinsic factors. There is evidence that NPCs form a self-supporting niche for cell maintenance and proliferation. However, molecular interactions and cell-cell contacts and the microenvironment within the neuroepithelium are largely unknown. We hypothesized that cellular proteases especially those associated with the cell surface of NPCs play a role in regulation of progenitor cells in the brain. METHODOLOGY/PRINCIPAL FINDINGS: In this work, we show that NPCs, isolated from striatal anlage of developing rat brain, express hepatocyte growth factor activator inhibitor-1 and -2 (HAI-1 and HAI-2 that are cell surface-linked serine protease inhibitors. In addition, radial glia cells derived from mouse embryonic stem cells also express HAI-1 and HAI-2. To study the functional significance of HAI-1 and HAI-2 in progenitor cells, we modulated their levels using expression plasmids or silencing RNA (siRNA transfected into the NPCs. Data showed that overexpression of HAI-1 or HAI-2 decreased cell proliferation of cultured NPCs, whilst their siRNAs had opposite effects. HAI-1 also influenced NPC differentiation by increasing the number of glial fibrillary acidic protein (GFAP expressing cells in the culture. Expression of HAI-1 in vivo decreased cell proliferation in developing neuroepithelium in E15 old animals and promoted astrocyte cell differentiation in neonatal animals. Studying the regulation of HAI-1, we observed that Bone morphogenetic protein-2 (BMP-2 and BMP-4 increased HAI-1 levels in the NPCs. Experiments using HAI-1-siRNA showed that these BMPs act on the NPCs partly in a HAI-1-dependent manner. CONCLUSIONS: This study shows that the cell-surface serine protease inhibitors, HAI-1 and HAI-2 influence proliferation and cell fate of NPCs and their expression levels are linked to BMP signaling. Modulation of the levels and actions of HAI-1

  11. Evaluation of osteogenic cell differentiation in response to bone morphogenetic protein or demineralized bone matrix in a critical sized defect model using GFP reporter mice.

    Science.gov (United States)

    Alaee, Farhang; Hong, Seung-Hyun; Dukas, Alex G; Pensak, Michael J; Rowe, David W; Lieberman, Jay R

    2014-09-01

    We evaluated the osteoprogenitor response to rhBMP-2 and DBM in a transgenic mouse critical sized defect. The mice expressed Col3.6GFPtopaz (a pre-osteoblastic marker), Col2.3GFPemerald (an osteoblastic marker) and α-smooth muscle actin (α-SMA-Cherry, a pericyte/myofibroblast marker). We assessed defect healing at various time points using radiographs, frozen, and conventional histologic analyses. GFP signal in regions of interest corresponding to the areas of new bone formation was quantified using a novel computer assisted algorithm. All defects treated with rhBMP-2 healed. In contrast, the majority of the defects in the DBM (27/30) and control (28/30) groups did not heal. Quantitation of pre-osteoblasts demonstrated a maximal response (% GFP + cells/TV) in the Col3.6GFPtopaz mice at day 7 (7.2% ± 6.0, p Col2.3GFP cells was seen at days 14 (8.04% ± 5.0) and 21 (8.31% ± 4.32), p < 0.05. In contrast, DBM and control groups showed a limited osteogenic response at all time points. In conclusion, we demonstrated that the BMP and DBM induce vastly different osteogenic responses which should influence their clinical application as bone graft substitutes. PMID:24888702

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

    Directory of Open Access Journals (Sweden)

    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.

  13. 骨形态发生蛋白2缓释载体的研究进展%Research Progress of Bone Morphogenetic Protein-2 Controlled-release Carrier

    Institute of Scientific and Technical Information of China (English)

    张以财; 焦力刚

    2012-01-01

    自体骨移植一直是骨修复的"金标准",但仍存在一些问题.异体骨移植同样存在着骨愈合缓慢及排斥反应等问题.随着组织工程学的发展,应用骨组织工程方法来修复骨缺损成为研究热点.骨组织工程主要包括支架材料、种子细胞、生长因子三个方面.骨形态发生蛋白2是目前最强的促骨生长因子,其在体内半衰期很短,必须依靠缓释载体才能发挥其较长效的促骨生长作用.%Autogenous bone graft has long been the " golden standard" of bone repair, while there are some remaining problems. Allograft also have many problems, such as slow bone healing and rejection etc. . With the development of tissue engineering, lots of eyes focus on bone tissue engineering to repair bone defects. There are three key points in bone tissue engineering namely scaffolds, seed cells and growth factor. Bone morphogenetic protein-2 is the most efficient factor to promote bone growth so far,but it has a very short half-time in vivo, which must rely on control-released carrier to fulfill its long-term bone growth-promoting effect.

  14. Effects of bone morphogenetic protein-4 on spatial memory and cholinergic expression in the dentate gyrus after fornix-fimbria transection in rats

    Institute of Scientific and Technical Information of China (English)

    Lei Liu; Yilong Xue; Jingkun Pan; Yazhuo Hu; Yuhong Gao; Yun Luo

    2008-01-01

    BACKGROUND: Previous experiments have confirmed bone morphogenetic proteins (BMPs) upregulate cholinergic expression in neurons isolated from the embryonic rat hippocampus and cerebral cortex. Therefore, BMPs could be useful for treating Alzheimer's disease and other neurodegenerative diseases. OBJECTIVE: BMP-4 was infused into the hippocampal dentate gyrus of fornix-fimbria transected rats to test the effects of BMP-4 on cholinergic expression in dentate gyrus neurons, and to observe changes in spatial memory behavior. DESIGN: A randomized controlled animal experiment. SETTING: Department of Neurosurgery and Laboratory for Cell Biology, Institute of Geriatrics, General Hospital of Chinese PLA.MATERIALS: Twenty-seven healthy adult male Sprague Dawley (SD) rats, weighing 250-300 g, were provided by the Laboratory Animal Center of the General Hospital of Chinese PLA. Reagents: BMP-4 (B-2680, Sigma Company) and choline acetyl transferase (ChAT) antibody (AB5042, Chemicon Company) were used in this study. Equipments: a rat stereotaxic instrument (type: SN-2N, Narushige Group, Japan) and Image-prog-plus image analysis software (Media Cybernetics company, USA) were used in this study. The protocol was carried out in accordance with ethical guidelines for the use and care of animals.METHODS: This experiment was performed in the Institute of Geriatrics, General Hospital of Chinese PLA between July 2004 and March 2005. Rats were randomly divided into 4 groups: Alzheimer's disease group (n = 7), normal control group (n = 5), BMP-4-Alzheimer's disease group (n = 8), and model group (n = 7). In the Alzheimer's disease group, the left hippocampal fornix-fimbria of rats was transected to mimic Alzheimer's disease symptoms. In the BMP-4-Alzheimer's disease group, 1 μL BMP-4 (10 mg/L) was perfused into the left dentate gyrus with a microinjector at 1 μL/min. In the model group, 1 μL saline was perfused into the same position by the same method. Twenty-eight days after injection

  15. Effects of LED phototherapy on bone defects grafted with MTA, bone morphogenetic proteins, and guided bone regeneration in a rodent model: a description of the bone repair by light microscopy

    Science.gov (United States)

    Pinheiro, Antonio Luiz B.; Aciole, Gilberth T. S.; Soares, Luiz G. P.; Correia, Neandder A.; N. dos Santos, Jean

    2011-03-01

    We carried out a histological analysis on surgical bone defects grafted or not with MTA, treated or not with LED, BMPs and GBR. We have used several models to assess the effects of laser on bone. Benefits of the isolated or combined use them on bone healing has been suggested. There is no previous report on their association with LED light. 90 rats were divided into 10 groups. On Groups II and I the defect were filled with the clot. On Group II, were further irradiated. On groups III-VI, defect was filled with MTA + Collagen gel (III); animals of group IV were further irradiated. On groups V and VI, the defects filled with the MTA were covered with a membrane. Animals of Group VI were further irradiated. On Groups VII and VIII a pool of BMPs was added to the MTA and was further irradiated. On groups IX and X, the MTA + BMP graft was covered with a membrane. On group X, the defect was further irradiated. LED (λ850 +/- 10nm, 150mW, A= 0.5cm2, 54s, 0.3W/cm2, 16 J/cm2) was applied at 48 h intervals during 15 days. Specimens were taken, processed, cut and stained with H&E and Sirius red and underwent histological analysis. The results showed that MTA seemed not being affected by LED light. However, its use positively affected healing around the graft. It is concluded that MTA is not affected by the LED light due to it characteristics, but beneficial results with LED usage was found.

  16. Identification of the role of bone morphogenetic protein (BMP) and transforming growth factor-β (TGF-β) signaling in the trajectory of serotonergic differentiation in a rapid assay in mouse embryonic stem cells in vitro.

    Science.gov (United States)

    Yamasaki, Atsushi; Kasai, Atsushi; Toi, Akihiro; Kurita, Maki; Kimoto, Saki; Hayata-Takano, Atsuko; Nakazawa, Takanobu; Nagayasu, Kazuki; Shintani, Norihito; Hashimoto, Ryota; Ito, Akira; Meltzer, Herbert Y; Ago, Yukio; Waschek, James A; Onaka, Yusuke; Matsuda, Toshio; Baba, Akemichi; Hashimoto, Hitoshi

    2015-02-01

    The mechanism by which extracellular molecules control serotonergic cell fate remains elusive. Recently, we showed that noggin, which inactivates bone morphogenetic proteins (BMPs), induces serotonergic differentiation of mouse embryonic (ES) and induced pluripotent stem cells with coordinated gene expression along the serotonergic lineage. Here, we created a rapid assay for serotonergic induction by generating knock-in ES cells expressing a naturally secreted Gaussia luciferase driven by the enhancer of Pet-1/Fev, a landmark of serotonergic differentiation. Using these cells, we performed candidate-based screening and identified BMP type I receptor kinase inhibitors LDN-193189 and DMH1 as activators of luciferase. LDN-193189 induced ES cells to express the genes encoding Pet-1, tryptophan hydroxylase 2, and the serotonin transporter, and increased serotonin release without altering dopamine release. In contrast, TGF-β receptor inhibitor SB-431542 selectively inhibited serotonergic differentiation, without changing overall neuronal differentiation. LDN-193189 inhibited expression of the BMP signaling target gene Id, and induced the TGF-β target gene Lefty, whereas the opposite effect was observed with SB-431542. This study thus provides a new tool to investigate serotonergic differentiation and suggests that inhibition of BMP type I receptors and concomitant activation of TGF-β receptor signaling are implicated in serotonergic differentiation. Candidate-based screening for serotonergic induction using a rapid assay in mouse embryonic stem cells revealed that the bone morphogenetic protein (BMP) type I receptor kinase inhibitors selectively induce serotonergic differentiation, whereas the TGF-β receptor inhibitor SB-431542 inhibits the differentiation. These results suggest that inhibition of BMP type I receptors and concomitant activation of transforming growth factor-β (TGF-β) receptor signaling are involved in the early trajectory of serotonergic

  17. A fusion between domains of the human bone morphogenetic protein-2 and maize 27 kD gamma-zein accumulates to high levels in the endoplasmic reticulum without forming protein bodies in transgenic tobacco

    Directory of Open Access Journals (Sweden)

    Valentina eCeresoli

    2016-03-01

    Full Text Available Human Bone Morphogenetic Protein-2 (hBMP2 is an osteoinductive agent physiologically involved in bone remodelling processes. A commercialized recombinant hBMP2 produced in mammalian cell lines is available in different clinical applications where bone regeneration is needed, but widespread use has been hindered due to an unfavorable cost/effective ratio. Protein bodies are very large insoluble protein polymers that originate within the endoplasmic reticulum by prolamine accumulation during the cereal seed development. The N-terminal domain of the maize prolamin 27 kD -zein is able to promote protein body biogenesis when fused to other proteins. To produce high yield of recombinant hBMP2 active domain (ad in stably transformed tobacco plants we have fused it to the γ-zein domain. We show that this zein-hBMP2ad fusion is retained in the endoplasmic reticulum without forming insoluble protein bodies. The accumulation levels are above 1% of total soluble leaf proteins, indicating that it could be a rapid and suitable strategy to produce hBMP2ad at affordable costs.

  18. 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.

  19. 骨形态发生蛋白-9对兔骨髓间充质干细胞诱导分化作用%Differentiation induced by bone morphogenetic protein-9 of rabbit bone marrow mesenchymal stem cells

    Institute of Scientific and Technical Information of China (English)

    谭富强; 刘渤; 刘浠; 欧东; 易威威; 温亚枫

    2015-01-01

    目的 分离、培养并鉴定新西兰兔骨髓间充质干细胞(BMSCs),观察BMSCs经腺病毒重组人骨形态发生蛋白-9(AdBMP-9)诱导后的成骨分化及其在明胶海绵上的生长.方法 采用全骨髓培养分离提取兔BMSCs,噻唑蓝(MTT)检测第2、3、4、5代细胞的增殖.流式细胞仪检测兔BMSCs表面抗原CD44和CD34.利用AdBMP-9转染第3代BMSCs,分别于诱导后7、14 d行碱性磷酸酶(ALP)染色、茜素红S染色和免疫荧光染色检测早期和晚期成骨标志物碱性磷酸酶、钙结节及骨钙素(OC)的表达.同时在14 d行油红O染色观察其成脂分化能力,荧光显微镜下观察BMSCs与明胶海绵复合生长.结果 成功分离提取兔BMSCs,经传代,细胞由长梭形变为短梭形,第3代形态、大小趋于稳定.MTT检测发现第2、3、4、5代细胞均呈对数生长,生长曲线近似“S”型,第2代细胞生长最慢,第4代生长最快(P<0.05).流式细胞仪检测显示,CD44和CD34的阳性率分别为94.38%和2.63%.AdBMP-9诱导后,可检测到早期和晚期成骨标志物及脂滴的生成,转染后的BMSCs可较好地与明胶海绵复合生长.结论 采用全骨髓培养法可分离得到较纯的兔BMSCs,在AdBMP-9诱导下,其可向成骨、成脂分化,且能较好地与明胶海绵复合生长.%Objective To isolate,culture and purify the New Zealand rabbit bone marrow mesenchymal stem cells (BMSCs),research the osteogenic differentiation ability of BMSCs induced by recombinant adenovirus bone morphogenetic protein-9 (AdBMP-9) and the growth of BMSCs on absorbable gelatin sponge,expect to provide cytology basis for the study of bone tissue engineering.Methods Separated and obtained BMSCs by whole bone marrow culture method,the proliferation of the 2nd,3rd,4th,and 5th cell passages were analyzed by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT).Flow cytometry was used to confirm the expression of surface antigen marker CD34 and CD44.Take the

  20. Differential effects of bone morphogenetic protein-2 and transforming growth factor-beta1 on gene expression of collagen-modifying enzymes in human adipose tissue-derived mesenchymal stem cells.

    Science.gov (United States)

    Knippenberg, Marlene; Helder, Marco N; Doulabi, Behrouz Zandieh; Bank, Ruud A; Wuisman, Paul I J M; Klein-Nulend, Jenneke

    2009-08-01

    Adipose tissue-derived mesenchymal stem cells (AT-MSCs) in combination with bone morphogenetic protein-2 (BMP-2) or transforming growth factor-beta1 (TGF-beta1) are under evaluation for bone tissue engineering. Posttranslational modification of type I collagen is essential for functional bone tissue with adequate physical and mechanical properties. We investigated whether BMP-2 (10-100 ng/mL) and/or TGF-beta1 (1-10 ng/mL) affect gene expression of alpha2(I) procollagen and collagen-modifying enzymes, that is, lysyl oxidase and lysyl hydroxylases 1, 2, and 3 (encoded by PLOD1, 2, and 3), by human AT-MSCs. BMP-2, but not TGF-beta1, increased alkaline phosphatase activity after 28 days, indicating osteogenic differentiation of AT-MSCs. At day 4, both BMP-2 and TGF-beta1 upregulated alpha2(I) procollagen and PLOD1, which was downregulated at day 28. TGF-beta1, but not BMP-2, downregulated PLOD3 at day 28. Lysyl oxidase was upregulated by TGF-beta1 at day 4 and by BMP-2 at day 7. Neither BMP-2 nor TGF-beta1 affected PLOD2. In conclusion, these results suggest that AT-MSCs differentially respond to BMP-2 and TGF-beta1 with changes in gene expression of collagen-modifying enzymes. AT-MSCs may thus be able to appropriately modify type I collagen to form a functional bone extracellular matrix for tissue engineering, dependent on the growth factor added. PMID:19231972

  1. 带血供肌瓣作为骨形态发生蛋白载体修复骨缺损的实验研究%Vascular muscle flap combined with bone morphogenetic protein for forming bone bridge to repair bone defect: experimental study

    Institute of Scientific and Technical Information of China (English)

    裴国献; 杨润功; 魏宽海; 金丹

    2001-01-01

    Objective To investigate the effect of vascular muscle flap as a carrier of bone morphogenetic protein (BMP) to repair long bone defect. Methods Vascular muscle flap with BMP and BMP alone were implanted into the experimental models. Their conditions of new bone formation were observed and compared. Additionally, bone defects were divided into 4 groups in random and repaired respectively with the vascular muscle flap combined with FS/BMP (group A), vascular muscle flap/BMP (group B), bloodless muscle flap/BMP (group C), and autolyzed antigen-extracted allogeneic bone (AAA)/BMP (group D). Their abilities of bone forming were observed. Results In the group of vascular muscle flap combined with BMP, a large amount of cartilage was formed in the gaps of muscles by 3 weeks. The cartilage was absorbed and replaced by normal bone containing hematopoietic bone marrow by 6 weeks with obvious muscle cell atrophy. The wet bone weight of the new bone was (253.52±20.63) mg,which was significantly larger than that of the control group (172.22±13.95) mg (P<0.01).In group A,the cartilage formed by 3 weeks and woven bone formed by 6 weeks;the haversion system formed and muscle cells disappeared by 9 weeks.Natural bone was found and the Tmax measured with torsion test was (0.82±0.04) N*m.The calcium content was (174.55±5.11) μg/g by 12 weeks.The ability of new bone formation in the 4 groups was in the following order: group A was similar to group D, group A>group B>group C. Conclusions Vascular muscle flap can serve as an effective carrier for BMP. Vascular muscle flap combined with FS as carrier is better than vascular muscle flap as a carrier alone.%目的探讨带血供肌瓣作为骨形态发生蛋白(BMP)载体修复骨缺损的可行性。方法观察带血供肌瓣复合BMP和单纯BMP组修复骨缺损时的成骨情况;对纤维蛋白粘合剂、带血供肌瓣、无血运肌瓣、同种异体脱钙骨4种不同BMP载体的成骨能力进行

  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. Histological observation on transforming growth factor- β compounded with bone morphogenetic protein as a pulp capping material%TGF-β复合BMP盖髓的组织学观察

    Institute of Scientific and Technical Information of China (English)

    李国华; 赵京宁; 王学英; 金岩; 牛忠英

    2000-01-01

    目的:用β转化生长因子复合骨形成蛋白(TGF-β/BMP)覆盖狗暴露牙髓,观察TGF-β/BMP的盖髓效果。方法:用活体狗牙作直接盖髓实验,并用组织学方法评价盖髓效果。结果:术后8周,TGF-β/BMP能够诱导牙髓成纤维细胞、内皮细胞增殖并抑制炎症反应,提高牙髓修复能力,有完整的牙本质桥形成。结论:TGF-β/BMP能促进狗牙髓组织修复。%AIM: Observation of the effects of transforming growth factor- β compounded with bone morphogenetic protein (TGF- β/BMP) on the exposed pulp of dogs. METHODS: The teeth of dogs were used for direct pulp capping experiment and the results were evaluated histopathologically. RESULt: Eight weeks postoperatively TGF- β/BMP was able to induce the proliferations of the pulp cells (fibroblasts)and endothelial cell, inhibit the inflammatory reaction of pulp, and possessed the ability to enhance the pulp repairing, complete dentin bridge was induced. CONCLUSION:TGF- β/BMP can promote the regeneration of dog's pulp tissue.

  4. Multiple roles of Activin/Nodal, bone morphogenetic protein, fibroblast growth factor and Wnt/β-catenin signalling in the anterior neural patterning of adherent human embryonic stem cell cultures

    Science.gov (United States)

    Lupo, Giuseppe; Novorol, Claire; Smith, Joseph R.; Vallier, Ludovic; Miranda, Elena; Alexander, Morgan; Biagioni, Stefano; Pedersen, Roger A.; Harris, William A.

    2013-01-01

    Several studies have successfully produced a variety of neural cell types from human embryonic stem cells (hESCs), but there has been limited systematic analysis of how different regional identities are established using well-defined differentiation conditions. We have used adherent, chemically defined cultures to analyse the roles of Activin/Nodal, bone morphogenetic protein (BMP), fibroblast growth factor (FGF) and Wnt/β-catenin signalling in neural induction, anteroposterior patterning and eye field specification in hESCs. We show that either BMP inhibition or activation of FGF signalling is required for effective neural induction, but these two pathways have distinct outcomes on rostrocaudal patterning. While BMP inhibition leads to specification of forebrain/midbrain positional identities, FGF-dependent neural induction is associated with strong posteriorization towards hindbrain/spinal cord fates. We also demonstrate that Wnt/β-catenin signalling is activated during neural induction and promotes acquisition of neural fates posterior to forebrain. Therefore, inhibition of this pathway is needed for efficient forebrain specification. Finally, we provide evidence that the levels of Activin/Nodal and BMP signalling have a marked influence on further forebrain patterning and that constitutive inhibition of these pathways represses expression of eye field genes. These results show that the key mechanisms controlling neural patterning in model vertebrate species are preserved in adherent, chemically defined hESC cultures and reveal new insights into the signals regulating eye field specification. PMID:23576785

  5. 钛网结合异体骨移植联合人骨形成蛋白与自体骨移植在种植前牙槽嵴骨增量中的应用对比%Comparison of Application of Titanium Mesh Combined with Allograft Combined with Human Bone Morphogenetic Protein and Autogenous Bone Transplantation in Alveolar Bone Augmentation

    Institute of Scientific and Technical Information of China (English)

    崔延军; 王红光; 程汇

    2015-01-01

    Objective To compare the application of titanium mesh combined with allograft combined with human bone morphogenetic protein and autogenous bone transplantation in alveolar bone augmentation.Methods A total of 46 cases receiving anterior implant plus alveolar bone increment admitted to Tianmen City First People′s Hospital from Jan.2008 to Dec.2011 were randomly divided into two groups according to random-number table method,group A(n =23) using titanium mesh combined with allograft combined with human bone morphogenetic protein,while group B (n =23) using autogenous bone graft.The alveolar ridge width,the incremental effects and postoperative bone implant stability were compared before and after surgery.Results Postoperative average alveolar ridge width of group A was significantly higher than that of group B [(6.9 ±0.5) mm vs (5.6 ±0.3) mm,P <0.01]; the cure rate of group A was 94.1%,of group B was 60.0%,and the clinical efficacy of group A was better than group B with statistically significant difference (P <0.05); no-loosening rate after 4 months implant was 91.2% in group A,50.6% in group B,the sta-bility of group A was much better than group B,with statistically significant difference(P <0.05).Conclu-sion Titanium mesh combined with allogeneic bone graft combined with human bone morphogenetic protein can significantly increase patient alveolar bone mass and help to stabilize the implant after surgery .%目的:比较钛网结合异体骨移植联合人骨形成蛋白与自体骨移植在种植前牙槽嵴骨增量中的应用效果。方法将2008年1月至2011年12月天门市第一人民医院收治的46例前牙种植并行牙槽嵴骨增量的患者依据随机数字表法分为两组:A 组23例,采用钛网结合异体骨移植联合人骨形成蛋白的方法;B 组23例,采用自体骨移植的方法。比较两组患者手术前后牙槽嵴宽度、骨增量效果及术后种植体稳定性。结果术后 A 组牙槽嵴

  6. Application of bone morphogenetic proteins in mandibular fast distraction osteogenesis%骨形态形成蛋白在下颌骨快速牵张成骨中的应用

    Institute of Scientific and Technical Information of China (English)

    刘浩; 王敏

    2012-01-01

    BACKGROUND: Distraction osteogenesis has became an effective method in treatment of different kinds of craniofacialdeformities and bone defects. However, the major disadvantage of this method is the long distraction and consolidation period,which may lead to severe complications during the distraction process.OBJECTIVE: To summarize the research progress of the application of bone morphogenetic proteins (BMPs) in fast distractionosteogenesis.METHODS: A computer-based online search in Pubmed database was performed to select the reviews and papers related toBMPs and distraction osteogenesis from 1989 to 2011.RESULTS AND CONCLUSION: A total of 32 literatures on the the application of BMPs in fast distraction osteogenesis wereincluded. BMPs have a strong osteogenic activity and capability of promoting regeneration and remodeling of bone. The presentresearch shows that BMPs can be used to accelerate new bone formation and shorten the treatment period. However, the clinicalapplication of BMPs needs further research.%背景:牵张成骨已经成为治疗不同类型颅面畸形和骨缺损的有效的方法,但是牵张成骨的主要缺点是牵张期和稳定期比较长,可能导致牵张过程中严重的并发症.目的:总结骨形态形成蛋白在快速牵张成骨过程中作用的研究现状.方法:电子检索计算机Pubmed 数据库(1989/2011)收录的骨形态形成蛋白和牵张成骨相关综述和论文报告.结果与结论:共纳入骨形态形成蛋白在快速牵张成骨中的作用相关文献32 篇.骨形态形成蛋白具有很强的成骨活性,能促进骨再生和骨改建.目前的研究显示应用骨形态形成蛋白能加快牵张成骨过程中新骨形成和缩短治疗的疗程.但是骨形态形成蛋白应用于临床还需要进一步的研究.

  7. Profiling bone morphogenetic proteins and transforming growth factor-βs by hTGF-β3 pre-treated coral-derived macroporous bioreactors: the power of one.

    Science.gov (United States)

    Ripamonti, Ugo; Dix-Peek, Thérèse; Parak, Ruqayya; Milner, Brenda; Duarte, Raquel

    2015-05-01

    To study the expression profile of bone morphogenetic proteins and transforming growth factor-βs (BMPs and TGFβs), coral-derived calcium carbonate-based macroporous bioreactors with limited conversion to hydroxyapatite (7% HA/CC) were pre-loaded with and without 250 μg hTGF-β3 and implanted in the rectus abdominis of 3 non-human primates Papio ursinus euthanized on day 60. To investigate the required dose of hNoggin, a BMPs antagonist that controls the induction of bone formation, 7% HA/CC were pre-loaded with 150 μg hNoggin, with 125 μg hTGF-β3/150 μg hNoggin, with or without 125 μg hTGF-β3 and implanted in the r. abdominis of 3 additional animals euthanized on day 90. Quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) evaluated the expression' profile of BMP-2, BMP-3, BMP-4, BMP-6, BMP-7 and TGF-β1, -β2, and -β3 in tissue generating bioreactors as well as in the adjacent r. abdominis muscle. On day 60, 250 μg hTGF-β3 induced bone formation at the periphery of the implanted bioreactors only. On day 90, 125 μg hTGF-β3/treated bioreactors showed the induction of bone formation throughout the macroporous spaces. Untreated bioreactors induced bone, 4.11% vs. 2.00% on days 60 and 90, respectively. In hTGF-β3/treated bioreactors, BMP-2 and BMP-3 were up-regulated at both time periods, both in the homogenized constructs and in the adjacent r. abdominis muscle whilst BMP-4 in the homogenized construct only. In untreated 7% HA/CC constructs, BMP-2 was up-regulated in the macroporous construct only. On day 60, 250 μg hTGF-β3/treated and untreated macroporous constructs showed up-regulation of TGF-β1 with a six fold increase vs. TGF-β1 expression in adjacent muscle of untreated constructs. TGF-β2 was down regulated in both untreated and 250 μg hTGF-β3/treated bioreactors. On day 60, 250 μg hTGF-β3/treated bioreactors showed TGF-β3 expression in untreated, treated and adjacent muscle tissues. On day 90, BMP-2 was up

  8. Lumbar interbody fusion with porous biphasic calcium phosphate enhanced by recombinant bone morphogenetic protein-2/silk fibroin sustained-released microsphere: an experimental study on sheep model.

    Science.gov (United States)

    Chen, Liang; Liu, Hai-Long; Gu, Yong; Feng, Yu; Yang, Hui-Lin

    2015-03-01

    Biphasic calcium phosphate (BCP) has been investigated extensively as a bone substitute nowadays. However, the bone formation capacity of BCP is limited owing to lack of osteoinduction. Silk fibroin (SF) has a structure similar to type I collagen, and could be developed to a microsphere for the sustained-release of rhBMP-2. In our previous report, bioactivity of BCP could be enhanced by rhBMP-2/SF microsphere (containing 0.5 µg rhBMP-2) in vitro. However, the bone regeneration performance of the composite in vivo was not investigated. Thus, the purpose of this study was to evaluate the efficacy of BCP/rhBMP-2/SF in a sheep lumbar fusion model. A BCP and rhBMP-2/SF microsphere was developed, and then was integrated into a BCP/rhBMP-2/SF composite. BCP, BCP/rhBMP-2 and BCP/rhBMP-2/SF were implanted randomly into the disc spaces of 30 sheep at the levels of L1/2, L3/4 and L5/6. After sacrificed, the fusion segments were evaluated by manual palpation, CT scan, biomechanical testing and histology at 3 and 6 months, respectively. The composite demonstrated a burst-release of rhBMP-2 (39.1 ± 2.8 %) on the initial 4 days and a sustained-release (accumulative 81.3 ± 4.9 %) for more than 28 days. The fusion rates, semi-quantitative CT scores, fusion stiffness in bending in all directions and histologic scores of BCP/rhBMP-2/SF were significantly greater than BCP and BCP/rhBMP-2 at each time point, respectively (P sheep using BCP constructs.

  9. Improved Osteointegration of Ti-6Al-4V-implants of Different Surface Texture by the Use of Bone Morphogenetic Protein-3 (BMP-3)

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    Half of altogether 60 cylindrical implant devices mode of titanium-aluminum-vanadium alloy( Ti-6Al-4 V) were plasma-sprayed with a hydroxyapatite-coating and the other half had a corundum blasted porous surface. 15 implants of each group of the titanium test implants were coated with 230μgporcine, high-purified BMP- 3-precipitate per implant. In each case a BMP- 3-coated and an uncoated control-device were implanted into the femoral part of the patellofemoral joint of the right and left leg of 30 adult giant rabbits. Histomorphological and histomorphometrical we found in both groups with BMP- 3-coated test devices an improved osteointegration. Statistical evaluation using the t-test for matched samples showed 5 weeks after surgery a significant higher volume of new formed bone of the BMP- 3-coated corundum-blasted or hydroxyapatite-coated Ti-6Al-4 V test devices compared to the non-coated controls of the same type (p < 0.01, t-test for matched samples). In both implatt groups with BMP-coating a synergetic effect was verifiable although the bone ongrowth in the hydroxyapatite coated implants was more extensive than in the corundum blasted implants. Light microscopy demonstrated osteointegration without connective tissue membrane around the surface of the implants. Our results indicate that composite metal implants, as used in endoprosthetics and implantology , are suitable carriers for BMP- 3 and improved fixation of the implants can be achieved. The hydroxyapatite surface is superior to the corundum-blasted surface with regards to the observed parameters because of its pronounced bioactivity and its osteoconductive characteristics.

  10. 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.

  11. RESEARCH PROGRESS OF BONE MORPHOGENETIC PROTEIN AND LIABILITY OF OSSIFICATION OF POSTERIOR LONGITUDINAL LIGAMENT%BMP与后纵韧带骨化症易患性的研究进展

    Institute of Scientific and Technical Information of China (English)

    方钊; 孙天威; Sandip Kumar Yadav

    2012-01-01

    目的 综述BMP与后纵韧带骨化症(ossification of the posterior longitudinal ligament,OPLL)易患性的研究进展.方法 查阅近年国内外有关BMP与OPLL易患性的相关参考文献并进行总结.结果 BMP基因的单核苷酸多态性(single nueleotide polymorphisms,SNPs)产生微效累加效应增加对OPLL的易感性,多种环境因素可通过增加BMPs基因的表达,促进OPLL的发生、发展.结论 BMPs易感基因的SNPs可促进个体对OPLL的易感性,SNPs的累加效应及与环境因素的相互作用则可影响个体对OPLL易患性的高低.%Objective To review the research progress of bone morphogenetic protein (BMP) and the liability of ossification of the posterior longitudinal ligament (OPLL). Methods Recent literature concerning BMP and the liability of OPLL was reviewed, analysed, and summarized. Results The single nucleotide polymorphisms (SNPs) of BMP gene may produce a minor cumulative effect and increase individual susceptibility to OPLL. A variety of environmental factors can promote the occurrence and development of OPLL by increasing the expression of BMP gene. Conclusion The SNPs of BMP gene may increase individual susceptibility to OPLL. However, interaction of cumulative effect of the SNPs and environmental factors can promote the liability to OPLL.

  12. Pregnancy-associated plasma protein-a production in rat granulosa cells: stimulation by follicle-stimulating hormone and inhibition by the oocyte-derived bone morphogenetic protein-15.

    Science.gov (United States)

    Matsui, Motozumi; Sonntag, Barbara; Hwang, Seong Soo; Byerly, Tara; Hourvitz, Ariel; Adashi, Eli Y; Shimasaki, Shunichi; Erickson, Gregory F

    2004-08-01

    Pregnancy-associated plasma protein-A (PAPP-A) is the major IGF binding protein-4 (IGFBP-4) protease in follicular fluid, consistent with its proposed role in folliculogenesis. Despite growing interest, almost nothing is known about how PAPP-A expression is regulated in any tissue. Here we show that FSH and oocytes regulate PAPP-A expression in granulosa cells (GCs). By in situ hybridization, ovary PAPP-A mRNA was markedly increased by pregnant mare serum gonadotropin treatment, and the message was localized to the membrana GCs but not cumulus GCs (CGCs) of dominant follicles. To explore the mechanism, we used primary cultures of rat GCs. Control (untreated) cells produced little or no PAPP-A spontaneously. Conversely, FSH markedly stimulated PAPP-A mRNA and protein in a dose- and time-dependent fashion. Interestingly, PAPP-A expression in isolated CGCs was also strongly induced by FSH, and the induction was inhibited by added oocytes. To investigate the nature of the inhibition, we tested the effect of oocyte-derived bone morphogenetic protein-15 (BMP-15). BMP-15 alone had no effect on basal levels of PAPP-A expression by cultures of membrana GCs or CGCs. However, BMP-15 markedly inhibited the FSH stimulation of PAPP-A production in a dose-dependent manner. The cleavage of IGFBP-4 by conditioned media from FSH-treated GCs was completely inhibited by anti-PAPP-A antibody, indicating the IGFBP-4 protease secreted by GCs is PAPP-A. These results demonstrate stimulatory and inhibitory roles for FSH and BMP-15, respectively, in regulating PAPP-A production by GCs. We propose that FSH and oocyte-derived BMP-15 form a controlling network that ensures the spatiotemporal pattern of GC PAPP-A expression in the dominant follicle. PMID:15087430

  13. Bases teóricas y aplicación clínica de las proteínas morfogenéticas óseas en cirugía maxilofacial Base theories and the clinical application of bone morphogenetic proteins in maxillofacial surgery

    Directory of Open Access Journals (Sweden)

    C.M. Ardila Medina

    2009-06-01

    Full Text Available Uno de los grandes avances en la neoformación ósea ha sido la identificación de factores de crecimiento importantes para ella como son las proteinas morfogenéticas óseas (PMO que regulan la diferenciación ósea y cartilaginosa in vivo. La depuración, clonación genética y expresión de las PMO han establecido las bases para el análisis celular y molecular del desarrollo y la regeneración ósea. El estudio genético de las PMO señala que son esenciales para la función normal animal y en la osteogénesis postfetal es importante en el desarrollo embrionario orgánico, esquelético y de los tejidos dentales y craneofaciales. La disponibilidad de las PMO proporciona retos y oportunidades para mejorar los conocimientos que regulan la regeneración ósea con el fin de optimizar los resultados en el paciente.One of the fundamental advances in bone neoformation has been the identification of important growth factors like the bone morphogenetic proteins that regulate live cartilage and bone differentiation. The cleansing, genetic cloning and expression of recombinant human bone morphogenetic proteins (BMP have laid the basis for cellular and molecular analysis of bone development and regeneration. The genetic study of the BMPs indicates that they are essential to the normal development and function of animals. BMP post-natal bone development is also very important in embryonic organic, skeletal, craniofacial and dental tissue development. The availability of BMPs provides several challenges and opportunities to improve insights into the mechanisms that regulate the regeneration of bone for optimal outcome in the patient.

  14. 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

  15. Nano-hydroxyapatite/collagen composited with recombinant human bone morphogenetic protein-2 and titanium membrane in repairing peripheral bone defects of instant dental implants%胶原基纳米骨复合重组人骨形成蛋白2及钛膜修复即刻钛种植体周围骨缺损

    Institute of Scientific and Technical Information of China (English)

    刘冰; 陈鹏; 王忠义; 柯杰; 李晓华; 汪正文

    2009-01-01

    BACKGROUND:Recently,with the rapid development of material science and bioscience,the technology of dental implant has made great progress,especially the immediate implant technology.But the size and shape of implant are usually not fit for tooth extraction wound,so it is an important factor that leads to failure when implant and tooth extraction wound can not form close tangency.Guided bone regeneration or bone grafting materials are usually used to solve this problem.OBJECTIVE:To study the effects of nano-hydroxyapatite/collogen (nHAC) with recombinant human bone morphogenetic protein-2(rhBMP-2) and titanium (Ti) membrane on repairing peripheral bone defects of instant implant.DESIGN,TIME AND SETTING:A randomized,controlled animal study was performed at the Central Laboratory,the Fourth Military Medical University of Chinese PLA between January 2005 and January 2006.MATERIALS:Ti screw implants (diameter 2 mm,length 10 mm,and pitch 0.4 mm) without the part that went through gum were offered by Nonferrous Metal Academy in Baoji,China.The nonabsorbable Ti membranes (2 cm×2 cm) were offered by Zhongbang Biomaterial Limited Company in Xi'an,China.The nHAC materials were gifted by professor Cui Fu-zhai from Material Science and Engineering Department of Tsinghua University and fabricated into 0.5 mm×0.5 mm×0.5 mm small blocks.rhBMP-2 was offered by the Academy of Military Medical Sciences in Beijing,China.rhBMP-2 was dissolved with hydrochloric carbamidine and then nHAC was immersed in it.Vacuumization,freeze-drying,and Ekibon degermation were followed.Each gram of nHAC compounds required approximately 1 mg rhBMP-2.METHODS:Four healthy purebred male dogs were included in this study.According to the methods to repair bone defects rhBMP-2+Ti membrane,nHAC composited with rhBMP-2 was implanted,covering Ti membrane.Six defects were made on the mandible on each side.MAIN OUTCOME MEASURES:At 6 and 12 weeks after implantation,new bone formation and the correlation of new

  16. The Effect of Recombinant Human Bone Morphogenetic Protein on the Proliferation and Alkaline Phosphalase Activity Becomefibre Cell%重组人骨形成蛋白对成纤维细胞增殖和碱性磷酸酶活性表达的影响

    Institute of Scientific and Technical Information of China (English)

    张翠; 韩金祥; 宋长征; 王世力; 张更林; 梁浩

    2003-01-01

    Objective To study the alkaline phosphalase activity in cells of expression of recombinant human bonemorphogenetic protein - 7 of becomefibre. Methods Alkaline phosphalase activity and cells prolifeyalion. The by using PNPPand MTT colorimetry methods. Results The BMP concentration been 7.0μg/L ~ 70μg/L of cell have increased, the alkalinephosphalase activity of high expression. Conclusion By the BMP- 7 effect high expression ALPase and cells proliferation. Theeffects of bone morphogenetic protein with high concentration cells prolifeyalion and ALPase expression.

  17. Molecular mechanism of bone formation and regeneration

    Institute of Scientific and Technical Information of China (English)

    Akira Yamaguchi

    2008-01-01

    @@ Bone formation and regeneration are mediated by the coordinate action of various factors. Among these, bone morphogenetic protein (BMP) and runt-related gene 2 (Runx2) play crucial roles in bone formation.

  18. 重组人骨形态发生蛋白2调节人脂肪间充质干细胞表达血管内皮生长因子***★%Recombinant human bone morphogenetic protein-2 adjusts expression of vascular endothelial growth factor in human adipose-derived mesenchymal stem cells

    Institute of Scientific and Technical Information of China (English)

    曹鑫; 金格勒; 杨毅; 陈慧锦; 殷剑

    2013-01-01

    BACKGROUND: Recombinant bone morphogenetic protein-2 can promote tissue engineering bone vascularization, but its biological rules targeting human cel s are not clear. At present, there is in which report on recombinant bone morphogenetic protein-2 adjusts the expression of vascular endothelial growth factor in human cel s. OBJECTIVE: To observe and compare the expression of vascular endothelial growth factor in human adipose-derived mesenchymal stem cel s on gene level and protein level at different time points after induced with human recombinant bone morphogenetic protein-2. METHODS: Adipose-derived mesenchymal stem cel s were separated from adult human adipose tissues and cultured until passage 3, then divided into induced group and control group. The cel s in the induced group were induced by human recombinant bone morphogenetic protein-2 which final concentration was 100 μg/L, then the samples were col ected at 3, 6, 12, 18, 24, 36 and 48 hours after induction. Reverse transcription-PCR and enzyme-linked immunosorbent assay were used to detect vascular endothelial growth factor expression on gene level and protein level, compared with the control group. RESULTS AND CONCLUSION: Human recombinant bone morphogenetic protein-2 adjusted vascular endothelial growth factor expression of adipose mesenchymal stem cel s in a time-dependent manner, and the expression of vascular endothelial growth factor changed at different time points. Compared with the control group, human recombinant bone morphogenetic protein-2 could suppress vascular endothelial growth factor expression at 3-6 hours (P < 0.05), while at 18-24 hours, human recombinant bone morphogenetic protein-2 could promote vascular endothelial growth factor expression (P < 0.05). These two time periods should be paid attention when using human recombinant bone morphogenetic protein-2 to promote tissue engineering bone vascularization.%  背景:重组人骨形态发生蛋白2可以促进组织工程骨

  19. ECTOPIC OSTEOGENESIS OF BONE MARROW STROMAL CELLS INDUCED BY BONE MORPHOGENETIC PROTEIN%骨髓基质干细胞在骨形成蛋白诱导下异位成骨及应用于人造骨的实验研究

    Institute of Scientific and Technical Information of China (English)

    董书堃; 文剑明; 毕?; 董愉

    2001-01-01

    Objective To investigate the ectopic osteogenesis of bone marrow stromal cells (MSC) induced by bone morphogenetic protein(BMP) in vitro and in vivo, providing the experimental evidence for making an artificial bone with its own capacity of bone formation. Methods MSC were separated and cultured from bone marrow of Wistar rats, MSC were co-cultured with BMP in vitro (cultured in plate and diffuse chamber). Artificial coral hydroxyapatites (CHA) with MSC and BMP were implanted into dorsal muscles of Wistar rats, their bone formation were observed by morphological examination, histochemistry and immunohistochemistry. Results Only cartilaginous matrix were produced by MSC in vitro (cultured in plate and diffuse chamber), and both cartilaginous and bone matrix production within the combined grafts were seen. The bone formation of experimental groups (CHA+BMP+MSC) was stronger than that of control A(CHA+MSC) and control B(CHA). Conclusion It may be possible to produce an artificial bone with its own capacity of bone formation by combined graft (CHA+BMP+MSC). There may be multiple factors as well as BMP inducing bone formation both in the whole body and the location of the implantation. Further research on these factors will have the significance for making the ideal artificial bone.%目的 研究经分离培养的骨髓基质干细胞(MSC)在骨形成蛋白(BMP)诱导下在体内外的异位成骨效应,为研制一种本身具有成骨能力的人造骨材料提供实验依据。方法 分离、培养Wistar大鼠MSC,体外实验将MSC+BMP分别在培养板和弥散小室内培养,体内实验将MSC+BMP与人工珊瑚骨(CHA)制成复合移植体,种植在大鼠背肌内,用形态学、组织化学和免疫组化方法观察其成骨效应。结果 MSC在体外(培养板和弥散小室)只形成软骨基质,在体内复合移植体(CHA+BMP+MSC)形成骨质,其成骨效应比对照组A(CHA+MSC)和对照组B(CHA)强。结论 复合移植体(CHA

  20. Application of bone morphogenetic protein 2 loaded nano-hydroxyapatite artificial bone in the correction and fusion of adult idiopathic scoliosis%骨形态发生蛋白2纳米人工骨在成人特发性脊柱畸形矫正融合中的应用

    Institute of Scientific and Technical Information of China (English)

    胡文; 黄旗凯; 苏佳灿; 李明

    2012-01-01

    背景:复合骨形态发生蛋白2 纳米人工骨具有独特的生物特性,模仿天然骨的成分及结构特征,可为细胞提供与天然骨相类似的微环境.目的:观察复合骨形态发生蛋白2 纳米人工骨与同种异体骨植骨在成人特发性脊柱畸形矫正融合的临床效果.方法:回顾分析69 例成人特发性脊柱侧弯患者资料,分别采用复合骨形态发生蛋白2 纳米人工骨移植36 例,同种异体骨移植33 例,植骨后第3,6 个月拍摄脊柱全长正侧位片,观察植骨融合情况.结果与结论:69 例患者畸形明显矫正,3,6 个月的影像学观测两组均可见骨小梁生长.植骨后6 个月,复合骨形态发生蛋白2 纳米人工骨组明显融合33 例,同种异体骨组26 例.复合骨形态发生蛋白2 纳米人工骨组早期融合率高于同种异体骨组(P < 0.05).提示成人特发性脊柱侧凸后路矫形手术中,复合骨形态发生蛋白2 纳米人工骨是比较理想的骨移植材料,在融合效果方面优于同种异体骨.%BACKGROUND: Bone morphogenetic protein 2 (BMP-2) loaded nano-hydroxyapatite artificial bone has unique biological properties that can imitate the component and structure of natural bone. It can provide cells a microenvironment which is similar to that of natural bone. OBJECTIVE: To investigate the clinical effects of BMP-2 loaded nano-hydroxyapatite artificial bone and allogeneic bone grafting on the correction and fusion of adult idiopathic scoliosis. METHODS: A retrospective review of 69 patients with adult idiopathic scoliosis was performed. These patients were randomly divided into two groups: group A and group B. In group A, 36 patients were received BMP-2 loaded nano-hydroxyapatite artificial bone; in group B, 33 patients were received allogeneic bone grafting. The anterioposterior and lateral full spinal films were taken at 3 and 6 months after operation, and the spinal fusion status in the two groups were observed and compared. RESULTS

  1. Correlation of trace element zinc with bone morphogenetic protein 7 and Stro-1+cells in proximal femur:predicting hip prosthesis life%股骨近端微量元素Zn与骨形态发生蛋白7及Stro-1+细胞的相关性:预测髋关节假体寿命

    Institute of Scientific and Technical Information of China (English)

    傅晓东; 王伟力; 沈奕; 李晓淼

    2014-01-01

    BACKGROUND:The correlation of zinc with Stro-1+cells and bone morphogenetic protein 7 surrounding the prosthesis may affect the bone fusion and survival rate in hip prosthesis. OBJECTIVE:To analyze the correlation of zinc content with Stro-1+cells and bone morphogenetic protein 7 in proximal femur. METHODS:Bone samples were obtained from the discarded metaphysis region of the proximal femur in 24 patients with primary total hip replacement. Bone marrow mesenchymal stem cells were cultured in vitro. At 14 days after culture, Stro-1+cells in bone marrow mesenchymal stem cells were detected using flow cytometry. Bone morphogenetic protein 7 expression in cellsupernatant was detected using enzyme-linked immunosorbent assay. Zinc content in supernatant was measured using radio-immunity assay. RESULTS AND CONCLUSION:No significant difference in the zinc content was detected in different age groups and different gender groups. Zinc content was positively associated with Stro-1+cells and bone morphogenetic protein 7 expression. The further study of the trace element zinc in proximal femur can predict and intervene the longevity of hip prosthesis.%背景:假体周围微量元素Zn的含量与骨形态发生蛋白7、Stro-1+细胞相关性可能影响髋关节假体的骨融合与生存率。  目的:分析股骨近端微量元素Zn与骨形态发生蛋白7、Stro-1细胞的相关性。  方法:24例初次髋关节置换患者,取术中股骨矩开槽时废弃骨块,提取细胞后体外培养骨髓间充质干细胞。培养14 d采用流式细胞仪检测骨髓间充质干细胞中的Stro-1+细胞,酶联免疫吸附测定试剂盒检测培养细胞离心上清液中骨形态发生蛋白7的表达,放射免疫荧光法检测培养细胞离心上清液中Zn含量。  结果与结论:Zn含量在不同年龄组及不同性别组差异无显著性意义;Zn与Stro-1+、骨形态发生蛋白7正相关联系。关于股骨近端微量元素Zn的进一

  2. Increased classical endoplasmic reticulum stress is sufficient to reduce chondrocyte proliferation rate in the growth plate and decrease bone growth.

    Directory of Open Access Journals (Sweden)

    Louise H W Kung

    Full Text Available Mutations in genes encoding cartilage oligomeric matrix protein and matrilin-3 cause a spectrum of chondrodysplasias called multiple epiphyseal dysplasia (MED and pseudoachondroplasia (PSACH. The majority of these diseases feature classical endoplasmic reticulum (ER stress and activation of the unfolded protein response (UPR as a result of misfolding of the mutant protein. However, the importance and the pathological contribution of ER stress in the disease pathogenesis are unknown. The aim of this study was to investigate the generic role of ER stress and the UPR in the pathogenesis of these diseases. A transgenic mouse line (ColIITgcog was generated using the collagen II promoter to drive expression of an ER stress-inducing protein (Tgcog in chondrocytes. The skeletal and histological phenotypes of these ColIITgcog mice were characterised. The expression and intracellular retention of Tgcog induced ER stress and activated the UPR as characterised by increased BiP expression, phosphorylation of eIF2α and spliced Xbp1. ColIITgcog mice exhibited decreased long bone growth and decreased chondrocyte proliferation rate. However, there was no disruption of chondrocyte morphology or growth plate architecture and perturbations in apoptosis were not apparent. Our data demonstrate that the targeted induction of ER stress in chondrocytes was sufficient to reduce the rate of bone growth, a key clinical feature associated with MED and PSACH, in the absence of any growth plate dysplasia. This study establishes that classical ER stress is a pathogenic factor that contributes to the disease mechanism of MED and PSACH. However, not all the pathological features of MED and PSACH were recapitulated, suggesting that a combination of intra- and extra-cellular factors are likely to be responsible for the disease pathology as a whole.

  3. Bio-oss combined with fibrin glue and bone morphogenetic protein-2 to repair mandibular defects%纤维蛋白胶复合骨形态发生蛋白2塑形Bio-oss修复下颌骨缺损**★

    Institute of Scientific and Technical Information of China (English)

    田刚; 徐晓刚; 周中华; 高建勇

    2013-01-01

      背景:Bio-oss 的颗粒状结构通常应用于洞形缺损的充填性移植,对于三壁以上的缺损修复难以成形。目的:评价 Bio-oss 以纤维蛋白胶复合骨形态发生蛋白2作为赋形材料后的成骨性能。方法:拔除9条杂种犬双侧下颌第2,4前臼齿及第2臼齿,造成1 cm×1 cm 的骨缺损区,将 Bio-oss+纤维蛋白胶+骨形态发生蛋白2、Bio-oss+纤维蛋白胶及 Bio-oss 材料分别植入第2,4前臼齿及第2臼齿骨缺损区。结果与结论:各组软组织均一期愈合。Bio-oss 复合纤维蛋白胶后,骨粉结合紧密,不易剥离。术后4,8,12周时 Bio-oss+纤维蛋白胶+骨形态发生蛋白2组新生骨百分率均高于其他两组(P <0.05)。表明纤维蛋白胶的加入可以解决 Bio-oss 成形困难的问题,骨形态发生蛋白2的加入可促进成骨效果。%BACKGROUND: Bio-oss granular structure is normal y used for hole-shaped defects in the form of fil ing transplantation, but it is difficult to forming for more than three-wal defects. OBJECTIVE: To evaluate the osteogenic activities of Bio-oss after combination with fibrin glue and bone morphogenetic protein-2 in the repair of canine mandibular defects. METHODS: The second and fourth premolar teeth and the second molar teeth were extracted bilateral y in nine hybrid canines, resulting in 1 cm × 1 cm bone defect. Bio-oss, Bio-oss+fibrin glue and Bio-oss+fibrin glue+bone morphogenetic protein-2 were implanted into bone defects of the second, fourth premolar teeth and the second molar teeth, respectively. RESULTS AND CONCLUSION: Stage Ⅰ healing of soft tissues was achieved in al animals. Bio-oss was closely combined with fibrin glue, which was difficult to be separated. The proportion of new bone was higher in the Bio-oss+fibrin glue+bone morphogenetic protein-2 group than in the other two groups at 4, 8, and 12 weeks after extraction (P < 0.05). It shows that fibrin glue can solve the difficulty in

  4. Simultaneous placement of nonvascularized bone graft and dental implant containing recombinant human bone morphogenetic protein-2: the results of ultra-structural examination in dogs%非血管化骨-人重组骨形成蛋白-2复合种植体同期移植的超微结构观察

    Institute of Scientific and Technical Information of China (English)

    李唐新; 郑林卿; 王大章; 陈刚

    2005-01-01

    目的:对于非血管化自体骨移植同期植入种植体,目前仍有争议.近年的研究表明:非血管化自体骨植入后,早期即可有新骨形成.本研究旨在探讨非血管化自体骨-种植体同期植入后种植体的愈合过程,并观察骨形成蛋白对与非血管化骨同期植入的种植体愈合过程的促进作用.方法:健康犬12只,随机分为2组.在犬双侧下颌角区各截取3cm×4cm骨段,实验组骨段内植入含有重组人骨形成蛋白-2的种植体,对照组植入普通纯钛种植体.植入种植体后,将骨块及种植体植回对侧下颌角,并以不锈钢丝固定.术后2、4、6、8及12周各处死2只动物,标本行扫描电子显微镜观察.结果:实验组种植体-骨界面在术后2周即可见明显的新骨形成,术后6~8周,已基本形成骨性结合;术后12周时,可见较为成熟的骨融合.而对照组骨融合在术后6~8周方开始形成,术后12周时仍未完成.实验结果显示,实验组骨融合的时间较对照组至少可提前4周.结论:骨形成蛋白的骨诱导活性可以促使种植体在植入后早期与非血管化骨形成骨融合,从而为提高同期植入种植体的成功率提供了新的途径.%PURPOSE: Simultaneous placement of dental implants with non-vascularized bone graft is still controversial,however, recent researches reveal that new bone formation can be obtained at early stage after bone grafting. The purpose of this study was to investigate the healing process of dental implants simultaneously placed in the nonvascularized grafted bones, and to estimate the effect of bone morphogenetic protein (BMP) on the healing of implants. METHODS: 12mongrel dogs were divided into 2 groups, 3cm×4cm bone segments were harvested from the bilateral mandibular angles.Two types of implants were applied. On the experimental sides, implants containing recombinant human bone morphogenetic protein-2 (rhBMP-2) were implanted, while on the opposite sides

  5. Expression of bone morphogenetic protein-2 during the distraction process in midpalatal suture of rats%腭中缝牵张成骨中骨形成蛋白2的表达

    Institute of Scientific and Technical Information of China (English)

    胡海琨; 周静; 王尧; 李婧; 何武林; 邹淑娟

    2011-01-01

    背景:正畸医生常常通过扩大腭中缝矫正上颌骨横向发育不足.骨形成蛋白2 可以诱导骨和软骨的形成,促进牵张成骨过程中的骨重建.然而关于骨形成蛋白2 在腭中缝牵张成骨中的时间空间表达规律尚不清楚.目的:观察骨形成蛋白2 在大鼠腭中缝牵张成骨过程中的表达规律.方法:实验选用80 只5 周龄雄性Wistar 大鼠,分为实验组和对照组(包括阴性对照和空白对照).将初始力值为50 g 的腭中缝扩大簧黏接到大鼠两侧上颌牙列上建立大鼠腭中缝牵张模型,牵张1,4,7,14 d 后,采用免疫组织化学和实时定量荧光PCR 方法分析骨形成蛋白2 蛋白和mRNA 在各加力时间点的表达.结果与结论:腭中缝扩张后骨形成蛋白2 蛋白表达水平显著增加,且存在时空表达差异,主要定位于腭中缝纤维组织、软骨细胞层、骨细胞和成骨细胞胞浆及其细胞外基质.同时,骨形成蛋白2 mRNA 表达也明显上调.提示腭中缝牵张力可刺激骨缝中骨形成蛋白2 蛋白和mRNA 的合成,在骨缝塑建过程中发挥重要作用.%BACKGROUND: Orthodontists usually use palatal suture expansion to solve the problem of maxillofacial deformity. Some studies have shown that bone morphogenetic protein-2 (BMP-2) can induce bone and cartilage formation, promote the distraction osteogenesis in the process of bone remodeling under mechanical tension forces. However, underlying mechanisms of BMP-2 that drive bone formation during palatal suture expansion remain unknown.OBJECTIVE: To investigate the law of BMP-2 expression in mid-palatal suture remodeling after subjecting to tensional strain loading.METHODS: Wistar male rats of 5 weeks old, with average weight of 70-80 g, were randomly divided into 2 groups, separately, Rats in experimental group were placed on the expansion appliance, with opening loops with an initial force of 50 g applied to mid-palatal suture for periods of 1, 4 ,7 and 14 days

  6. 纳米羟基磷灰石复合骨形态发生蛋白2与骨髓基质干细胞的体外培养%Nano-hydroxyapatite/bone morphogenetic protein-2 culture with bone marrow stem cells in vitro

    Institute of Scientific and Technical Information of China (English)

    代平; 张洪; 陈新来; 袁建辉

    2012-01-01

    BACKGROUND: Whether a combination of the nano-hydroxyapatite (nHA) scaffolds with bone morphogenetic protein-2 (BMP-2) is superimposed to promote or inhibit the bone marrow stromal stem cells, as well as its biocompatibility, remain unclear.OBJECTIVE: To observe the biocompatibility and bone formation activity of nHA/BMP-2 co-cultured with rabbit bone marrow stem cells in vitro.METHODS: Bone marrow stem cells obtained from rabbits were cultured and proliferated in DMEM medium in vitro. The cells at the third passage were inoculated into four mediums and according divided into four groups: control group, BMP-2 group, nHa group, and nHa/BMP-2 group. RESULTS AND CONCLUSION: The cell diplo-proliferation time of control group and nHa group was longer than that in BMP-2 group and nHa/BMP-2 group. The cells proliferative activity calculated by MTT assay and bone formation activity based on the alkaline phosphatase method demonstrated statistical significant difference in BMP-2 group and nHa/BMP-2 group compared with control and nHa group (P < 0.01). Experimental findings indicate that, the tissue formation of nHA/BMP-2 not only has good biocompatibility with Bone marrow stem cells, but also could bring into full play the effect of BMP-2 for promoting the proliferation, differentiation, and bone formation activity of bone marrow stem cells.%背景:纳米级羟基磷灰石支架材料复合骨形态发生蛋白2因子组织构建模式组合后对骨髓基质干细胞的作用是叠加促进或抑制作用以及其生物相容性如何?目的:验证纳米羟基磷灰石复合骨形态发生蛋白2与骨髓基质干细胞在体外共同培养下的生物相容性和成骨性.方法:将兔骨髓基质干细胞体外培养、传代和扩增,经鉴定后将第3代细胞分别接种在对照组、骨形态发生蛋白2组、纳米羟基磷灰石组、纳米羟基磷灰石/骨形态发生蛋白2组4种培养液中.结果与结论:对照组和纳米羟基磷灰石组的细胞倍

  7. 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

    Background Although various systemic and local factors such as abnormal carbohydrate or calcium metabolism,aging,and hormonal disturbances have been suggested as causes of ossification of the posterior longitudinal ligament (OPLL),the etiology of OPLL is not fully understood.The purpose of this study was to investigate whether bone morphogenetic protein (BMP)-2 is a candidate gene to modify the susceptibility of OPLL and the mechanism of signal transduction in ossification.Methods A total of 420 OPLL patients and 506 age-and sex-matched controls were studied.The complete coding sequence of the human BMP-2 gene was analyzed using polymerase chain reaction (PCR) and direct sequencing.All single nucleotide polymorphisms (SNPs) were detected and genotyped.BMP-2 expression vectors containing positive polymorphisms were constructed and transfected into the C3H10T1/2 cells.The expression of BMP-2 and the Smad signal pathway in positive cell clones were detected by Western blotting.The alkaline phosphatase (ALP) activity was determined using quantitative detection kits.Results The frequencies for the 109T>G and 570A>T polymorphisms were different between the case and control groups.The "TG" genotype in 109T>G polymorphism is associated with the occurrence of OPLL,the frequency of the "G"allele is significantly higher in patients with OPLL than in control subjects (P <0.001).The "AT" genotype in 570A>T polymorphism is associated with the occurrence of OPLL,the frequency of the "T" allele is significantly higher in patients with OPLL than in control subjects (P=0.005).Western blotting analysis revealed that the expression of P-Smad1/5/8protein transfected by wild-type or mutant expression vectors were significantly higher than control groups (P <0.05),but there was no statistical difference in each experimental group (P >0.05).The expression of Smad4 protein transfected by wild-type or mutant expression vectors was significantly higher than control groups (P

  8. 重组骨形成蛋白-2与珊瑚人工骨复合物应用于拔牙窝修复的动物实验研究%The effects of coral artificial bone composite of recombinant hmnan bone morphogenetic protein-2 on reconstruction of extraction sockets:an experimetal study on dogs

    Institute of Scientific and Technical Information of China (English)

    孔卫东; 林巍; 李小兰; 邓国珍; 沈丽佳

    2001-01-01

    Aim:To evaluate the bone repairing ability of coral artificial bone composite of rhBMP -2(rhBMP-2/CAB) and coral artificial bone(CAB) implanted into immediate extraction sockets. Meth-ods: 12 adult dogs served as the experimental animals. Immediately after extraction of the upper secondand third incisors, the alveolar septum between extraction sockets was resected bilaterally. RhBMP-2/CAB and CAB were implanted respectively into each extraction site. The animals were sacrificed at the 4th, 8th and 12th weeks respectively after implantation. The bone repairing ability of the two grafts wasanalyzed with histologic and image analysis system. Results: RhBMP - 2/CAB has a good effect on therepairing ability of extraction sockets. The implants were absorbed gradually after they were implanted in-to extraction sockets. In the meantime, the new bone was formed in extraction sockets. The implants werereplaced completely by bone at 12 weeks. The ratio of new bone formation of rhBMP-2/CAB was signif-icantly higher than that of CAB at different period( P < 0.05). Conclusion: The repairing ability and ef-fect of rbBMP -2/CAB in extraction sockets are obviously better than those of CAB.%目的:探讨重组骨形成蛋白 - 2(recombinant human bone morphogenetic protein , rhBMP - 2)/ 珊瑚人工骨复合物(复合骨)与珊瑚人工骨(珊瑚骨)在拔牙窝修复中的作用。方法:12只成年狗作为实验动物,拔除两侧上颌第2及第3切牙,并去除牙槽窝之间的牙槽间隔,一侧随即植入复合骨,对侧植人珊瑚骨作为对照。并于植骨后4、8、12周取材,采用组织学观察及计算机图像分析方法,观察比较两种植入材料在拔牙窝内的骨修复能力及修复效果。结果:复合骨具有较强的骨修复作用,植入牙槽窝后,材料被逐渐降解吸收,新骨不断形成,12周后,植入材料完全被成熟的骨组织取代;图像分析结果显示复合骨组新生骨形成的比值明

  9. Changes of Human Recombination Bone Morphogenetic Protein-2 in Bone and Marrow in Tail Suspended%模拟失重下大鼠骨和骨髓中人重组骨形成蛋白-2的变化

    Institute of Scientific and Technical Information of China (English)

    傅崇建; 杨连甲; 曹新生; 陈希哲; 张立藩

    2001-01-01

    目的研究模拟失重骨质和骨髓内人重组骨形成蛋白-2(Human recombination bone morphogeneticprotein-2,rhBMP-2)形态学的变化.方法选用SD大鼠,随机配对分为悬吊组和自由活动组(5只/组),实验期为14、28 d.组织标本行原位杂交.结果尾吊组大鼠骨质和骨髓内rhBMP-2的表达明显弱于对照组(P<0.05);尾吊组14 d rhBMP-2的表达明显强于28 d(P<0.05).结论大鼠后肢去负荷导致骨和骨髓rhBMP-2含量的降低.

  10. Classically and alternatively activated bone marrow derived macrophages differ in cytoskeletal functions and migration towards specific CNS cell types

    Directory of Open Access Journals (Sweden)

    Dijkstra Christine D

    2011-05-01

    Full Text Available Abstract Background Macrophages play an important role in neuroinflammatory diseases such as multiple sclerosis (MS and spinal cord injury (SCI, being involved in both damage and repair. The divergent effects of macrophages might be explained by their different activation status: classically activated (CA/M1, pro-inflammatory, macrophages and alternatively activated (AA/M2, growth promoting, macrophages. Little is known about the effect of macrophages with these phenotypes in the central nervous system (CNS and how they influence pathogenesis. The aim of this study was therefore to determine the characteristics of these phenotypically different macrophages in the context of the CNS in an in vitro setting. Results Here we show that bone marrow derived CA and AA macrophages have a distinct migratory capacity towards medium conditioned by various cell types of the CNS. AA macrophages were preferentially attracted by the low weight ( Conclusion In conclusion, since AA macrophages are more motile and are attracted by NCM, they are prone to migrate towards neurons in the CNS. CA macrophages have a lower motility and a stronger adhesion to ECM. In neuroinflammatory diseases the restricted migration and motility of CA macrophages might limit lesion size due to bystander damage.

  11. 基因重叠延伸拼接PCR法钩建骨形态发生蛋白成熟肽真核表达载体的研究%Construction of a eukaryote expression vector containing bone morphogenetic protein-2 mature peptide by SOE-PCR method

    Institute of Scientific and Technical Information of China (English)

    段小红; 陈苏民; 柴玉波; 徐可为

    2002-01-01

    Objective To construct an eukaryote expression vector containing bone morphogenetic protein 2 (BMP 2) mature peptide. Methods Gene splicing by overlapping extension PCR (SOE PCR) method was used to clone BMP2 signal peptide and mature peptide and their fusion fragment.The fusion fragment was cloned into an eukaryote expressing vector pcDNA3.1/myc His(- )A. The sequence of the fusion fragment of BMP2 signal peptide and mature peptide was identified.Results The sequence of the fusion fragment was correct comparing with BMP2 signal peptide and mature peptide published by NCBI.Conclusion The vector pcDNA3.1/myc His(- )A BMP2sm constructed in this experiment was suitable to applying in eukaryotic expression of BMP2.

  12. Bone morphogenetic protein 2 stimulated osteo-chondrogenic differentiation of patellar tendon-derived stem cells isolated from a failed tendon-healing animal model of tendinopathy%骨形态发生蛋白2诱导慢性腱病大鼠肌腱干细胞体外成骨、成软骨分化

    Institute of Scientific and Technical Information of China (English)

    林禹丞; 王宸; 芮云峰; 成心锟; 马良彧

    2014-01-01

    BACKGROUND:The pathogenesis of tendinopathy remains unclear and hence treatment of tendinopathy is usualy paliative. OBJECTIVE:To investigate the effects of bone morphogenetic protein 2 on the osteogenic and chondrogenic differentiation of patelar tendon-derived stem cels isolated from colagenase-induced tendinopathy ratsin vitro. METHODS: Patelar tendon-derived stem cels were isolated from patelar tendons of colagenase-induced tendinopathy rats. The multi-differentiation potential of patelar tendon-derived stem cels at passage 3 was identified by osteogenic, adipogenic and chondrogenic differentiation assays. The patelar tendon-derived stem cels were cultured to the 3rd passage in complete culture medium, and then the cels were divided into two groups with (experimental group) or without recombinant human bone morphogenetic protein 2 (control group) until the cels reached confluence for 7 days. Their osteogenic response to bone morphogenetic protein 2in vitro was examined by alizarin red S staining of calciumnodule formation and quantification assay. The patelar tendon-derived stem cellpelets were cultured in complete culture medium with (experimental group) or without bone morphogenetic protein 2 (control grup) for 21 days. Chondrogenic differentiation of the cellpelets was evaluated by hematoxylin-eosin staining, alcian blue staining, immunohistochemical staining for Sox9 and colagen type II. RESULTS AND CONCLUSION:Primary patelar tendon-derived stem cels from the tendinopathy rats culturedin vitro showed clonal growth; after passage, spindle fibroblast-like and flat-like cels were detectable. The cels were positive for oil red O staining at 10 days after adipogenic induction, positive for alizarin red staining at 7 days after osteogenic induction, and positive for hematoxylin-eosin staining and immunohistochemical staining of colagen type II at 14 days after chondrogenic induction. After patelar tendon-derived stem cels were induced with recombinant human bone

  13. Proteínas morfogenéticas ósseas associadas a osso esponjoso autógeno na reparação de falhas experimentais na calota craniana de coelhos (Oryctolagus cuniculus Bone morphogenetic proteins associated with autogenous bone graft in the reparation of calvarial experimental defects of rabbits (Oryctolagus cuniculus

    Directory of Open Access Journals (Sweden)

    B.S. Monteiro

    2007-12-01

    ão determinou maior preenchimento ósseo.Aspects of bone repair were evaluated after implantation of bone morphogenetic proteins (BMP in different concentrations. They were carried by autogenous bone graft in defects created on skulls of 20 adult, young female rabbits, randomizedly divided into five experimental groups and were observed at five times. After exposure of skull bones, six bone defects on the fronto-parietal region of each animal were performed. The defect I was not filled, the II was completed filled with 3mg of autogenous bone graft and the defects III, IV, V, and VI were filled with autogenous bone graft associated with 0.5; 1; 2 and 5mg of BMP, respectively. In the post-mortem mesoscopic evaluations, it was observed that, independently of the treatment period of the defects, the bony filling began from the borders to the center, and from the botton to the surface of the lessions. The bony filling of the defect I was the smallest when compared with the others defects, in all the observation moments. It was also verified that until 2mg the higher the concentration of BMP used, better was the bone cover. Microscopically, it was verified in the first evaluations, on the seventh day, that the bony growth started from the borders and from the bottom of the lesion, with mobilization and differentiation of cells deriving from the periosteum and the meninges, respectively. In the subsequent evaluations, the osteoblastic activity also derived from "ossification islands" to ossification centers, located in the center of the flaw. The trabecular formation increased proportionally with the concentration of BMP used, and the apposition and bony organization increased proportionally with the time of observation. The presence of cartilaginous tissue was verified in all the flaws. In conclusion, the use the higher concentration of BMP did not determinate the better new bone formation. The association of BMP with autogenous bone graft contributed to the formation of new bony

  14. 骨形态发生蛋白家族及其受体在生殖调控中的作用%Review of the role of bone morphogenetic protein family and its receptors in the reproductive modulation

    Institute of Scientific and Technical Information of China (English)

    管峰; 杨利国; 程瑞禾; 曹少先

    2005-01-01

    OBJECTIVE:Bone morphogenetic protein (BMP) plays a vital role in the prevention and treatment of skeleton diseases, recently researches on the molecular mechanism of sheep prolific FecB gene indicated that BMP and its receptors have important influence on animal follicular development. In this study the influence of different type BMPs andits receptors on the follicular development was reviewed in order to explore effective modulation on animal reproduction.DATA SOURCES: Computer was applied to retrieve Medline database on the related literatures from January 1998 to June 2005. The retrieval words were "BMP" and "BMPR" that combined respectively. Language in the articles was limited to English. Simultaneously related articles were also computer searched in China periodical full text database and Wanfang databases from January 1996 to December 2005 with the retrieval words of "BMP, BMPR", that limiting the article language to Chinese.STUDY SELECTION: At first, the document was retrieved, altogether 200 studies on BMP and its receptors were enrolled including 140 Chinese literatures and 60 English literatures.DATA EXTRACTION: these literatures were screened and 30 were included for relating to the BMP characteristic, as well as the influence of BMP and its receptors on follicular development and reproductive endocrine.DATA SYNTHESIS: Of the 30 literatures, 18 experiments discussed the function of BMP and its receptors and its signal transduction mechanism,12 were about the influence of different BMP on reproductive cell secretion, as well as receptor mutation on ovulation.CONCLUSION: BMPs family plays vital role in animal reproductive modulation, current experiments prove that the changes of signal transduction due to BMP receptor gene mutation has made breakthrough for the exploration of the prolific mechanism in sheep. Moreover studies on follicular development modulation and ovulation mechanism are liable to provide theoretical reference for the prolific

  15. Mineralization reaction during osteogenic differentiation of myoblasts stimulated by bone morphogenetic protein 2***☆%重组人骨形成蛋白2诱导成肌细胞成骨分化中的矿化反应

    Institute of Scientific and Technical Information of China (English)

    张力; 王伟

    2012-01-01

    BACKGROUND: In recent years, it has been confirmed by a variety of ways that myoblasts can differentiate into osteoblasts under the induction of recombinant human bone morphogenetic protein 2 (rhBMP-2).OBJECTIVE: To explore the mineralization reaction during the osteogenic differentiation of myoblasts under the induction of recombinant rhBMP-2 and the feasibility of osteogenic phenotype expression by in vitro induction. METHODS: Myoblasts were isolated and harvested from neonatal Wistar rats using differential velocity adherent technique and trypsinization method. After in vitro culture, purification and identification, myoblasts at passage 3 were induced by a medium containing rhBMP-2 for 21 days. Myoblasts in the control group were cultured in vitro in complete medium without rhBMP-2 for 21 days. RESULTS AND CONCLUSION: After rhBMP-2 induction, myoblast proliferation gradually slowed down. A small quantity of opaque secretory granules were found in the cytoplasm on day 8 after induction; the number of opaque secretory granules increased on day 14 after induction; and a great quantity of opaque secretory granules were found in the cytoplasm on day 21 after induction while the myoblasts without induction fused into contractile myotubes. The alkaline phosphatase activity of the induced myoblasts increased as time extended; myoblasts reacted positively in the alkaline phosphatase staining, immunochemical staining for type Ⅰ collagen and calcium node staining on day 21 after induction. These findings suggest that mineralization reaction is found in rat myoblasts by rhBMP-2 induction and myoblasts can differentiate into osteoblasts under certain inducing conditions in vitro.%背景:近年来成肌细胞在重组人骨形态发生蛋白2诱导下向成骨细胞分化已经通过多种方式得到了证实.目的:探讨成肌细胞在重组人骨形态发生蛋白2诱导下向成骨分化过程的矿化反应及其体外诱导表达成骨表型的可行性.方法:采

  16. Correlation between concentration of serum bone morphogenetic protein-7 and obesity in adult women%血清骨形成蛋白-7浓度与女性肥胖的相关性研究

    Institute of Scientific and Technical Information of China (English)

    曾俊; 姜友昭; 陈兵

    2011-01-01

    Objective To measure serum bone morphogenetic protein-7 (BMP-7) concentration in a dult women and to determine correlation between BMP-7 concentration and obesity, so as to provide a new target for obesity therapy. Methods Sixty-five obese women were enrolled in an obesity group, and one hundred and thirty-four adult women having normal body mass indexes were enrolled in a control group. Clinical data inclu ding age, height, weight, systolic blood pressure, diastolic blood pressure, waist circumference, and hip circ umference were recorded. Then body mass index and waist-hip ratio were calculated. Metabolic parameters such as serum total cholesterol, triglyceride, LDL-cholesterol, HDL-cholesterol, fasting glucose, and uric acid were tested. Serum BMP-7 concentration was detected through enzyme-linked immunosorbent assay (ELISA). The parameters of the two groups were compared. The correlation between serum BMP-7 concentration and met abolic parameters were analyzed. Results Serum BMP-7 concentration in the obesity group was significantly lower than that in the control group ( P < 0. 01 ). Serum BMP-7 concentration was negatively correlated with age, body mass index, systolic blood pressure, waist circumference, total cholesterol, and LDL-cholesterol (r = - 0. 181, - 0. 248, - 0. 143, - 0. 148, - 0. 169, and - 0. 177, respectively, P < 0. 05 ). Multiple stepwise regression analysis results showed that the body mass index was the only independent factor influencing the serum BMP-7 concentration after being adjusted by age, body mass index, systolic blood pressure, waist circumference, total cholesterol, LDL-cholesterol, diastolic blood pressure, mean arterial blood pressure, waist hip ratio, uric acid, triglyceride, HDL-cholesterol, and fasting glucose. Corncltusion In adult women, serum BMP-7 concentration is negatively correlated with body mass index, suggesting that BMP-7 may be a potential target for woman obesity therapy.%目的检

  17. 骨形态发生蛋白、碱性成纤维细胞生长因子生物材料在关节软骨缺损修复中的生物性能%Biological properties of bone morphogenetic proteins and basic fibroblast growth factor in biological materials for repair of articular cartilage defect

    Institute of Scientific and Technical Information of China (English)

    董君博

    2016-01-01

    BACKGROUND:Articular cartilage regeneration can be regulatedbyautocrineorparacrinesecretionof various cytokines. OBJECTIVE:To analyze biological properties of bone morphogenetic proteins and basic fibroblast growth factor in biological materials for repair of articular cartilage defect. METHODS:Forty New Zealand white rabbits were used and equaly randomized intofourgroups: fibrin, basic fibroblast growth factor, bone morphogenetic protein, and combined treatment (basic fibroblast growth factor combined with bone morphogenetic protein) groups, respectively.Bioactivescaffolds with fibrin, basic fibroblast growth factor,bone morphogenetic protein, and basic fibroblast growth factor combined with bone morphogenetic protein were injected to repair the articular cartilage defect. Therapeutic effect andbiological properties of biological materials were compared. RESULTS AND CONCLUSION:(1) Inthefibrin group,tworabbits appearedto havelimps. Inthebasic fibroblast growth factor group hand functionwaslimited inonerabbit. Inthebone morphogenetic protein group, one had a limpandonewasin a limitation of activity. Inthecombined treatment group,rabbitsrecovered wel andshowedno differencesintheknee joint before and aftersurgery (P  目的:分析骨形态发生蛋白、碱性成纤维细胞生长因子生物材料在关节软骨缺损修复中的生物性能。  方法:选取40只新西兰家兔,随机分为4组,纤维蛋白组、碱性成纤维细胞生长因子组、骨形态发生蛋白组、复合组(骨形态发生蛋白+碱性成纤维细胞生长因子),每组10只。建立兔关节软骨缺损模型,止血彻底后将纤维蛋白、碱性成纤维细胞生长因子、骨形态发生蛋白以及骨形态发生蛋白、碱性成纤维细胞生长因子复合等材料组成的支架分别植入缺损部位。比较不同注射材料在家兔关节软骨缺损中的效果及复合材料的生物性能。  结果与结论:①关节软骨缺损修复情

  18. Silk fibroin-compound bone cement/recombinant human bone morphogenetic protein-2 to repair sheep vertebral defects%丝素蛋白/双相磷酸钙/半水硫酸钙/重组人骨形态发生蛋白-2骨水泥的制备及修复椎体骨缺损的实验研究

    Institute of Scientific and Technical Information of China (English)

    王根林; 陈广东; 朱雪松; 朱志军; 谢瑞娟; 卢神州; 张波; 夏太宝; 杨惠林

    2015-01-01

    目的 研制丝素蛋白(SF)/双相磷酸钙(BCP)/半水硫酸钙(CSH)/重组人骨形态发生蛋白-2(rhBMP-2)骨水泥,并探讨其在绵羊椎体内的成骨作用. 方法 制备SF/BCP/CSH/rhBMP-2骨水泥,分别在12只绵羊的L2 L3、L4椎体内制作直径为6.0mm、深度为10 mm的圆柱型骨缺损模型,在3个缺损处随机植入SF/BCP/CSH/rhBMP-2骨水泥作为实验组,植入聚甲基丙烯酸甲酯(PMMP)作为对照组,另一椎体缺损处不植入任何材料作为空白对照组.术后3、6个月分别随机处死6只绵羊进行CT、组织学和生物力学检查.结果 CT和组织学检查显示:术后3个月实验组椎体密度与正常椎体相似,骨缺损修复基本完成,术后6个月骨缺损修复完成;对照组术后3、6个月时PMMP无降解,并与骨之间结合疏松,表面无新骨形成;空白对照组术后3、6个月时骨缺损一直存在.生物力学测试显示:术后3、6个月时实验组椎体抗压强度和刚度与正常椎体相比差异无统计学意义(P>0.05). 结论 SF/BCP/CSH/rhBMP-2骨水泥具有良好的成骨作用,在成骨过程中能维持椎体的力学性能,有望成为经皮椎体强化术的一种可降解、具成骨作用的填充剂.%Objective To prepare compound bone cement of silk fibroin/biphasic calcium phosphate/alpha-calcium sulphate hemihydrate/recombinant human bone morphogenetic protein-2 (SF/BCP/CSH/rhBMP-2) and to study its osteogenesis capacity for sheep vertebral defects.Methods Compound bone cement SF/BCP/CSH/rhBMP-2 was prepared and a cylindrical bone defect (6.0 mm in diameter and 10 mm in depth) was created at lumbar vertebrae 2,3 and 4 by open operation in 12 sheep.The injured lumbar vertebrae in each sheep were randomly divided into 3 study groups.The experimental group was implanted with the SF/BCP/CSH/rhBMP-2,the control group with polymethylmethacrylate (PMMA),and the blank control group with nothing.At 3 and 6 months postoperation,6 random sheep were sacrificed for

  19. 冻干硬脑膜内骨形成蛋白-自固化磷酸钙复合移植修复骨缺损%Repairing bone defects using bone morphogenetic protein and calcium phosphate cement combined with freeze-dried dura mater

    Institute of Scientific and Technical Information of China (English)

    邹国耀; 吴恒烜

    2009-01-01

    背景:骨形成蛋白和自固化磷酸钙各自有着良好的成骨能力,冻干硬脑膜内骨形成蛋白和自固化磷酸钙复合移植存在优化成骨效能的可能性.目的:以冻干硬脑膜为膜材料,观察膜内充填材料骨形成蛋白复合自固化磷酸钙移植修复节段性骨缺损的效果.设计、时间及地点:随机分组设计,动物体内组织病理学对照观察,于2006-07/2007-07在广西医科大学动物实验室完成.对象:健康成年新西兰大白兔28只,雌雄不限,体质量1.5~2.5 kg.方法:实验兔28只,其中4只用于取硬脑膜.其余24只随机分成A,B两大组,每组12只.A组制造双侧兔桡骨中段10 mm的骨缺损.一侧骨缺损用骨形成蛋白、自固化磷酸钙、冻干硬脑膜复合移植修复,为骨形成蛋白组, 另一侧不予处理作为空白对照组.B组制造单侧兔桡骨中段10 mm的骨缺损,用骨髓、自固化磷酸钙、冻干硬脑膜复合移植修复称骨髓组.主要观察指标:于术后第1,2,4,6,8,10,12周分别行双侧桡骨X射线检查.观察骨缺损处的新骨形成及骨修复情况.并于术后第2,4,8,12周切取标本行组织学检查及成骨面积分析.结果:在术后第4,8,12周,骨形成蛋白组的成骨面积大于骨髓组(P<0.05),而在实验早期(术后2周)两组间差异无显著性意义(P>0.05);在实验的各个时期,骨形成蛋白组和骨髓组的成骨面积均明显大于空白组(P<0.01).X射线结果显示,骨形成蛋白组在10~12周出现明显骨痂塑形现象;组织学病理切片结果显示,骨形成蛋白组在12周时桡骨可见成熟骨髓,骨缺损处为成熟的板层骨连接.结论:骨形成蛋白复合自固化磷酸钙与冻干硬脑膜移植具有良好的成骨作用.%BACKGROUND: Both bone morphogenetic protein (BMP) and calcium phosphate cement (CPC) have excellent osteogenic capability, so, it is possible to optimize osteogenic efficiency by combing BMP, CPC and freeze-dried dura mater (FDDM

  20. 激素性股骨头坏死硬化带与骨形态蛋白关系的研究%Study on the relationship between sclerosis rim and bone morphogenetic proteins of osteonecrosis of the femoral head

    Institute of Scientific and Technical Information of China (English)

    石少辉; 李子荣; 王佰亮; 孙伟; 程立明; 潘琳; 王冉东

    2010-01-01

    目的 通过对股骨头坏死(ONFH)患者硬化带形成情况进行回顾性分析及其组织学观察,探讨骨形态蛋白(BMP4)与硬化带关系,为股骨头坏死个性化治疗提供理论依据.方法 2005年11月至2007年11月共治疗激素性ONFH全髋关节置换患者184髋,患者平均年龄(47±7)岁,依此把患者分为高(>54岁)、中(40~54岁)和低(<40岁)3个年龄组,分析比较3组患者硬化带形成比率.从184髋中选取部分股骨头标本,包括高年龄组患者股骨头18髋,低年龄组11髋,中年龄组股骨头标本20髋(有无硬化带形成者各10髋).股骨头冠状面正中剖开,在负重区和非负重区取材,行常规HE染色、苦味酸-天狼星红染色、电镜制备和BMP4蛋白免疫组化染色.BMP4蛋白免疫组化染色强度用图像分析软件计算其平均光密度.结果 硬化带在组织学上表现为骨小梁增粗,结构紊乱,但骨细胞结构同正常骨细胞,且处于高分泌状态.中年龄组ONFH患者硬化带形成比例为71.4%(105/147),显著高于低年龄组患者(45.5%,5/11)和高年龄组患者(38.5%,10/26)(P均<0.01).中年组患者股骨头BMP4平均光密度为0.32±0.14,明显高于低年龄组0.20±0.17和高年龄组0.19±0.27,且差异具有统计学意义(P均<0.05);中年龄组患者无硬化带形成者BMP4平均光密度分别为0.16±0.1l,有硬化带形成患者为0.28±0.13,差异具有统计学意义(P<0.01).有硬化带形成患者出现髋关节疼痛到关节置换时间为(49±11)个月,显著长于无硬化带形成者(15±2)个月,差异具有统计学意义(P<0.01).结论 ONFH患者硬化带形成与BMP4表达强弱呈正相关,BMP的高表达可能促进硬化带的形成.%Objectives To analyze retrospectively the formation and histological changes of sclerosis rim in patients with osteonecrosis of the femoral head ( ONFH), and to study the relationship between bone morphogenetic proteins (BMP4) and sclerosis rim, so as to acquire

  1. 腺病毒携带骨形态发生蛋白14基因转染脂肪干细胞修复损伤关节软骨%Adipose-derived stem cells transfected with adenovirus carrying bone morphogenetic protein 14 for repair of articular cartilage injury

    Institute of Scientific and Technical Information of China (English)

    马洪斌; 李运祥; 王铭伦

    2015-01-01

    BACKGROUND:The articular cartilage has weak self-repair ability, mainly due to its lack of trophoblast cels in blood vessels and slow cel metabolism. Current treatment methods cannot restore the original function of the cartilage tissue, and cartilage tissue engineering in recent years has garnered increasing attention. OBJECTIVE:To observe the effect of adipose-derived stem cels transfected with bone morphogenetic protein 14 combined with type I colagen sponge scaffold on the repair of articular cartilage injury in the knee of rabbits. METHODS: Adipose-derived stem cels were isolated and cultured from rabbit subcutaneous adipose tissue, and transfected with Ad-CMV-BMP-14-IRES-hrGFP-1. Type I colagen sponge scaffold with the transfected adipose-derived stem cels was used to repair articular cartilage injury in the knee of rabbits. Twelve weeks after operation, the articular tissue was taken for gross assessment and histological evaluation. RESULTS AND CONCLUSION: The expressions of bone morphogenetic protein 14, type II colagen and Sox-9 were higher in cels transfected with bone morphogenetic protein 14 than untransfected ones. At 12 weeks after operation, adipose-derived stem cels transfected with bone morphogenetic protein 14 combined with type I colagen sponge scaffold had good repair effect on articular cartilage injuries, and the injured cartilage tissues were smooth and had good texture, color and integration junction; adipose-derived stem cels combined with type I colagen sponge scaffold could partialy repair the injured cartilage tissues that had similar color and texture to normal tissues, and there was a remarkable boundary between the repaired tissue and normal cartilage tissue;simple type I colagen sponge scaffold was almost colapsed, and no hyaline cartilage tissue formed. These findings indicate that transfection of bone morphogenetic protein 14 can strengthen the ability of adipose-derived stem cels dramaticaly to repair cartilage injuries.%背景

  2. 纤维蛋白凝胶复合骨形态发生蛋白和庆大霉素缓释药物对感染性骨缺损的修复%Fibrin glue/bone morphogenetic protein complex plus slow-release gentamicin for repairing infected bone defects in rabbits

    Institute of Scientific and Technical Information of China (English)

    高秋明; 刘兴炎; 董晓萍; 葛宝丰; 白孟海; 陈克明

    2005-01-01

    背景:慢性骨髓炎临床处理较为棘手,手术常需分期进行,目前尚无好的方法予以一期修复.目的:探讨将纤维蛋白凝胶(FG)作为骨形态发生蛋白(BMP)及庆大霉素的共同载体,一期修复感染性骨缺损的可行性.设计:完全随机对照实验研究.单位:解放军兰州军区兰州总医院全军创伤骨科中心.材料:实验在兰州军区兰州总医院骨科研究所完成.对象为体质量1.9~2.4kg的48只成年健康青紫兰兔,雌雄不限,购自甘肃省兰州市生物制品研究所.干预:48只青紫兰兔,制作慢性骨髓炎模型,清创后造成胫骨近侧干骺端内侧1.5 cm长半环形骨缺损,采用3种方法进行处理:A组,植入FG,BMP和庆大霉素复合物;B组,植入FG/BMP复合物,C组,作为空白对照.主要观察指标:术后观察动物一般情况,做骨培养及细菌计数,X射线拍片及组织学检查.结果:A组感染控制及骨修复均良好,感染控制率、再生骨量明显优于B组.B,C两组在感染控制率上无显著差异.C组动物骨修复差.结论:FG,BMP及庆大霉素复合物具有促进成骨及抗感染的双重作用,可用于感染性骨缺损及污染严重的开放性损伤造成的骨缺损的修复.%BACKGROUND: Chronic osteomyelitis is difficult to manage clinically, and two or more operations were commonly needed. No satisfactory method for one-stage repair has been currently available.OBJECTIVE: To examine the possibility of using fibrin glue(FG) as the common carrier for both bone morphogenetic protein(BMP) and gentamicin for one-stage repair of infected bone defects.DESIGN: A completely randomized controlled experiment.SETTING: Center of Orthopaedic Surgery, Lanzhou General Hospital of Lanzhou Area Command of of Chinese PLA.MATERIALS: The experiment was conducted using 48 healthy adult Chinchilla rabbits of either sex on normal diet with body mass of 1.9 to 2.4 kg,provided by the Institute of Biological Products, Lanzhou, Gansu Province

  3. Regulatory Mechanism of Bone Morphogenetic Proteins 6 on Iron Metabolism During Exercise%运动对骨形态发生蛋白6介导的机体铁代谢调节机制的研究进展

    Institute of Scientific and Technical Information of China (English)

    孙娟; 王海涛; 刘玉倩; 王羽; 王金霞

    2012-01-01

    骨形态发生蛋白6(BMP6)为TGF-β超家族中一员,它产生于骨髓源性间质干细胞(BMSC)及造血干细胞,是一种调节成骨细胞和成软骨细胞分化的骨生长因子,在骨缺损的修复中具有重要作用.运动可促进BMP6的表达.研究发现,BMP6也是铁调素的重要的内源调节子,可以上调铁调素的表达,而铁调素是肠铁吸收的负调节子.因此,运动引起的BMP6表达增加,可以促进机体铁的吸收和释放,从而对运动中维持机体铁的动态平衡有重要的调控作用.%Bone morphogenetic protein 6(BMP6) is a member of the transforming growth factor-β family, it is produced by bone marrow-mesenchymal (BMSC) and hematopoietic stem cells. BMP6 is a potent protein for future treatment strategies of bone regeneration as it is a very important regulator of bone ho-meostasis and is a kind of adjusting the osteoblast and cartilage cells of bone growth factors. Moreover,it is also released by osteoclasts as a key bone coupling factor recruiting osteoblasts to the resorption site. So it has a good application potential in all kinds of bone defect repair. Sports can promote expression of BMP6. Recent study shows that BMP6 can up-regulation of hepcidin expression. However,hepcidin is the negative regulators and down-regulation of intestinal iron absorbing. So exercise-induced increased expression of BMP6 and promotes iron absorption and release. Consequently,to maintain iron homeostasis in the sport has an important regulatory role.

  4. Factors to influence the stability of the prosthesis after total hip replacement: Bone marrow mesenchymal stromal cells, bone morphogenetic protein and osteogenic potential%骨髓间充质干细胞、骨形态发生蛋白和骨发生潜力与髋关节置换后假体的稳定性

    Institute of Scientific and Technical Information of China (English)

    李晓淼; 沈奕; 王伟力; 任卫平

    2011-01-01

    BACKGROUND: The relationship between the osteogenic potential of the bone marrow microenvironment and long term stabilityafter total hip replacement is not clear yet. The author makes a point, the fit intensity of the prosthesis can be predict through theosteogenic potential analysis of the bone marrow.OBJECTIVE: To investigate the relationship between the activities of bone marrow mesenchymal stem cells, expression ofosteogenic protein-signaling pathway related genes, osteogenic potential and the stability of the prosthesis.METHODS: Bone marrow mesenchymal stem cells (BMSCs) were prepared from bone marrow aspirate obtained from theproximal femur metaphysis during total hip replacement (THR) surgery. Twelve patients were included in this study (8 men and 4women, ages 50-84, body mass index 21.5-50). The isolated BMSCs were culture-expanded to passage one; non-confluent,undifferentiated cells were harvested for flow cytometry or for RNA isolation. Linear regression analysis was used to assess thecorrelation among indicators of osteogenic potential.RESULTS AND CONCLUSION: The number of Stro -1+ cells, activity of alkaline phosphatase and expression ofosteoblasts-related genes from BMSCs of these 12 patients varied significantly. There was a positive correlation between cellsexpressing the Stro-1 surface marker and bone morphogenetic protein receptor 1a, MSX2, Runx2 and the activity of alkalinephosphatase (P < 0.05), there was a significant correlation between the activity of alkaline phosphatase and the expression ofRunx2 after the cells was cultured by osteoblats (P < 0.05). There was a highly diverse of the bone marrow microenvironmentosteogenic potential among THR patients. The potential impact of the BMSCs profiles on the long term outcome of total joint replacement patients warrants further investigation.%背景:骨髓微环境的成骨潜力与全髋关节置换后假体长期稳定性之间的关系尚不清楚.作者提出一个观点,通过骨髓成骨潜

  5. 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.

  6. 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.

  7. Bone

    Science.gov (United States)

    Helmberger, Thomas K.; Hoffmann, Ralf-Thorsten

    The typical clinical signs in bone tumours are pain, destruction and destabilization, immobilization, neurologic deficits, and finally functional impairment. Primary malignant bone tumours are a rare entity, accounting for about 0.2% of all malignancies. Also benign primary bone tumours are in total rare and mostly asymptomatic. The most common symptomatic benign bone tumour is osteoid osteoma with an incidence of 1:2000.

  8. Finite element modelling versus classic beam theory: comparing methods for stress estimation in a morphologically diverse sample of vertebrate long bones.

    Science.gov (United States)

    Brassey, Charlotte A; Margetts, Lee; Kitchener, Andrew C; Withers, Philip J; Manning, Phillip L; Sellers, William I

    2013-02-01

    Classic beam theory is frequently used in biomechanics to model the stress behaviour of vertebrate long bones, particularly when creating intraspecific scaling models. Although methodologically straightforward, classic beam theory requires complex irregular bones to be approximated as slender beams, and the errors associated with simplifying complex organic structures to such an extent are unknown. Alternative approaches, such as finite element analysis (FEA), while much more time-consuming to perform, require no such assumptions. This study compares the results obtained using classic beam theory with those from FEA to quantify the beam theory errors and to provide recommendations about when a full FEA is essential for reasonable biomechanical predictions. High-resolution computed tomographic scans of eight vertebrate long bones were used to calculate diaphyseal stress owing to various loading regimes. Under compression, FEA values of minimum principal stress (σ(min)) were on average 142 per cent (±28% s.e.) larger than those predicted by beam theory, with deviation between the two models correlated to shaft curvature (two-tailed p = 0.03, r(2) = 0.56). Under bending, FEA values of maximum principal stress (σ(max)) and beam theory values differed on average by 12 per cent (±4% s.e.), with deviation between the models significantly correlated to cross-sectional asymmetry at midshaft (two-tailed p = 0.02, r(2) = 0.62). In torsion, assuming maximum stress values occurred at the location of minimum cortical thickness brought beam theory and FEA values closest in line, and in this case FEA values of τ(torsion) were on average 14 per cent (±5% s.e.) higher than beam theory. Therefore, FEA is the preferred modelling solution when estimates of absolute diaphyseal stress are required, although values calculated by beam theory for bending may be acceptable in some situations.

  9. Bone tissue as a systemic endocrine regulator.

    Science.gov (United States)

    Zofkova, I

    2015-01-01

    Bone is a target tissue for hormones, such as the sex steroids, parathormon, vitamin D, calcitonin, glucocorticoids, and thyroid hormones. In the last decade, other "non-classic" hormones that modulate the bone tissue have been identified. While incretins (GIP and GLP-1) inhibit bone remodeling, angiotensin acts to promote remodeling. Bone morphogenetic protein (BMP) has also been found to have anabolic effects on the skeleton by activating bone formation during embryonic development, as well as in the postnatal period of life. Bone has also been identified as an endocrine tissue that produces a number of hormones, that bind to and modulate extra-skeletal receptors. Osteocalcin occupies a central position in this context. It can increase insulin secretion, insulin sensitivity and regulate metabolism of fatty acids. Moreover, osteocalcin also influences phosphate metabolism via osteocyte-derived FGF23 (which targets the kidneys and parathyroid glands to control phosphate reabsorption and metabolism of vitamin D). Finally, osteocalcin stimulates testosterone synthesis in Leydig cells and thus may play some role in male fertility. Further studies are necessary to confirm clinically important roles for skeletal tissue in systemic regulations. PMID:25470522

  10. 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

  11. 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

  12. Bone

    International Nuclear Information System (INIS)

    Bone scanning provides information on the extent of primary bone tumors, on possible metastatic disease, on the presence of osteomyelitis prior to observation of roentgenographic changes so that earlier therapy is possible, on the presence of collagen diseases, on the presence of fractures not disclosed by x-ray films, and on the evaluation of aseptic necrosis. However, the total effect and contribution of bone scanning to the diagnosis, treatment, and ultimate prognosis of pediatric skeletal diseases is, as yet, unknown. (auth)

  13. Classically and alternatively activated bone marrow derived macrophages differ in cytoskeletal functions and migration towards specific CNS cell types

    NARCIS (Netherlands)

    Vereyken, Elly J. F.; Heijnen, Priscilla D. A. M.; Baron, Wia; de Vries, Elga H. E.; Dijkstra, Christine D.; Teunissen, Charlotte E.

    2011-01-01

    Background: Macrophages play an important role in neuroinflammatory diseases such as multiple sclerosis (MS) and spinal cord injury (SCI), being involved in both damage and repair. The divergent effects of macrophages might be explained by their different activation status: classically activated (CA

  14. 骨缝牵引中联合应用骨形态发生蛋白-2和骨保护素的实验研究%The effect of bone morphogenetic protein-2 and osteoprotegerin in trans-sutural distraction osteogenesis

    Institute of Scientific and Technical Information of China (English)

    姚玉胜; 黄华; 常世民; 王程越; 王桂君

    2012-01-01

    目的 探索上颌骨在骨缝牵引时加入缓释骨形态发生蛋白-2 (BMP-2)和骨保护素(OPG)对新骨形成的影响.方法 以24只杂种犬为研究对象,随机分为A、B、C组.通过手术在上颌骨腭横缝植入自制的新型牵引器.A、C组术后5d在牵引区附近注射缓释重组人骨形态发生蛋白-2/聚乳酸-羟基乙酸共聚物/纤维蛋白胶(rhBMP-2/PLGA/FS),B、C组在牵引3周后注射人骨保护素/纤维蛋白胶(rhOPG/FS).牵引1、2、4、6周后处死动物,采集标本进行组织学染色,并通过组织计量学方法检测腭横缝的组织改建情况.结果 A、C组骨缝区成骨细胞功能活跃,透射电镜显示细胞内有大量高尔基复合体、线粒体及粗面内质网.牵引6周时,A、B、C组成骨细胞指数分别为38.5±7.7、35.7±6.5、41.7±11.0,破骨细胞指数分别为5.9±1.0、1.2±0.3、2.8±0.4,骨小梁厚度分别为(38.36±13.28)、(66.20±9.16)、(51.85±9.92) μm;B、C组表现出骨密度增加及破骨细胞指数下降.结论 本实验所用牵引器能促进新骨生成;BMP-2与OPG在骨缝牵引过程中有协同作用,可以促进新骨形成及骨改建.%Objective To determine if locally administered bone morphogenetic protein-2 (BMP-2) and osteoprote-gerin (OPG) improved osteogenesis and new bone formation by trans-sutural distraction osteogenesis. Methods Twenty four dogs were divided into three groups randomly and received new internal trans-sutural distraction osteogenesis treat-ment. Five days after operation, infusion apparatus with double-tube was inserted to submucosa near the distracted zone to deliver controlled release agent of recombinant human bone morphogenetic protein-2/poly Qactic-co-glycolie acid)/ fibrin sealant (rhBMP-2/PLGA/FS) in group A and group C. Recombinant human osteoprotegerin/fibrin sealant (rhOPG/ FS) was injected three weeks later in group B and group C. Histology staining and bone histomorphometry were used to measure the changes of

  15. 肺动脉高压对内皮祖细胞与骨形成蛋白-2的影响%The effection of idiopathic pulmonary hypertension on endothelial progenitor cells and bone morphogenetic protein-2

    Institute of Scientific and Technical Information of China (English)

    张韩; 李彦明; 刘枫; 万琪琳; 程冠昌; 洪岩; 陈君柱

    2012-01-01

    Objective To investigate the effectiong of idiopathic pulmonary arterial hypertension (IPAH ) on hone morphogenetic protein-2 ( BMP-2 ) and counts of endothelial progenitor cells ( EPC ) , and the co relationg between and BMP-2 and pidmary arterial pressnre(PAP) and the counts of EPC. Methods The patients with IPAH (fi=28 ) diagnosed by the examination of right heart floating catheters for pulmonary arterial pressure were selected as experimental group, and healthy volunteers were selected as control group. The concentration of plasma BMP-2 was detected by using enzyme-linked immnnosorbent assay ( ELISA) and EPC in peripheral blood were counted under the microscope. Results The difference in plasma BMP-2 had statistical significance between IP AN group and contrlo group [ ( 0.1294 ± 0.0292 ) μg/mL vs. (0.0898 ± 0.0295 )μg/mL, P<0.01], and the difference in EPC counts also had statistical significance [ ( 26.75 ± 5.87 ) piece vs. (42.65 ± 8.37 ) picee, P<0.01]. The relation of BMP-2 and PAP was positive, while negative between BMP-2 and EPC. Conclusion IPAH caused the increase of BMP-2 while desease of EPC, the relation between BMP-2 and PAP or BMP-2 and EPC was existed in IPAH patients.%目的 分析特发性肺动脉高压(IPAH)对血浆骨形成蛋白2(BMP-2)的浓度和外周血内皮祖细胞(EPC)数量的影响以及BMP-2与肺动脉压(PAP)及EPC的关系.方法 选取经右心漂浮导管检测肺动脉压确诊的IPAH住院患者28例为试验组;同时选取健康志愿者20例为对照组.采用酶联免疫吸附法(enzyme linked immunosorbent assay,ELISA)法测定血浆BMP-2的浓度,同时显微镜下计数外周血EPC.统计分析两组差异并对BMP-2与PAP和EPC的相关性进行分析.结果 IPAH患者血浆BMP-2水平高于对照组,差异有统计学意义[(0.1294±0.0292)μg/ml vs.(0.0898±0.0295)μg/ml,P<0.01],外周血EPC数量低于正常对照组,EPC数量具差异有统计学意义[(26.75±5.87)个 vs.(42.65±8.37)个,P<0.01].BMP

  16. 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

  17. 医用生物蛋白胶对注射型骨形态发生蛋白成骨活性的影响%Influence of fibrin sealant on osteoinductive ability of inject-type bone morphogenetic protein

    Institute of Scientific and Technical Information of China (English)

    王登虎; 刘建; 李丹; 胡蕴玉; 袁志

    2002-01-01

    Objective To observe influence of fibrin sealant(FS) on osteoinductive ability of inject type BMP.Method The inject type BMP power was dissolved in the main glue part or thrombin part of FS, then mixed with the main glue part or thrombin part of FS into gel, observe coagulating time, then implant composite into the thigh muscle pouch of mice to evaluate their capacity to induce new bone formation, and compared to the single BMP implant group.Result There was no difference in the coagulating time between two mixing method, the osteoinductive ability of implants BMP dissolved in the main glue part or thrombin part of FS group was higher than that of simply BMP implant group.Conclusion FS was perfect carrier to inject type BMP.

  18. 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

  19. Effect of bovine bone morphogenetic proteins on radius fracture healing in rabbits Efeito de proteínas morfogenéticas ósseas de origem bovina na consolidação de fraturas induzidas no rádio de coelhos

    Directory of Open Access Journals (Sweden)

    Alfredo Feio da Maia Lima

    2007-08-01

    Full Text Available PURPOSE: To investigate the effect of bovine bone morphogenetic proteins (bBMPs bound to hydroxyapatite plus collagen in the healing of unstable radius fractures. METHODS: A transverse fracture was induced at the mid of the diaphysis in both radii on 15 Norfolk rabbits with average age of 5.5 months and 3.5kg. A mixture of bBMPs bound to thin powdered hydroxyapatite (bBMP-HA and bovine collagen as agglutinant was applied to the right radius fracture site. The left radius fracture was considered control and no treatment was used. After 30, 60 and 90 days (5 rabbits/period the rabbits were euthanized and the radii were collected for histological analysis. RESULTS: The descriptive histological analysis revealed that repair was similar for both forelimbs. The histomorphometric analysis showed that the mean area of newly formed bone was 867442.16 mm², 938743.00 mm² and 779621.06 mm² for the control forelimbs, and 841118.47 mm², 788038.76mm² and 618587.24 mm² for the treated forelimbs at 30, 60 and 90 days, respectively. Thus the newly formed bone area was 12.17% larger in the forelimbs treated with bBMP-HA/collagen than in the control forelimbs (pOBJETIVO: Investigar a influência de Proteínas Morfogenéticas Ósseas de origem bovina (bBMPs ligadas a hidroxiapatita mais colágeno na consolidação de fraturas instáveis do rádio. MÉTODOS: Em 15 coelhos com aproximadamente 5,5 meses de idade e peso médio de 3,5kg foi realizada uma fratura transversa na porção média da diáfise do rádio de ambos os membros. Na fratura do rádio direito foi aplicada mistura de bBMPs ligadas à hidroxiapatita (bBMP-HA e colágeno bovino como aglutinante e na do rádio esquerdo, considerada controle, nenhum tratamento foi usado. Os coelhos (cinco por período foram submetidos à eutanásia aos 30, 60 e 90 dias após a cirurgia para realização do processamento histológico e análise microscópica. RESULTADOS: A análise histológica descritiva revelou que

  20. Interleukin 10 Suppresses the Function of Mouse Bone Marrow-Derived Dendritic Cells Infected with Classical Swine Fever Virus C-Strain

    Directory of Open Access Journals (Sweden)

    Fu-Ying Zheng, Guo-Zhen Lin* and Zhi-Zhong Jing

    2013-07-01

    Full Text Available Interleukin (IL-10 inhibits the functions of antigen-presenting cells (APCs, including dendritic cells (DCs, however, the precise mechanism of action of IL-10 has not been fully elucidated. In this work, the effects of IL-10 on classical swine fever virus (CSFV C-strain-infected mouse bone marrow-derived immature DCs (BM-imDCs were studied. Additional IL-10 suppressed the maturation of the infected BM-imDCs by down-regulating the expression levels of the surface molecules CD80, CD86 and major histocompatibility complex (MHC classII, while the autocrine IL-10 had no significant effect on the maturation status of the cells. Both additional and autocrine IL-10 markedly inhibited the secretion production of IL-12P40 derived from the BM-imDCs infected with the C-strain, and reduced the capacity of DCs to promote allogeneic naive T cell proliferation. These results showed that IL-10 may play an important role in the DCs-dependent immune response induced by CSFV C-strain.

  1. 家兔骨形态发生蛋白4基因(BMP4)启动子甲基化与杂种优势的关系%Relationship of Methylation of Rabbit Bone Morphogenetic Protein 4 Gene(BMP4) Promoter Region with Heterosis

    Institute of Scientific and Technical Information of China (English)

    冯凯; 石福岳; 孙露露; 潘雨来; 胡春辉; 吴信生

    2012-01-01

    Bone morphogenetic protein 4 (BMP-4) plays an important role in animal bone growth and organism development. In this study, the methylation pattern of CpG island of bone morphogenetic protein 4 {BMP4) gene promoter was detected using methylation-specific PCR (MSP), and compared and analyzed with carcass traits in four rabbit population of 80, New Zealand (NZ) rabbit(New Zealand Oryctolagus cuniculus), Fujian Yellow (FY) rabbit(Fujian Yellow 0. cuniculus) and reciprocal cross between NZ and FY, 20 of each population. The results showed that cross populations on slaughter traits were higher than that of the average of FY rabbit and NZ rabbit, and they were lower than that of NZ rabbit but no significant (p>0.05). It was very significant(p0.05). Methylation level of NZ rabbit was significant compared with FY Rabbit and FY rabbitxNZ rabbit (P.05) . Slaughter traits were different under different methylation level, but they did not match very well with methylation level and this might be cross by the methylation state of specific site. This study suggest a theoretical reference for explaining the relationship between methylation of BMP4 promoter region and heterosis and whether methylation of BMP4 promoter region can be a molecular marker or not.%骨形态发生蛋白4(BMP4)对动物骨组织的生长及动物机体生长发育起着重要的影响.本研究通过甲基化特异性PCR(methylation-specific PCR,MSP)方法检测4个家兔群体共80只家兔(新西兰兔(New Zealand Oryctolagus cuniculus)、福建黄兔(Fujian Yellow O.cuniculus)以及这两个品种正反交2个群体各20只)BMP4基因启动子CpG岛甲基化的状态,并结合屠体性状进行比对分析,为探索能否将BMP4基因启动子甲基化作为分子标记用于辅助育种,并阐明启动子甲基化与杂种优势的关系.结果显示,2个杂交群体的屠宰性能均高于福建黄兔与新西兰白兔的均值,虽低于新西兰兔但差异不显著(p>0.05),与福建

  2. Effect of recombinant human bone morphogenetic-4 and recombinant human insulin-like growth factor-Ⅰ on the proliferation and differentiation of rat osteoblasts%人重组骨形成蛋白-4与人重组胰岛素样生长因子-Ⅰ联合应用对大鼠成骨细胞的影响

    Institute of Scientific and Technical Information of China (English)

    万贤凤; 兰泽栋; 曾琳; 赵华; 熊红珍; 包丽娜

    2013-01-01

    目的 探讨人重组骨形成蛋白-4(recombinant human bone morphogenetic protein-4,rhBMP-4)与人重组胰岛素样生长因子-Ⅰ(recombinant human insulin-like growth factor-Ⅰ,rhIGF-Ⅰ)联合应用对大鼠成骨细胞生长增殖及分化能力的影响.方法 取大鼠颅盖骨组织块,采用改良组织块混合酶消化法培养成骨细胞,将第四代成骨细胞与10 ng/mL rhBMP-4(rhBMP-4组)、10 ng/mL rhIGF-Ⅰ(rhIGF-Ⅰ组)、10 ng/mL rhBMP-4加10ng/mLrhIGF-Ⅰ(联合组)、无血清低糖培养基(对照组)共同培养3d,用噻唑蓝法测定细胞的增殖情况,用碱性磷酸酶试剂盒检测细胞碱性磷酸酶的活性,用羟脯氨酸试剂盒检测成骨细胞分泌Ⅰ型胶原的量.结果 第3天时,4组促进大鼠成骨细胞增殖能力测定的光密度值差异具有统计学意义(F =4.080,P=0.016),碱性磷酸酶活性差异具有统计学意义(F=4.070,P=0.016),成骨细胞分泌Ⅰ型胶原的差异具有统计学意义(F=3.204,P=0.038);与对照组相比,rhBMP-4组,rhIGF-Ⅰ组及联合组,都可增强成骨细胞的增殖分化能力,但rhBMP-4和rhIGF-Ⅰ联合应用不比单独应用的作用强.结论 rhBMP-4与rhIGF-Ⅰ联合应用,不能协同促进大鼠成骨细胞增殖及分化能力.

  3. 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

  4. 慢性肾脏疾病患者各期骨形态蛋白-2水平变化及其影响因素%Changes of plasma bone morphogenetic protein-2 and its related factors in chronic kidney disease patients at different stages

    Institute of Scientific and Technical Information of China (English)

    胡明亮; 黄莺; 雷艳; 刘榕君; 徐庆东; 郑智华

    2013-01-01

    目的 探讨慢性肾脏疾病(chronic kidney disease,CKD)1-5期患者血清骨形态蛋白-2 (Bone morphogenetic protein 2,BMP-2)水平变化及其可能的影响因素. 方法 收集CKD各期的154例血液样本.测定血清BMP-2水平和常规生化测定肾功能、白蛋白、C-反应蛋白(CRP)及钙磷代谢等.并进行相关及多元回归分析. 结果 CKD1~5期各有26、22、26、20、28例,血液透析32例,对照28例.与正常对照比较,CKD4,CKD5期及血液透析患者血清BMP-2水平明显升高;血清BMP-2水平在CKD患者下列情况下显著升高:血磷大于1.4mmol/L或钙磷沉积大于55 mg2/d12;血清白蛋白低于35g/L;C-反应蛋白大于3000 μ g/L.相关分析结果提示,BMP-2与血磷水平,钙磷乘积,C-反应蛋白,血尿素氮,血肌酐呈显著正相关;与血清白蛋白和肾小球滤过率呈显著负相关.多元回归分析示:血磷及CRP显著影响BMP-2的独立因素. 结论 BMP-2在CKD中晚期和血液透析患者血清中明显升高;残存肾功能、钙磷代谢、炎症和白蛋白可能与CKD患者血清BMP-2水平有关;血磷和炎症是影响BMP-2的主要因素.%Objectives To investigate the variation of serum bone morphogenetic protein 2 (BMP-2),and the influences of eGFR,calcium-phosphate metabolism,inflammmation,lipid profile and nutrition index on BMP-2 production in chronic kidney disease (CKD) patients at different stages.Methods A cross-sectional study was performed in 154 CKD patients at different stages.BMP-2 was measured by ELISA,and other biochemistry parameters were assyed as well.Results We enrolled 26,22,26,20,and 28 CKD patients at the stage of 1,2,3,4and 5,respectively,and 32 CKD patients on maintenance hemodialysis (MHD) in this study.Twenty-eight healthy subjects were used as normal controls.(a) Serum BMP-2 increased significantly in CKD patients at stages of 4 and 5 and in those on MHD.(b) Serum BMP-2 was siginificant higher in CKD patients with plasma phosphate >1.4 mmol/l or

  5. Acidic preparations of platelet concentrates release bone morphogenetic protein-2.

    OpenAIRE

    Wahlström, Ola; Linder, Cecilia; Kalén, Anders; Magnusson, Per

    2008-01-01

    BACKGROUND AND PURPOSE: Growth factors released from platelets have potent effects on fracture and wound healing. The acidic tide of wound healing, i.e. the pH within wounds and fractures, changes from acidic pH to neutral and alkaline pH as the healing process progresses. We investigated the influence of pH on lysed platelet concentrates regarding the release of growth factors. MATERIAL AND METHODS: Platelet concentrates free of leukocyte components were lysed and incubated in buffers with p...

  6. Bone morphogenetic proteins and the polycystic ovary syndrome

    NARCIS (Netherlands)

    E.L.A.F. van Houten (Leonie); J.S.E. Laven (Joop); Y.V. Louwers (Yvonne); A. McLuskey; A.P.N. Themmen (Axel); J.A. Visser (Jenny)

    2013-01-01

    textabstractBackground: Polycystic Ovary Syndrome (PCOS) is defined by two out of the following three criteria being met: oligo- or anovulation, hyperandrogenism, and polycystic ovaries. Affected women are often obese and insulin resistant. Although the etiology is still unknown, members of the Tran

  7. Construction and identification of vascular endothelial growth factor 121 and bone morphogenetic protein-2 genes co-expressing recombinant adenovirus vector%血管内皮生长因子121和骨形态蛋白2双基因共表达重组腺病毒载体的构建及鉴定

    Institute of Scientific and Technical Information of China (English)

    钟声; 刘丹平; 刘素伟; 李晓禹; 李谌; 李媛

    2011-01-01

    背景:人血管内皮生长因子121和骨形态蛋白2在激素性股骨头坏死骨缺损中均具有成血管成骨作用,目前国内在以人血管内皮生长因子121和骨形态蛋白2基因联合治疗激素性股骨头坏死方面少有报道.目的:构建人血管内皮生长因子121与人骨形态发生蛋白2双基因腺病毒穿梭质粒.方法:将质粒pShuttle-CMV-VEGF121-IRES-hrGFP-1经Kpn Ⅰ/Xba Ⅰ酶切后,将BMP2片段定向连入pShuttle-CMV- VEGF121-IRES,构建可同时表达2个目的基因重组质粒pShuttle-CMV-V EGF121-IRES-BMP2,注入H5a细胞扩增,铺板,筛选阳性菌落,提取质粒,进行酶切分析及序列测定.将已构建确认正确的腺病毒质粒,经BJ5183-AD-1电转感受态细胞进行电穿孔后,铺板,筛选阳性菌落,提取质粒,进行酶切分析,PCR检测和序列分析.结果与结论:酶切分析及核酸序列测定证实重组质粒构建正确,提示实验成功构建了血管内皮生长121及骨形态蛋白2双基因共表达重组腺病毒载体.%BACKGROUND: Vascular endothelial growth factor 121 (VEGF121) and bone morphogenetic protein-2 (BMP-2) play an important role in the development and formation of bones and vessels. At present, there are few reports about the treatment of pathogenesis of steroid-induced avascular necrosis of the femoral head (SANFH) by VEGF121 combined with BMP-2 gene in China.OBJECTIVE: To construct VEGF121 and BMP-2 genes adenovirus shuttle plasmid pShuttle-CMV-V EGF121-IRES-BMP2. METHODS: After Plasmid pShuttle-CMV-VEGF121-IRES-hrGFP-1 through Kpn I/Xba I, BMP-2 fragments were directionally connected to pShuttle-CMV-VEGF121-IRES. Simultaneous expression of two gene plasmid pShuttle-CMV-VEGF121-IRES was constructed, and injected with H5a cells expansion, planking, screening positive colonies, extracting plasmid, and then was undergo restriction analysis and sequencing. The correct adenovirus plasmid which has been constructed and confirmed after through BJ5183-AD-1

  8. 重组人类骨形态蛋白2复合自固化磷酸钙材料在体内的血管化%Vascularization of autosetting calcium phosphate cultivated with recombinant human bone morphogenetic protein 2

    Institute of Scientific and Technical Information of China (English)

    王炜; 玛依拉·吾甫尔; 阿不都赛米·艾买提; 艾合买提江·玉素甫

    2011-01-01

    BACKGROUND: Deep fascia promotes vascularization of tissue-engineered bone, which is a mature technology, but different animal species and different implant materials can result in a great difference in vascularization.OBJECTIVE: To compare the vascularization of autosetting calcium phosphate cement cultivated with recombinant human bone morphogenetic protein 2 (rhBMP-2) and a single autosetting calcium phosphate cement implant in beagle dogs with deep fasica flaps. METHODS: Twelve healthy adult beagle dogs were respectively implanted with autosetting calcium phosphate cement cultivated with rhBMP-2 in the left thigh (experimental sides) and a single autosetting calcium phosphate cement in right thigh (control sides). The vascularization in each condition was assessed by experiment study (Physical, Massion stain, the hematoxylin-eosin stain, ⅧRAg marked) at time intervals of 2, 4, 8 and 16 weeks after operation.RESULTS AND CONCLUSION: In experimental groups and in control groups, vascularization was found. New vessels invaded in scaffold with time. In experimental groups, the amount of vessels and the expression of ⅧRAg were stronger than those in control groups at 2, 4, 8, and 16 weeks. The deep fasica flaps have great effect on the vascularization. The deep fasica flap binding with rhBMP-2 is proved to be the better in vascularization of autosetting calcium phosphate cement.%背景:深筋膜瓣促进组织工程骨血管化是一种成熟的技术,但动物种属不同、植入材料不同均会使血管化的结果产生较大的差异.目的:比较复合重组人类骨形态蛋白2的自固化磷酸钙人工骨和单纯的自固化磷酸钙人工骨在比格犬带蒂筋膜瓣内的血管再生能力.方法:分别将复合重组人骨形态蛋白2的自固化磷酸钙人工骨和单纯的自固化磷酸钙人工骨包裹于12只成年比格犬腰背部两侧带蒂深筋膜瓣中,于术后第2,4,8,16周各随机选取3只动物摘取血管化标本,进行大

  9. Morphogenetic Litter Types of Bog Spruce Forests

    OpenAIRE

    T. T. Efremova; A. F. Avrova; S. P. Efremov

    2015-01-01

    For the first time the representation of moss litter morphogenetic structure of valley-riverside and streamside spruce forests was determined for the wetland intermountain area of Kuznetsk Alatau. In general, the litter of (green moss)-hypnum spruce forest can be characterized as medium thickness (9–17 cm) with high storage of organic matter (77–99 t/ha), which differs in neutral environmental conditions pH 6.8–7.0 and high percentage of ash 11–28 %. Formation litter types were identified, w...

  10. 骨形态发生蛋白与碱性成纤维细胞生长因子联合修复软骨缺损的效果评价%Effects of recombinant human bone morphogenetic protein combined with basic fibroblast growth factor on the repair of articular cartilage defects

    Institute of Scientific and Technical Information of China (English)

    朱国华; 蔡建平; 郭翠玲; 廖家新; 刘勇; 罗洪涛; 许国华; 胡红涛

    2012-01-01

    背景:多种细胞生长因子在骨软骨代谢过程中的协同作用越来越受到重视,但目前复合细胞生长因子修复软骨缺损报道较少,且修复效果尚无定论.目的:探讨骨形态发生蛋白和碱性成纤维细胞生长因子联合应用修复关节软骨缺损的效果.方法:24 只日本大耳白兔建立骨软骨缺损模型后随机等分为4 组,对照组缺损处仅填塞明胶海绵,其他3 组在对照组基础上,缺损处分别注射骨形态发生蛋白和碱性成纤维细胞生长因子、骨形态发生蛋白、碱性成纤维细胞生长因子.结果与结论:大体观察显示联合应用2 种细胞因子后,软骨缺损面基本修复但稍不平整,单独使用其中1 种细胞因子缺损面未完全修复,对照组无明显修复.联合应用2 种细胞因子缺损部位软骨细胞数多于其他3 组(P < 0.05),且Ⅱ型胶原免疫组化染色深于其他组.提示联合应用骨形态发生蛋白和碱性成纤维细胞生长因子可以促进关节软骨损伤的修复,疗效优于单独应用骨形态发生蛋白或碱性成纤维细胞生长因子.%BACKGROUND: The synergy of various cell growth factors attracts more and more attention in the course of cartilage metabolism.However, there are few reports of repairing cartilage defects with combined cell growth factors, and the effect remains unknown atpresent.OBJECTIVE: To study the repairing effect of recombinant human bone morphogenetic protein (rhBMP) combined with basicfibroblast growth factor (bFGF) on articular cartilage defects.METHODS: After the model of articular cartilage defects was made, 24 Japan big-eared white rabbits were randomly divided intofour groupsforintervention: rhBMP combined with bFGF (group A), single rhBMP (group B), single bFGF (group C), the fourthgroup was without injection and just filled with gelatin sponge (group D).RESULTS AND CONCLUSION: In general observation, articular cartilage defects were basically repaired but slightly

  11. 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.

  12. 转腺病毒-人骨形态发生蛋白7软骨细胞分泌的透明质酸和Ⅱ型胶原%Secretion of type Ⅱ collagen and hyaluronic acid in chondrocytes transfected by adenovirus-bone morphogenetic protein 7

    Institute of Scientific and Technical Information of China (English)

    张洁; 刘巍; 朱新辉; 周怡

    2011-01-01

    BACKGROUND: Chondrocytes are limited in tissue engineering due to their poor self-dividing capacity and defifferentiation.OBJECTIVE: To investigate the expression of bone morphogenetic protein 7 (BMP-7) in chondrocytes transfected by adenovirus BMP-7 and the effects of transfection on chondrocyte secretion of type Ⅱ collagen and hyaluronic acid.METHODS: Adenoviral vector containing BMP-7 was prepared and then transfected into rabbit passage chondrocytes. BMP-7 mRNA and protein expressions in chondrocytes were detected. Changes in type Ⅱ collagen and hyaluronic acid in chondrocytes were determined.RESULTS AND CONCLUSION: At 48 and 72 hours after transfection, RT -PCR and western blot analysis showed that BMP-7 mRNA and protein expressions in the chondrocytes were increased; RT-PCR and ELISA showed the type Ⅱ collagen and hyaluronic acid in the chondrocytes were also obviously increased. These findings suggest that BMP-7 can be successfully transfected into chondrocytes by adenovirus and promote the secretion of type Ⅱ collagen and hyaluronic acid.%背景:软骨细胞自身分裂能力不强和去分化现象限制了其在组织工程中的应用.目的:观察腺病毒-骨形态发生蛋白7转染兔软骨细胞后骨形态发生蛋白7的表达及其对软骨细胞分泌Ⅱ型胶原和透明质酸功能的影响.方法:包装骨形态发生蛋白7腺病毒载体,将其转染至兔第2代软骨细胞.检测骨形态发生蛋白7 mRNA及蛋白的表达;检测软骨细胞中Ⅱ型胶原和透明质酸的变化.结果与结论:转染腺病毒-骨形态发生蛋白7后48,72 h,RT-PCR和Western blot方法显示软骨细胞表达的骨形态发生蛋白7 mRNA和蛋白均明显增加,RT-PCR和ELISA显示软骨细胞分泌的Ⅱ型胶原和透明质酸也显著增加.说明应用腺病毒可成功将骨形态发生蛋白7转染至兔软骨细胞,并能促进软骨细胞分泌Ⅱ型胶原和透明质酸.

  13. Molecular Cloning and Sequence Analysis of Full-Length cDNA Encoding Human Bone Morphogenetic Protein-7%人骨形态发生蛋白-7全长基因cDNA的克隆和序列分析

    Institute of Scientific and Technical Information of China (English)

    李新友; 刘淼; 李曙明; 姚煜; 王全颖; 杨广笑

    2003-01-01

    Objective: To clone the full-length human bone morphogenetic protein-7 ( BMP-7) gene and analyse its sequence, to aid in investigation of its function and structure. Methods: TotalRNA was isolated from Chinese fetal kidney by the acid guanidinium thiocyanate phenol-chloroformmethod. Two overlapping segments of human BMP-7 cDNA were obtained by reverse transcription(RT)-PCR. Fallowing application, the two segments were ligated to each other and subcloned intoPGEM-7 easy vector to form PEGM-T easy/hBMP-7 recombinant plasmid. Sanger dideoxy chain-ter-mination method was used to sequence the cDNA. Results: There was 750 bp fragment obtained RT-PCR using # 2 primer from 5' end of BMP-7 gene (PCR by using # 2 and # 1) ,and 540 bp frag-merit from 3' end was generated by RT-PCR using # 4 primer (PCR using # 3 and # 4). Full-lengthcDNA encoding BMP-7 was obtained by religation of two segments. When compared with hBMP-7 se-quence in Gene bank (XM30619) ,our full-length BMP- 7 cDNA has a G instead of a T at nucleotide862. This change results in valine substituting for phenylalanine in the protein. Conclusion: This isthe first time that BMP-7 cDNA was successfully cloned from Chinese fetal kidney. BMP-7 cDNAplays an important role in healing injuries of the osteo-articular system. This makes BMP-7 is an at-tractive target for various clinical applications.%目的:克隆人骨形态发生蛋白-7(BMP-7)全长基因,并进行测序及序列分析,研究其结构和功能.方法:采用异硫氰酸胍一步法从人胎儿肾中提取总RNA,利用逆转录-聚合酶链反应(RT-PCR)的方法,分段扩增出hBMP-7全长基因cDNA,与PGEM-T easy连接成PGEM-T easy/hBMP-7重组质粒,采用Sanger双脱氧链终止法测定基因序列.结果:以4号特异引物引导的RT-PCR扩增出BMP-7基因3'端540 bp片段,以2号特异引物引导的RT-PCR扩增出BMP-7基因5'端750 bp片段,重组连接两片段得到BMP-7全长基因cDNA.与Genebank上发表的hBMP-7序列(XM30619)

  14. 明胶海绵复合重组人骨形态发生蛋白-7植入物的体内异位成骨实验%Experimental study on ectopic osteogenesis by implants of gelatin sponge combined with recombinant human bone morphogenetic protein-7

    Institute of Scientific and Technical Information of China (English)

    王国栋; 李萍; 韩金祥; 王世立; 刘丽娜

    2012-01-01

    目的:考察以明胶海绵为载体的重组人骨形态发生蛋白-7(rhBMP-7)在小鼠体内异位成骨能力,评价大肠杆菌表达的rhBMP-7生物学活性.方法:昆明种小鼠随机分为两组,将复合rh-BMP-7的明胶海绵植入小鼠肌间隙作为实验组,对照组植入明胶海绵,分别于术后1、2、3、4周取出埋植材料,HE染色进行组织学观察,测定蛋白含量、钙含量与碱性磷酸酶(ALP)活性.结果:复合rhBMP-7的明胶海绵组在术后2、3、4周有骨细胞类似细胞和钙化灶的形成,术后2、3、4周蛋白含量、ALP活性和钙含量均明显高于明胶海绵对照组.结论:明胶海绵复合rhBMP-7植入小鼠体内有较强的异位成骨能力,是良好的生物载体,可用于rhBMP-7体内活性检测.%AIM: To investigate the ectopic osteogenetic capacity of gelatin sponge contained with recombinant human bone morphogenetic protein-7 (rhBMP-7) by animal experiment and evaluate the biologic activity of rhBMP-7 ex-pressed in Escherichia coli. METHODS: KM mice were divided into two groups randomly. Gelatin sponge contained with rhBMP-7 were implanted into intramuscular spatium of mice as experimental group, while gelatin sponge were implanted as control group. The mice were sac-rificed and the tissue samples were harvested at 1st, 2nd, 3rd and 4th week after implantation. Tissue response was observed by HE staining. The contents of proteins and calcium were meas-ured and the activities of alkaline phosphatase (ALP) were detected. RESULTS: HE staining showed that some cells similar to osteocytes and calcific tissues were formed in the group of gelat-in sponge contained with rhBMP-7 after implan-tation at 2nd, 3rd and 4th week. The contents of proteins and calcium and the activities of ALP in experimental group were significantly higher than those in the control group which implanted with gelatin sponge at 2nd, 3rd and 4th week. CONCLUSION; The gelatin sponge combined with rhBMP-7 could induce ectopic

  15. The correlation analysis between environmental factors, bone morphogenetic protein-4 and transforming growth factor beta-3 polymorphisms in nonsyndromic cleft lip with or without cleft palate%BMP4、TGF-β3基因多态性与环境暴露在非综合征性唇腭裂发生中的交互作用

    Institute of Scientific and Technical Information of China (English)

    林健燕; 栾荣生; 郭泽强; 林新勤; 汤洪洋; 陈苑萍

    2010-01-01

    目的 探讨环境暴露因素、骨形态生成蛋白4(BMP4)基因、转化生长因子β3(transforming growth factor beta-3,TGF-β3)基因之间的交互作用在非综合征性唇腭裂(nonsyndromic cleft lip and cleft palate,NSCLP)发生中的可能作用.方法 通过问卷调查获取环境暴露资料.用聚合酶链反应(PCR)-限制性片段长度多态性(restriction fragment length polymorphism,RFLP)技术对对照组(200例)和NSCLP组(200例)各基因位点的多态性进行检测.采用多因子降维法(multifactor djmensionality reduction,MDR)分析基因之间、基因与环境之间的交互作用关系,并对筛选的交互作用关系用Logistic回归进行验证.结果 BMP4 T538C、TGF-β3 C641A和TGF-β3G15572-三个单核苷酸多态性(single nucleotide polymorphism,SNP)位点间的交互作用与NSCLP的发生无关联.基因与环境交互作用分析发现,BMP4 T538C与母亲妊娠早期被动吸烟、母亲妊娠早期感染史对NSCLP的发生具有交互作用;TGF-β3G15572-与母亲妊娠早期被动吸烟、母亲妊娠早期感染史、父亲知晓妊娠前吸烟、父亲知晓妊娠前饮酒、母亲妊娠早期补充维生素对NSCLP的发生具有交互作用.经Logistic回归验证,结果一致.结论 NSCLP是基因与环境因素共同作用的结果,易感基因多态性影响着个体对环境因素的反应,研究它们之间的相互关系对阐明NSCLP的病因及发病机制具有重要意义.%Objective To investigate the effects of interactions among environmental factors, bone morphogenetic protein-4 ( BMP4 ) and transforming growth factor beta-3 ( TGF-β3 ) polymorphisms on nonsyndromic cleft lip and cleft palate (NSCLP) . MethodsThe data of environmental exposures were collected with questionnaires.Genotypes were determined with techniques of polymerase chain reactionrestriction fragment length polymorphism. Interactions between genes, environmental factors and NSCLP were analyzed using multifactor dimensionality

  16. Association of the genetic variations of bone morphogenetic protein 7 gene with diabetes and insulin resistance in Xinjiang Uygur population%骨形态发生蛋白-7基因变异与新疆维吾尔族人糖尿病和胰岛素抵抗的相关性

    Institute of Scientific and Technical Information of China (English)

    严治涛; 李南方; 郭艳英; 姚晓光; 王红梅; 胡君丽

    2011-01-01

    目的 探讨骨形态发生蛋白-7(bone morphogenetic protein 7,BMP7)基因变异与新疆维吾尔族人糖尿病、胰岛素抵抗的关系.方法 采用以流行病学调查为基础的病例-对照研究,选取717名(男276人、女441人)维吾尔族人作为研究对象,根据是否患有糖尿病分成糖尿病组(502例,男191例、女311例)和正常对照组(215人,男85人、女130人).首先在48例维吾尔族糖尿病患者中测序筛查 BMP7基因功能区的变异位点,选取代表性变异位点应用TaqMan-PCR技术在研究人群中进行基因型鉴定并开展病例-对照关联研究.结果 在 BMP7基因的功能区共发现5个新的和8个已知的变异位点.BMP7基因的2个代表性变异位点rs6025422、rs17480735均符合Hardy-Weinberg平衡.男性人群中rs6025422变异的AA、AG、GG基因型在糖尿病组及正常对照组中的频率分布差异有统计学意义(P0.05),而总人群及女性人群中rs6025422变异基因型频率分布在病例、对照组间差异无统计学意义(P>0.05).男性人群中rs6025422变异不同基因型组间空腹血糖、空腹胰岛素水平、HOMA指数存在差异,并且AA、AG、GG 3组呈现递减趋势(P0.05). There was significant difference of genotype distribution of rs6025422 between type 2 diabetes mellitus and control groups in the male population (P0.05), but there was no difference in total and female population (P>0.05). And the means of fasting blood glucose (FBG), fasting insulin and HOMA-index significantly decreased in individuals with AA, AG and GG genotypes of rs6025422 in male population (P0.05). The logistic regression analysis showed that GG genotype of rs6025422 variation might be a protective factor for diabetes in male (OR=0.637,95% confidence interval 0.439-0.923,P<0.05). Conclusion The present study suggests that the rs6025422 polymorphism in BMP7 gene may be associated with diabetes mellitus and insulin resistance in Uygur men.

  17. 骨形态发生蛋白2/7异二聚体对人脂肪间充质干细胞成骨分化的促进作用%Promoted role of bone morphogenetic protein 2/7 heterodimer in the osteogenic differentiation of human adipose-derived stem cells

    Institute of Scientific and Technical Information of China (English)

    张晓; 刘云松; 吕珑薇; 陈彤; 吴刚; 周永胜

    2016-01-01

    Objective:To investigate the role of bone morphogenetic protein 2/7 heterodimer (BMP-2/7)in the osteogenesis of human adipose-derived stem cells (hASCs).Methods:hASCs were exposed to three different treatments in vitro:osteogenic medium with 1 50 μg/L BMP-2/7 (experimental group), osteogenic medium alone (OM group)and proliferation medium (PM group).After 1 ,4 and 7 days of osteogenic induction,the amount of cellular DNA was measured to investigate the cytotoxicity.After 7 and 1 4 days,alkaline phosphatase (ALP)staining and quantification were performed to test the activity of ALP.After 21 and 28 days,the calcification deposition was determined by Alizarin Red S (ARS)stai-ning and quantification.The expressions of the osteoblast-related genes were tested on days 1 ,4,7 and 1 4.In the in vivo study,6 nude mice were used and 4 groups were set and implanted subcutaneously into the back of nude mice:(1 )β-TCP scaffold only (scaffold control group );(2 )β-TCP scaffold with hASCs cultured by PMin vitro for 1 week (PMcontrol group);(3)β-TCP scaffold with hASCs cultured by OM in vitro for 1 week (OM control group);(4)β-TCP scaffold with hASCs cultured by OM with 1 50 μg/L BMP-2/7 in vitro for 1 week (test group).After 4 weeks of implantation,histological staining was performed to evaluate the in vivo osteogenesis of hASCs.Results:After induction for 1 day,there was no significant difference between the experimental group and the PM group on the cellular DNA con-tent (P>0.05 ).After 4 days,the cellular DNA content increased under the stimulation of BMP-2/7 (P0.05).ALP ac-tivity was higher by the induction of BMP-2/7 than in OMalone and PM(P<0.05).More mineraliza-tion deposition and more expressions of osteoblast-related genes such as Runx2,ALP,COL-1 A1 and OC were determined in the experimental group at different time points (P<0.05).HE staining showed that, in the test group and OM control group,the extracellular matrix (ECM)with eosinophilic staining were observed

  18. 细胞自噬在骨形成蛋白4促大鼠 H9 C2心肌细胞肥大中的作用及机制%Role of autophagy in the motivation of rat myocardial hypertrophy in H9c2 cells induced by bone morpho-genetic protein 4 and its mechanism

    Institute of Scientific and Technical Information of China (English)

    陶业珍; 李建华; 刘亚坤; 王佩佩; 袁宇

    2016-01-01

    Objective Bone morphogenetic protein 4 ( BMP4) induces rat myocardial hypertrophy in H9c2 cells, but the spe-cific mechanism remains unclear .The study aimed to elucidate the role of autophagy in myocardial hypertrophy and its relationship with extracellular signal regulating kinase ( ERK1/2) signal transduction pathway . Methods H9c2 cardiomyocytes were randomly divided into 4 groups:control group, BMP4 group, BMP4+PD98059 (ERK1/2 signal pathway inhibitor) group and BMP4+3MA (autophagy inhibitor) group.With PD98059(50μmol/L) and 3MA(5mmol/L) blocking for 30min, BMP4 (50μg/L) were added.Expressions of tiny tube related proteins 1 light chain 3 (LC3) and p-ERK1/2 were detec-ted after culturing for 30min.48h later, measurements were made on cell surface area , average protein content and α-smooth muscle actin (α-SMA ) protein expression level .Cell morphology and size were measured respectively by inverted microscope and Image J software .Total protein content was detected by BCA , and western blot was used to measure the expressions of LC3, ERK1/2, p-ERK1/2 and α-SMA. Resul ts 30min later, the expressions of LC3 and p-ERK1/2 were significantly higher in BMP4 group than in control group [(1.54 ±0.05) vs (1.95 ±0.11),(0.94 ±0.04) vs (1.33 ± 0.06),P0.05). Conclusion Autophagy may participate in BMP4-induced rat myo-cardial hypertrophy in H9c2 cells through ERK1/2 signal transduction pathway .The clinical treatment of myocardial hypertrophy may benefit from the blocking of autophagy or ERK 1/2 signal transduction pathway .%目的:骨形成蛋白4( bone morphogenetic protein 4, BMP4)可诱导大鼠H9C2心肌细胞肥大,为进一步寻求其调控机制,文中探讨细胞自噬在心肌肥大中的作用及其与细胞外信号调节激酶(extracellular signal regulating kinase , ERK1/2)的相互关系。方法将H9C2心肌细胞随机分为4组:对照组、BMP4组、BMP4+ERK1/2信号通路抑制剂( PD98059)组、BMP4

  19. 不同有机溶剂对缓释重组人骨形态发生蛋白2微胶囊的影响%Effects of different organic solvents on slow-release recombinant human bone morphogenetic protein-2 microcapsules

    Institute of Scientific and Technical Information of China (English)

    李夏林; 易伟宏; 靳安民; 闵少雄

    2015-01-01

    BACKGROUND:In literatures, the recombinant human bone morphogenetic protein-2 (rhBMP-2) loaded microcapsules can be fabricated by double emulsion solvent evaporation method with different organic solvents, such as methylene chloride, ethyl acetate or their mixture. But so far it is not determined yet which one is better. OBJECTIVE: To optimize the preparation method of microcapsules encapsulating rhBMP-2 and to compare the effects of different organic solvents on the microcapsules. METHODS:Polylactic acid-polyethylene glycol-polylactic acid copolymer as microcapsules was used to prepare rhBMP-2 loaded microcapsules with double emulsion solvent evaporation method. Four kinds of organic solvents, methylene chloride (group A), mixture of methylene chloride and ethyl acetate (group B), ethyl acetate (group C) and acetyl acetone (group D) were chosen as oil phases to compare their effects on microcapsule's morphology, diameter, and encapsulation efficiency. Passage 3 bone marrow mesenchymal stem cels from rats were co-cultured with prepared microcapsules for 14 days, and then alkaline phosphatase activity was detected. RESULTS AND CONCLUSION:Compared with the other organic solvents, dichloromethane could cause microcapsules with the smaler and more uniform shape (4-10 microns) and the highest encapsulation efficiency; the microcapsules prepared by mixture of methylene chloride and ethyl acetate had relatively wide size distribution and moderate encapsulation efficiency; the microcapsules prepared by acetylacetone were difficult to form and keep the bioactivity of rhBMP-2. After cultured with rat bone marrow mesenchymal stem cels for 14 days, the alkaline phosphatase activity in groups A, B and C was significantly higher than that in group D and there was no significant difference between group A and group B; the alkaline phosphatase activity in groups A and B was significantly higher than that in group C (P< 0.05). The results show the rhBMP-2-loaded microcapsules

  20. Morphogenetic Engineering Toward Programmable Complex Systems

    CERN Document Server

    Sayama, Hiroki; Michel, Olivier

    2012-01-01

    Generally, spontaneous pattern formation phenomena are random and repetitive, whereas elaborate devices are the deterministic product of human design. Yet, biological organisms and collective insect constructions are exceptional examples of complex systems that are both self-organized and architectural.   This book is the first initiative of its kind toward establishing a new field of research, Morphogenetic Engineering, to explore the modeling and implementation of “self-architecturing” systems. Particular emphasis is placed on the programmability and computational abilities of self-organization, properties that are often underappreciated in complex systems science—while, conversely, the benefits of self-organization are often underappreciated in engineering methodologies.   Altogether, the aim of this work is to provide a framework for and examples of a larger class of “self-architecturing” systems, while addressing fundamental questions such as   > How do biological organisms carry out morphog...

  1. Classical antiparticles

    Energy Technology Data Exchange (ETDEWEB)

    Costella, J.P.; McKellar, B.H.J.; Rawlinson, A.A.

    1997-03-01

    We review how antiparticles may be introduced in classical relativistic mechanics, and emphasize that many of their paradoxical properties can be more transparently understood in the classical than in the quantum domain. (authors). 13 refs., 1 tab.

  2. Particle gun-mediated bone morphogenetic protein-2 gene transfection for treatment of chronic bone defects%基因枪介导的骨形态发生蛋白2基因转染治疗陈旧性骨缺损

    Institute of Scientific and Technical Information of China (English)

    朱小萌; 王翀; 宋兴华; 詹玉林; 李文举

    2014-01-01

    背景:体内外研究都已证实骨形态发生蛋白具有调节成骨细胞和成软骨细胞的分化、诱导异位骨形成、促进骨折愈合、控制哺乳动物骨骼不同形态特征形成的功能。  目的:使用含有骨形态发生蛋白2基因真核表达质粒的基因枪进行局部基因注射以治疗陈旧骨缺损。  方法:72只新西兰大白兔建立陈旧兔桡骨中段骨缺损模型,按所截骨长度均分1.5 cm组、2.0 cm和2.5 cm组。各组又随机分为治疗组(骨形态发生蛋白2基因转染组)和对照组(自然愈合组)。于转染后1,3,8,9周拍摄X射线平片,1,3,8和9周取骨折间软组织行骨形态发生蛋白2的Western blot检测,于1,3,8和9周时取标本大体观察,评价愈合情况。  结果与结论:①大体标本观察发现治疗组骨痂生成量多于对照组。②治疗组转染后1,3,8,9周的Lane-Sandhu X射线评分优于对照组,差异均有显著性意义(P OBJECTIVE:To treat chronic bone defects using particle gun containing BMP2 gene eukaryotic expression plasmid via local injection. METHODS:A total of 72 healthy New Zealand white rabbits were applied to establish chronic bone defect model in the rabbit radius. According to the length of bone defect, the rabbits were divided into three groups:1.5 cm group, 2.0 cm group, 2.5 cm group. Each group was further randomly assigned into two subgroups:treatment group (BMP-2 gene transfection) and control group (natural y healing). X-ray examinations were performed at 1, 3, 8 and 9 weeks after transfection, and soft tissue between the bone defects was harvested to detect BMP-2 using western blot analysis;and radius specimens were taken for gross observation at the same time points, to evaluate the healing. RESULTS AND CONCLUSION:(1) Gross specimen observation:bone cal us formation in treatment group was general y more than that in control group. (2) Lane-Sandhu X-ray score in treatment group

  3. A morphogenetic study of sporangia-partitioning complex

    Directory of Open Access Journals (Sweden)

    H. K. Goswami

    2015-05-01

    Full Text Available The bilobed sporangia in the species of Anthoceros, Isoetes and Ophioglossum are described. The morphogenetic importance of the process of "fission" in evolutionary development of sporangia in pteridophytes is discussed.

  4. 鸡冠花黄酮对糖尿病大鼠骨形成蛋白表达及肾小管重吸收功能的干预作用%Effect of cristata L flavonoid on expression of bone morphogenetic protein and function of tubular reabsorption of rats with diabetes mellitus

    Institute of Scientific and Technical Information of China (English)

    陈正跃; 李万里; 赵辉; 宋向凤; 郭晓玲; 尉辉杰

    2005-01-01

    鼠骨组织骨形成蛋白2表达明显下降,补充鸡冠花黄酮类化合物后动物骨骨形成蛋白2表达升高,糖尿病大鼠的尿钙和尿钠的排出显著降低,肾小管的重吸收功能提高.%BACKGROUND: Cristata L flavonoid is a kind of plant estrin, which possesses multiple physiological function, has no toxicity and adverse effect, and is effective in treating and preventing osteoporosis.OBJECTIVE: To study the effect of cristata L flavonoid on bone morphogenetic protein, urine inorganic salt and content of lysozyme of rats with diabetes mellitus (DM).DESIGN: Randomized grouping design and controlled study.SETTING: Pharmaceutical Laboratory of Xinxiang Medical College.MATERIALS: The experiment was completed in the Xinxiang Medical College from September to December 2003. Totally 24 health male SD rats were randomly divided into three groups: normal control group, diabetes mellitus (DM) group, DM + cristata L flavonoid group with 8 in each group.were injected intraperineally with 60 mg/kg streptozotocin, and 48-72 hours later, blood of rear caudal vein was collected to measure total blood glucose.Rats were determined as DM if the blood glucose was ≥ 16.7 mmol/L; oth erwise, 60 mg/kg streptozotocin was injected once more. After modeling,cristata L flavonoid and rats in normal control group were given the same was measured with atomic absorbency method and content of urine sodium histochemistry of bone morphogenic protein-2 (BMP2) in bone was detected with streptavidin tagged by peroxidase and immunohistochemic expression lysozyme reflected reabsorption function of renal tubule was measured with with t-test. MAIN OUTCOME MEASURES: Comparison between content of calcium, sodium, kalium in urine and lysozyme and immunohistochemic expression of BMP2 10-week intervention later.calcium and sodium in urine in DM model group were obviously higher than those in normal control group, but content of kalium in urine was obviously lower (P < 0.05-0.01). Contents of calcium in urine

  5. Morphogenetic Litter Types of Bog Spruce Forests

    Directory of Open Access Journals (Sweden)

    T. T. Efremova

    2015-02-01

    Full Text Available For the first time the representation of moss litter morphogenetic structure of valley-riverside and streamside spruce forests was determined for the wetland intermountain area of Kuznetsk Alatau. In general, the litter of (green moss-hypnum spruce forest can be characterized as medium thickness (9–17 cm with high storage of organic matter (77–99 t/ha, which differs in neutral environmental conditions pH 6.8–7.0 and high percentage of ash 11–28 %. Formation litter types were identified, which depend on the content of mineral inclusions in organogenic substrate and the degree of its drainage. The differentiation of litter subhorizons was performed, visual diagnostic indicators of fermentative layers were characterized, and additional (indexes to indicate their specificity were developed. Peat- and peaty-fermentative, humified-fermentative and (black mold humus-fermentative layers were selected. Peat- and peaty-fermentative layers are characterized by content of platy peat macroaggregates of coarse vegetable composition, the presence of abundant fungal mycelium and soil animals are the primary decomposers – myriopoda, gastropoda mollusks. Humified-fermentative layers are identified by including the newly formed amorphous humus-like substances, nutty-granular structural parts of humus nature and soil animals’ humificators – enchytraeids and earthworms. (Black mold humus-fermentative layers are diagnosed by indicators with similar humified-fermentative, but differ from them in clay-humus composition of nutty-granular blue-grey parts. The nomenclature and classification of moss litter were developed on the basis of their diagnostic characteristics of fermentative layers – peat, peaty, reduced peaty, (black mold humus-peaty, reduced (black mold humus-peaty. Using the method of discriminant analysis, we revealed that the physical-chemical properties, mainly percentage of ash and decomposition degree of plant substrate, objectively

  6. BMP-7对IL-1β作用下软骨细胞合成和分解表型的影响%Effects of bone morphogenetic protein-7 on anabolic and catabolic phenotypes of interleukin-1β-treated chondrocytes

    Institute of Scientific and Technical Information of China (English)

    张昀; 王会超; 肖涟波

    2014-01-01

    Objective To investigate the effects of bone morphogenetic protein (BMP)-7 on anabolic and catabolic phenotypes of murine chondrocytes treated with interleukin (IL)-1βand supply scientific data for osteoarthritis (OA)treatment using BMP-7.Methods Primary cultured murine chondrocytes were divided into six groups:nontreatment group and IL-1β(5 ng/ml)group as control groups,groups of different concentrations of BMP-7 (10,50,200 ng/ml)mixed with IL-1β(5 ng/ml)and BMP-7 (200 ng/ml)only group as experiment groups.After 24 h treatment,reverse transcription-quantitative polymerase chain reaction (RT-qPCR)were conducted to determine the expression levels of anabolic factors,including type Ⅱcol agen (ColⅡ),aggrecan and SRY-related high mobility group-box (Sox)9,and catabolic factors,including matrix metal oproteinase (MMP)-3,MMP-13 and a disintegrin and metal oproteinase with thrombospondin motifs (ADAMTS)-5.The protein levels of MMP-3 and MMP-13 in cel culture medium were measured with enzyme-linked immunosorbent assay (ELISA) kits.Results Under IL-1βstimulation,the phenotype of chondrocytes shifted from anabolic to catabolic.With BMP-7 added,the depressed anabolic factors were recovered and catabolic factors were suppressed in a concentration-dependent manner.BMP-7 at a dose of 200 ng/ml demonstrated the best effects of pro-anabolic and anti-catabolic against IL-1β.The BMP-7 only group showed increased expression of aggrecan,but not ColⅡor Sox9.Conclusion The therapeutic effects of BMP-7 for OA are mediated by its pro-anabolic and anti-catabolic effects on chondrocytes under proinflammatory environment.%目的探讨在炎症因子白细胞介素(IL)-1β刺激下,骨形态发生蛋白(BMP)-7对小鼠关节软骨细胞合成表型及分解表型的作用,为 BMP-7用于骨关节炎(OA)治疗提供科学证据。方法将原代培养的小鼠关节软骨细胞分为6组,对照组包括未加处理的空白组、IL-1β(5 ng

  7. Classics Online.

    Science.gov (United States)

    Clayman, Dee L.

    1995-01-01

    Appraises several databases devoted to classical literature. Thesaurus Linguae Graecae (TLG) contains the entire extant corpus of ancient Greek literature, including works on lexicography and historiography, extending into the 15th century. Other works awaiting completion are the Database of Classical Bibliography and a CD-ROM pictorial dictionary…

  8. Classical integrability

    Science.gov (United States)

    Torrielli, Alessandro

    2016-08-01

    We review some essential aspects of classically integrable systems. The detailed outline of the sections consists of: 1. Introduction and motivation, with historical remarks; 2. Liouville theorem and action-angle variables, with examples (harmonic oscillator, Kepler problem); 3. Algebraic tools: Lax pairs, monodromy and transfer matrices, classical r-matrices and exchange relations, non-ultralocal Poisson brackets, with examples (non-linear Schrödinger model, principal chiral field); 4. Features of classical r-matrices: Belavin–Drinfeld theorems, analyticity properties, and lift of the classical structures to quantum groups; 5. Classical inverse scattering method to solve integrable differential equations: soliton solutions, spectral properties and the Gel’fand–Levitan–Marchenko equation, with examples (KdV equation, Sine-Gordon model). Prepared for the Durham Young Researchers Integrability School, organised by the GATIS network. This is part of a collection of lecture notes.

  9. 大鼠脊髓损伤后骨形态发生蛋白2表达变化的规律及意义%Dynamic expression of bone morphogenetic protein 2 and its clinical significance after spinal cord injury in rat

    Institute of Scientific and Technical Information of China (English)

    马敏杰; 贺西京; 王国毓; 臧全金; 李锋涛; 刘宇

    2011-01-01

    脊髓灰质区实施.%Objective:To observe the dynamic expression of bone morphogenetic protein 2 (BMP2) after spinal cord injury in rat,especially the changes on different time point and in different site,and to investigate the optimal time point and site for inhibiting BMP2 expression.Method:A total of 40 Sprague Dawley rats were randomly assigned into 5 groups: 1-day-after-impact group,3-day-after-impact group,7-day-after-impact group,14-day-after-impact group and sham operation group with 8 rats in each group.After making skin incision centered as T10,the whole T10 and T9 and T11 partial laminar were removed to expose the spinal cord. Spinal cord injury models were created by NYU impactor. After that,behavior testing of all rats was assessed by using the Basso-Beattie-Bresnahan (BBB) locomotor rating scale before and after the perfusion. Each group of rats were perfused with 4% paraformaldehyde in heart on the 1st,3th,7th,14th day-afterimpact,and then HE staining was used to observe the difference between the sham operation group and test groups. Meanwhile,immunohistochemistry was used to evaluate the level of BMP2 in the injuried region. Result: BBB score showed no significant difference among the spinal cord injury groups at the same time point (P> 0.05).By HE staining, the tissue structure of sham operation group showed clear and orderly,on the contrary, it was disorderly in rest groups. According to the result of immunohistochemistry,significant difference was detected between the model group and sham operation group (P<0.05).Compared with the sham operation group,the mean number of BMP2 positive cells in 1-day-after-impact group was 13.70±4.81 and 7.23±3.14 for the gray and white matter respectively,9.37±3.61 and 5.63±2.23 in 3-day-after-impact group,6.17±1.81 and 4.17±1.24 in 7-day-after-impact group,and 4.36±1.60 and 1.87±1.13 in 14-day-after-impact group.The BMP2-positive cells in gray matter increased more significantly than white matter (P<0.01).Conclusion:The number of BMP2

  10. Classical Motion

    OpenAIRE

    Mould, Richard A

    2003-01-01

    Preciously given rules allow conscious systems to be included in quantum mechanical systems. There rules are derived from the empirical experience of an observer who witnesses a quantum mechanical interaction leading to the capture of a single particle. In the present paper it is shown that purely classical changes experienced by an observer are consistent with these rules. Three different interactions are considered, two of which combine classical and quantum mechanical changes. The previous...

  11. Power-frequency electromagnetic field promotes mRNA expressions of bone morphogenetic protein-2 and transforming growth factor-beta 1 in bone marrow mesenchymal stem cells%工频电磁场对小鼠骨髓间充质干细胞骨形态发生蛋白2和转化生长因子β1mRNA表达的刺激

    Institute of Scientific and Technical Information of China (English)

    陈继革; 吴华; 葛保健; 方真华

    2007-01-01

    BACKGROUND:Studies confirm that electromagnetic field (EMF) can promote the synthesis and secretion of many bone growth factors,and some growth factors can induce the osteoblastic directional differentiation of bone marrow mesenchymal stem cells (MSCs).OBJECTIVE: To investigate the effect of power-frequency EMF on mRNA expressions of bone morphogenetic protein-2 (BMP-2) and transforming growth factor-beta 1 (TGF-β1) in mouse bone marrow MSCs cultured in vitro.DESTGN: Single sample, block design, observation and controlled animal trial.SETTING: Department of Traumatic Surgery, Tongji Hospital Affiliated to Tongji Medical .College, Huazhong University of Science and Technology.MATERIALS: This trial was carried out in the laboratory of Department of Traumatic Surgery, Tongji Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology during February to December 2005. ①Twenty Kunming mice of clean grade were selected for harvest of bone marrow MSCs. ②Magnetic field generator,which could generate EMF with 0 to 100 mT field strength and successive adjustable 50 Hz sinusoidal wave, was developed by Wuhan Naval University of Engineering. ③ Primer was all synthesized by Saibaisheng Bioengineering Co.,Ltd., Beijing.NETHODS: ① The involved mice were sacrificed by cervical dislocation. Bilateral femora and tibia were harvested. Bone marrow MSCs were isolated and cultured in vitro, and the second generation of cells were used for the trial. ②Different intensities of EMF stimulation tests: Negative control group, positive control group, EMF 0.4, 0.8 and 1.6 mT stimulation groups were set. Five bottles of cells of the second generation were chosen from each group for test. The cells in the negative control group and positive control group were not exposed to EMF. But medium containing osteogenic inductor(10-8 mol/L dexamethasone, 10 mmol/L β-sodium glycerophosphate and 50 mg/L Vitamin C included) was added in the positive control group

  12. Mistura de proteínas morfogenéticas ósseas, hidroxiapatita, osso inorgânico e colágeno envolta por membrana de pericárdio no preenchimento de defeito ósseo segmentar em coelhos Mixture of bone morphogenetic protein, hydroxyapatite, inorganic bone and collagen interposed by pericardium barrier membrane in the filling of the segmental bone defect in rabbits

    Directory of Open Access Journals (Sweden)

    R.B. Ciani

    2006-02-01

    Full Text Available Avaliou-se o uso de biomaterial de origem bovina na regeneração de defeitos ósseos segmentares empregando-se 12 coelhos, fêmeas, da raça Norfolk, com idade de seis meses e pesos entre 3 e 4,5kg. Realizou-se falha segmentar bilateral de um centímetro de comprimento na diáfise do rádio, com inclusão do periósteo. No membro direito, o defeito foi delimitado por membrana de pericárdio liofilizada, contendo em seu interior mistura de proteínas morfogenéticas ósseas adsorvidas a hidroxiapatita, colágeno liofilizado e osso inorgânico. No membro esquerdo, o defeito não recebeu tratamento. Radiografias foram obtidas ao término do procedimento cirúrgico e aos sete, 30, 60, 90, 120 e 150 dias de pós-operatório. Após eutanásia de seis coelhos aos 60 dias e seis aos 150 dias de pós-cirúrgico, os resultados radiográficos e histológicos mostraram que a regeneração óssea foi inibida nos defeitos segmentares tratados com o biomaterial.Biomaterials of bovine origin in regenerating segmental bone defects were evaluated. Twelve six-month old Norfolk rabbits, weighting 3 to 4.5kg were used. A 1cm long segmental defect was created in the radial diaphysis, including the periosteum, of both forelimbs. In the right forelimb, the defect was filled using a mixture of bone morphogenic proteins adsorbed to hydroxyapatite, agglutinant of lyophilized collagen in granules and anorganic cortical bone in granules delimited by a pericardial membrane. In the left forelimb, the defect did not receive treatment and served as a control. Radiographies were taken immediately after surgery and at seven, 30, 60, 90, 120 and 150 days post-operatively. Six rabbits were euthanized at 60 days and the other six at 150 days post-surgery for histological evaluation. Radiographic and histological results revealed that bone regeneration was inhibited in the segmental defects receiving biomaterials.

  13. Osteotransductive bone cements.

    Science.gov (United States)

    Driessens, F C; Planell, J A; Boltong, M G; Khairoun, I; Ginebra, M P

    1998-01-01

    Calcium phosphate bone cements (CPBCs) are osteotransductive, i.e. after implantation in bone they are transformed into new bone tissue. Furthermore, due to the fact that they are mouldable, their osteointegration is immediate. Their chemistry has been established previously. Some CPBCs contain amorphous calcium phosphate (ACP) and set by a sol-gel transition. The others are crystalline and can give as the reaction product dicalcium phosphate dihydrate (DCPD), calcium-deficient hydroxyapatite (CDHA), carbonated apatite (CA) or hydroxyapatite (HA). Mixed-type gypsum-DCPD cements are also described. In vivo rates of osteotransduction vary as follows: gypsum-DCPD > DCPD > CDHA approximately CA > HA. The osteotransduction of CDHA-type cements may be increased by adding dicalcium phosphate anhydrous (DCP) and/or CaCO3 to the cement powder. CPBCs can be used for healing of bone defects, bone augmentation and bone reconstruction. Incorporation of drugs like antibiotics and bone morphogenetic protein is envisaged. Load-bearing applications are allowed for CHDA-type, CA-type and HA-type CPBCs as they have a higher compressive strength than human trabecular bone (10 MPa).

  14. The composite of bone morphogenetic protein-2 and poly(lactic-co-glycolic acid)-tricalcium phosphate plus different vascularized tissues to repair large segmental radial defects in sheep%复合骨形态发生蛋白-2的人工骨结合带血供组织修复羊桡骨大段骨缺损的实验研究

    Institute of Scientific and Technical Information of China (English)

    徐建强; 周密; 张树明; 李长庚; 杨飞; 孙锁柱; 王长江; 王克利

    2012-01-01

    目的 探讨复合骨形态发生蛋白-2的聚乳酸-乙醇酸共聚物/磷酸三钙(PLGA-TCP-BMP-2)人工骨结合不同自体带血供组织移植修复羊桡骨大段骨缺损的效果. 方法 将30只绵羊制作成30 mm桡骨骨缺损模型,随机分为5组:PLGA-TCP-BMP-2人工骨及带血供的长段尺骨组(A组)、PLGA-TCP-BMP-2人工骨及带血供的屈指长肌肌腹组(B组)、PLGA-TCP-BMP-2人工骨及带血供的尺骨骨膜组(C组)、PLGA-TCP-BMP-2人工骨组(D组)及不植人任何材料组(E组),每组6只.各组均以钢板固定桡骨缺损区.术后当天及4、12、24周行手术部位X线摄片,术后24周处死动物行CT及组织学检查. 结果 X线片及CT检查显示:术后24周A、B、C组桡骨缺损处完全成骨修复,皮质骨与髓腔的轮廓清晰;D组亦能完全修复,但新生骨密度及髓腔轮廓清晰度均不如前3组;E组无有效骨痂形成.Samantha放射学评分和Lane-Sandhu放射学评分显示:A组评分高于其他4组,差异均有统计学意义(P<0.05).组织学检查结果显示:A组新生骨完全修复骨缺损区;B、C组新生骨与断端皮质骨融合,新生骨痂较为纤细;D组新生板层骨及骨陷窝排列较为紊乱;E组无骨连接表现.A、B、C、D、E组Lane-Sandhu组织学评分平均分别为(11.3±0.6)、(10.8±0.8)、(10.7±0.9)、(10.2±1.1)、(4.5±1.2)分,5组比较差异有统计学意义(F=5.891,P=0.026),其中A组评分高于其他4组,差异均有统计学意义(P<0.05).结论 PLGA-TCP-BMP-2人工骨结合不同自体带血供组织移植能满意修复羊桡骨30 mm的骨缺损.%Objective To study effects of the artificial composite bone of bone morphogenetic protein (BMP-2) and poly ( lactic-co-glycolic acid) -tricalcium phosphate(PLGA-TCP) with different vascularized tissues on repairing the large segmental radial defects in sheep. Methods Defects of 30 mm were made in the middle radial segments in 30 sheep which were randomized into 5 groups.In group A

  15. Classical electrodynamics

    CERN Document Server

    Schwinger, Julian Seymour; Milton, K A; Tsai, W Y

    1998-01-01

    This text for the graduate classical electrodynamics course was left unfinished upon Julian Schwinger's death in 1994, but was completed by his coauthors, who have brilliantly recreated the excitement of Schwinger's novel approach. Classical Electrodynamics captures Schwinger's inimitable lecturing style, in which everything flows inexorably from what has gone before. An essential resource for both physicists and their students, the book includes a "Reader's Guide", which describes the major themes in each chapter, suggests a possible path through the book, and identifies topics for inclusion

  16. Classical Motion

    CERN Document Server

    Mould, R A

    2003-01-01

    Preciously given rules allow conscious systems to be included in quantum mechanical systems. There rules are derived from the empirical experience of an observer who witnesses a quantum mechanical interaction leading to the capture of a single particle. In the present paper it is shown that purely classical changes experienced by an observer are consistent with these rules. Three different interactions are considered, two of which combine classical and quantum mechanical changes. The previously given rules support all of these cases. Key Words: brain states, conscious observer, detector, measurement, probability current, state reduction, von Neumann, wave collapse.

  17. A Morphogenetic Design Approach with Embedded Structural Analysis

    DEFF Research Database (Denmark)

    Jensen, Mads Brath; Kirkegaard, Poul Henning; Holst, Malene Kirstine

    2010-01-01

    The present paper explores a morphogenetic design approach with embedded structural analysis for architectural design. A material system based on a combined space truss and membrane system has been derived as a growth system with inspiration from natural growth of plants. The structural system is...

  18. BONE IN OSTEOPETROSIS

    Directory of Open Access Journals (Sweden)

    Ramkumar

    2014-04-01

    Full Text Available Osteopetrosis, a generalized developmental bone disease due to genetic disturbances, characterized by failure of bone re sorption and continuous bone formation making the bone hard, dense and brittle. Bones of intramembranous ossification and enchondrial ossification are affected genetically and symmetrically. During the process of disease the excess bone formation obliterates the cranial foramina and presses the optic, auditory and facial nerves resulting in defective vision, impaired hearing and facial paralysis. The bone formation in osteopetrosis affects bone marrow function leading to severe anemia and deficient of blood cells. The bone devoid of blood supply due to compression of blood vessels by excess formation of bone are prone to osteomyelitic changes with suppuration and pathological fracture if exposed to infection. Though the condition is chronic progressive, it produces changes leading to fatal condition, it should be studied thoroughly by everyone and hence this article presents a classical case of osteopetrosis with detailed description and discussion for the benefit of readers

  19. 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...

  20. Morphogenetic mechanisms of blood vessel fusion in the Zebrafish embryo

    OpenAIRE

    Herwig, Lukas Walter

    2012-01-01

    The formation of a vascular network requires the connection and formation of a lumen between individual endothelial sprouts, a process called vessel fusion or anastomosis. In the vertebrate trunk of the zebrafish (Danio rerio), the intersegmental vessels (ISVs) develop by angiogenesis, i.e. the formation of new vessels by pre-existing vessels, in a conserved metameric manner, which allows the analysis of morphogenetic mechanisms of blood vessel development. From the dorsal aorta (DA) individu...

  1. Classical tachyons

    International Nuclear Information System (INIS)

    A review of tachyons, with particular attention to their classical theory, is presented. The extension of Special Relativity to tachyons in two dimensional is first presented, an elegant model-theory which allows a better understanding also of ordinary physics. Then, the results are extended to the four-dimensional case (particular on tachyon mechanics) that can be derived without assuming the existence of Super-luminal reference-frames. Localizability and the unexpected apparent shape of tachyonic objects are discussed, and it is shown (on the basis of tachyon kinematics) how to solve the common causal paradoxes. In connection with General Relativity, particularly the problem of the apparent superluminal expansions in astrophysics is reviewed. The problem (still open) of the extension of relativitic theories to tachyons in four dimensions is tackled, and the electromagnetic theory of tachyons, a topic that can be relevant also for the experimental side, is reviewed. (Author)

  2. Autologous stem cell transplantation for patients aged 60 years or older with refractory or relapsed classical Hodgkin's lymphoma: a retrospective analysis from the French Society of Bone Marrow Transplantation and Cell Therapies (SFGM-TC).

    Science.gov (United States)

    Stamatoullas, A; Brice, P; Gueye, M S; Mareschal, S; Chevallier, P; Bouabdallah, R; Nguyenquoc, S; Francois, S; Turlure, P; Ceballos, P; Monjanel, H; Bourhis, J-H; Guillerm, G; Mohty, M; Biron, P; Cornillon, J; Belhadj, K; Bonmati, C; Dilhuydy, M-S; Huynh, A; Bernard, M; Chrétien, M-L; Peffault de Latour, R; Tilly, H

    2016-07-01

    This report retrospectively analyzed the outcome of 91 patients aged 60 years or older with refractory/relapsed (R/R) classical Hodgkin's lymphoma (cHL) who underwent autologous stem cell transplantation (ASCT) between 1992 and 2013 and were reported to the French Society of Bone Marrow Transplantation and Cell Therapies registry. The median age at transplant was 63 years. The majority of patients exhibited disease chemosensitivity to salvage treatment (57 complete responses, 30 partial responses, 1 progressive disease and 3 unknown). The most frequent conditioning regimen consisted of BCNU, cytarabine, etoposide, melphalan (BEAM) chemotherapy (93%). With a median follow-up of 54 months, 5-year estimates of overall survival (OS) and progression free survival (PFS) for the entire group were 67 and 54%, respectively. Despite the missing data, in univariate analysis, the number of salvage chemotherapy lines (1-2 versus ⩾3) significantly influenced the OS, unlike the other prognostic factors (stage III-IV at relapse, disease status before ASCT and negative positron emission tomography (PET) scan) encountered in younger patients. In spite of its limitations, this retrospective study with a long-term follow-up suggests that ASCT is a valid treatment option for chemosensitive R/R cHL in selected elderly patients, with an acceptable rate of toxicity.

  3. Concomitant Classic Hodgkin Lymphoma of Lymph Node and cMYC-Positive Burkitt Leukemia/Lymphoma of the Bone Marrow Presented Concurrently at the Time of Presentation: A Rare Combination of Discordant Lymphomas

    Science.gov (United States)

    Soliman, Dina S.; Fareed, Shehab; Alkuwari, Einas; El-Omri, Halima; Al-Sabbagh, Ahmad; Gameel, Amna; Yassin, Mohamed

    2016-01-01

    Discordant lymphoma is rare condition in which different types of malignant lymphomas occurring in different anatomic sites. The two diseases may present clinically as concurrent or sequential disease (10). Herein we are reporting a Pakistani female in her 60s, a carrier of hepatitis B virus with multiple comorbidities presented with cervical lymphadenopathy, diagnosed as Hodgkin’s lymphoma, mixed cellularity. During the staging workup, the patient was discovered to have extensive bone marrow (BM) involvement by Burkitt leukaemia/lymphoma (BL). Cytogenetic analysis revealed positivity for t(8;14)(q24;q32) confirmed by Fluorescence In Situ Hybridization (FISH) for IGH/MYC. Epstein-Barr virus (EBV) was demonstrated heavily in our case, with (EBV) DNA of 24,295,560 copies/ml by PCR at time of presentation, in addition, the neoplastic cells in both diagnostic tissues (cervical lymph node and BM) demonstrated positivity for EBV. A diagnosis of concomitant EBV related discordant lymphoma (classical Hodgkin lymphoma (cHL) and Burkitt lymphoma (BL) in leukemic phase was made. Among all reported cases, this case is highly exceptional because it is the first case of discordant/composite lymphoma, with this combination and concomitant presentation. Since we are dealing with a case with an exceptionally rare combination, we found it significant to elaborate more on its clinical features, contributing factors including EBV role, response to treatment, complications, and prognosis.

  4. 以钙磷骨水泥为载体重组人血管内皮细胞生长因子与重组人骨形态发生蛋白-2复合体对异体脱蛋白骨修复骨关节缺损的促进效应%Calcium phosphate cement attaching with recombinant human vascular endothelial growth factor and recombinant human bone morphogenetic protein-2 promotes deproteinized osteoarticular allograft to repair osteoarticular defect

    Institute of Scientific and Technical Information of China (English)

    瞿向阳; 蒋电明; 安洪

    2007-01-01

    8、12及16周A组血管内皮细胞生长因子和BMP-2的面积积分吸光度值明显高于B、C组,差异有统计学意义(P<0.01).③墨汁灌注微血管分析结果显示A组术后各期移植物内新生血管较多,部分趋向成熟,与B、C组比较均有统计学意义(P<0.01).④术后4周时各组手术侧膝关节较对侧血流量均增高,但A组显著增高,8周时进一步增高,12周时达到顶峰,16周时略有下降,但仍较B、C组高,差异有显著性意义(P<0.01).⑤A组三点抗弯曲应力,强于B、C组(P<0.01).结论:重组脱蛋白骨关节材料具有较强的再血管化和成骨能力,可早期与受体达到骨愈合修复骨关节缺损并最终成为自身组织.%BACKGROUND: Deproteinized bone has three diamensions frame profitting bone cells to adhere to, new capillaries and interstitial cells to enter, osteoblasts to differentiate and extracellular matrix to synthesize. Calcium phosphate cement (CPC) is a new in-ceramic bone cement that can degradate, which has plasticity, no heat production, invariably mechanics intension and porosity.OBJECTIVE: To explore the ability of CPC attaching with human vascular endothelial growth factor (rhVEGF) and recombinant human bone morphogenetic protein-2 (rhBMP-2) in promoting deproteinized osteoarticular allograft to repair osteoarticular defect.DESIGN: Randomly control observation.SETTING: Department of Orthopaedics, the First Affiliated Hospital, Chongqing Medical University.MATERIALS: A total of 42 adult hybridization dogs of both genders and weighing (10±0.5) kg were provided by Animal Center of Chongqing Medical University. RhVEGF was provided by Beijing Boaosen Biotechnology Co., Ltd.; rhBMP-2 by Guangzhou Dahui Biotechnology Co., Ltd.; CPC by Shanghai Ruibang Biotechnology Co., Ltd.METHODS: The experiment was carried out in the Laboratory of Orthopaedics (Municipal Laboratory), Clinical College,Chongqing Medical University from March to September 2006. A total of 36

  5. Bone tumor

    Science.gov (United States)

    Tumor - bone; Bone cancer; Primary bone tumor; Secondary bone tumor ... The cause of bone tumors is unknown. They often occur in areas of the bone that grow rapidly. Possible causes include: Genetic defects ...

  6. Bone cysts: unicameral and aneurysmal bone cyst.

    Science.gov (United States)

    Mascard, E; Gomez-Brouchet, A; Lambot, K

    2015-02-01

    Simple and aneurysmal bone cysts are benign lytic bone lesions, usually encountered in children and adolescents. Simple bone cyst is a cystic, fluid-filled lesion, which may be unicameral (UBC) or partially separated. UBC can involve all bones, but usually the long bone metaphysis and otherwise primarily the proximal humerus and proximal femur. The classic aneurysmal bone cyst (ABC) is an expansive and hemorrhagic tumor, usually showing characteristic translocation. About 30% of ABCs are secondary, without translocation; they occur in reaction to another, usually benign, bone lesion. ABCs are metaphyseal, excentric, bulging, fluid-filled and multicameral, and may develop in all bones of the skeleton. On MRI, the fluid level is evocative. It is mandatory to distinguish ABC from UBC, as prognosis and treatment are different. UBCs resolve spontaneously between adolescence and adulthood; the main concern is the risk of pathologic fracture. Treatment in non-threatening forms consists in intracystic injection of methylprednisolone. When there is a risk of fracture, especially of the femoral neck, surgery with curettage, filling with bone substitute or graft and osteosynthesis may be required. ABCs are potentially more aggressive, with a risk of bone destruction. Diagnosis must systematically be confirmed by biopsy, identifying soft-tissue parts, as telangiectatic sarcoma can mimic ABC. Intra-lesional sclerotherapy with alcohol is an effective treatment. In spinal ABC and in aggressive lesions with a risk of fracture, surgical treatment should be preferred, possibly after preoperative embolization. The risk of malignant transformation is very low, except in case of radiation therapy.

  7. The Effect of Heparan Sulfate Application on Bone Formation during Distraction Osteogenesis

    OpenAIRE

    Gdalevitch, Marie; Kasaai, Bahar; Alam, Norine; DOHIN, Bruno; Lauzier, Dominique; Hamdy, Reggie C.

    2013-01-01

    Bone morphogenetic proteins (BMPs) are recognized for their ability to induce bone formation in vivo and in vitro. Their osteogenic and osteoinductive properties are tightly regulated by the secretion of specific BMP antagonists, which have been shown to physically bind and sometimes be blocked by the extracellular proteoglycan heparan sulphate side chains (from hereon referred to as HS). The purpose of this study was to investigate if local application of 5 µg of HS proteoglycan to a bone re...

  8. Advanced BMP Gene Therapies for Temporal and Spatial Control of Bone Regeneration

    OpenAIRE

    Wilson, C.G.; Martín-Saavedra, F.M.; Vilaboa, N.; Franceschi, R.T.

    2013-01-01

    Spatial and temporal patterns of bone morphogenetic protein (BMP) signaling are crucial to the assembly of appropriately positioned and shaped bones of the face and head. This review advances the hypothesis that reconstitution of such patterns with cutting-edge gene therapies will transform the clinical management of craniofacial bone defects attributed to trauma, disease, or surgical resection. Gradients in BMP signaling within developing limbs and orofacial primordia regulate proliferation ...

  9. Anterior Lumbar Intervertebrai Fusion with Artificial Bone in Place of Autologous Bone

    Institute of Scientific and Technical Information of China (English)

    徐卫国; 陈安民; 冯旭; 印卫锋

    2003-01-01

    The feasibility of anterior lumbar intervertebral fusion with artificial bone in place of au-togenous bone was investigated. Porous hydroxyapatite(HA)/ZrO2 ceramics loading bone morpho-genetic protein (BMP) were implanted after removal of lumbar vertebral disc in rabbits. The adja-cent intervertebral discs were also removed by the same way and autogenous illic bone was implan-ted. SEM observation and biomechanical test were carried out. Compound bone had a bit lower os-teoinductive activity than autogenous bone by SEM(Osteoindutive activity of artificial bone in 12weeks was the same as that of autogenous bone in 9 weeks). Biomechanical test revealed that com-pound bone had lower anti-pull strength than autogenous bone (P<0. 001), but there was no sig-nificant difference in anti-pull strength between compound bone at 12th week and autogenous boneat 9th week (P>0.05). It was concluded that compound bone could be applied for anterior spinalfusion, especially for those patients who can't use autogenous bone.

  10. 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

  11. Morphogenetic and structural responses of tropical plants submitted to defoliation

    Directory of Open Access Journals (Sweden)

    Leandro Martins Barbero

    2016-01-01

    Full Text Available Leaf emergence and elongation and the structure they confer to the forage canopy are quantified based on morphogenetic and structural characteristics of the canopy. The emergence and balance of tillers is known as tillering. Both morphogenesis and tillering confer the production potential to the pasture. This process is influenced by the intensity and frequency of defoliation. Pastures exhibit phenotypic plasticity when submitted to intense and frequent grazing in order to adapt to this adverse environmental condition. Furthermore, factors such as plant age and fertilization influence the growth pattern. A population with a young age profile or a fertilized pasture has more accelerated rates of morphogenesis and requires adjustment in pasture management. In addition to these factors, the seasonal distribution pattern of rain, temperature and photoperiod leads to variations in the growth pattern of pastures over the year. When these conditions are favorable for plant growth, the rates of morphogenesis are accelerated and adjustments in management are necessary. Thus, pasture management differs between the rainy and dry seasons, mainly because of the different growth patterns during these periods. Indeed, several factors influence the growth of pasture plants; however, appropriate maintenance of the leaf area index (LAI of the pasture under continuous or intermittent stocking provides satisfactory results of pasture-based farming systems. Given the above, management targets considering morphogenetic parameters of the plant, in conjunction with the maintenance of an adequate LAI, show that continuously stocked pastures should be kept under optimal conditions for both plant growth and animal consumption. These conditions coincide with the maintenance heights of the forage canopy recommended for each species or cultivar. Similarly, under intermittent stocking, the optimal condition for pasture management, i.e., when regrowth should be interrupted

  12. Bone Biopsy

    Science.gov (United States)

    ... Physician Resources Professions Site Index A-Z Bone Biopsy Bone biopsy uses a needle and imaging guidance ... limitations of Bone Biopsy? What is a Bone Biopsy? A bone biopsy is an image-guided procedure ...

  13. Bone Diseases

    Science.gov (United States)

    ... avoid smoking and drinking too much alcohol. Bone diseases can make bones easy to break. Different kinds ... break Osteogenesis imperfecta makes your bones brittle Paget's disease of bone makes them weak Bones can also ...

  14. Morphogenetic responses ofPopulus alba L. under salt stress

    Institute of Scientific and Technical Information of China (English)

    Mejda Abassi; Khaled Mguis; Zoubeir Béjaoui; Ali Albouchi

    2014-01-01

    The morphogenetic responses to salt stress of TunisianPopu-lus alba clones were studied in order to promote their plantation in dam-aged saline areas. One year-old plants of threeP. alba clones (MA-104, MA-195 and OG) were subjected to progressive salt stress by irrigation during two consecutive years. The plants were grown in a nursery, inside plastic receptacles containing sandy soil and were irrigated with tap water (control) or 3-6 g/l NaCl solution. During this study, leaf epinasty, elongation rate, vigor, internode length, plant architecture, and number of buds were evaluated. Test clone response was highly dependent on the applied treatment and degree of accommodation.The most pronounced alterations were induced under 6g/l of NaCl treatment including leaf epinasty, leaf elongation rate delay, vigor decrease, internode length shortening, and morphogenetic modifications. These responses were less noticeable in the MA-104 clone with respect to the two other clones. The salt effect induced a delay in the leaf elongation rate on the MA-195 and OG clones leading to an early leaf maturity. The vigour and internode length of the MA-104 clone was less affected than the other clones. The OG clone was the most salt-sensitive thus, it developed shorter branches and more buds number than MA-195 and MA-104. The effect of long-term salt stress was to induce early flowering of theP. alba clones which suggests that mechanism of salt accommodation could be devel-oped.

  15. Effect of bone morphogenetic protein-7 (BMP-7 on in vitro survival of caprine preantral follicles Efeito da proteína morfogenética óssea 7 (BMP-7 para a sobrevivência in vitro de folículos pré-antrais caprinos

    Directory of Open Access Journals (Sweden)

    Valdevane R. Araújo

    2010-04-01

    Full Text Available This study was conducted in order to verify the effect of different concentrations of BMP-7 in the in vitro survival and development of caprine preantral follicles. Fragments of caprine ovarian cortical tissue were cultured for 1 or 7 days in Minimum Essential Medium (MEM+ supplemented with different concentrations of BMP-7 (1, 10, 50 or 100ng/ml. Non-cultured fragments or those cultured for 1 or 7 days were processed for classical histology and transmission electron microscopy (TEM. Parameters such as follicular survival, activation and growth were evaluated. The results showed that, after 1 or 7 days of culture, the percentage of morphologically normal follicles was significantly reduced in all treatments when compared with fresh control, except at 1ng/ml of BMP-7 for 1 day. In addition, the concentration of 10ng/ml of BMP-7 significantly increases follicular diameter from day 1 to 7 of culture. There was no influence of the other concentrations of BMP-7 regarding to the follicular and oocyte diameter. Ultrastructure studies confirmed follicular integrity after 7 days of culture in 1ng/ml BMP-7. In conclusion, small concentrations of BMP-7 can improve the survival and growth of caprine preantral follicles during in vitro culture.O presente trabalho foi conduzido de modo a se verificar o efeito de diferentes concentrações da BMP-7 no desenvolvimento in vitro de folículos pré-antrais caprinos. Fragmentos de tecido cortical ovariano caprino foram cultivados por 1 ou 7 dias em Minimum Essential Medium (MEM+ suplementado com diferentes concentrações de BMP-7 (1, 10, 50 ou 100ng/ml. Os fragmentos não cultivados ou aqueles cultivados por 1 ou 7 dias foram processados para histologia clássica e microscopia eletrônica de transmissão (TEM, sendo avaliados parâmetros morfológicos indicativos de viabilidade, ativação e crescimento. Os resultados mostraram que o percentual de folículos morfologicamente normais diminuiu significativamente em

  16. Classical competing risks

    CERN Document Server

    Crowder, Martin J

    2001-01-01

    If something can fail, it can often fail in one of several ways and sometimes in more than one way at a time. There is always some cause of failure, and almost always, more than one possible cause. In one sense, then, survival analysis is a lost cause. The methods of Competing Risks have often been neglected in the survival analysis literature. Written by a leading statistician, Classical Competing Risks thoroughly examines the probability framework and statistical analysis of data of Competing Risks. The author explores both the theory of the subject and the practicalities of fitting the models to data. In a coherent, self-contained, and sequential account, the treatment moves from the bare bones of the Competing Risks setup and the associated likelihood functions through survival analysis using hazard functions. It examines discrete failure times and the difficulties of identifiability, and concludes with an introduction to the counting-process approach and the associated martingale theory.With a dearth of ...

  17. Classicalization of Quantum Variables

    CERN Document Server

    Koide, T

    2014-01-01

    A systematic procedure to extract classical degrees of freedom in quantum mechanics is formulated using the stochastic variational method. With this classicalization, a hybrid model constructed from quantum and classical variables (quantum-classical hybrids) is derived systematically. In this procedure, conservation laws such as energy are maintained, and Eherefest`s theorem is still satisfied with modification. The criterion for the applicability of quantum-classical hybrids is also investigated.

  18. What classicality? Decoherence and Bohr's classical concepts

    CERN Document Server

    Schlosshauer, Maximilian

    2010-01-01

    Niels Bohr famously insisted on the indispensability of what he termed "classical concepts." In the context of the decoherence program, on the other hand, it has become fashionable to talk about the "dynamical emergence of classicality" from the quantum formalism alone. Does this mean that decoherence challenges Bohr's dictum and signifies a break with the Copenhagen interpretation-for example, that classical concepts do not need to be assumed but can be derived? In this paper we'll try to shine some light down the murky waters where formalism and philosophy cohabitate. To begin, we'll clarify the notion of classicality in the decoherence description. We'll then discuss Bohr's and Heisenberg's take on the quantum-classical problem and reflect on different meanings of the terms "classicality" and "classical concepts" in the writings of Bohr and his followers. This analysis will allow us to put forward some tentative suggestions for how we may better understand the relation between decoherence-induced classical...

  19. Playing with bone and fat

    DEFF Research Database (Denmark)

    Gimble, Jeffrey M.; Zvonic, Sanjin; Floyd, Z. Elisabeth;

    2006-01-01

    The relationship between bone and fat formation within the bone marrow microenvironment is complex and remains an area of active investigation. Classical in vitro and in vivo studies strongly support an inverse relationship between the commitment of bone marrow-derived mesenchymal stem cells or s...... or stromal cells to the adipocyte and osteoblast lineage pathways. In this review, we focus on the recent literature exploring the mechanisms underlying these differentiation events and discuss their implications relevant to osteoporosis and regenerative medicine....

  20. Bone cysts: unicameral and aneurysmal bone cyst.

    Science.gov (United States)

    Mascard, E; Gomez-Brouchet, A; Lambot, K

    2015-02-01

    Simple and aneurysmal bone cysts are benign lytic bone lesions, usually encountered in children and adolescents. Simple bone cyst is a cystic, fluid-filled lesion, which may be unicameral (UBC) or partially separated. UBC can involve all bones, but usually the long bone metaphysis and otherwise primarily the proximal humerus and proximal femur. The classic aneurysmal bone cyst (ABC) is an expansive and hemorrhagic tumor, usually showing characteristic translocation. About 30% of ABCs are secondary, without translocation; they occur in reaction to another, usually benign, bone lesion. ABCs are metaphyseal, excentric, bulging, fluid-filled and multicameral, and may develop in all bones of the skeleton. On MRI, the fluid level is evocative. It is mandatory to distinguish ABC from UBC, as prognosis and treatment are different. UBCs resolve spontaneously between adolescence and adulthood; the main concern is the risk of pathologic fracture. Treatment in non-threatening forms consists in intracystic injection of methylprednisolone. When there is a risk of fracture, especially of the femoral neck, surgery with curettage, filling with bone substitute or graft and osteosynthesis may be required. ABCs are potentially more aggressive, with a risk of bone destruction. Diagnosis must systematically be confirmed by biopsy, identifying soft-tissue parts, as telangiectatic sarcoma can mimic ABC. Intra-lesional sclerotherapy with alcohol is an effective treatment. In spinal ABC and in aggressive lesions with a risk of fracture, surgical treatment should be preferred, possibly after preoperative embolization. The risk of malignant transformation is very low, except in case of radiation therapy. PMID:25579825

  1. Bone Grafts

    Science.gov (United States)

    ... repair and rebuild diseased bones in your hips, knees, spine, and sometimes other bones and joints. Grafts can also repair bone loss caused by some types of fractures or cancers. Once your body accepts the bone ...

  2. Morphogenetic classification of coal seam washouts in Donbass mines

    Energy Technology Data Exchange (ETDEWEB)

    Shul' ga, V.F.; Vashchenko, V.I.

    1982-09-01

    The paper evaluates washout types in coal seams in Donbass mines. Five washout types are characterized: trough-shaped, V-shaped or U-shaped, lentil-shaped, consisting of groups of small lentils and discontinuous washouts which consist of a number of coal and rock partings. Each of the 5 washout types is shown in a scheme. The following aspects of coal seam washouts are discussed: dimensions, shape, angle of inclination of trough walls, washout dimensions in relation to coal seam thickness, rock types filling washout zones. Effects of seam washouts on longwall mining are analyzed. Morphogenetic characteristics of 5 washout groups are given. Investigations show that trough-shaped, U or V-shaped washouts are of epigenetic origin and lentil-shaped, discontinuous washouts consisting of a number of rock and coal partings and washouts with groups of rock lentils are of syngenetic origin. Washout classification is shown in a table. Classification is aimed at optimizing the mining system in washout zones. It considers washout dimensions, washout dimensions in relation to coal seam thickness and rock type filling the washout (sandstone, agrillite or aleurite). System for coding information on washouts is described.

  3. Morphological evidence for a morphogenetic field in gastropod mollusc eggs.

    Science.gov (United States)

    Tyler, S E; Butler, R D; Kimber, S J

    1998-01-01

    Eggs of the marine gastropod Crepidula fornicata examined by confocal imaging of FITC-lectin binding to the surface, and cryoscopic-SEM both reveal a surface architecture of linear structures organized around the animal-vegetal axis, which is spatially related to the anterior-posterior (a-p) axis of the subsequent embryo. A series of structures is also orientated with reference to specific micromere quartets formed during spiral cleavage. Thus, the surface architecture may provide a visible marker for a morphogenetic field which generates the a-p axis and organizes the cleavage pattern. Moreover, this architecture is co-extensive with that found on the vegetal, polar lobe-bearing region of eggs, as described by others, and which varies between gastropod taxa with varied types of body form. Confocal imaging reveals a distinct localization of F-actin to the architecture of the lobe region. However, the integrity of this F-actin is not responsible for the maintenance of the surface architecture. The significance of these findings to our understanding of the generation of diversity within the Gastropoda and general ontogenic mechanisms is discussed.

  4. Lineage and morphogenetic analysis of the cardiac valves.

    Science.gov (United States)

    de Lange, Frederik J; Moorman, Antoon F M; Anderson, Robert H; Männer, Jörg; Soufan, Alexandre T; de Gier-de Vries, Corrie; Schneider, Michael D; Webb, Sandra; van den Hoff, Maurice J B; Christoffels, Vincent M

    2004-09-17

    We used a genetic lineage-labeling system to establish the material contributions of the progeny of 3 specific cell types to the cardiac valves. Thus, we labeled irreversibly the myocardial (alphaMHC-Cre+), endocardial (Tie2-Cre+), and neural crest (Wnt1-Cre+) cells during development and assessed their eventual contribution to the definitive valvar complexes. The leaflets and tendinous cords of the mitral and tricuspid valves, the atrioventricular fibrous continuity, and the leaflets of the outflow tract valves were all found to be generated from mesenchyme derived from the endocardium, with no substantial contribution from cells of the myocardial and neural crest lineages. Analysis of chicken-quail chimeras revealed absence of any substantial contribution from proepicardially derived cells. Molecular and morphogenetic analysis revealed several new aspects of atrioventricular valvar formation. Marked similarities are seen during the formation of the mural leaflets of the mitral and tricuspid valves. These leaflets form by protrusion and growth of a sheet of atrioventricular myocardium into the ventricular lumen, with subsequent formation of valvar mesenchyme on its surface rather than by delamination of lateral cushions from the ventricular myocardial wall. The myocardial layer is subsequently removed by the process of apoptosis. In contrast, the aortic leaflet of the mitral valve, the septal leaflet of the tricuspid valve, and the atrioventricular fibrous continuity between these valves develop from the mesenchyme of the inferior and superior atrioventricular cushions. The tricuspid septal leaflet then delaminates from the muscular ventricular septum late in development. PMID:15297379

  5. Bone within a bone

    Energy Technology Data Exchange (ETDEWEB)

    Williams, H.J.; Davies, A.M. E-mail: wendy.turner@roh.nhs.uk; Chapman, S

    2004-02-01

    The 'bone within a bone' appearance is a well-recognized radiological term with a variety of causes. It is important to recognize this appearance and also to be aware of the differential diagnosis. A number of common conditions infrequently cause this appearance. Other causes are rare and some remain primarily of historical interest, as they are no longer encountered in clinical practice. In this review we illustrate some of the conditions that can give the bone within a bone appearance and discuss the physiological and pathological aetiology of each where known.

  6. In anemia of multiple myeloma hepcidin is induced by increased bone-morphogenetic protein-2

    Science.gov (United States)

    Hepcidin is the principal iron-regulatory hormone and pathogenic factor in anemia of inflammation. Patients with multiple myeloma (MM) frequently present with anemia. We showed that MM patients had increased serum hepcidin, which inversely correlated with hemoglobin, suggesting that hepcidin contrib...

  7. Bone morphogenetic protein activity and connective tissue growth factor in renal and vascular disease

    NARCIS (Netherlands)

    Leeuwis, J.W.

    2011-01-01

    Response to renal injury is dependent on growth factors that determine how resident cells act, which cells are attracted to the site of injury, and how these resident cells, together with infiltrating cells and their surrounding matrix act together. These mechanisms are not confined to the kidney an

  8. Bone morphogenetic proteins in inflammation, glucose homeostasis and adipose tissue energy metabolism

    DEFF Research Database (Denmark)

    Grgurevic, Lovorka; Christensen, Gitte Lund; Schulz, Tim J;

    2016-01-01

    implicated in pancreas development as well as control of adult glucose homeostasis. Lastly, we review the recently recognized role of BMPs in brown adipose tissue formation and their consequences for energy expenditure and adiposity. In summary, BMPs play a pivotal role in metabolism beyond their role...... homeostasis (anaemia, hemochromatosis) and oxidative damage. The second and third parts of this review focus on BMPs in the development of metabolic pathologies such as type-2 diabetes mellitus and obesity. The pancreatic beta cells are the sole source of the hormone insulin and BMPs have recently been...... in skeletal homeostasis. However, increased understanding of these pleiotropic functions also highlights the necessity of tissue-specific strategies when harnessing BMP action as a therapeutic target....

  9. Connective tissue growth factor and bone morphogenetic proteins in diabetic nephropathy

    NARCIS (Netherlands)

    Nguyen, T.Q.

    2008-01-01

    Diabetes mellitus is a severe and rapidly growing problem in health care, accounting for approximately 150 million patients worldwide. Patients with diabetes are at increased risk to develop diabetic nephropathy, which is currently the most important cause of end-stage renal disease in large parts o

  10. Signaling by bone morphogenetic proteins directs formation of an ectodermal signaling center that regulates craniofacial development.

    Science.gov (United States)

    Foppiano, Silvia; Hu, Diane; Marcucio, Ralph S

    2007-12-01

    We previously described a signaling center, the Frontonasal Ectodermal Zone (FEZ) that regulates growth and patterning of the frontonasal process (FNP). The FEZ is comprised of FNP ectoderm flanking a boundary between Sonic hedgehog (Shh) and Fibroblast growth factor 8 (Fgf8) expression domains. Our objective was to examine BMP signaling during formation of the FEZ. We blocked BMP signaling throughout the FNP prior to FEZ formation by infecting chick embryos at stage 10 (HH10) with a replication-competent avian retrovirus encoding the BMP antagonist Noggin. We assessed gene expression patterns in the FNP 72 h after infection (approximately HH22) and observed that Shh expression was reduced or absent. In the mesenchyme, we observed that Bmp2 transcripts were absent while the Bmp4 expression domain was expanded proximally. In addition to the molecular changes, infected embryos also exhibited facial malformations at 72 and 96 h after infection suggesting that the FEZ did not form. Our data indicate that reduced cell proliferation, but not apoptosis, in the mesenchyme contributed to the phenotype that we observed. Additionally, adding exogenous SHH into the mesenchyme of RCAS-Noggin-infected embryos did not restore Bmp2 and Bmp4 to a normal pattern of expression. These data indicate that BMP signaling mediates interactions between tissues in the FNP that regulate FEZ formation; and that the correct pattern of Bmp2 and Bmp4, but not Bmp7, expression in the FNP mesenchyme requires signaling by the BMP pathway.

  11. Strategies to Target the Bone Morphogenetic Protein Signalling Pathway in Lung Disease

    OpenAIRE

    Purcell, James

    2011-01-01

    Lung disease and lung injury are responsible for 20% of deaths of the Irish population every year, and the country has the 2nd highest death rate in Europe for respiratory diseases. Conditions related to the respiratory system are the second largest long term illness by young adults. Lung cancer is the largest cause of cancer related death in Europe as a whole. New and refined mechanisms of drug delivery for the prevention, cure or delayed progression of disease, represents a pathway for t...

  12. rBMP Represses Wnt Signaling and Influences Skeletal Progenitor Cell Fate Specification During Bone Repair

    OpenAIRE

    Minear, Steve; Leucht, Philipp; Miller, Samara; Helms, Jill A.

    2010-01-01

    Bone morphogenetic proteins (BMPs) participate in multiple stages of the fetal skeletogenic program from promoting cell condensation to regulating chondrogenesis and bone formation through endochondral ossification. Here, we show that these pleiotropic functions are recapitulated when recombinant BMPs are used to augment skeletal tissue repair. In addition to their well-documented ability to stimulate chondrogenesis in a skeletal injury, we show that recombinant BMPs (rBMPs) simultaneously su...

  13. An Investigation of Coral Based Bioactive Composite Bone in a Critical-sized Cranial Defects

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    1 IntroductionNatural coral is a porous three-dimensional biocompatible material with osteo-conductivity~([1]). Recombinant human bone morphogenetic protein-2 (rhBMP-2) is a member of TGF-β family possessing strong osteoinductive properties~([2]). Collagen has been demonstrated efficacy in sustained releasing growth factor due to gradually absorption of collagen matrix~([3]). And bone marrow derived mesenchymal stem cells (BMSCs) have been chosen as seed cells owing to the capacity of differentiating into o...

  14. Quantum computing classical physics.

    Science.gov (United States)

    Meyer, David A

    2002-03-15

    In the past decade, quantum algorithms have been found which outperform the best classical solutions known for certain classical problems as well as the best classical methods known for simulation of certain quantum systems. This suggests that they may also speed up the simulation of some classical systems. I describe one class of discrete quantum algorithms which do so--quantum lattice-gas automata--and show how to implement them efficiently on standard quantum computers.

  15. Novel osteoinductive photo-cross-linkable chitosan-lactide-fibrinogen hydrogels enhance bone regeneration in critical size segmental bone defects

    OpenAIRE

    Kim, Sungwoo; Bedigrew, Katherine; Guda, Teja; Maloney, William J.; Park, Sangwon; Wenke, Joseph C.; Yang, Yunzhi Peter

    2014-01-01

    The purpose of this study was to develop and characterize a novel photo-cross-linkable chitosan-lactide-fibrinogen (CLF) hydrogel and evaluate the efficacy of bone morphogenetic protein-2 (BMP-2) containing CLF hydrogel for osteogenesis in vitro and in vivo. We synthesized the CLF hydrogels and characterized their chemical structure, degradation rate, compressive modulus, and in vitro BMP-2 release kinetics. We evaluated bioactivities of the BMP-2 containing CLF hydrogels (0, 50, 100, and 500...

  16. Molecular mechanisms of bone formation in spondyloarthritis.

    Science.gov (United States)

    González-Chávez, Susana Aideé; Quiñonez-Flores, Celia María; Pacheco-Tena, César

    2016-07-01

    Spondyloarthritis comprise a group of inflammatory rheumatic diseases characterized by its association to HLA-B27 and the presence of arthritis and enthesitis. The pathogenesis involves both an inflammatory process and new bone formation, which eventually lead to ankylosis of the spine. To date, the intrinsic mechanisms of the pathogenic process have not been fully elucidated, and our progress is remarkable in the identification of therapeutic targets to achieve the control of the inflammatory process, yet our ability to inhibit the excessive bone formation is still insufficient. The study of new bone formation in spondyloarthritis has been mostly conducted in animal models of the disease and only few experiments have been done using human biopsies. The deregulation and overexpression of molecules involved in the osteogenesis process have been observed in bone cells, mesenchymal cells, and fibroblasts. The signaling associated to the excessive bone formation is congruent with those involved in the physiological processes of bone remodeling. Bone morphogenetic proteins and Wnt pathways have been found deregulated in this disease; however, the cause for uncontrolled stimulation remains unknown. Mechanical stress appears to play an important role in the pathological osteogenesis process; nevertheless, the association of other important factors, such as the presence of HLA-B27 and environmental factors, remains uncertain. The present review summarizes the experimental findings that describe the signaling pathways involved in the new bone formation process in spondyloarthritis in animal models and in human biopsies. The role of mechanical stress as the trigger of these pathways is also reviewed. PMID:26838262

  17. Entanglement in Classical Optics

    CERN Document Server

    Ghose, Partha

    2013-01-01

    The emerging field of entanglement or nonseparability in classical optics is reviewed, and its similarities with and differences from quantum entanglement clearly pointed out through a recapitulation of Hilbert spaces in general, the special restrictions on Hilbert spaces imposed in quantum mechanics and the role of Hilbert spaces in classical polarization optics. The production of Bell-like states in classical polarization optics is discussed, and new theorems are proved to discriminate between separable and nonseparable states in classical wave optics where no discreteness is involved. The influence of the Pancharatnam phase on a classical Bell-like state is deived. Finally, to what extent classical polarization optics can be used to simulate quantum information processing tasks is also discussed. This should be of great practical importance because coherence and entanglement are robust in classical optics but not in quantum systems.

  18. Developmental Design of Synthetic Bacterial Architectures by Morphogenetic Engineering.

    Science.gov (United States)

    Pascalie, Jonathan; Potier, Martin; Kowaliw, Taras; Giavitto, Jean-Louis; Michel, Olivier; Spicher, Antoine; Doursat, René

    2016-08-19

    (divergence of the homology). Such morphogenetic phenotypes open the way to more complex shapes made of a recursive array of core bodies and limbs and, most importantly, to an evolutionary developmental exploration of unplanned functional forms. PMID:27244532

  19. The rebirth of the morphogenetic field as an explanatory tool in biology

    Directory of Open Access Journals (Sweden)

    Perović Slobodan

    2013-01-01

    Full Text Available I discuss two uses of the concept of the morphogenetic field, a tool of the 19th century biology motivated by particular ontological views of the time, which has been re-emerging and increasingly relevant in explaining microbiological phenomena. I also consider the relation of these uses to the Central Dogma of modern biology as well as Modern Synthesis of Darwinism and genetics. An induced morphogenetic field is determined by a physical (e.g., gravitational field, or it acquires a physical (e.g., visco-elastic field’s characteristics. Such a morphogenetic field presents only a weak challenge to the Central Dogma of Modern Synthesis by indirectly, albeit severely, constraining variability at the molecular level. I discuss explanations that introduce structural inheritance in ciliate protozoa, as well as the experimental evidence on which these arguments are based. The global cellular morphogenetic field is a unit of such inheritance. I discuss relevant cases of structural inheritance in ciliates that bring about internal cellular as well as functional changes and point out that DNA is absent in the cortex and that RNA controls neither intermediary nor the global level of the field. I go on to argue that utilizing knowledge of known physical fields may advance explanations and understanding of the morphogenetic field in ciliates as the unit of both development and inheritance. [Projekat Ministarstva nauke Republike Srbije, br. 179041: Dynamic Systems in nature and society: Philosophical and empirical aspects

  20. 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.

  1. Phylogeny of subclass Scuticociliatia (Protozoa, Ciliophora) using combined data inferred from genetic, morphological, and morphogenetic evidence

    Science.gov (United States)

    Yi, Zhenzhen; Wang, Yangang; Lin, Xiaofeng; Al-Rasheid, Khaled A. S.; Song, Weibo

    2010-07-01

    Gene sequence-based genealogies of scuticociliates are different from those produced by morphological analyses. For this reason, 11 representative scuticociliates and two ambiguously related genera were chosen to test the ability of combined phylogenetic analyses using both gene sequences and morphological/morphogenetic characteristics. Analyses of both the SSrRNA gene sequences and the combined datasets revealed a consistent branching pattern. While the terminal branches and the order level relationships were generally well resolved, the family level relationships remain unresolved. However, two other trees based on ITS1-5.8S-ITS2 region sequences and morphological/morphogenetic characters showed limited information, due to a lack of informative sites in these two datasets. Our data suggest, however, that the combined analysis of morphological/morphogenetic characters and gene sequences did produce some changes to the phylogenetic estimates of this group.

  2. Entanglement in Classical Optics

    OpenAIRE

    Ghose, Partha; Mukherjee, Anirban

    2013-01-01

    The emerging field of entanglement or nonseparability in classical optics is reviewed, and its similarities with and differences from quantum entanglement clearly pointed out through a recapitulation of Hilbert spaces in general, the special restrictions on Hilbert spaces imposed in quantum mechanics and the role of Hilbert spaces in classical polarization optics. The production of Bell-like states in classical polarization optics is discussed, and new theorems are proved to discriminate betw...

  3. Bidirectional coherent classical communication

    OpenAIRE

    Harrow, Aram W.; Leung, Debbie W.

    2005-01-01

    A unitary interaction coupling two parties enables quantum or classical communication in both the forward and backward directions. Each communication capacity can be thought of as a tradeoff between the achievable rates of specific types of forward and backward communication. Our first result shows that for any bipartite unitary gate, bidirectional coherent classical communication is no more difficult than bidirectional classical communication — they have the same achievable rate regions. ...

  4. Classical, Semi-classical and Quantum Noise

    CERN Document Server

    Poor, H; Scully, Marlan

    2012-01-01

    David Middleton was a towering figure of 20th Century engineering and science and one of the founders of statistical communication theory. During the second World War, the young David Middleton, working with Van Fleck, devised the notion of the matched filter, which is the most basic method used for detecting signals in noise. Over the intervening six decades, the contributions of Middleton have become classics. This collection of essays by leading scientists, engineers and colleagues of David are in his honor and reflect the wide  influence that he has had on many fields. Also included is the introduction by Middleton to his forthcoming book, which gives a wonderful view of the field of communication, its history and his own views on the field that he developed over the past 60 years. Focusing on classical noise modeling and applications, Classical, Semi-Classical and Quantum Noise includes coverage of statistical communication theory, non-stationary noise, molecular footprints, noise suppression, Quantum e...

  5. Teleportation via classical entanglement

    CERN Document Server

    Rafsanjani, Seyed Mohammad Hashemi; Magaña-Loaiza, Omar S; Boyd, Robert W

    2015-01-01

    We present a classical counterpart to quantum teleportation that uses classical entanglement instead of quantum entanglement. In our implementation we take advantage of classical entanglement among three parties: orbital angular momentum (OAM), polarization, and the radial degrees of freedom of a beam of light. We demonstrate the teleportation of arbitrary OAM states, in the subspace spanned by any two OAM states, to the polarization of the same beam. Our letter presents the first classical demonstration of a commonly-perceived--quantum phenomenon that requires entanglement among more than two parties.

  6. Effects of Cadmium on BMP Induced Bone Formation

    Institute of Scientific and Technical Information of China (English)

    陈秋生; 徐顺清

    2003-01-01

    To demonstrate the direct effects of cadmium on activities of bone morphogenetic protein (BMP), a complex containing BMP and cadmium chloride (CdCl2) was implanted beneath the abdominal skin of young male Wistar rats. The activity of BMP was studied by observing the histological changes, and measuring the activity of alkaline phosphatase (ALP) and acid phosphatase (ACP) and calcium content of the implants at different time points. Our results showed that during bone formation induced by BMP, cadmium inhibited the activities of osteoblasts and osteoclasts, and slowed the deposition of calcium. It is concluded that cadmium can directly affect biological activities of BMP directly.

  7. 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.

  8. 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.

  9. 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.

  10. Lectures on Classical Integrability

    CERN Document Server

    Torrielli, Alessandro

    2016-01-01

    We review some essential aspects of classically integrable systems. The detailed outline of the lectures consists of: 1. Introduction and motivation, with historical remarks; 2. Liouville theorem and action-angle variables, with examples (harmonic oscillator, Kepler problem); 3. Algebraic tools: Lax pairs, monodromy and transfer matrices, classical r-matrices and exchange relations, non-ultralocal Poisson brackets, with examples (non-linear Schroedinger model, principal chiral field); 4. Features of classical r-matrices: Belavin-Drinfeld theorems, analyticity properties, and lift of the classical structures to quantum groups; 5. Classical inverse scattering method to solve integrable differential equations: soliton solutions, spectral properties and the Gel'fand-Levitan-Marchenko equation, with examples (KdV equation, Sine-Gordon model). Prepared for the Durham Young Researchers Integrability School, organised by the GATIS network. This is part of a collection of lecture notes.

  11. SWALLOWED FISH BONES IN MALI

    Directory of Open Access Journals (Sweden)

    Sacko HB

    2015-07-01

    Full Text Available Objective: To study the different aspects, clinical, diagnostic and therapeutic of 114 cases of fish bones in the upper digestive tract . Methods: One hundred fourteen patients with fish bones suspected in the upper digestive tract were admitted in our department between February 2010 and October 2012. Results: There was a predominance of the male: 66 men (58%. The average age of the patients was 26 years with extremes 3 to 62 years old. The tongue base and vallecula are constituted the principals locations 66.66%. In the majority of the cases the fish bones were removed by direct pharyngoscopy in 43.86 %. We have not notified any serious complications. Conclusion: Therefore this study shows the foreign fish bones are frequently just as well in children as adult. The fish bones are particularly lodged in tongue base. The classical methods of extraction are permit to remove the all foreign fish bones.

  12. Cleavage of proBDNF to BDNF by a tolloid-like metalloproteinase is required for acquisition of in vitro eyeblink classical conditioning.

    Science.gov (United States)

    Keifer, Joyce; Sabirzhanov, Boris E; Zheng, Zhaoqing; Li, Wei; Clark, Timothy G

    2009-11-25

    The tolloid/bone morphogenetic protein-1 family of metalloproteinases have an important role in the regulation of embryonic pattern formation and tissue morphogenesis. Studies suggest that they participate in mechanisms of synaptic plasticity in adults, but very little is known about their function. Recently, we isolated a reptilian ortholog of the tolloid gene family designated turtle tolloid-like gene (tTll). Here, we examined the role of tTLL in an in vitro model of eyeblink classical conditioning using an isolated brainstem preparation to assess its role in synaptic plasticity during conditioning. Analysis by real-time reverse transcription-PCR shows that an extracellularly secreted form of tTLL, tTLLs, is transiently expressed in the early stages of conditioning during conditioned response acquisition, whereas a cytosolic form, tTLLc, is not. Short interfering RNA (siRNA)-directed gene knockdown and rescue of tTLL expression demonstrate that it is required for conditioning. Significantly, we show that tTLLs cleaves the precursor proBDNF into mature BDNF in cleavage assay studies, and application of recombinant tTLLs protein alone to preparations results in induction of mature BDNF expression. The mature form of BDNF is minimally expressed in preparations treated with anti-tTLL siRNA, and the synaptic incorporation of both GluR1- and GluR4-containing AMPA receptors is significantly reduced, resulting in suppression of conditioning. This is the first study to demonstrate that expression of an extracellularly secreted tolloid-like metalloproteinase is regulated in the early stages of classical conditioning and functions in the conversion of proBDNF to mature BDNF. The mature form of BDNF is required for synaptic delivery of AMPA receptors and acquisition of conditioned responses.

  13. 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

  14. Davidson and classical pragmatism

    Directory of Open Access Journals (Sweden)

    Paula Rossi

    2007-06-01

    Full Text Available In this paper I wish to trace some connections between Donald Davidson's work (1917-2003 and two major representatives of the classical pragmatist movement: Charles S. Peirce (1839-1914 and William James (1842-1910. I will start with a basic characterization of classical pragmatism; then, I shall examine certain conceptions in Peirce's and James' pragmatism, in order to establish affinities with Davidson´s thought. Finally, and bearing in mind the previous con-nections, I will reflect briefly on the relevance –often unrecognized- of classical pragmatist ideas in the context of contemporary philosophi-cal discussions.

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

    OpenAIRE

    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, ...

  16. Platelet-rich fibrin-induced bone marrow mesenchymal stem cell differentiation into osteoblast-like cells and neural cells

    Institute of Scientific and Technical Information of China (English)

    Qi Li; Yajun Geng; Lei Lu; Tingting Yang; Mingrui Zhang; Yanmin Zhou

    2011-01-01

    Bone marrow mesenchymal stem cells were allowed to develop for 14 days in a platelet-rich fibrin environment. Results demonstrated that platelet-rich fibrin significantly promoted bone marrow mesenchymal stem cell proliferation. In addition, there was a dose-dependent increase in Runt-related transcription factor-2 and bone morphogenetic protein-2 mRNA expression, as well as neuron-specific enolase and glial acidic protein. Results showed that platelet-rich fibrin promoted bone marrow mesenchymal stem cell proliferation and differentiation of osteoblastlike cells and neural cells in a dose-dependent manner.

  17. 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.

  18. 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

  19. [Ectopic bone induction by human fetal enamel proteins].

    Science.gov (United States)

    Wang, W

    1993-11-01

    Mixture of amelogenin, enamelin and soluble dentin proteins with plaster of Paris and distilled water were implanted in the left thigh-muscle pouch of C57BL/6 T mice, and PLP or BSA/PLP were implanted in the contralateral limbs for controls. The hind limbs were examined by means of microradiographic and histological methods three weeks after the implantation. Implants of PLP, BSA/PLP or E/PLP did not evoke formation of new cartilage or bone. Roentgenography showed highly mineralized tissues in the implantation areas of A/PLP or D/PLP, histological examination confirmed this as induced new bone or cartilage formation. Thus it indicates that amelogenins and soluble dentin proteins have bone induction activity as bone morphogenetic protein, they could induce the differentiation of mesenchymal cell in the muscles into chondrocyte and osteocyte. PMID:8033649

  20. Study on Z-H/BMP Toughened Compound Artificial Bone and Its Osteogenesis

    Institute of Scientific and Technical Information of China (English)

    XU Wei-guo; CHEN An-min; SUN Shu-zhen

    2003-01-01

    The purpose of this study was to find a kind of new artificial bone for anterior spinal fusion.ZrO2 stabilized by Y2O3 ( Y- PSZ), porous hydroxyapatite ( HA ) and bone morphogenetic protein (BMP) were used to make artificial compound bone ( Y2O3 ) ZrO2 -HA/ BMP( Z-H/ BMP ) , whose function was tested, microstructure and mineralogic composition constitution were analysised by SEM and XRD , and the corresponding animal tests were porformed. Osteogenesis of the material was observed by eyes, histology and SEM. Experimental results show that the component and ossific activity of Z-H/BMP were satisfactory.

  1. On Noncommutative Classical Mechanics

    CERN Document Server

    Djemai, A E F

    2003-01-01

    In this work, I investigate the noncommutative Poisson algebra of classical observables corresponding to a proposed general Noncommutative Quantum Mechanics, \\cite{1}. I treat some classical systems with various potentials and some Physical interpretations are given concerning the presence of noncommutativity at large scales (Celeste Mechanics) directly tied to the one present at small scales (Quantum Mechanics) and its possible relation with UV/IR mixing.

  2. Davidson and classical pragmatism

    OpenAIRE

    Paula Rossi

    2007-01-01

    In this paper I wish to trace some connections between Donald Davidson's work (1917-2003) and two major representatives of the classical pragmatist movement: Charles S. Peirce (1839-1914) and William James (1842-1910). I will start with a basic characterization of classical pragmatism; then, I shall examine certain conceptions in Peirce's and James' pragmatism, in order to establish affinities with Davidson´s thought. Finally, and bearing in mind the previous con-nections, I will reflect brie...

  3. Bone Densitometry (Bone Density Scan)

    Science.gov (United States)

    ... of DXA Bone Densitometry? What is a Bone Density Scan (DXA)? Bone density scanning, also called dual-energy x-ray absorptiometry ( ... is today's established standard for measuring bone mineral density (BMD). An x-ray (radiograph) is a noninvasive ...

  4. Combination of calcium sulfate and simvastatin-controlled release microspheres enhances bone repair in critical-sized rat calvarial bone defects.

    Science.gov (United States)

    Fu, Yin-Chih; Wang, Yan-Hsiung; Chen, Chung-Hwan; Wang, Chih-Kuang; Wang, Gwo-Jaw; Ho, Mei-Ling

    2015-01-01

    Most allogenic bone graft substitutes have only osteoconductive properties. Developing new strategies to improve the osteoinductive activity of bone graft substitutes is both critical and practical for clinical application. Previously, we developed novel simvastatin-encapsulating poly(lactic-co-glycolic acid) microspheres (SIM/PLGA) that slowly release simvastatin and enhance fracture healing. In this study, we combined SIM/PLGA with a rapidly absorbable calcium sulfate (CS) bone substitute and studied the effect on bone healing in critical-sized calvarial bone defects in a rat model. The cytotoxicity and cytocompatibility of this combination was tested in vitro using lactate dehydrogenase leakage and a cell attachment assay, respectively. Combination treatment with SIM/PLGA and the CS bone substitute had no cytotoxic effect on bone marrow stem cells. Compared with the control, cell adhesion was substantially enhanced following combination treatment with SIM/PLGA and the CS bone substitute. In vivo, implantation of the combination bone substitute promoted healing of critical-sized calvarial bone defects in rats; furthermore, production of bone morphogenetic protein-2 and neovascularization were enhanced in the area of the defect. In summary, the combination of SIM/PLGA and a CS bone substitute has osteoconductive and osteoinductive properties, indicating that it could be used for regeneration of bone in the clinical setting. PMID:26664114

  5. Low Bone Density

    Science.gov (United States)

    ... Density Exam/Testing › Low Bone Density Low Bone Density Low bone density is when your bone density ... people with normal bone density. Detecting Low Bone Density A bone density test will determine whether you ...

  6. In vivo bone regeneration using a novel porous bioactive composite

    Energy Technology Data Exchange (ETDEWEB)

    Xie En [Department of Orthopaedics and Traumatology, Xijing Hospital, Fourth Military Medical University, Xi' an (China); Hu Yunyu [Department of Orthopaedics and Traumatology, Xijing Hospital, Fourth Military Medical University, Xi' an (China)], E-mail: orth1@fmmn.edu.cn; Chen Xiaofeng [College of Materials Science and Engineering, South China University of Technology University, Guangzhou (China); Bai Xuedong; Li Dan [Department of Orthopaedics and Traumatology, Xijing Hospital, Fourth Military Medical University, Xi' an (China); Ren Li [College of Materials Science and Engineering, South China University of Technology University, Guangzhou (China); Zhang Ziru [Foreign Languages School, Northwest University Xi' an (China)

    2008-11-15

    Many commercial bone graft substitutes (BGS) and experimental bone tissue engineering scaffolds have been developed for bone repair and regeneration. This study reports the in vivo bone regeneration using a newly developed porous bioactive and resorbable composite that is composed of bioactive glass (BG), collagen (COL), hyaluronic acid (HYA) and phosphatidylserine (PS), BG-COL-HYA-PS. The composite was prepared by a combination of sol-gel and freeze-drying methods. A rabbit radius defect model was used to evaluate bone regeneration at time points of 2, 4 and 8 weeks. Techniques including radiography, histology, and micro-CT were applied to characterize the new bone formation. 8 weeks results showed that (1) nearly complete bone regeneration was achieved for the BG-COL-HYA-PS composite that was combined with a bovine bone morphogenetic protein (BMP); (2) partial bone regeneration was achieved for the BG-COL-HYA-PS composites alone; and (3) control remained empty. This study demonstrated that the novel BG-COL-HYA-PS, with or without the grafting of BMP incorporation, is a promising BGS or a tissue engineering scaffold for non-load bearing orthopaedic applications.

  7. Classically-Controlled Quantum Computation

    OpenAIRE

    Perdrix, Simon; Jorrand, Philippe

    2004-01-01

    Quantum computations usually take place under the control of the classical world. We introduce a Classically-controlled Quantum Turing Machine (CQTM) which is a Turing Machine (TM) with a quantum tape for acting on quantum data, and a classical transition function for a formalized classical control. In CQTM, unitary transformations and measurements are allowed. We show that any classical TM is simulated by a CQTM without loss of efficiency. The gap between classical and quantum computations, ...

  8. Elementary classical hydrodynamics

    CERN Document Server

    Chirgwin, B H; Langford, W J; Maxwell, E A; Plumpton, C

    1967-01-01

    Elementary Classical Hydrodynamics deals with the fundamental principles of elementary classical hydrodynamics, with emphasis on the mechanics of inviscid fluids. Topics covered by this book include direct use of the equations of hydrodynamics, potential flows, two-dimensional fluid motion, waves in liquids, and compressible flows. Some general theorems such as Bernoulli's equation are also considered. This book is comprised of six chapters and begins by introducing the reader to the fundamental principles of fluid hydrodynamics, with emphasis on ways of studying the motion of a fluid. Basic c

  9. Classical mechanics with Maxima

    CERN Document Server

    Timberlake, Todd Keene

    2016-01-01

    This book guides undergraduate students in the use of Maxima—a computer algebra system—in solving problems in classical mechanics. It functions well as a supplement to a typical classical mechanics textbook. When it comes to problems that are too difficult to solve by hand, computer algebra systems that can perform symbolic mathematical manipulations are a valuable tool. Maxima is particularly attractive in that it is open-source, multiple-platform software that students can download and install free of charge. Lessons learned and capabilities developed using Maxima are easily transferred to other, proprietary software.

  10. Classical Holographic Codes

    CERN Document Server

    Brehm, Enrico M

    2016-01-01

    In this work, we introduce classical holographic codes. These can be understood as concatenated probabilistic codes and can be represented as networks uniformly covering hyperbolic space. In particular, classical holographic codes can be interpreted as maps from bulk degrees of freedom to boundary degrees of freedom. Interestingly, they are shown to exhibit features similar to those expected from the AdS/CFT correspondence. Among these are a version of the Ryu-Takayanagi formula and intriguing properties regarding bulk reconstruction and boundary representations of bulk operations. We discuss the relation of our findings with expectations from AdS/CFT and, in particular, with recent results from quantum error correction.

  11. Classic Problems of Probability

    CERN Document Server

    Gorroochurn, Prakash

    2012-01-01

    "A great book, one that I will certainly add to my personal library."—Paul J. Nahin, Professor Emeritus of Electrical Engineering, University of New Hampshire Classic Problems of Probability presents a lively account of the most intriguing aspects of statistics. The book features a large collection of more than thirty classic probability problems which have been carefully selected for their interesting history, the way they have shaped the field, and their counterintuitive nature. From Cardano's 1564 Games of Chance to Jacob Bernoulli's 1713 Golden Theorem to Parrondo's 1996 Perplexin

  12. Learning Classical Music Club

    CERN Multimedia

    Learning Classical Music Club

    2010-01-01

    There is a new CERN Club called “Learning Classical Music at CERN”. We are aiming to give classical music lessons for different instruments (see link) for students from 5 to 100 years old. We are now ready to start our activities in the CERN barracks. We are now in the enrollment phase and hope to start lessons very soon ! Club info can be found in the list of CERN Club: http://user.web.cern.ch/user/Communication/SocialLifeActivities/Clubs/Clubs.html Salvatore Buontempo Club President

  13. Bone Cancer

    Science.gov (United States)

    ... cancer. Surgery is often the main treatment for bone cancer. Other treatments may include amputation, chemotherapy, and radiation therapy. Because bone cancer can come back after treatment, regular follow-up visits are important. NIH: National ...

  14. Factors affecting morphogenetic potential in oilseed rape roots of the Skrzeszowicki and Start cultivars

    Directory of Open Access Journals (Sweden)

    Janina Rogozińska

    2014-02-01

    Full Text Available The effect of the origin of root segments, seedling age, growth substances and gelled or liquid media were tested in respect to the morphogenetic potential of rape root segments of Skrzeszowicki (high glucosinolate content and Start (low glucosinolate content cultivars. Callus and roots were formed on all root segments after an approximately 2 week growth period; buds were formed after ca. 4 weeks only on segments adjacent to the hypocotyl. Higher concentrations of auxin and cytokinins were required for bud induction. Cultivar differences in the morphogenetic responses of the root segments were found. They were manifested by the more abundant callus formation (BAP+NAA and more numerous lateral roots and buds (KIN+IBA on segments from the Skrzeszowicki cultivar than from the Start cultivar.

  15. Strong Coupling and Classicalization

    CERN Document Server

    Dvali, Gia

    2016-01-01

    Classicalization is a phenomenon in which a theory prevents itself from entering into a strong-coupling regime, by redistributing the energy among many weakly-interacting soft quanta. In this way, the scattering process of some initial hard quanta splits into a large number of soft elementary processes. In short, the theory trades the strong coupling for a high-multiplicity of quanta. At very high energies, the outcome of such a scattering experiment is a production of soft states of high occupation number that are approximately classical. It is evident that black hole creation in particle collision at super-Planckian energies is a result of classicalization, but there is no a priory reason why this phenomenon must be limited to gravity. If the hierarchy problem is solved by classicalization, the LHC has a chance of detecting a tower of new resonances. The lowest-lying resonances must appear right at the strong coupling scale in form of short-lived elementary particles. The heavier members of the tower must b...

  16. Nuclear motion is classical

    CERN Document Server

    Frank, Irmgard

    2016-01-01

    The notion from ab-initio molecular dynamics simulations that nuclear motion is best described by classical Newton dynamics instead of the time-dependent Schr{\\"o}dinger equation is substantiated. In principle a single experiment should bring clarity. Caution is however necessary, as temperature dependent effects must be eliminated when trying to determine the existence of a zero-point energy.

  17. Classics in What Sense?

    Science.gov (United States)

    Camic, Charles

    2008-01-01

    They seem the perfect bookends for the social psychologist's collection of "classics" of the field. Two volumes, nearly identical in shape and weight and exactly a century old in 2008--each professing to usher "social psychology" into the world as they both place the hybrid expression square in their titles but then proceed to stake out the field…

  18. Mecanica Clasica (Classical Mechanics)

    CERN Document Server

    Rosu, H C

    1999-01-01

    First Internet undergraduate course on Classical Mechanics in Spanish (Castellano). This is about 80% of the material I covered during the January-June 1999 semester at IFUG in the Mexican city of Leon. English and Romanian versions are in (slow) progress and hopefully will be arXived. For a similar course on Quantum Mechanics, see physics/9808031

  19. Classical galactosaemia revisited

    NARCIS (Netherlands)

    A.M. Bosch

    2006-01-01

    Classical galactosaemia (McKusick 230400) is an: autosomal recessive disorder of galactose metabolism, caused by a deficiency of the enzyme galactose-1-phosphate uridyltransferase (GALT; EC 2.7.712). Most patients present in the neonatal period, after ingestion of galactose, with jaundice, hepatospl

  20. The Classical Cake Problem

    Science.gov (United States)

    Nelson, Norman N.; Fisch, Forest N.

    1973-01-01

    Discussed are techniques of presentation and solution of the Classical Cake Problem. A frosted cake with a square base is to be cut into n pieces with the volume of cake and frosting the same for each piece. Needed are minimal geometric concepts and the formula for the volume of a prism. (JP)

  1. Classicism and Romanticism.

    Science.gov (United States)

    Huddleston, Gregory H.

    1993-01-01

    Describes one teacher's methods for introducing to secondary English students the concepts of Classicism and Romanticism in relation to pictures of gardens, architecture, music, and literary works. Outlines how the unit leads to a writing assignment based on collected responses over time. (HB)

  2. Classical and quantum satisfiability

    CERN Document Server

    de Araújo, Anderson; 10.4204/EPTCS.81.6

    2012-01-01

    We present the linear algebraic definition of QSAT and propose a direct logical characterization of such a definition. We then prove that this logical version of QSAT is not an extension of classical satisfiability problem (SAT). This shows that QSAT does not allow a direct comparison between the complexity classes NP and QMA, for which SAT and QSAT are respectively complete.

  3. Mecanica Clasica (Classical Mechanics)

    OpenAIRE

    H. C. Rosu

    1999-01-01

    First Internet graduate course on Classical Mechanics in Spanish (Castellano). This is about 80% of the material I covered during the January-June 1999 semester at IFUG in the Mexican city of Leon. English and Romanian versions are in (slow) progress and hopefully will be arXived. For a similar course on Quantum Mechanics, see physics/9808031

  4. Classical Mechanics Laboratory

    Science.gov (United States)

    Brosing, Juliet W.

    2006-12-01

    At Pacific University we have included a lab with our upper division Classical Mechanics class. We do a combination of physical labs (air resistance, harmonic motion, amusement park physics), Maple labs (software), and projects. Presentation of some of the labs, results and challenges with this course will be included.

  5. Classical Mythology. Fourth Edition.

    Science.gov (United States)

    Morford, Mark P. O.; Lenardon, Robert J.

    Designed for students with little or no background in classical literature, this book introduces the Greek and Roman myths of creation, myths of the gods, Greek sagas and local legends, and presents contemporary theories about the myths. Drawing on Homer, Hesiod, Pindar, Vergil, and others, the book provides many translations and paraphrases of…

  6. Children's Classics. Fifth Edition.

    Science.gov (United States)

    Jordan, Alice M.

    "Children's Classics," a 1947 article by Alice M. Jordan reprinted from "The Horn Book Magazine," examines the dynamics and appeal of some of the most famous books for young readers, including "Alice in Wonderland,""The Wind in the Willows,""Robinson Crusoe," and "Andersen's Fairy Tales." Paul Hein's annotated bibliography, a revision of Jordan's…

  7. Morphogenetic movements driving neural tube closure in Xenopus require myosin IIB

    OpenAIRE

    Rolo, Ana; Skoglund, Paul; Keller, Ray

    2008-01-01

    Vertebrate neural tube formation involves two distinct morphogenetic events -convergent extension (CE) driven by medio-lateral cell intercalation, and bending of the neural plate driven largely by cellular apical constriction. However, the cellular and molecular biomechanics of these processes are not understood. Here, using tissue-targeting techniques, we show that the myosin IIB motor protein complex is essential for both these processes, as well as for conferring resistance to deformation ...

  8. Role of Ess1 in growth, morphogenetic switching, and RNA polymerase II transcription in Candida albicans.

    Directory of Open Access Journals (Sweden)

    Dhanushki Samaranayake

    Full Text Available Candida albicans is a fungal pathogen that causes potentially fatal infections among immune-compromised individuals. The emergence of drug resistant C. albicans strains makes it important to identify new antifungal drug targets. Among potential targets are enzymes known as peptidyl-prolyl cis/trans isomerases (PPIases that catalyze isomerization of peptide bonds preceding proline. We are investigating a PPIase called Ess1, which is conserved in all major human pathogenic fungi. Previously, we reported that C. albicans Ess1 is essential for growth and morphogenetic switching. In the present study, we re-evaluated these findings using more rigorous genetic analyses, including the use of additional CaESS1 mutant alleles, distinct marker genes, and the engineering of suitably-matched isogenic control strains. The results confirm that CaEss1 is essential for growth in C. albicans, but show that reduction of CaESS1 gene dosage by half (δ/+ does not interfere with morphogenetic switching. However, further reduction of CaEss1 levels using a conditional allele does reduce morphogenetic switching. We also examine the role of the linker α-helix that distinguishes C. albicans Ess1 from the human Pin1 enzyme, and present results of a genome-wide transcriptome analysis. The latter analysis indicates that CaEss1 has a conserved role in regulation of RNA polymerase II function, and is required for efficient termination of small nucleolar RNAs and repression of cryptic transcription in C. albicans.

  9. External fixation of femoral defects in athymic rats: Applications for human stem cell implantation and bone regeneration

    Directory of Open Access Journals (Sweden)

    Terasa Foo

    2013-01-01

    Full Text Available An appropriate animal model is critical for the research of stem/progenitor cell therapy and tissue engineering for bone regeneration in vivo. This study reports the design of an external fixator and its application to critical-sized femoral defects in athymic rats. The external fixator consists of clamps and screws that are readily available from hardware stores as well as Kirschner wires. A total of 35 rats underwent application of the external fixator with creation of a 6-mm bone defect in one femur of each animal. This model had been used in several separate studies, including implantation of collagen gel, umbilical cord blood mesenchymal stem cells, endothelial progenitor cells, or bone morphogenetic protein-2. One rat developed fracture at the proximal pin site and two rats developed deep tissue infection. Pin loosening was found in nine rats, but it only led to the failure of external fixation in two animals. In 8 to 10 weeks, various degrees of bone growth in the femoral defects were observed in different study groups, from full repair of the bone defect with bone morphogenetic protein-2 implantation to fibrous nonunion with collagen gel implantation. The external fixator used in these studies provided sufficient mechanical stability to the bone defects and had a comparable complication rate in athymic rats as in immunocompetent rats. The external fixator does not interfere with the natural environment of a bone defect. This model is particularly valuable for investigation of osteogenesis of human stem/progenitor cells in vivo.

  10. The classic project

    International Nuclear Information System (INIS)

    Exchange of data and algorithms among accelerator physics programs is difficult because of unnecessary differences in input formats and internal data structures. To alleviate these problems a C++ class library called CLASSIC (Class Library for Accelerator System Simulation and Control) is being developed with the goal to provide standard building blocks for computer programs used in accelerator design. It includes modules for building accelerator lattice structures in computer memory using a standard input language, a graphical user interface, or a programmed algorithm. It also provides simulation algorithms. These can easily be replaced by modules which communicate with the control system of the accelerator. Exchange of both data and algorithm between different programs using the CLASSIC library should present no difficulty

  11. Randomness: quantum versus classical

    CERN Document Server

    Khrennikov, Andrei

    2015-01-01

    Recent tremendous development of quantum information theory led to a number of quantum technological projects, e.g., quantum random generators. This development stimulates a new wave of interest in quantum foundations. One of the most intriguing problems of quantum foundations is elaboration of a consistent and commonly accepted interpretation of quantum state. Closely related problem is clarification of the notion of quantum randomness and its interrelation with classical randomness. In this short review we shall discuss basics of classical theory of randomness (which by itself is very complex and characterized by diversity of approaches) and compare it with irreducible quantum randomness. The second part of this review is devoted to the information interpretation of quantum mechanics (QM) in the spirit of Zeilinger and Brukner (and QBism of Fuchs et al.) and physics in general (e.g., Wheeler's "it from bit") as well as digital philosophy of Chaitin (with historical coupling to ideas of Leibnitz). Finally, w...

  12. Classical and statistical thermodynamics

    CERN Document Server

    Rizk, Hanna A

    2016-01-01

    This is a text book of thermodynamics for the student who seeks thorough training in science or engineering. Systematic and thorough treatment of the fundamental principles rather than presenting the large mass of facts has been stressed. The book includes some of the historical and humanistic background of thermodynamics, but without affecting the continuity of the analytical treatment. For a clearer and more profound understanding of thermodynamics this book is highly recommended. In this respect, the author believes that a sound grounding in classical thermodynamics is an essential prerequisite for the understanding of statistical thermodynamics. Such a book comprising the two wide branches of thermodynamics is in fact unprecedented. Being a written work dealing systematically with the two main branches of thermodynamics, namely classical thermodynamics and statistical thermodynamics, together with some important indexes under only one cover, this treatise is so eminently useful.

  13. Injuries in classical ballet

    Directory of Open Access Journals (Sweden)

    Adriana Coutinho de Azevedo Guimarães

    2008-06-01

    Full Text Available This study aimed to elucidate what injuries are most likely to occur due to classical ballet practice. The research used national and international bibliography. The bibliography analysis indicated that technical and esthetical demands lead to a practice of non-anatomical movements, causing the ballet dancer to suffer from a number of associated lesions. Most of the injuries are caused by technical mistakes and wrong training. Troubles in children are usually due to trying to force external rotation at hip level and to undue use of point ballet slippers. The commonest lesions are in feet and ankles, followed by knees and hips. The rarest ones are in the upper limbs. These injuries are caused by exercise excess, by repetitions always in the same side and by wrong and early use of point slippers. The study reached the conclusion that incorrect application of classical ballet technique predisposes the dancers to characteristic injuries.

  14. Classical Diophantine equations

    CERN Document Server

    1993-01-01

    The author had initiated a revision and translation of "Classical Diophantine Equations" prior to his death. Given the rapid advances in transcendence theory and diophantine approximation over recent years, one might fear that the present work, originally published in Russian in 1982, is mostly superseded. That is not so. A certain amount of updating had been prepared by the author himself before his untimely death. Some further revision was prepared by close colleagues. The first seven chapters provide a detailed, virtually exhaustive, discussion of the theory of lower bounds for linear forms in the logarithms of algebraic numbers and its applications to obtaining upper bounds for solutions to the eponymous classical diophantine equations. The detail may seem stark--- the author fears that the reader may react much as does the tourist on first seeing the centre Pompidou; notwithstanding that, Sprind zuk maintainsa pleasant and chatty approach, full of wise and interesting remarks. His emphases well warrant, ...

  15. Classical Weyl Transverse Gravity

    CERN Document Server

    Oda, Ichiro

    2016-01-01

    We study various classical aspects of the Weyl transverse (WTDiff) gravity in a general space-time dimension. First of all, we clarify a classical equivalence among three kinds of gravitational theories, those are, the conformally-invariant scalar tensor gravity, Einstein's general relativity and the WTDiff gravity via the gauge fixing procedure. Secondly, we show that in the WTDiff gravity the cosmological constant is a mere integration constant as in unimodular gravity, but it does not receive any radiative corrections unlike the unimodular gravity. A key point in this proof is to construct a covariantly conserved energy-momentum tensor, which is achieved on the basis of this equivalence relation. Thirdly, we demonstrate that the Noether current for the Weyl transformation is identically vanishing, thereby implying that the Weyl symmetry existing in both the conformally-invariant scalar tensor gravity and the WTDiff gravity is a "fake" symmetry. We find it possible to extend this proof to all matter fields,...

  16. Computation in Classical Mechanics

    CERN Document Server

    Timberlake, Todd

    2007-01-01

    There is a growing consensus that physics majors need to learn computational skills, but many departments are still devoid of computation in their physics curriculum. Some departments may lack the resources or commitment to create a dedicated course or program in computational physics. One way around this difficulty is to include computation in a standard upper-level physics course. An intermediate classical mechanics course is particularly well suited for including computation. We discuss the ways we have used computation in our classical mechanics courses, focusing on how computational work can improve students' understanding of physics as well as their computational skills. We present examples of computational problems that serve these two purposes. In addition, we provide information about resources for instructors who would like to include computation in their courses.

  17. Concepts of classical optics

    CERN Document Server

    Strong, John

    2004-01-01

    An intermediate course in optics, this volume explores both experimental and theoretical concepts, offering practical knowledge of geometrical optics that will enhance students' comprehension of any relevant applied science. Its exposition of the concepts of classical optics is presented with a minimum of mathematical detail but presumes some knowledge of calculus, vectors, and complex numbers.Subjects include light as wave motion; superposition of wave motions; electromagnetic waves; interaction of light and matter; velocities and scattering of light; polarized light and dielectric boundarie

  18. Sociology and Classical Liberalism

    OpenAIRE

    KLEIN, Daniel; Stern, Lotta

    2005-01-01

    We advocate the development of a classical-liberal character within professional sociology. The American Sociological Association (ASA) is taken as representative of professional sociology in the United States. We review the ASA’s activities and organizational statements, to show the association’s leftist character. Internal criticism is often very uneasy about leftist domination of the field. We present survey results establishing that, in voting and in policy views, the ASA membership is mo...

  19. Revisiting a Classic

    Science.gov (United States)

    Rogers, Ibram

    2008-01-01

    As a 26-year-old English teacher in 1958, Chinua Achebe had no idea that the book he was writing would become a literary classic, not only in Africa but also throughout the world. He could only try to articulate the feelings he had for his countrymen and women. Achebe had a burning desire to tell the true story of Africa and African humanity. The…

  20. Injuries in classical ballet

    OpenAIRE

    Adriana Coutinho de Azevedo Guimarães; Joseani Paulini Neves Simas

    2008-01-01

    This study aimed to elucidate what injuries are most likely to occur due to classical ballet practice. The research used national and international bibliography. The bibliography analysis indicated that technical and esthetical demands lead to a practice of non-anatomical movements, causing the ballet dancer to suffer from a number of associated lesions. Most of the injuries are caused by technical mistakes and wrong training. Troubles in children are usually due to trying to force external ...

  1. A Classic's New Charm

    Institute of Scientific and Technical Information of China (English)

    WANG HAIRONG

    2010-01-01

    @@ North Korea's Phibada Opera Troupe arrived in Beijing on May3,bringing with it a Korean opera adapted from China's classic novel A Dream of Red Mansions written by Cao Xueqin(around 1715-63),a great novelist of the Qing Dynasty(1644-1911).The troupe,invited by the Chinese Ministry of Culture,is one of the largest performing groups having visited China in recent years.

  2. Diffusion of Classical Solitons

    OpenAIRE

    Dziarmaga, J.; Zakrzewski, W.

    1998-01-01

    We study the diffusion and deformation of classical solitons coupled to thermal noise. The diffusion coefficient for kinks in the $\\phi^4$ theory is predicted up to the second order in $kT$. The prediction is verified by numerical simulations. Multiskyrmions in the vector O(3) sigma model are studied within the same formalism. Thermal noise results in a diffusion on the multisoliton collective coordinate space (moduli space). There are entropic forces which tend, for example, to bind pairs of...

  3. Classical Maxwellian polarization entanglement

    CERN Document Server

    Carroll, John E

    2015-01-01

    An explanation of polarization entanglement is presented using Maxwells classical electromagnetic theory.Two key features are required to understand these classical origins.The first is that all waves diffract and weakly diffracting waves,with a principal direction of propagation in the laboratory frame, travel along that direction at speeds ever so slightly less than c.This allows nontrivial Lorentz transformations that can act on selected forward F waves or selected waves R traveling in the opposite direction to show that both can arise from a single zero momentum frame where all the waves are transverse to the original principal direction.Such F and R waves then both belong to a single relativistic entity where correlations between the two are unremarkable.The second feature requires the avoidance of using the Coulomb gauge.Waves, tending to plane waves in the limit of zero diffraction,can then be shown to be composed of two coupled sets of E and B fields that demonstrate the classical entanglement of F an...

  4. Conditional Deletion of BMP7 from the Limb Skeleton Does Not Affect Bone Formation or Fracture Repair

    OpenAIRE

    Tsuji, Kunikazu; Cox, Karen; Gamer, Laura; Graf, Daniel; Economides, Aris; Rosen, Vicki

    2010-01-01

    While the osteoinductive activity of recombinant bone morphogenetic protein 7 (BMP7) is well established, evaluation of the role of endogenous BMP7 in bone formation and fracture healing has been hampered by perinatal lethality in BMP7 knockout mice. Here we employ conditional deletion of BMP7 from the embryonic limb prior to the onset of skeletogenesis to create limb bones lacking BMP7. We find that the absence of locally produced BMP7 has no effect on postnatal limb growth, articular cartil...

  5. Osteoporosis: Modern Paradigms for Last Century’s Bones

    OpenAIRE

    Kruger, Marlena C.; Wolber, Frances M.

    2016-01-01

    The skeleton is a metabolically active organ undergoing continuously remodelling. With ageing and menopause the balance shifts to increased resorption, leading to a reduction in bone mineral density and disruption of bone microarchitecture. Bone mass accretion and bone metabolism are influenced by systemic hormones as well as genetic and lifestyle factors. The classic paradigm has described osteoporosis as being a “brittle bone” disease that occurs in post-menopausal, thin, Caucasian women wi...

  6. Treatment of Temporal Bone Fractures.

    Science.gov (United States)

    Diaz, Rodney C; Cervenka, Brian; Brodie, Hilary A

    2016-10-01

    Traumatic injury to the temporal bone can lead to significant morbidity or mortality and knowledge of the pertinent anatomy, pathophysiology of injury, and appropriate management strategies is critical for successful recovery and rehabilitation of such injured patients. Most temporal bone fractures are caused by motor vehicle accidents. Temporal bone fractures are best classified as either otic capsule sparing or otic capsule disrupting-type fractures, as such classification correlates well with risk of concomitant functional complications. The most common complications of temporal bone fractures are facial nerve injury, cerebrospinal fluid (CSF) leak, and hearing loss. Assessment of facial nerve function as soon as possible following injury greatly facilitates clinical decision making. Use of prophylactic antibiotics in the setting of CSF leak is controversial; however, following critical analysis and interpretation of the existing classic and contemporary literature, we believe its use is absolutely warranted. PMID:27648399

  7. Temporal bone imaging

    Energy Technology Data Exchange (ETDEWEB)

    Lemmerling, Marc [Algemeen Ziekenhuis Sint-Lucas, Gent (Belgium). Dept. of Radiology; Foer, Bert de (ed.) [Sint-Augustinus Ziekenhuis, Wilrijk (Belgium). Dept. of Radiology

    2015-04-01

    Complete overview of imaging of normal and diseased temporal bone. Straightforward structure to facilitate learning. Detailed consideration of newer imaging techniques, including the hot topic of diffusion-weighted imaging. Includes a chapter on anatomy that will be of great help to the novice interpreter of imaging findings. Excellent illustrations throughout. This book provides a complete overview of imaging of normal and diseased temporal bone. After description of indications for imaging and the cross-sectional imaging anatomy of the area, subsequent chapters address the various diseases and conditions that affect the temporal bone and are likely to be encountered regularly in clinical practice. The classic imaging methods are described and discussed in detail, and individual chapters are included on newer techniques such as functional imaging and diffusion-weighted imaging. There is also a strong focus on postoperative imaging. Throughout, imaging findings are documented with the aid of numerous informative, high-quality illustrations. Temporal Bone Imaging, with its straightforward structure based essentially on topography, will prove of immense value in daily practice.

  8. [Bone diseases].

    Science.gov (United States)

    Uebelhart, Brigitte; Rizzoli, René

    2016-01-13

    Calcium intake shows a small impact on bone mineral density and fracture risk. Denosumab is a more potent inhibitor of bone resorption than zoledronate. Abaloparatide, PTHrP analog, increases bone mineral density and decreases fracture incidence. Teriparatide could be delivered via a transdermic device. Romosozumab and odanacatib improve calculated bone strength. Sequential or combined treatments with denosumab and teriparatide could be of interest, but not denosumab followed by teriparatide. Fibrous dysplasia, Paget disease and hypophosphatasia are updated, as well as atypical femoral fracture and osteonecrosis of the jaw. PMID:26946704

  9. On Classical Ideal Gases

    Directory of Open Access Journals (Sweden)

    Laurent Chusseau

    2013-02-01

    Full Text Available We show that the thermodynamics of ideal gases may be derived solely from the Democritean concept of corpuscles moving in vacuum plus a principle of simplicity, namely that these laws are independent of the laws of motion, aside from the law of energy conservation. Only a single corpuscle in contact with a heat bath submitted to a z and t-invariant force is considered. Most of the end results are known but the method appears to be novel. The mathematics being elementary, the present paper should facilitate the understanding of the ideal gas law and of classical thermodynamics even though not-usually-taught concepts are being introduced.

  10. A Classic Through Eternity

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    FIVE years ago, an ancient Chinese air was beamed to outer space as a PR exercise. To humankind, music is a universal language, so the tune seemed an ideal medium for communication with extraterrestrial intelligence. So far there has been no response, but it is believed that the tune will play for a billion years, and eventually be heard and understood. The melody is called High Mountain and Flowing Stream, and it is played on the guqin, a seven-stringed classical musical instrument similar to the zither.

  11. Mechanics classical and quantum

    CERN Document Server

    Taylor, T T

    2015-01-01

    Mechanics: Classical and Quantum explains the principles of quantum mechanics via the medium of analytical mechanics. The book describes Schrodinger's formulation, the Hamilton-Jacobi equation, and the Lagrangian formulation. The author discusses the Harmonic Oscillator, the generalized coordinates, velocities, as well as the application of the Lagrangian formulation to systems that are partially or entirely electromagnetic in character under certain conditions. The book examines waves on a string under tension, the isothermal cavity radiation, and the Rayleigh-Jeans result pertaining to the e

  12. Probability representation of classical states

    NARCIS (Netherlands)

    Man'ko, OV; Man'ko, [No Value; Pilyavets, OV

    2005-01-01

    Probability representation of classical states described by symplectic tomograms is discussed. Tomographic symbols of classical observables which are functions on phase-space are studied. Explicit form of kernel of commutative star-product of the tomographic symbols is obtained.

  13. The Marine Sponge-Derived Inorganic Polymers, Biosilica and Polyphosphate, as Morphogenetically Active Matrices/Scaffolds for the Differentiation of Human Multipotent Stromal Cells: Potential Application in 3D Printing and Distraction Osteogenesis

    Directory of Open Access Journals (Sweden)

    Xiaohong Wang

    2014-02-01

    Full Text Available The two marine inorganic polymers, biosilica (BS, enzymatically synthesized from ortho-silicate, and polyphosphate (polyP, a likewise enzymatically synthesized polymer consisting of 10 to >100 phosphate residues linked by high-energy phosphoanhydride bonds, have previously been shown to display a morphogenetic effect on osteoblasts. In the present study, the effect of these polymers on the differential differentiation of human multipotent stromal cells (hMSC, mesenchymal stem cells, that had been encapsulated into beads of the biocompatible plant polymer alginate, was studied. The differentiation of the hMSCs in the alginate beads was directed either to the osteogenic cell lineage by exposure to an osteogenic medium (mineralization activation cocktail; differentiation into osteoblasts or to the chondrogenic cell lineage by incubating in chondrocyte differentiation medium (triggering chondrocyte maturation. Both biosilica and polyP, applied as Ca2+ salts, were found to induce an increased mineralization in osteogenic cells; these inorganic polymers display also morphogenetic potential. The effects were substantiated by gene expression studies, which revealed that biosilica and polyP strongly and significantly increase the expression of bone morphogenetic protein 2 (BMP-2 and alkaline phosphatase (ALP in osteogenic cells, which was significantly more pronounced in osteogenic versus chondrogenic cells. A differential effect of the two polymers was seen on the expression of the two collagen types, I and II. While collagen Type I is highly expressed in osteogenic cells, but not in chondrogenic cells after exposure to biosilica or polyP, the upregulation of the steady-state level of collagen Type II transcripts in chondrogenic cells is comparably stronger than in osteogenic cells. It is concluded that the two polymers, biosilica and polyP, are morphogenetically active additives for the otherwise biologically inert alginate polymer. It is proposed that

  14. Numerical calculation of classical and non-classical electrostatic potentials

    CERN Document Server

    Christensen, D; Neyenhuis, B; Christensen, Dan; Durfee, Dallin S.; Neyenhuis, Brian

    2006-01-01

    We present a numerical exercise in which classical and non-classical electrostatic potentials were calculated. The non-classical fields take into account effects due to a possible non-zero photon rest mass. We show that in the limit of small photon rest mass, both the classical and non-classical potential can be found by solving Poisson's equation twice, using the first calculation as a source term in the second calculation. Our results support the assumptions in a recent proposal to use ion interferometry to search for a non-zero photon rest mass.

  15. Classical Physics and Quantum Loops

    Energy Technology Data Exchange (ETDEWEB)

    Barry R. Holstein; John F. Donoghue

    2004-05-01

    The standard picture of the loop expansion associates a factor of h-bar with each loop, suggesting that the tree diagrams are to be associated with classical physics, while loop effects are quantum mechanical in nature. We discuss examples wherein classical effects arise from loop contributions and display the relationship between the classical terms and the long range effects of massless particles.

  16. Fano Interference in Classical Oscillators

    Science.gov (United States)

    Satpathy, S.; Roy, A.; Mohapatra, A.

    2012-01-01

    We seek to illustrate Fano interference in a classical coupled oscillator by using classical analogues of the atom-laser interaction. We present an analogy between the dressed state picture of coherent atom-laser interaction and a classical coupled oscillator. The Autler-Townes splitting due to the atom-laser interaction is analogous to the…

  17. Morphogenetic changes occurring in the regenerating newt tail under changed gravity conditions

    Science.gov (United States)

    Radugina, Elena A.; Grigoryan, Eleonora N.; Dvorochkin, Natasha; Almeida, Eduardo

    2012-07-01

    It is widely accepted that gravity greatly affects animal physiology, development, and alters gene expression. Recently it became apparent that it can also affect tissue morphogenesis. In our work, we developed special laboratory conditions that allow us to produce the gravity-dependent alterations in tail regenerates of the newt Pleurodeles waltl. We examined the dynamic morphogenetic changes during 50-day tail regeneration using computer morphometric analysis. Changes that we observed under these conditions were comparable with those found earlier in our spaceflight experiments. The newts kept in aquarium deep water (low g) after 1/3 tail amputation developed normal lanceolate regenerates. In contrast, the animals that stayed on the moist mat (1g) developed tail regenerates curved ventrally, with tips almost touching the mat. The similar results were obtained with a 12-day centrifugation at 2g. The study of the regenerate morphology in low g, 1g, and 2g animal groups allowed us to determine the stage at which the morphological changes in regenerates become apparent, and to detect the main morphological events associated with the development of tail curve, such as bending of ependymal tube and reorientation of the forming cartilage. We describe cellular processes foregoing observed tissue morphogenetic changes, such as cell migration, condensation in cell population, and unequal proliferation in different areas of epidermis and blastema. Cell proliferation in epidermis and blastema of tails regenerated under the conditions of different gravitational load was evaluated by BrdU assay. In 1g newts, cell proliferation increased within the dorso-apical region of the regenerates compared with that in low g group. These results provide us with a valuable insight into the regenerative tissue homostasis that involves cell division, cell death, and migration in the newt regenerating tail. In addition, these findings could provide us with better understanding of the

  18. Talking Bones.

    Science.gov (United States)

    Johnson, Jaclyn; Kassing, Sharon

    2002-01-01

    Describes cooperation with the Saint Louis Zoo to provide opportunities for elementary school students to learn about bones, how animals move, what they eat, and how much they grow. Uses biofacts which include bones, skulls, and other parts to make the laboratory a hands-on experience for students. (YDS)

  19. Bone Markers

    Science.gov (United States)

    ... bone turnover: C-telopeptide (C-terminal telopeptide of type 1 collagen (CTx)) – a marker for bone resorption. It is ... resorption include: N-telopeptide (N-terminal telopeptide of type 1 collagen (NTx)) – a peptide fragment from the amino terminal ...

  20. Bone densitometry

    DEFF Research Database (Denmark)

    Ravn, Pernille; Alexandersen, P; Møllgaard, A

    1999-01-01

    The bisphosphonates have been introduced as alternatives to hormone replacement therapy (HRT) for the treatment and prevention of postmenopausal osteoporosis. The expected increasing application in at clinical practice demands cost-effective and easily handled methods to monitor the effect on bone....... The weak response at the distal forearm during antiresorptive treatment has restricted the use of bone densitometry at this region. We describe a new model for bone densitometry at the distal forearm, by which the response obtained is comparable to the response in other regions where bone densitometry...... is much more expensive and technically complicated. By computerized iteration of single X-ray absorptiometry forearm scans we defined a region with 65% trabecular bone. The region was analyzed in randomized, double-masked, placebo- controlled trials: a 2-year trial with alendronate (n = 69), a 1-year...

  1. Nucleosynthesis in classical novae

    Science.gov (United States)

    José, Jordi; Hernanz, Margarita; Iliadis, Christian

    2006-10-01

    Classical novae are dramatic stellar explosions with an energy release that is only overcome by supernovae and gamma-ray bursts. These unique cataclysmic events constitute a crucible where different scientific disciplines merge, including astrophysics, nuclear and atomic physics, cosmochemistry, high-energy physics or computer science. In this review, we focus on the nucleosynthesis accompanying nova outbursts. Theoretical predictions are compared with the elemental abundances inferred from observations of the nova ejecta as well as with the isotopic abundance ratios measured in meteorites. Special emphasis is given to the interplay between nova outbursts and the Galactic abundance pattern and on the synthesis of radioactive nuclei for which γ-ray signals are expected. Finally, we analyze the key role played by nuclear physics in our understanding of the nova phenomenon by means of recent experiments and a thorough account of the impact of nuclear uncertainties.

  2. Mechanical Systems, Classical Models

    CERN Document Server

    Teodorescu, Petre P

    2009-01-01

    This third volume completes the Work Mechanical Systems, Classical Models. The first two volumes dealt with particle dynamics and with discrete and continuous mechanical systems. The present volume studies analytical mechanics. Topics like Lagrangian and Hamiltonian mechanics, the Hamilton-Jacobi method, and a study of systems with separate variables are thoroughly discussed. Also included are variational principles and canonical transformations, integral invariants and exterior differential calculus, and particular attention is given to non-holonomic mechanical systems. The author explains in detail all important aspects of the science of mechanics, regarded as a natural science, and shows how they are useful in understanding important natural phenomena and solving problems of interest in applied and engineering sciences. Professor Teodorescu has spent more than fifty years as a Professor of Mechanics at the University of Bucharest and this book relies on the extensive literature on the subject as well as th...

  3. Grassmannization of classical models

    CERN Document Server

    Pollet, Lode; Prokof'ev, Nikolay V; Svistunov, Boris V

    2016-01-01

    Applying Feynman diagrammatics to non-fermionic strongly correlated models with local constraints might seem generically impossible for two separate reasons: (i) the necessity to have a Gaussian (non-interacting) limit on top of which the perturbative diagrammatic expansion is generated by Wick's theorem, and (ii) the Dyson's collapse argument implying that the expansion in powers of coupling constant is divergent. We show that for arbitrary classical lattice models both problems can be solved/circumvented by reformulating the high-temperature expansion (more generally, any discrete representation of the model) in terms of Grassmann integrals. Discrete variables residing on either links, plaquettes, or sites of the lattice are associated with the Grassmann variables in such a way that the partition function (and correlations) of the original system and its Grassmann-field counterpart are identical. The expansion of the latter around its Gaussian point generates Feynman diagrams. A proof-of-principle implement...

  4. Citation classics in epilepsy

    Directory of Open Access Journals (Sweden)

    Maryann Wilson

    2013-01-01

    Full Text Available BACKGROUND: The impact of a scientific article is proportional to the citations it has received. In this study, we set out to identify the most cited works in epileptology in order to evaluate research trends in this field. METHODS: According to the Web of Science database, articles with more than 400 citations qualify as "citation classics". We conducted a literature search on the ISI Web of Science bibliometric database for scientific articles relevant to epilepsy. RESULTS: We retrieved 67 highly cited articles (400 or more citations, which were published in 31 journals: 17 clinical studies, 42 laboratory studies, 5 reviews and 3 classification articles. Clinical studies consisted of epidemiological analyses (n=3, studies on the clinical phenomenology of epilepsy (n=5 – including behavioral and prognostic aspects – and articles focusing on pharmacological (n=6 and non-pharmacological (n=3 treatment. The laboratory studies dealt with genetics (n=6, animal models (n=27, and neurobiology (n=9 – including both neurophysiology and neuropathology studies. The majority (61% of citation classics on epilepsy were published after 1986, possibly reflecting the expansion of research interest in laboratory studies driven by the development of new methodologies, specifically in the fields of genetics and animal models. Consequently, clinical studies were highly cited both before and after the mid 80s, whilst laboratory researches became widely cited after 1990. CONCLUSIONS: Our study indicates that the main drivers of scientific impact in the field of epileptology have increasingly become genetic and neurobiological studies, along with research on animal models of epilepsy. These articles are able to gain the highest numbers of citations in the time span of a few years and suggest potential directions for future research.

  5. Bone Regeneration from PLGA Micro-Nanoparticles

    Science.gov (United States)

    Ortega-Oller, Inmaculada; Padial-Molina, Miguel; Galindo-Moreno, Pablo; O'Valle, Francisco; Jódar-Reyes, Ana Belén; Peula-García, Jose Manuel

    2015-01-01

    Poly-lactic-co-glycolic acid (PLGA) is one of the most widely used synthetic polymers for development of delivery systems for drugs and therapeutic biomolecules and as component of tissue engineering applications. Its properties and versatility allow it to be a reference polymer in manufacturing of nano- and microparticles to encapsulate and deliver a wide variety of hydrophobic and hydrophilic molecules. It additionally facilitates and extends its use to encapsulate biomolecules such as proteins or nucleic acids that can be released in a controlled way. This review focuses on the use of nano/microparticles of PLGA as a delivery system of one of the most commonly used growth factors in bone tissue engineering, the bone morphogenetic protein 2 (BMP2). Thus, all the needed requirements to reach a controlled delivery of BMP2 using PLGA particles as a main component have been examined. The problems and solutions for the adequate development of this system with a great potential in cell differentiation and proliferation processes under a bone regenerative point of view are discussed. PMID:26509156

  6. Bone Regeneration from PLGA Micro-Nanoparticles

    Directory of Open Access Journals (Sweden)

    Inmaculada Ortega-Oller

    2015-01-01

    Full Text Available Poly-lactic-co-glycolic acid (PLGA is one of the most widely used synthetic polymers for development of delivery systems for drugs and therapeutic biomolecules and as component of tissue engineering applications. Its properties and versatility allow it to be a reference polymer in manufacturing of nano- and microparticles to encapsulate and deliver a wide variety of hydrophobic and hydrophilic molecules. It additionally facilitates and extends its use to encapsulate biomolecules such as proteins or nucleic acids that can be released in a controlled way. This review focuses on the use of nano/microparticles of PLGA as a delivery system of one of the most commonly used growth factors in bone tissue engineering, the bone morphogenetic protein 2 (BMP2. Thus, all the needed requirements to reach a controlled delivery of BMP2 using PLGA particles as a main component have been examined. The problems and solutions for the adequate development of this system with a great potential in cell differentiation and proliferation processes under a bone regenerative point of view are discussed.

  7. 15-zinc finger protein Bloody Fingers is required for zebrafish morphogenetic movements during neurulation.

    Science.gov (United States)

    Sumanas, Saulius; Zhang, Bo; Dai, Rujuan; Lin, Shuo

    2005-07-01

    A novel zebrafish gene bloody fingers (blf) encoding a 478 amino acid protein containing fifteen C(2)H(2) type zinc fingers was identified by expression screening. As determined by in situ hybridization, blf RNA displays strong ubiquitous early zygotic expression, while during late gastrulation and early somitogenesis, blf expression becomes transiently restricted to the posterior dorsal and lateral mesoderm. During later somitogenesis, blf expression appears only in hematopoietic cells. It is completely eliminated in cloche, moonshine but not in vlad tepes (gata1) mutant embryos. Morpholino (MO) knockdown of the Blf protein results in the defects of morphogenetic movements. Blf-MO-injected embryos (morphants) display shortened and widened axial tissues due to defective convergent extension. Unlike other convergent extension mutants, blf morphants display a split neural tube, resulting in a phenotype similar to the human open neural tube defect spina bifida. In addition, dorsal ectodermal cells delaminate in blf morphants during late somitogenesis. We propose a model explaining the role of blf in convergent extension and neurulation. We conclude that blf plays an important role in regulating morphogenetic movements during gastrulation and neurulation while its role in hematopoiesis may be redundant.

  8. Your Bones

    Science.gov (United States)

    ... a fall! If you play sports like football, soccer, lacrosse, or ice hockey, always wear all the ... to strengthen your bones is through exercise like running, jumping, dancing, and playing sports. Take these steps ...

  9. Loss of mesenchymal bone morphogenetic protein signaling leads to development of reactive stroma and initiation of the gastric neoplastic cascade

    Science.gov (United States)

    Roy, Sébastien A. B.; Allaire, Joannie M.; Ouellet, Camille; Maloum-Rami, Faiza; Pomerleau, Véronique; Lemieux, Étienne; Babeu, Jean-Philippe; Rousseau, Jasmin; Paquet, Marilène; Garde-Granger, Perrine; Boudreau, François; Perreault, Nathalie

    2016-09-01

    Bmps are morphogens involved in various gastric cellular functions. Studies in genetically-modified mice have shown that Bmp disruption in gastric epithelial and stromal cell compartments leads to the development of tumorigenesis. Our studies have demonstrated that abrogation of gastric epithelial Bmp signaling alone was not sufficient to recapitulate the neoplastic features associated with total gastric loss of Bmp signaling. Thus, epithelial Bmp signaling does not appear to be a key player in gastric tumorigenesis initiation. These observations suggest a greater role for stromal Bmp signaling in gastric polyposis initiation. In order to identify the specific roles played by mesenchymal Bmp signaling in gastric homeostasis, we generated a mouse model with abrogation of Bmp signaling exclusively in the gastro-intestinal mesenchyme (Bmpr1aΔMES). We were able to expose an unsuspected role for Bmp loss of signaling in leading normal gastric mesenchyme to adapt into reactive mesenchyme. An increase in the population of activated-fibroblasts, suggesting mesenchymal transdifferentiation, was observed in mutant stomach. Bmpr1aΔMES stomachs exhibited spontaneous benign polyps with presence of both intestinal metaplasia and spasmolytic-polypeptide-expressing metaplasia as early as 90 days postnatal. These results support the novel concept that loss of mesenchymal Bmp signaling cascade acts as a trigger in gastric polyposis initiation.

  10. The bone morphogenetic protein antagonist gremlin 1 is overexpressed in human cancers and interacts with YWHAH protein

    Directory of Open Access Journals (Sweden)

    Hur Soo

    2006-03-01

    Full Text Available Abstract Background Basic studies of oncogenesis have demonstrated that either the elevated production of particular oncogene proteins or the occurrence of qualitative abnormalities in oncogenes can contribute to neoplastic cellular transformation. The purpose of our study was to identify an unique gene that shows cancer-associated expression, and characterizes its function related to human carcinogenesis. Methods We used the differential display (DD RT-PCR method using normal cervical, cervical cancer, metastatic cervical tissues, and cervical cancer cell lines to identify genes overexpressed in cervical cancers and identified gremlin 1 which was overexpressed in cervical cancers. We determined expression levels of gremlin 1 using Northern blot analysis and immunohistochemical study in various types of human normal and cancer tissues. To understand the tumorigenesis pathway of identified gremlin 1 protein, we performed a yeast two-hybrid screen, GST pull down assay, and immunoprecipitation to identify gremlin 1 interacting proteins. Results DDRT-PCR analysis revealed that gremlin 1 was overexpressed in uterine cervical cancer. We also identified a human gremlin 1 that was overexpressed in various human tumors including carcinomas of the lung, ovary, kidney, breast, colon, pancreas, and sarcoma. PIG-2-transfected HEK 293 cells exhibited growth stimulation and increased telomerase activity. Gremlin 1 interacted with homo sapiens tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, eta polypeptide (14-3-3 eta; YWHAH. YWHAH protein binding site for gremlin 1 was located between residues 61–80 and gremlin 1 binding site for YWHAH was found to be located between residues 1 to 67. Conclusion Gremlin 1 may play an oncogenic role especially in carcinomas of the uterine cervix, lung, ovary, kidney, breast, colon, pancreas, and sarcoma. Over-expressed gremlin 1 functions by interaction with YWHAH. Therefore, Gremlin 1 and its binding protein YWHAH could be good targets for developing diagnostic and therapeutic strategies against human cancers.

  11. Drosophila 60A gene, another transforming growth factor beta family member, is closely related to human bone morphogenetic proteins.

    OpenAIRE

    Wharton, K. A.; Thomsen, G H; Gelbart, W. M.

    1991-01-01

    The 60A gene, a member of the transforming growth factor beta superfamily of signaling proteins, has been identified in Drosophila melanogaster. From its inferred protein sequence we predict the precursor is secreted and processed to release a growth factor-like molecule. The 60A gene is expressed throughout development with peaks of transcription during early embryogenesis, in pupae, and in adult males. The putative 60A protein shows greater sequence similarity to three vertebrate family mem...

  12. The bone morphogenetic protein antagonist gremlin 1 is overexpressed in human cancers and interacts with YWHAH protein

    International Nuclear Information System (INIS)

    Basic studies of oncogenesis have demonstrated that either the elevated production of particular oncogene proteins or the occurrence of qualitative abnormalities in oncogenes can contribute to neoplastic cellular transformation. The purpose of our study was to identify an unique gene that shows cancer-associated expression, and characterizes its function related to human carcinogenesis. We used the differential display (DD) RT-PCR method using normal cervical, cervical cancer, metastatic cervical tissues, and cervical cancer cell lines to identify genes overexpressed in cervical cancers and identified gremlin 1 which was overexpressed in cervical cancers. We determined expression levels of gremlin 1 using Northern blot analysis and immunohistochemical study in various types of human normal and cancer tissues. To understand the tumorigenesis pathway of identified gremlin 1 protein, we performed a yeast two-hybrid screen, GST pull down assay, and immunoprecipitation to identify gremlin 1 interacting proteins. DDRT-PCR analysis revealed that gremlin 1 was overexpressed in uterine cervical cancer. We also identified a human gremlin 1 that was overexpressed in various human tumors including carcinomas of the lung, ovary, kidney, breast, colon, pancreas, and sarcoma. PIG-2-transfected HEK 293 cells exhibited growth stimulation and increased telomerase activity. Gremlin 1 interacted with homo sapiens tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, eta polypeptide (14-3-3 eta; YWHAH). YWHAH protein binding site for gremlin 1 was located between residues 61–80 and gremlin 1 binding site for YWHAH was found to be located between residues 1 to 67. Gremlin 1 may play an oncogenic role especially in carcinomas of the uterine cervix, lung, ovary, kidney, breast, colon, pancreas, and sarcoma. Over-expressed gremlin 1 functions by interaction with YWHAH. Therefore, Gremlin 1 and its binding protein YWHAH could be good targets for developing diagnostic and therapeutic strategies against human cancers

  13. Classical Fourier analysis

    CERN Document Server

    Grafakos, Loukas

    2014-01-01

    The main goal of this text is to present the theoretical foundation of the field of Fourier analysis on Euclidean spaces. It covers classical topics such as interpolation, Fourier series, the Fourier transform, maximal functions, singular integrals, and Littlewood–Paley theory. The primary readership is intended to be graduate students in mathematics with the prerequisite including satisfactory completion of courses in real and complex variables. The coverage of topics and exposition style are designed to leave no gaps in understanding and stimulate further study. This third edition includes new Sections 3.5, 4.4, 4.5 as well as a new chapter on “Weighted Inequalities,” which has been moved from GTM 250, 2nd Edition. Appendices I and B.9 are also new to this edition.  Countless corrections and improvements have been made to the material from the second edition. Additions and improvements include: more examples and applications, new and more relevant hints for the existing exercises, new exercises, and...

  14. The Classical Electron Problem

    CERN Document Server

    Gill, T L; Lindesay, J

    2001-01-01

    In this paper, we construct a parallel image of the conventional Maxwell theory by replacing the observer-time by the proper-time of the source. This formulation is mathematically, but not physically, equivalent to the conventional form. The change induces a new symmetry group which is distinct from, but closely related to the Lorentz group, and fixes the clock of the source for all observers. The new wave equation contains an additional term (dissipative), which arises instantaneously with acceleration. This shows that the origin of radiation reaction is not the action of a "charge" on itself but arises from inertial resistance to changes in motion. This dissipative term is equivalent to an effective mass so that classical radiation has both a massless and a massive part. Hence, at the local level the theory is one of particles and fields but there is no self-energy divergence (nor any of the other problems). We also show that, for any closed system of particles, there is a global inertial frame and unique (...

  15. Time, classical and quantum

    Science.gov (United States)

    Aniello, P.; Ciaglia, F. M.; Di Cosmo, F.; Marmo, G.; Pérez-Pardo, J. M.

    2016-10-01

    We propose a new point of view regarding the problem of time in quantum mechanics, based on the idea of replacing the usual time operator T with a suitable real-valued function T on the space of physical states. The proper characterization of the function T relies on a particular relation with the dynamical evolution of the system rather than with the infinitesimal generator of the dynamics (Hamiltonian). We first consider the case of classical hamiltonian mechanics, where observables are functions on phase space and the tools of differential geometry can be applied. The idea is then extended to the case of the unitary evolution of pure states of finite-level quantum systems by means of the geometric formulation of quantum mechanics. It is found that T is a function on the space of pure states which is not associated with any self-adjoint operator. The link between T and the dynamical evolution is interpreted as defining a simultaneity relation for the states of the system with respect to the dynamical evolution itself. It turns out that different dynamical evolutions lead to different notions of simultaneity, i.e., the notion of simultaneity is a dynamical notion.

  16. Classics in radio astronomy

    CERN Document Server

    Sullivan, Woodruff Turner

    1982-01-01

    Radio techniques were the nrst to lead astronomy away from the quiescent and limited Universe revealed by traditional observations at optical wave­ lengths. In the earliest days of radio astronomy, a handful of radio physicists and engineers made one startling discovery after another as they opened up the radio sky. With this collection of classic papers and the extensive intro­ ductory material, the reader can experience these exciting discoveries, as well as understand the developing techniques and follow the motivations which prompted the various lines of inquiry. For instance he or she will follow in detail the several attempts to detect radio waves from the sun at the turn of the century; the unravelling by Jansky of a "steady hiss type static"; the incredible story of Reber who built a 9 meter dish in his backyard in 1937 and then mapped the Milky Way; the vital discoveries by Hey and colleagues of radio bursts from the Sun and of a discrete source in the constellation of Cygnus; the development of re...

  17. Extended symmetrical classical electrodynamics.

    Science.gov (United States)

    Fedorov, A V; Kalashnikov, E G

    2008-03-01

    In this paper, we discuss a modification of classical electrodynamics in which "ordinary" point charges are absent. The modified equations contain additional terms describing the induced charges and currents. The densities of the induced charges and currents depend on the vector k and the vectors of the electromagnetic field, E and B . It is shown that the vectors E and B can be defined in terms of two four-potentials and the components of k are the components of a four-tensor of the third rank. The Lagrangian of the modified electrodynamics is defined. The conditions are derived at which only one four-potential determines the behavior of the electromagnetic field. It is also shown that static modified electrodynamics can describe the electromagnetic field in the inner region of an electric monopole. In the outer region of the electric monopole the electric field is governed by the Maxwell equations. It follows from boundary conditions at the interface between the inner and outer regions of the monopole that the vector k has a discrete spectrum. The electric and magnetic fields, energy, and angular momentum of the monopole are found for different eigenvalues of k .

  18. Classical transport in disordered systems

    Science.gov (United States)

    Papaioannou, Antonios

    This thesis reports on the manifestation of structural disorder on molecular transport and it consists of two parts. Part I discusses the relations between classical transport and the underlying structural complexity of the system. Both types of molecular diffusion, namely Gaussian and non- Gaussian are presented and the relevant time regimes are discussed. In addition the concept of structural universality is introduced and connected with the diffusion metrics. One of the most robust techniques for measuring molecular mean square displacements is magnetic resonance. This method requires encoding and subsequently reading out after an experimentally controlled time, a phase φ to the spins using magnetic field gradients. The main limitation for probing short diffusion lengths L(t) ˜ 1micro m with magnetic resonance is the requirement to encode and decode the phase φ in very short time intervals. Therefore, to probe such displacements a special probe was developed equipped with a gradient coil capable of delivering magnetic field gradients of approximately 90 G/cmA . The design of the probe is reported. Part I also includes a discussion of experiments of transport in two qualitatively different disordered phantoms and reports on a direct observation of universality in one-dimension. The results reveal the universal power law scaling of the diffusion coefficient at the long-time regime and illustrate the essence of structural universality by experimentally determining the structure correlation function of the phantoms. In addition, the scaling of the diffusive permeability of the phantoms with respect to the pore size is investigated. Additional work presented includes a detailed study of adsorption of methane gas in Vycor disordered glass. The techniques described in Part I of this thesis are widely used for measuring structural parameters of porous media, such as the surface-to-volume ratio or diffusive permeability. Part II of this thesis discusses the

  19. Classical and quantum effective theories

    CERN Document Server

    Polonyi, Janos

    2014-01-01

    A generalization of the action principle of classical mechanics, motivated by the Closed Time Path (CTP) scheme of quantum field theory, is presented to deal with initial condition problems and dissipative forces. The similarities of the classical and the quantum cases are underlined. In particular, effective interactions which describe classical dissipative forces represent the system-environment entanglement. The relation between the traditional effective theories and their CTP extension is briefly discussed and few qualitative examples are mentioned.

  20. Population in the classic economics

    OpenAIRE

    Adnan Doğruyol

    2013-01-01

    Growth subject in economics is an important factor of development. Classic economics ecole indicates the population as main variable which tender of growth. On the other hand T. R. Malthus is known as economist who regards population as a problem and brings up it among the classical economists. However, Adam Smith is an intellectual who discussed population problem earlier on the classic economics theory. According to Adam Smith one of the main factors that realise the growth is labour. In ad...

  1. Hemophagocytic syndrome in classic dengue fever

    Directory of Open Access Journals (Sweden)

    Sayantan Ray

    2011-01-01

    Full Text Available A 24-year-old previously healthy girl presented with persistent fever, headache, and jaundice. Rapid-test anti-dengue virus IgM antibody was positive but anti-dengue IgG was nonreactive, which is suggestive of primary dengue infection. There was clinical deterioration during empiric antibiotic and symptomatic therapy. Bone marrow examination demonstrated the presence of hemophagocytosis. Diagnosis of dengue fever with virus-associated hemophagocytic syndrome was made according to the diagnostic criteria of the HLH 2004 protocol of the Histiocyte Society. The patient recovered with corticosteroid therapy. A review of literature revealed only a handful of case reports that showed the evidence that this syndrome is caused by dengue virus. Our patient is an interesting case of hemophagocytic syndrome associated with classic dengue fever and contributes an additional case to the existing literature on this topic. This case highlights the need for increased awareness even in infections not typically associated with hemophagocytic syndrome.

  2. Innovations in classical hormonal targets for endometriosis.

    Science.gov (United States)

    Pluchino, Nicola; Freschi, Letizia; Wenger, Jean-Marie; Streuli, Isabelle

    2016-01-01

    Endometriosis is a chronic disease of unknown etiology that affects approximately 10% of women in reproductive age. Several evidences show that endometriosis lesions are associated to hormonal imbalance, including estrogen synthesis, metabolism and responsiveness and progesterone resistance. These hormonal alterations influence the ability of endometrial cells to proliferate, migrate and to infiltrate the mesothelium, causing inflammation, pain and infertility. Hormonal imbalance in endometriosis represents also a target for treatment. We provide an overview on therapeutic strategies based on innovations of classical hormonal mechanisms involved in the development of endometriosis lesions. The development phase of new molecules targeting these pathways is also discussed. Endometriosis is a chronic disease involving young women and additional biological targets of estrogen and progesterone pharmacological manipulation (brain, bone and cardiovascular tissue) need to be carefully considered in order to improve and overcome current limits of long-term medical management of endometriosis.

  3. Primary hyperparathyroidism with classic and severe skeletal involvement

    OpenAIRE

    Sandoval, Mark Anthony S; Paz-Pacheco, Elizabeth

    2010-01-01

    A 63-year-old woman has had multiple repeated fractures. A diagnosis of primary hyperparathyroidism (PHPT) was made after she was found to be hypercalcaemic with an elevated level of intact parathyroid hormone (iPTH). Radiographs revealed classic and severe bone findings in PHPT, features which were common in the past but are thought to be rare at this modern age. She also had nephrolithiasis and osteoporosis. An enlarged parathyroid gland was seen on ultrasound and CT scan, and hyperfunction...

  4. A Classic Beauty

    Science.gov (United States)

    2007-01-01

    M51, whose name comes from being the 51st entry in Charles Messier's catalog, is considered to be one of the classic examples of a spiral galaxy. At a distance of about 30 million light-years from Earth, it is also one of the brightest spirals in the night sky. A composite image of M51, also known as the Whirlpool Galaxy, shows the majesty of its structure in a dramatic new way through several of NASA's orbiting observatories. X-ray data from NASA's Chandra X-ray Observatory reveals point-like sources (purple) that are black holes and neutron stars in binary star systems. Chandra also detects a diffuse glow of hot gas that permeates the space between the stars. Optical data from the Hubble Space Telescope (green) and infrared emission from the Spitzer Space Telescope (red) both highlight long lanes in the spiral arms that consist of stars and gas laced with dust. A view of M51 with the Galaxy Evolution Explorer telescope shows hot, young stars that produce lots of ultraviolet energy (blue). The textbook spiral structure is thought be the result of an interaction M51 is experiencing with its close galactic neighbor, NGC 5195, which is seen just above. Some simulations suggest M51's sharp spiral shape was partially caused when NGC 5195 passed through its main disk about 500 million years ago. This gravitational tug of war may also have triggered an increased level of star formation in M51. The companion galaxy's pull would be inducing extra starbirth by compressing gas, jump-starting the process by which stars form.

  5. Innovation: the classic traps.

    Science.gov (United States)

    Kanter, Rosabeth Moss

    2006-11-01

    Never a fad, but always in or out of fashion, innovation gets rediscovered as a growth enabler every half dozen years. Too often, though, grand declarations about innovation are followed by mediocre execution that produces anemic results, and innovation groups are quietly disbanded in cost-cutting drives. Each managerial generation embarks on the same enthusiastic quest for the next new thing. And each generation faces the same vexing challenges- most of which stem from the tensions between protecting existing revenue streams critical to current success and supporting new concepts that may be crucial to future success. In this article, Harvard Business School professor Rosabeth Moss Kanter reflects on the four major waves of innovation enthusiasm she's observed over the past 25 years. She describes the classic mistakes companies make in innovation strategy, process, structure, and skills assessment, illustrating her points with a plethora of real-world examples--including AT&T Worldnet, Timberland, and Ocean Spray. A typical strategic blunder is when managers set their hurdles too high or limit the scope of their innovation efforts. Quaker Oats, for instance, was so busy in the 1990s making minor tweaks to its product formulas that it missed larger opportunities in distribution. A common process mistake is when managers strangle innovation efforts with the same rigid planning, budgeting, and reviewing approaches they use in their existing businesses--thereby discouraging people from adapting as circumstances warrant. Companies must be careful how they structure fledgling entities alongside existing ones, Kanter says, to avoid a clash of cultures and agendas--which Arrow Electronics experienced in its attempts to create an online venture. Finally, companies commonly undervalue and underinvest in the human side of innovation--for instance, promoting individuals out of innovation teams long before their efforts can pay off. Kanter offers practical advice for avoiding

  6. Bone marrow transplant

    Science.gov (United States)

    Transplant - bone marrow; Stem cell transplant; Hematopoietic stem cell transplant; Reduced intensity nonmyeloablative transplant; Mini transplant; Allogenic bone marrow transplant; Autologous bone marrow transplant; Umbilical ...

  7. Bone morbidity in chronic myeloproliferative neoplasms

    DEFF Research Database (Denmark)

    Farmer, Sarah; Ocias, Lukas Frans; Vestergaard, Hanne;

    2015-01-01

    Patients with the classical Philadelphia chromosome-negative chronic myeloproliferative neoplasms including essential thrombocythemia, polycythemia vera and primary myelofibrosis often suffer from comorbidities, in particular, cardiovascular diseases and thrombotic events. Apparently, there is also...... neoplasms. Chronic inflammation has been suggested to explain the initiation of clonal development and progression in chronic myeloproliferative neoplasms. Decreased bone mineral density and enhanced fracture risk are well-known manifestations of many chronic systemic inflammatory diseases. As opposed to...... systemic mastocytosis (SM) where pathogenic mechanisms for bone manifestations probably involve effects of mast cell