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Schwartz, Daniel. "Development of an Aqueous Suspension of Recombinant Human Bone Morphogenetic Protein-2 (rhBMP-2)." Diss., lmu, 2005. http://nbn-resolving.de/urn:nbn:de:bvb:19-44316.
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Cruz, Erin E. "OSSEOINTEGRATION OF TEMPORARY ANCHORAGE DEVICES USING RECOMBINANT HUMAN BONE MORPHOGENETIC PROTEIN-2." DigitalCommons@CalPoly, 2010. https://digitalcommons.calpoly.edu/theses/343.
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Over the past 5 years, the use of titanium implants as temporary anchorage devices (TADs) has become an important tool in clinical orthodontic practices. The use of TADs have provided orthodontists a way of moving teeth against fixed objects rather than against the surrounding teeth, which tend to counteract desired motion. At present, viable attachment of TADs involves direct insertion through gingival tissue and piercing of the bone. Surface modifications such as sandblasted and acid-etched treatment or bone morphogenetic protein surface treatment, however, can be applied to the TADs to promote enhanced osseointegration, thereby allowing the TADs to serve as stable anchors while avoiding bone puncture. In this study, a comparison was made between sandblasted/acid-etched TADs and sandblasted/acid-etched/recombinant human bone morphogenetic protein-2 (rhBMP-2) treated TADs to determine whether rhBMP-2 promotes enhanced osseointegration. A total of 10 rats (4 controls and 6 treated with rhBMP-2) were used in the study, with 1 TAD placed on the skull of each rat. At the end of 6 weeks, the animals were euthanized by carbon dioxide asphyxiation, and bone blocks, each containing a TAD, were prepared for histological examination and biomechanical characterization. The results of this study showed that TADs treated with rhBMP-2 had greater bone formation at the bone-implant interface and an increase in total implant stability.
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Kaihara, Shinji. "Effect of FK506 on osteoinduction by recombinant human bone morphogenetic protein-2." Kyoto University, 2003. http://hdl.handle.net/2433/148767.
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Tamura, Kayo. "The effect of nicotine and smoking on osteoinduction by recombinant human bone morphogenetic protein-2." Kyoto University, 2014. http://hdl.handle.net/2433/189662.
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Cruz, Eden E. "THE EFFECT OF RECOMBINANT HUMAN BONE MORPHOGENETIC PROTEIN-2 ON THE OSSEOINTEGRATION OF TEMPORARY ANCHORAGE DEVICES." DigitalCommons@CalPoly, 2010. https://digitalcommons.calpoly.edu/theses/331.
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Titanium has been widely used for dental implants, and in particular, roughened titanium surfaces have provided a means for increasing bone apposition and strengthening the implant-to-bone interface. Finding a way to further increase osseointegration is important because there is a significant clinical benefit to patients if a stable anchor can be established instead of anchoring orthodontic hardware to the molars. In this study, the effect of recombinant human bone morphogenetic protein-2 (rhBMP-2) on the ability of temporary anchorage devices (TADs) to osseointegrate was investigated. The temporary anchorage devices (TADs) used in this study were manufactured from commercially pure titanium and divided into 2 types of treatments: (1) sandblasted and acid-etched (i.e. the control) and (2) sandblasted and acid-etched treated with Medtronic INFUSE® Bone Graft (recombinant human bone morphogenetic protein-2 placed on an absorbable collagen sponge). The implants were placed on the cranial bones of 10 adult male Sprague-Dawley rats. The rats were euthanized by carbon dioxide asphyxiation 6 weeks following surgery for histological examination and biomechanical testing. The results from visual inspection and biomechanical testing showed that the sandblasted and acid-etched TADs treated with rhBMP-2 promoted better osseointegration than TADs that were only sandblasted and acid-etched. Specifically, surface modified TADs treated with rhBMP-2 on bottom showed an increased surface coverage by bone and an increase in the adhesion strength at the TAD-to-bone interface.
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Yong, Mostyn R. "Characterisation of Polycaprolatone-Based Scaffold Plus Recombinant Human Morphogenetic Protein - 2 (RHBMP-2) in an Ovine Thoracic Spine Model." Thesis, Queensland University of Technology, 2013. https://eprints.qut.edu.au/64093/1/Mostyn_Yong_Thesis.pdf.
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This thesis represents a step forward in the development of a pre-clinical model investigating a suitable substitute for host bone for use in human spinal fusion.
By way of an animal model, it examines the biological performance of a novel bone graft substitute comprised of a combination of a custom-designed biodegradable material and biologics.
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Shaheen, Ibrahim Ahmed. "Studies of the effects of recombinant human bone morphogenetic protein-2 on human periodontal ligament cells in vitro." Thesis, Queen Mary, University of London, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.267481.
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Mao, Liangyan. "Assessment of Bone Regeneration in a Rat Femur Defect Model Following Recombinant Human Bone Morphogenetic Protein 2 Delivery from Keratin Hydrogels with Tunable Rates of Degradation: Micro-CT Analysis and Histology." Miami University / OhioLINK, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=miami148068386349526.
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Forbes-Robertson, Sarah Anne Natasha. "Structure and expression of the chicken bone morphogenetic protein-2 gene." Thesis, University College London (University of London), 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.244093.
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Zhou, Lixiong, and 周立雄. "Differential action of bone morphogenetic protein BMP-2 and BMP-7 on nucleus pulposus cells of intervertebral disc." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2014. http://hdl.handle.net/10722/209509.
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Low back pain (LBP) is associated with intervertebral disc (IVD) degeneration and exerts enormous socioeconomic burdens on the society. The nucleus pulposus (NP) is the structural and functional core of the IVD, and plays vital roles in its homeostasis. Although the etiology of IVD degeneration is not fully understood, the cellular changes of the NP have been proposed to be associated with degeneration. Conventional management for IVD degeneration primarily targets to relieve LBP and other symptoms without restoring or preserving disc function. Novel therapeutic strategies have emerged with an aim to retard or even reverse disc degeneration. In particular, the use of growth factors, such as the bone morphogenetic proteins (BMP), has received considerable attention due to their anabolic effects on extracellular matrix (ECM) synthesis by NP cells.
BMP-2 and BMP-7 are of great interest for their involvement in osteogenesis, chondrogenesis, and development and maintenance of the IVD. To date, the benefits of BMP-2 on disc degeneration are controversial, given the inconsistent findings from animal model studies. The effectiveness of BMP-7 in disc repair, however, has been well demonstrated both in vitro and in vivo. A better understanding of the differences between BMP-2 and BMP-7 regulatory action on NP cells may facilitate future applications of BMP in disc repair/regeneration.
This study hypothesized that BMP-2 and BMP-7 act differentially on human NP cells via different signal transduction processes. The differential effect of BMP-2 and BMP-7 was first tested in bovine NP cells using a three-dimensional culture system (alginate beads). Both BMP-2 and BMP-7 enhanced ECM production and phenotypic characteristics of bovine NP cells. Notably, BMP-7 was significantly more potent than BMP-2 in this regard. The effects of BMPs were further tested on non-degenerated (ND-NP) and degenerated (D-NP) human NP cells. The DMMB assay revealed that BMP-7 exerted a superior up-regulatory action on GAG production of D-NP cells compared to BMP-2. Furthermore, the overall response of D-NP cells to BMP-2 and BMP-7 was significantly lower than ND-NP cells.
Immunohistochemical staining and quantitative RT-PCR assays demonstrated that D-NP cells possess a more fibroblastic and less chondrocyte-like phenotype than ND-NP cells. At the mRNA level, the BMP receptor BMPR1A was not expressed in D-NP cells. BMP-7, but not BMP-2, induced expression of BMPR1A in D-NP cells. On the other hand, gene expression of selected TGF-β pathway components and hypoxia pathway components were significantly up-regulated by BMP-2 but down-regulated by BMP-7. These findings suggest that D-NP cells can activate differential molecular cascades in response to BMP-2 and BMP-7.
In conclusion, this study showed a superior effect of BMP7 in up-regulation of classical BMP signaling components including BMP receptor BMPR1A. The reduced responsiveness of D-NP cells to BMP-2 and BMP-7 stimulation may be related to a different expression pattern of BMP receptors. This study provides insights into the differential regulatory actions of BMP-2 and BMP-7 on human NP cells and facilitates the future application of BMPs in managing disc degeneration.<br>published_or_final_version<br>Orthopaedics and Traumatology<br>Doctoral<br>Doctor of Philosophy
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Wei, Fei. "The osteoimmune effect of bone morphogenetic protein-2 in bone regeneration and biomaterial modification." Thesis, Queensland University of Technology, 2020. https://eprints.qut.edu.au/198148/1/Fei_Wei_Thesis.pdf.
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Bone morphogenetic protein-2 (BMP2), one of most well-known osteoinductive molecules, has been extensively used in the orthopedics and dentistry. However, inflammatory reactions are regularly reported for its side effect. This project investigated the immune environment induced by BMP2 and unveiled the regulation of BMP2 in the cross talk between immune cells and bone forming cells. This project provides better understanding of BMP2 application in the treatment of fracture healing and bone-related diseases.
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Li, Jingxuan. "EVALUATION OF BONE MORPHOGENETIC PROTEIN-2 RELEASE FROM KERATIN SCAFFOLDS IN VITRO AND IN VIVO." Miami University / OhioLINK, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=miami1462919774.
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Simon, Michaela. "Der Einfluss von Bone Morphogenetic Protein (BMP-)2, BMP-4 und BMP-7 auf die Regulation der Proliferation und Differenzierung von hämatopoetischen Vorläuferzellen aus dem peripheren Blut." kostenfrei, 2009. http://www.opus-bayern.de/uni-regensburg/volltexte/2009/1393/.
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Bressan, Michael C. "BMP signaling and tenascin-C in vascular development and remodeling /." Access full-text from WCMC, 2009. http://proquest.umi.com/pqdweb?did=1619205491&sid=1&Fmt=2&clientId=8424&RQT=309&VName=PQD.
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Chatzinikolaidou, Maria. "Untersuchungen zur Immobilisierung und Freisetzung von rekombinantem humanem bone morphogenetic Protein 2 (BMP-2) in biologisch aktiver Form auf metallischen Implantatoberflächen." [S.l.] : [s.n.], 2004. http://deposit.ddb.de/cgi-bin/dokserv?idn=975072633.
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Henkenberens, Christoph [Verfasser]. "Der Effekt von Bone Morphogenetic Protein-2 (BMP-2) bei bakteriell kontaminierten Tibiaschaftfrakturen : eine experimentelle Studie an einem Rattenmodell / Christoph Henkenberens." Gießen : Universitätsbibliothek, 2013. http://d-nb.info/1065184352/34.
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Valcourt, Ulrich. "Mécanismes cellulaires et moléculaires de la différenciation des chondrocytes induite par un facteur morphogénétique, la Bone Morphogenetic Protein-2 (BMP-2)." Lyon 1, 2001. http://www.theses.fr/2001LYO10222.
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La Bone morphogenetic protein-2 (BMP-2) est un facteur de signalisation apparenté aux TGF (Transforming growth factor)-β et impliqué dans la formation du squelette. Nous avons analysé les effets de la BMP-2 sur l'expression du phénotype de chondrocytes murins immortalisés (cellules MC615) ou embryonnaires primaires. La BMP-2 déclenche trois réponses concomitantes dans les chondrocytes : (i) la maintenance et même la simulation de leur phénotype différencié, (ii) leur maturation hypertrophique et (iii) leur différenciation ostéoblastique. Les formes activées des récepteurs de type I aux membres de la superfamille du TGF-β ont été surexprimées dans des chondrocytes afin d'élucider leur rôle dans ce processus de maturation et de différenciation ostéoblastique. En utilisant un système d'expression adénoviral, nous avons montré que les récepteurs activés ALK-1, -2, -3 et -6 reproduisent la maturation hypertrophique des chondrocytes induite par BMP-2. En outre, le récepteur ALK-2 activé induit également leur différenciation en ostéoblastes. Les protéines de signalisation intracellulaire Smad6 et 7 inhibent la différenciation hypertrophique et ostéoblastique des chondrocytes en réponse à BMP-2, mais ne sont pas suffisantes pour induire leur différenciation ostéoblastique. En revanche, les protéines Smad6 et 7 inhibent la différenciation hypertrophique et ostéoblastique des chondrocytes induite par BMP-2. Enfin, ce système de différenciation "éprouvette" a permis d'identifier un nouveau gène dont l'expression est induite par BMP-2, le gène Bat (BMP-2 activated transcript). L'expression du gène Bat est retrouvée chez la souris au niveau des chondrocytes hypertrophiques des éléments squelettiques appendiculaires et axiaux. Ce résultat suggère une implication éventuelle du gène Bat dans les processus d'ossification endochondrale.
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Claus, Stéphanie. "Régulation du phénotype de chondrocytes humains par la Bone Morphogenetic Protein-2 : retombées pour l’ingénierie tissulaire du cartilage." Thesis, Lyon 1, 2010. http://www.theses.fr/2010LYO10277.
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Le but de cette étude était d’évaluer si la bone morphogenetic protein (BMP)-2 pouvait aider à contrôler le phénotype de chondrocytes humains dans des conditions de culture à long terme nécessaires pour la transplantation de chondrocytes autologues (TCA). Nous avons aussi évalué le potentiel de la BMP-2 comme facteur de réparation du cartilage, en combinaison avec un biomatériau à base de collagène, pour étendre la technique aux lésions arthrosiques. Des chondrocytes humains ont été cultivés selon la procédure utilisée pour la TCA. Nous avons évalué la réponse des chondrocytes à la BMP-2 en culture monocouche ou dans les éponges de collagène par des analyses par PCR en temps réel, par Western blotting et Immunohistochimie.L’ajout de BMP-2 améliore le caractère chondrogénique des chondrocytes humains amplifiés en monocouche. L’effet stimulateur de la BMP-2 sur l’expression du collagène de type II a été observé au niveau des gènes mais aussi des protéines, ce qui est une propriété essentielle pour la reconstruction d’une matrice cartilagineuse. Nos résultats ont aussi montré que dans des chondrocytes tout d’abord amplifiés en monocouche puis cultivés en éponges de collagène en présence de BMP-2, la BMP-2 est capable de restaurer l’expression du gène COL2A1 et la synthèse de collagène de type II qui avaient été perdues pendant l’amplification. De manière importante, aucun signe de maturation hypertrophique ou d’induction ostéogénique n’a été détecté. Cette étude est la première à révéler le bénéfice de l’ajout de BMP-2 à des chondrocytes humains comme un agent thérapeutique pour la réparation du cartilage<br>The aim of this study was to investigate if bone borphogenetic brotein (BMP)-2 could help to control human chondrocytes phenotype in long-term culture conditions necessary for autologous chondrocyte implantation (ACI). We also evaluated the potential of BMP-2 as a repair factor in combination with collagen-based biomaterials, to extend the technique to osteoarthritic lesions. Human chondrocytes were cultured independently, according to the procedure used for ACI. We evaluated the responsiveness of chondrocytes to BMP-2 when cultured in monolayer or within collagen sponges using Real-time PCR, Western blotting and Immunohistochemistry. Exogenous BMP-2 improved the chondrogenic character of human chondrocytes when amplified in monolayer. The stimulatory effect of BMP-2 on type II collagen expression was observed not only at the mRNA level but also at the protein level, and this is crucial for cartilage matrix reconstruction. Our data with human chondrocytes first amplified in monolayer then cultured in collagen sponges in the presence of BMP-2 have revealed that BMP-2 is able to restore COL2A1 gene expression and type II collagen synthesis that were lost during the amplification step. Importantly, no sign of hypertrophic maturation or osteogenic induction was detected beside the chondrogenic stimulatory effect of BMP-2. This study is the first to reveal the benefit of adding exogenous BMP-2 to human chondrocytes as a therapeutic agent for cartilage repair
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Mundy, Christina Maria. "The Interaction Between Connective Tissue Growth Factor and Bone Morphogenetic Protein-2 During Osteoblast Differentiation and Function." Diss., Temple University Libraries, 2014. http://cdm16002.contentdm.oclc.org/cdm/ref/collection/p245801coll10/id/269581.
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Cell Biology<br>Ph.D.<br>Connective tissue growth factor (CTGF/CCN2) and bone morphogenetic protein (BMP)-2 are both produced and secreted by osteoblasts. Both proteins have been shown to have independent effects in regulating osteoblast proliferation, maturation and mineralization. However, how these two proteins interact during osteoblast differentiation remains unknown. In Chapters 2 and 3, we utilized two cell culture model systems, osteoblasts derived from CTGF knockout (KO) mice and osteoblasts infected with an adenovirus, which over-expresses CTGF (Ad-CTGF), to investigate the effects of CTGF and BMP-2 on osteoblast development and function in vitro. To observe differences in osteoblast maturation and mineralization, we performed alkaline phosphatase (ALP) staining and activity and alizarin red staining, respectively. Contrary to a previously published report, osteoblast maturation and mineralization were similar in osteogenic cultures derived from KO and wild type (WT) calvaria in the absence of BMP-2 stimulation. Interestingly, in KO and WT osteoblast cultures stimulated with BMP-2, the KO osteoblast cultures exhibited increased alkaline phosphatase staining and activity and had larger, fused nodules stained with alizarin red than WT osteoblast cultures. This increase in osteoblast differentiation was accompanied by increased protein levels of phosphorylated Smad 1/5/8 and mRNA expression levels of bone morphogenetic protein receptor Ib. These data confirm enhanced osteoblast maturation and mineralization in BMP-2 induced KO osteoblast cultures. We also examined osteoblast differentiation in cultures that were infected with Ad-CTGF and in control cultures. Continuous over-expression of CTGF resulted in decreased ALP staining and activity, alizarin red staining, and mRNA expression of osteoblast markers in both unstimulated and BMP-2 stimulated cultures. Impaired osteoblast differentiation in cultures over-expressing CTGF was accompanied by decreased protein levels of phosphorylated Smad 1/5/8. In addition to the functional assays that we performed on WT and KO osteoblast cultures, we performed ChIP assays to investigate differences in binding occupancy of transcription factors on the Runx2 and Osteocalcin promoters in BMP-2 induced WT and KO osteoblast cultures. We demonstrate that in BMP-2 induced WT and KO osteoblast cultures, there was greater Smad 1 and JunB occupancy on the Runx2 promoter and Runx2 occupancy on the Osteocalcin promoter in BMP-2 induced KO osteoblast cultures compared to WT cultures. Collectively, the data demonstrate that CTGF acts to negatively regulate BMP-2 induced signaling and osteoblast differentiation. In Chapter 4, we synthesized an active His-tagged BMP-2 recombinant protein to track surface binding of BMP-2 in CTGF WT and KO osteoblasts. We amplified mature BMP-2 in genomic DNA, which was inserted correctly into a pET-28b(+) vector. We ran a SDS-PAGE gel and stained with Coomassie blue to show that we successfully induced BMP-2 in bacteria cells, extracted the protein using urea, and purified and eluted the protein using Nickel charged agarose beads and imidazole elution buffer. Furthermore, by Western blot analysis using anti-His antibody, we confirmed the presence of the His-tag on the BMP-2 protein. Lastly, ALP staining on osteoblast cultures stimulated with our synthesized BMP-2 exhibited increased staining compared to the unstimulated osteoblast cultures, which confirmed the activity of our His-tagged BMP-2 protein. Future studies utilizing this protein will demonstrate that CTGF acts as an extracellular antagonist by limiting the amount of BMP-2 available for receptor binding.<br>Temple University--Theses
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Crönlein, Moritz [Verfasser], and Thomas [Akademischer Betreuer] Frangen. "In vitro Zellkultur-Studie über die Signifikanz von Bone Morphogenetic Protein-2 (BMP-2) im Prozess der Knochen-Sehnen-Integration / Moritz Crönlein. Betreuer: Thomas Frangen." Marburg : Philipps-Universität Marburg, 2012. http://d-nb.info/1027183727/34.
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Carvalho, Sara Catarina da Silva. "O papel das BMPs na regeneração óssea." Master's thesis, [s.n.], 2015. http://hdl.handle.net/10284/5139.
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Projeto de Pós-Graduação/Dissertação apresentado à Universidade Fernando Pessoa como parte dos requisitos para obtenção do grau de Mestre em Medicina Dentária<br>O tecido ósseo quando lesado possui capacidade de regeneração. No entanto, na presença de certas patologias ou lesões, esta capacidade poderá ser comprometida. Neste contexto, a fração de uma proteína foi isolada da matriz óssea desmineralizada, denominando-se Bone Morphogenetic Proteins (BMPs) ou Proteínas Morfogenéticas do Osso; descobertas pelo Dr. Marshall Urist em 1965. Estas proteínas parecem constituir uma boa alternativa no contorno deste problema, uma vez que possuem capacidade de formar cartilagem e novo osso (inclusive osso heterotópico). O seu uso clínico foi aprovado pela Food and Drug Administration (FDA), respetivamente a BMP 7 e BMP 2. Devido ao seu potencial osteoindutivo e osteocondutivo, vários estudos in vitro e in vivo têm decorrido desde a sua descoberta. Sendo que estes fatores tornaram-se de grande interesse em várias áreas como a Ortopedia na Medicina e Cirurgia Oral na Medicina Dentária.
Esta revisão bibliográfica tem como intuito o esclarecimento a partir da informação disponível acerca destas proteínas, nomeadamente, a sua constituição, mecanismos de ação, fatores condicionantes e potenciadores da sua ação, aplicações clínicas (inclusive na área da Medicina Dentária) e limitações no seu uso como fator regenerativo. Bone tissue when injured has the ability of regeneration. However, in the presence of certain pathologies or lesions, this ability can be compromised. In this context, a fraction of a protein was isolated from the demineralized bone matrix, called Bone Morphogenetic Proteins (BMPs); discovered by Dr. Marshall Urist in 1965. These proteins appear to be a good alternative to the overcome this problem, as they possess the ability to form new cartilage and bone, even heterotopic bone. Their clinical use was approved by Food and Drug Administration (FDA), respectively BMP 7 and BMP 2. Due to their osteoinductive and osteoconductive potential, several in vitro and in vivo studies have occurred since their discovery. Therefore these factors have become of great interest in various fields such as Orthopedics in Medicine and Oral Surgery in Dentistry.
This literature review has the aim to clarify the available information about these proteins, namely, their constitution, mechanisms of action, conditioning factors and enhancers of their action, clinical applications (including in the field of Dentistry) and limitations of their use as a regenerative factor.
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Anyango, Joseph Ochieng. "Physico-chemical modification of kafirin microstructures for application as biomaterials." Thesis, University of Pretoria, 2012. http://hdl.handle.net/2263/29708.
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Microparticles produced from kafirin, the sorghum grain prolamin protein, by molecular selfassembly using coacervation with acetic acid solvent are vacuolated. They have shown considerable potential for encapsulation of antioxidants and for preparation of high quality free-standing bioplastic films. However, the functional quality of these kafirin microstructures needs to be improved to exploit their potential application, particularly as biomaterials. Wet heat, transglutaminase and glutaraldehyde treatments were used to modify the physical structure and chemical properties of the kafirin microstructures. Heat treatment (50–96°C) increased microparticle average size by up to four-fold to ≈20 μm, probably due to disulphide cross-linking of kafirin proteins. The vacuoles within these microparticles enlarged up to >10-fold, probably due to greater expansion of air within the microparticles with higher temperature, as the vacuoles are probably footprints of air bubbles. As with heat treatment, glutaraldehyde (10–30%) treatment resulted in oval microparticles, up to about four-fold larger than the control, probably due to covalent glutaraldehyde-polypeptide linkage. Transglutaminase (0.1–0.6%) treatment had only slight effect on the size and shape of microparticles, probably because kafirin has very low lysine content, inhibiting transglutaminase-catalysed cross-linking through ε-(-glutamyl)-lysine bonding. Surface morphology using atomic force microscopy indicated that the microparticles apparently comprised coalesced nanostructures. With heat and transglutaminase treatments, the microparticles seemed to be composed of round nanostructures that coalesced into random irregular shapes, indicative of non-linear protein aggregation. In contrast, with glutaraldehyde treatment, the nanostructures were spindle-shaped and had a unidirectional orientation, probably due to linear alignment of the nanostructures controlled by glutaraldehyde-polypeptide linkage. Thin (<50 μm) films prepared from kafirin microparticles and conventional cast kafirin films were compared in terms of their water stability and other related properties. Films cast from microparticles were more water-stable compared to conventional kafirin films, probably because the large vacuoles within the kafirin microparticles may have enhanced protein solubility in the casting solution, thereby improving the film matrix cohesion. The films prepared from microparticles treated with glutaraldehyde were more water-stable compared to the control, despite the loss of plasticizer, probably due to formation of the covalent glutaraldehyde-polypeptide linkages. The potential of modified kafirin microparticles to bind bone morphogenetic protein-2 (BMP- 2) was investigated. Compared to a collagen standard, the BMP-2 binding capacity of control, heat-treated, transglutaminase-treated and glutaraldehyde-treated kafirin microparticles were 7%, 18%, 34% and 22% higher, respectively, probably mainly due to the vacuoles within the microparticles creating greater binding surface area. The safety, biodegradability and effectiveness of kafirin microparticle film and kafirin microparticle film-BMP-2 system in inducing bone growth were determined by a subcutaneous bioassay using a rat model. Kafirin microparticle film and kafirin microparticle film-BMP-2 system was non-irritant to the animals, probably because kafirin is non-allergenic. The kafirin microparticle film implants showed signs of some degradation but a large proportion of these implants was still intact by Day 28 post implantation, probably because of the low susceptibility of kafirin to mammalian proteolytic enzymes. Kafirin microparticle film-BMP-2 system did not induce bone growth, probably mainly due to low BMP-2 dosage and short study duration. Modification of kafirin microparticles by wet heat or glutaraldehyde treatment both result in increased size of the microparticles with similar gross structure. However, it is apparent that with both treatments the proteins within the pre-formed kafirin microparticles undergo some form of further assisted-assembly through different mechanisms. It seems that heat-induced disulphide cross-linking reinforces a layer around the nanostructures, probably rich in γ- kafirin polypeptides, that stabilizes the structure of the nanostructures. In contrast, glutaraldehyde-treatment appears to destabilize this structure-stabilizing layer through formation of γ-kafirin polypeptide-glutaraldehyde covalent bonding. This probably offsets the balance of attractive and repulsive forces between the different kafirin subclasses within the nanostructures, thereby resulting in collapsed nanostructures and linear realignment. A deeper understanding of the mechanism of kafirin self-assembly will be important for further development of kafirin microstructures for different applications.<br>Thesis (PhD)--University of Pretoria, 2012.<br>Food Science<br>unrestricted
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Wahedi, Mastura, Aaron M. Wortham, Mark D. Kleven, et al. "Matriptase-2 suppresses hepcidin expression by cleaving multiple components of the hepcidin induction pathway." AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC, 2017. http://hdl.handle.net/10150/626185.
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Systemic iron homeostasis is maintained by regulation of iron absorption in the duodenum, iron recycling from erythrocytes, and iron mobilization from the liver and is controlled by the hepatic hormone hepcidin. Hepcidin expression is induced via the bone morphogenetic protein (BMP) signaling pathway that preferentially uses two type I (ALK2 and ALK3) and two type II (ActRIIA and BMPR2) BMP receptors. Hemojuvelin (HJV), HFE, and transferrin receptor-2 (TfR2) facilitate this process presumably by forming a plasma membrane complex with BMP receptors. Matriptase-2 (MT2) is a protease and key suppressor of hepatic hepcidin expression and cleaves HJV. Previous studies have therefore suggested that MT2 exerts its inhibitory effect by inactivating HJV. Here, we report that MT2 suppresses hepcidin expression independently of HJV. In Hjv(-/-) mice, increased expression of exogenous MT2 in the liver significantly reduced hepcidin expression similarly as observed in wild-type mice. Exogenous MT2 could fully correct abnormally high hepcidin expression and iron deficiency in MT2(-/-) mice. In contrast to MT2, increased Hjv expression caused no significant changes in wild-type mice, suggesting that Hjv is not a limiting factor for hepcidin expression. Further studies revealed that MT2 cleaves ALK2, ALK3, ActRIIA, Bmpr2, Hfe, and, to a lesser extent, Hjv and Tfr2. MT2-mediated Tfr2 cleavage was also observed in HepG2 cells endogenously expressing MT2 and TfR2. Moreover, iron-loaded transferrin blocked MT2-mediated Tfr2 cleavage, providing further insights into the mechanism of Tfr2's regulation by transferrin. Together, these observations indicate that MT2 suppresses hepcidin expression by cleaving multiple components of the hepcidin induction pathway.
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Palosaari, H. (Heidi). "Matrix metalloproteinases (MMPs) and their specific tissue inhibitors (TIMPs) in mature human odontoblasts and pulp tissue:the regulation of expressions of fibrillar collagens, MMPs and TIMPs by growth factors, transforming growth factor-β1 (TGF-β1) and bone morphogenetic protein-2 (BMP-2)". Doctoral thesis, University of Oulu, 2003. http://urn.fi/urn:isbn:9514270789.
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Abstract
Dentin formation in physiological and pathological conditions has been widely studied, but the events and regulation are still not completely understood. Odontoblasts, terminally differentiated post-mitotic cells located in a single cell layer around pulp tissue, synthesize and mineralize dentin organic matrix. Growth factors, such as TGF-β1 and BMP-2, have been implicated in the regulation of the responses of odontoblasts and pulp tissue to external irritation. Matrix metalloproteinases (MMPs), a family of 28 endopeptidases collectively capable of degrading virtually all extracellular matrix components, and their specific tissue inhibitors (TIMPs) participate in the organo- and morphogenesis, physiological tissue turnover and pathological tissue destruction in many tissues, but very little is known about their presence, function, and regulation in the dentin-pulp complex cells and tissues. The aim of the work presented in this thesis was to analyze the expression and regulation of collagens, MMPs and TIMPs by TGF-β1 and BMP-2 in mature human odontoblasts and pulp tissue. Odontoblasts synthesize and secrete type I and type III collagens, with no clear effect of TGF-β1 on their expression levels. MMP-1, -2, -8, -9, -10, -11, -14, -15, -16, -19 and TIMP-1, -2, -3 and -4 were expressed by both odontoblasts and pulp tissue. MMP-3 and MMP-12 were not expressed in native odontoblasts or pulp tissue, and MMP-7, -24, and -25 were expressed only in odontoblasts. MMP-2, -10, -14, -20 and -23 were expressed more abundantly in odontoblasts, whereas pulp tissue expressed more MMP-13 and MMP-17. Growth factors differentially regulated the expression of different MMPs and TIMPs within and among the cells and tissues studied. In odontoblasts, MMP-1, -8 and -14 were down-regulated, but MMP-7, MMP-9, TIMP-1 and TIMP-3 up-regulated, by either TGF-β1 or BMP-2, alone or in combination. In pulp tissue, growth factors up-regulated the expression of MMP-1, -2, -10, -13, -17 and TIMP-3, but down-regulated TIMP-4. The widespread of expression of MMPs and TIMPs by mature human odontoblasts and pulp tissue suggests that they may participate in dentin matrix organization prior to mineralization, and that growth factors may further control dentin matrix modeling, not by regulating the synthesis of type I or III collagens as previously believed, but rather by differentially regulating each MMPs and TIMPs.
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Cirano, Fabiano Ribeiro. "Influência de diferentes superfícies de titânio na adesão, proliferação e diferenciação de células semelhantes a osteoblastos de ratos (osteo-1) em culturas, na presença ou não da proteína morfogenética óssea recombinante-2 (rhBMP-2)." Universidade de São Paulo, 2007. http://www.teses.usp.br/teses/disponiveis/23/23146/tde-08042008-180815/.
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Este estudo analisou a influência de diferentes superfícies de titânio na adesão, proliferação e diferenciação de células semelhantes a osteoblastos de rato (osteo-1) em culturas, na presença ou não da proteína morfogenética óssea recombinante-2 (rhBMP-2). As células osteo-1 foram cultivadas sobre as seguintes superfícies de titânio: 1. superfície lisa, 2. superfície desgastada com partículas de areia e condicionamento ácido (SLA) e 3. superfície desgastada com partículas de areia e condicionamento ácido sob proteção de nitrogênio e armazenadas em solução isotônica de cloreto de sódio (SLActive), na presença ou não de 20 ng/ml de rhBMP-2. Foram analisadas a adesão celular em 24 horas, o conteúdo total de proteínas, o conteúdo de colágeno e a atividade de fosfatase alcalina em 7, 14 e 21 dias e a formação de nódulos calcificados em 21 dias. Os resultados mostraram que a adesão não foi influenciada nem pelo tipo de superfície nem pelo tratamento com rhBMP-2 (p=0,0936). Quando relacionamos o conteúdo total de proteínas ao número total de células, percebemos que a proliferação não foi influenciada pelo tipo de superfície de titânio, porém a adição de rhBMP-2 levou a uma redução estatisticamente significante na superfície SLA aos 21 dias (p=0,0000). Em relação à diferenciação, pudemos observar que o tipo de superfície não influenciou o conteúdo total de proteínas, o conteúdo de colágeno e a formação de nódulos calcificados em quaisquer dos períodos analisados. A atividade de fosfatase alcalina somente foi influenciada pelo tipo de superfície aos 14 dias, onde o grupo C/SLAactive apresentou valores inferiores ao grupo C/Liso (p=0,0000). A adição de rhBMP-2 promoveu uma maior influência sobre o processo de diferenciação, levando a uma redução estatisticamente significante no conteúdo total de proteínas na superfície SLA aos 21 dias (p=0,0000), a um aumento estatisticamente significante no conteúdo de colágeno na superfície SLActive no período de 7 dias (p=0,0005) e a uma diminuição estatisticamente significante na atividade de fosfatase alcalina na superfície lisa nos períodos de 14 e 21 dias, na superfície SLA aos 14 dias e na superfície SLActive aos 21 dias (p=0,0000). Somente a formação de nódulos calcificados não sofreu influência da adição de rhBMP-2.<br>This study has analyzed the influence of different titanium surfaces in the adhesion, proliferation and differentiation of rat osteoblast-like cells (osteo-1 culture), in the presence or not, of the recombinant bone morphogenetic protein-2 (rhBMP-2). The osteo-1 cells were grown on the following titanium surfaces: 1. smooth surface; 2. coarse grit-blasted and acid-etched surface (SLA); and 3. coarse grit-blasted and acid-etched surface under nitrogen protection, and stored in sodium chloride isotonic solution (SLActive), in the presence or not, of 20 ng/ml of rhBMP-2. It was analyzed the cell adhesion in 24 hours, the total protein content, the collagen content, and the alkaline phosphatase in 7, 14 and 21-day periods, and also the formation of calcified nodules in 21 days. The results showed that the adhesion was neither influenced by the surface type, nor by the treatment with rhBMP-2 (p=0.0936). When we related the total protein content to the total number of cells, we noticed that the proliferation was not influenced by the titanium surface type; however, the addition of rhBMP-2 led to a statistically significant reduction on the SLA surface at 21 days (p=0.0000). Concerning the differentiation, we could observe that the surface type did not influence the total content of proteins, the collagen content and the formation of calcified nodules in any of the analyzed periods. The alkaline phosphatase activity was only influenced by the surface type at 14 days, where the group C/SLActive presented lower values than the group C/Smooth (p=0.0000). The addition of rhBMP- 2 promoted a bigger influence over the differentiation process, thus leading to a statistically significant reduction in the total protein content on the SLA surface at 21 days (p=0.0000), a statistically significant increase in the collagen content on the surface SLActive in the 7-day period (p=0.0005), a statistically significant reduction in the alkaline phosphatase activity on the smooth surface in the 14 and 21-day periods, on the SLA surface at 14 days, and on the SLActive surface at 21 days (p=0.0000). Only the formation of calcified nodules did not undergo influence of the rhBMP-2 addition.
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Polo, Cristiane Ibanhes. "A utilização da proteína morgogenética óssea recombinante humana 2 com carreadores adicionais: análise histomorfométrica e por microtomografia computadorizada 3D." Universidade de São Paulo, 2013. http://www.teses.usp.br/teses/disponiveis/23/23149/tde-28082014-153908/.
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A utilização de osteoindutores como a proteína morfogenética óssea recombinante humana tipo 2 (rhBMP-2) em cirurgia oral e maxilofacial para reparação e regeneração óssea tem aumentado progressivamente. Porém, suas indicações ainda estão limitadas a preenchimento de cavidades e pequenas reconstruções. Este estudo teve como objetivo analisar e comparar, por meio da microtomografia computadorizada tridimensional (Micro-TC 3D) e histomorfometria, a arquitetura óssea, a taxa de osso neoformado e a taxa de biodegradação do -Tricálcio Fostato (-TCP), Fosfato de Cálcio Bifásico (BCP) e Osso Mineral Bovino (BBM), utilizados como carreadores adicionais à rhBMP-2/esponja de colágeno (ACS) em um modelo de regeneração óssea guiada (ROG) vertical em calvária de coelhos. Quatro cilindros de titânio foram fixados à calvária de 20 coelhos da raça Nova Zelândia. No Grupo 1 (n = 10), 3 cilindros foram aleatoriamente preenchidos com um dos materiais teste utilizados como carreadores e um cilindro foi preenchido com coágulo sanguíneo (CO). No Grupo 2 (n = 10), os cilindros foram aleatoriamente designados para os mesmos materiais e coágulo sanguíneo, com a adição da rhBMP-2/ACS. Após 14 semanas de reparação, as amostras foram coletadas e enviadas para a aquisição de imagens da Micro-TC e processamento histológico. De acordo com a análise histomorfométrica, a área óssea média para o Grupo 2 (com rhBMP-2) foi maior do que no Grupo 1 (sem rhBMP-2) para os materiais BCP e -TCP (p <0,001). Não houve diferença entre os grupos para BBM e CO (p> 0,05). Em relação às taxas de reabsorção, a área média dos materiais remanescentes no Grupo 2 foi menor do que no Grupo 1 para todos os materiais (p <0,001) e BBM e -TCP obtiveram a maior taxa de reabsorção nos dois grupos (BBM = -TCP > BCP). A análise da micro-TC revelou que no Grupo 2, BCP e -TCP apresentaram maior volume ósseo médio (BV) do que no Grupo 1 (p <0,05). Não houve diferença entre os grupos para os materiais BBM e CO (p> 0,05). O volume médio de materiais restantes (MV) para o Grupo 2 foi menor do que no Grupo 1 para BBM e -TCP (p <0,05), sem diferença significante entre os grupos para BCP (p = 0,848). A análise dos parâmetros Fator Padrão Trabecular (Tb.Pf) e Índice de Modelo Estrutural (SMI) mostrou no Grupo 2 valores negativos para BCP e -TCP, indicando melhor interconectividade e presença de arquitetura trabecular mais achatada e côncava, indicadores de melhor qualidade e resistência óssea. Pelos resultados apresentados concluiu-se que a utilização da rhBMP-2/ACS associada aos materiais carreadores BCP (Fosfato de Cálcio Bifásico) e -TCP (-Fosfato Tricálcio) aumentou significativamente a formação óssea neste modelo de ROG em calvária de coelhos além de acelerar a biodegradação dos materiais BBM (Osso Mineral Bovino) e -TCP (-Fosfato Tricálcio) neste modelo de ROG.<br>The use of osteoinductors as the human recombinant bone morphogenetic protein 2 type 2 (rhBMP-2) in oral and maxillofacial surgery for bone regeneration and repair has progressively increased. However, indications are still limited to filling of cavities and small reconstructions. However, its indications are still limited to filling of cavities and small reconstructions. This study aimed to analyze and compare, by means of three-dimensional microtomography (Micro-CT 3D) and histomorphometry, the bone architecture, the rate of newly formed bone and the biodegradation rate of beta tricalcium phosphate (-TCP), biphasic calcium phosphate (BCP), and mineral bovine bone mineral (BBM) used as additional carriers to rhBMP-2/absorbable collagen sponge (ACS) in a vertical guided bone regeneration model (GBR) in rabbit calvarium. Four titanium cylinders were fixed to the calvarium of 22 New Zealand rabbits. In Group 1 (n = 10), 3 cylinders were randomly filled with one of the test materials and 1 cylinder was filled with a blood clot (CL). In Group 2 (n = 10), the cylinders were randomly assigned to the same materials and blood clot, with the addition of rhBMP-2. After 14 weeks of healing the samples were collected and sent to 3D Micro-CT image acquisition and histological processing. According to histomorphometric analysis, the mean bone area in Group 2 (with rhBMP-2) was greater than in Group 1 (without rhBMP-2) to materials BCP and -TCP (p<0.001). There was no difference between groups to BBM and CL (p>0.05). Regarding the resorption rates, the mean area of remaining materials in Group 2 was lower than in Group 1 to all materials (p<0.001) and BBM and -TCP had the greater resorption rate in both groups (BBM= -TCP >BCP). The Micro-CT analysis revealed that in Group 2, BCP and -TCP had greater mean bone volume (BV) than in Group 1 (p<0.05). There was no difference between groups to materials BBM and CL (p>0.05). The mean volume of remaining materials (MV) in Group 2 was lower than in Group 1 to BBM and -TCP (p<0.05). There was no difference between groups to BC (p=0.848). The analysis of the parameters Trabecular Pattern Factor (Tb.Pf) and Structure Model Índex (SMI), in Group 2 showed negative values for BCP and -TCP, indicating better interconnectivity and presence of more plate-like and trabecular architecture more flattened and concave, indicators of better quality and bone strength. By presented results it was concluded that the use of rhBMP-2/ACS associated with the carriers materials biphasic calcium phosphate (BCP) and beta tricalcium phosphate (-TCP) used as additional carriers, significantly increased bone formation in addition to accelerate the resorption of the materials BO (bovine bone mineral) and -TCP in this guided bone regeneration model in rabbit calvaria.
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Althini, Susanna. "Experimental Studies of BMP Signalling in Neuronal Cells." Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis Univ.-bibl. [distributör], 2003. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-3398.
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Farré, Guasch Elisabet. "Adipose Stem Cells from Buccal Fat Pad and Abdominal Adipose Tissue for Bone tissue Engineering." Doctoral thesis, Universitat Internacional de Catalunya, 2011. http://hdl.handle.net/10803/31987.
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ABSTRACT
Background and Objective: Stem cells offer an interesting tool for tissue engineering, but the clinical applications are limited by donor site morbidity and low cell number upon harvest. Recent studies have identified an abundant source of stem cells in subcutaneous adipose tissue. These adipose stem cells (ASC), are able to differentiate to several lineages and express multiple growth factors, which makes them suitable for clinical application. Buccal fat pad (BFP), an adipose encapsulated mass in the oral cavity, could represent an easy access source for dentists and oral surgeons. Biosynthetic substitutes such as β-tricalcium phosphate (β-TCP), hydroxyapatite (HA), and mixtures of HA/β-TCP (biphasic calcium phosphate; BCP) have been successfully used as bone graft biomaterials. Growth factors stimulating osteogenic differentiation are also interesting for bone tissue engineering applications. We aimed to investigate whether BFP is a rich source of ASC, and whether ASC triggered for only 15 min with bone morphogenetic protein-2 (BMP-2), and seeded onto different calcium phosphate scaffolds composed of β-TCP alone or mixtures of HA/β-TCP, could stimulate bone formation.
Materials & Methods: ASC obtained from subcutaneous abdominal adipose tissue and BFP were counted and analyzed by flow cytometry, to determine ASC cell number, phenotype and percentage. At two weeks of culture, the multipotent differentiation potential of ASC from BFP was analyzed. Furthermore, fresh ASC either or not stimulated with 10ng/ml BMP-2 for 15min were seeded on different calcium phosphate scaffolds. ASC attachment, proliferation and osteogenic differentiation was analyzed and compared.
Results: BFP contained ~30% of ASC. The ASC number obtained per gram of adipose tissue from BFP at one week of culture was 2-fold higher than in subcutaneous abdominal adipose tissue. Angiogenic marker expression was also higher, and ASC showed multipotent differentiation potential as well. Fifteen min BMP-2 treatment increased ASC cell proliferation and osteogenic differentiation on BCP composed of 60% HA and 40% β-TCP, but not on other scaffolds containing less percentage of HA.
Conclusions: Buccal fat pad is a rich alternative source of ASC suitable for bone tissue engineering. Short stimulation of only 15 minutes with BMP-2 is enough to stimulate ASC proliferation and osteogenic differentiation. Therefore ASC could be treated shortly with BMP-2 and seeded on BCP with 60% HA to improve bone regeneration.
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Heisterkamp, Claus Martin. "Die Wiederherstellung der Unterkieferkontinuität mittels rhBMP-2 (Recombinant Human Bone Morphogenetic Protein-2) nach ausgedehnten Resektionen im Minischwein." Doctoral thesis, 2003. https://nbn-resolving.org/urn:nbn:de:bvb:20-opus-9548.
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In der vorliegenden tierexperimentellen Studie wurde die Möglichkeit der direkten Rekonstruktion eines ausgedehnten Unterkieferdefekts mittels eines osteoinduktiven Implantats untersucht. Weiterhin sollte überprüft werden, ob ein heterotop (im M. latissimus dorsi) induziertes Knochentransplantat sich als autologer Knochen zur Unterkiefer-Rekonstruktion eignet. Eine mikrostrukturelle Analyse des Knochens ermöglichte vergleichende Aussagen zur Qualität des neugebildeten Knochens. An zehn ausgewachsenen Göttinger Minischweinen wurde ein einseitiger, 5cm langer Unterkieferkontinuitätsdefekt gesetzt. Dieser wurde bei der Hälfte der Tiere direkt mit einem rhBMP-2-haltigen, 50x25x15mm großen, kollagenen Träger (ICBM, insoluble collagenous bone matrix) rekonstruiert. Bei der zweiten Hälfte wurde dieser Träger zunächst in eine Muskeltasche des M. latissimus dorsi heterotop implantiert. Der neugebildete Knochen wurde nach acht Wochen zur Rekonstruktion in den Unterkiefer transplantiert. Bei direkter Rekonstruktion des Unterkiefers mit einem osteoinduktiven Implantat (8mg rhBMP-2) zeigten alle Versuchstiere röntgenologisch bereits nach acht Wochen eine komplette knöcherne Konsolidierung des gesetzten Unterkieferkontinuitätsdefekts. Nach 12 Wochen ist im Bereich des Defektes fein strukturierter, spongiöser Knochen entstanden, der sich zu den Randbereichen hin in seiner Mikroarchitektur kortikalisähnlich verdichtet und große Anteile lamellären Knochens enthält. Der gesamte Defekt wird von einem biomechanisch hochwertigen, sich funktional anpassenden Knochen überbrückt. Innerhalb der Kontrollgruppe findet keine Konsolidierung des Defektes statt. Aufgrund der mangelnden knöchernen Stabilisierung des Defektes kommt es zu ausgedehnten Resorptionen sowie zu reaktiven Knochneubildungen. Nach heterotoper Implantation von BMP-2 in den M. latissimus kommt es innerhalb von acht Wochen zu einem von peripher nach zentral fortschreitenden knöchernen Umbau des ICBM-Trägers. Der in der Peripherie des Trägers wachsende Knochen ist stark porös, inhomogen und unstrukturiert. Er ist durchsetzt mit Fettmark und von minderer biomechanischer Qualität. Nach Transplantation in den Unterkieferdefekt stirbt dieser autologe Knochen fast vollständig ab und zerfällt nekrotisch. Er wird von derben Bindegewebe umwachsen und abschließend resorbiert. Es bildet sich eine schwache, unvollständige Knochenbrücke aus. Die direkte Rekonstruktion eines ausgedehnten, biomechanisch belasteten Defektes mit einem osteoinduktiven Implantat erwies sich als die überlegene Methode. Das hierbei entstehende knöcherne Regenerat erfährt eine unmittelbare funktionelle Strukturierung. Die Notwendigkeit zu extensiven adaptiven Umbauvorgängen wird hierdurch minimiert<br>Background: Direct mandibular reconstruction with an osteoinductive implant was compared with intramuscular prefabricated bone serving as an autologous bone transplant following an extensive continuity resection of the lower jaw in Göttinger mini-pigs. Method: In ten full-grown mini-pigs a one-sided continuity defect (5cm) was created in the lower jaw. In four animals it was filled with a 50x25x15 mm3 collagenous carrier enhanced by rhBMP-2. In two animals only the carrier was implanted as a control. In four animals the osteoinductive carrier was implanted into a pouch of the latissimus dorsi. After 3 months the graft was harvested and transplanted to close the mandibular defect. Bone regeneration and consolidation of the defects was analyzed radiographically, histologically and micromorphometrically. Results:Following implantation of the osteoinductive implant, complete osseus consolidation of the continuity defect in the lower jaw was observed in all animals. The defects were completely filled with a biomechanically stable bone which showed signs of functional adaption. The transplantation of the heterotopical prefabricated bone did not lead to functional stability quickly enough. In the periphery only an incomplete bony bridge was formed which was interrupted by large pseudarthrosis. No consolidation of the defects was found in the control group. Conclusion: Direct reconstruction of an extensive, biomechanically loaded defect with an osteoinductive implant proved to be the superior method. The osseus regeneration observed shows an immediate functional orientation. The necessity for extensive adaptive remodeling is thus minimized
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Schwartz, Daniel Hans [Verfasser]. "Development of an aqueous suspension of recombinant human bone morphogenetic protein-2 (rhBMP-2) = Entwicklung einer wässrigen Suspension des recombinanten menschlichen Knochenwachstumsproteins-2 (rhBMP-2) / vorgelegt von Daniel Hans Schwartz." 2005. http://d-nb.info/977660974/34.
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Heisterkamp, Claus Martin [Verfasser]. "Die Wiederherstellung der Unterkieferkontinuität mittels rhBMP-2 (recombinant human bone morphogenetic protein-2) nach ausgedehnten Resektionen im Minischwein / vorgelegt von Claus Martin Heisterkamp." 2004. http://d-nb.info/972095748/34.
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Chen, Shu-Jiuan, and 陳淑娟. "The Study of Evaluating the Bone Regenerations of Hydroxyapatite/Collagen Microspheres with Recombinant Human Bone Morphogenetic Protein 2 as Bone Graft Materials." Thesis, 2003. http://ndltd.ncl.edu.tw/handle/31859018027736248778.
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Yeh, Tsu-Te, and 葉祖德. "The Short-Term Therapeutic Effect of Recombinant Human Bone Morphogenetic Protein-2 on Collagenase Induced Experimental Osteoarthritis of the Lumbar Facet Joint in Rats." Thesis, 2007. http://ndltd.ncl.edu.tw/handle/04342959185490604627.
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博士<br>國防醫學院<br>醫學科學研究所<br>95<br>Background: Osteoarthritis (OA) of the lumbar facet joint is one of the sources of low back pain. Even after spinal fusion or artificial disc implantation surgery, facet joint arthrosis is one of the reasons leading to unsatisfactory results. There are no references reporting on an OA model of the lumbar facet joint in rats. The therapeutic effect of recombinant human bone morphogenetic protein-2 (rhBMP-2) on the lumbar facet joint OA is still unknown.
Objective: The objectives of this research were to establish an animal model to investigate primary experimental osteoarthritis of the lumbar facet joints after collagenase injection in rats, and the effects on chondrocytes apoptosis. We also want to determine whether an intra-articular injection of rhBMP-2 alleviates cartilage degradation in this model of OA of the lumbar facet joint.
Methods: Collagenase (1 U, 10 U, or 50 U) or saline was intra-articularly injected into the right side lumbar facet joints. The left side facet joint served as the normal control. The cartilage, synovium and subchondral bone were examined by histological and histochemical methods at 1, 3, and 6 weeks post-injection. The cartilage and synovium were graded using the OARSI score and a synovium score system. Apoptotic cells induced by one unit of collagenase were quantified by the TUNEL method. In the rhBMP-2 treatment study, the right side facet joint OA model was created by an intra-articular injection of 5 U of collagenase two weeks before treatment. The OA rats were divided into 4 groups: 1) no treatment, or intra-articular injection of either 2) saline, 3) rhBMP-2 10 ng, or 4) rhBMP-2 100 ng. At 3 and 6 weeks after treatment, histological analyses were performed on the cartilage, synovium, subchondral bone and bone marrow. The cartilage and synovium were graded using a modified Mankin score and a synovium score system. Extracellular type II collagen was evaluated by immunohistochemistry.
Results: The degeneration of the cartilage and changes of synovium and subchondral bone were found to be dependent on both the dose of collagenase and the time post-surgery. Apoptotic chondrocytes were significantly increased above the control group. OA rats treated with rhBMP-2 at both dosages tested showed reduced severity of their cartilage lesions compared with untreated and saline-treated groups. There was a statistically significant difference in the modified Mankin score compared to the untreated and saline-treated groups. However, some rhBMP-2-treated rats at the higher dose (100 ng) showed, as a side effect, joint space obliteration caused by cartilage overgrowth. Also OA rats treated with 100 ng of rhBMP-2 displayed a significant synovium reaction at 3 weeks compared with that in other groups. Immunohistochemical analysis showed that treatment with rhBMP-2 significantly increased the content of type II collagen
Conclusion: The lumbar facet joints subjected to collagenase developed OA-like changes. These changes can be quantified and compared. This model provides a useful tool for the further study of the pathogenesis of OA and the effects of compounds that have the potential to inhibit enzyme associated damage to cartilage cells. The potential efficacy of rhBMP-2 in the alleviation of arthritic changes of OA of the lumbar facet joint is also demonstrated. However, treatment with a high dosage of rhBMP-2 caused adverse side effects in some animals.
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Yong, Tseh-Hwan, Elizabeth A. Hager, and Jackie Y. Ying. "Apatite-Polymer Composite Particles for Controlled Delivery of BMP-2." 2003. http://hdl.handle.net/1721.1/3924.
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We have developed a versatile delivery platform comprising a novel composite of two biomaterials with proven track records: apatite and poly(lactic-co-glycolic acid) (PLGA). These composites have been tested in the delivery of a model protein, bovine serum albumin (BSA), as well as a growth factor, bone morphogenetic protein-2 (BMP-2), which is a potent inducer of bone formation. The controlled release strategy is based on the use of a polymer with acidic degradation products to control the dissolution of a basic inorganic component, resulting in protein release. The release profile can be modified systematically by changing variables that affect polymer degradation and/or apatite dissolution, such as polymer molecular weight, polymer composition, apatite loading, and apatite particle size. We have found that an increase in polymer molecular weight and polymer hydrophobicity led to slower polymer degradation, and in turn, slower apatite dissolution and protein release. Protein release was enhanced by reducing apatite particle size and by lowering the apatite content in the composites. We anticipate that this delivery platform can be extended to the controlled release of other therapeutic proteins and chemicals.<br>Singapore-MIT Alliance (SMA)
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Bui, Matthew. "The effect of phosphate deficiency on BMP-2 treated C3H10T1/2 mesenchymal stem cells." Thesis, 2018. https://hdl.handle.net/2144/30902.
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There are approximately 600,000 cases of delayed or aberrant fracture healing in people each year, with a small subset of these fractures experiencing disunion. Dietary phosphate deficiency has been shown to impair oxidative phosphorylation and decrease BMP-2 mediated chondrogenic differentiation during fracture healing. Prior studies using pre-committed chondro-progenitor ATDC5 cell line grown in phosphate deficient media showed that energy consumption was linked to protein production and collagen hydroxylation but inversely related to matrix mineralization. The goal of this study was to further define the relationship between energy consumption and BMP-2 mediated stem cell chondrogenic differentiation and further examine how dietary phosphate, and promotion of collagen hydroxylation via ascorbate availability effected these processes.
C3H10T1/2 murine cells, a multi-potential cell line, were expanded in pre-differentiation growth medium (DMEM with 10% FBS and 1% Pen/Strep). Once cells reached 60% confluence (day 0), they were grown in differentiating media (α-MEM with 5% FBS and 1X insulin-transferrin-selenium) containing either 100% (1mM) or 25% (0.25mM) inorganic phosphate (Pi), ± 200ng/mL BMP-2(BMP), and ±0.2 mM L-ascorbic acid (AA). In total, there were 8 groups with varying combinations of these three substances. Intracellular lipid, total DNA, protein, and hydroxyproline (HP) content were examined. Chondrocyte gene expression (Col2a1, Acan, ColXa1) and adipocyte gene expression (Pparg, Plin1, Ucp1) were measured to check for cell lineage commitment and specific differentiation of the C3H10T1/2. All measurements were acquired at day 8.
The +BMP differentiation media groups contained significantly less DNA content and more protein content than the –BMP differentiation media groups (both p<0.0001). There was also a significant interaction between phosphate and ascorbic acid treatment (p=0.0296), with 25% Pi +AA groups producing significantly more protein than 100% Pi +AA groups. Hydroxyproline production was not different in 100% Pi or 25% Pi conditions (p=0.2951). AA presence in culture media led to greater HP production than culture media lacking AA (p=0.0035) There was a trend of an interaction between phosphate content and AA availability (p=0.0744). 100% Pi ±AA groups produced significantly different amounts of HP while 25% Pi ±AA groups did not produce significantly different amount of HP. Col2a1, Acan, and ColXa1 expression were all increased in +BMP groups. Ascorbic acid treatment groups expressed significantly more Col2a1and Acan than –AA groups. 100% Pi media led to greater Acan expression over 25% Pi groups (p=0.0009), whereas 25% Pi media trended to lead to greater ColXa1 expression over 100% Pi groups (p=0.0734). Pparg and Plin1 expression were increased in the 25% Pi condition. There were no significant differences in expression of Ucp1.
C3H10T1/2 cells were significantly affected by phosphate concentration, BMP-2 treatment, and ascorbic acid supplementation. Phosphate deficiency hindered maturation of early chondrocytes into proliferating chondrocytes while also promoting MSC differentiation into the adipocyte cell lineage. Hypertrophic chondrocyte expression was decreased in phosphate deficient media, which may coincide with increased protein production observed in low phosphate conditions. BMP-2 promoted chondrogenesis which resulted in increased protein production. Whereas, lack of ascorbic acid in cell culture media led to decreased hydroxyproline production.
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Zhou, Jing-Jing Aileen. "Enhancing Production of Recombinant BMP-2 in Mammalian Cell Culture Systems by Inhibition of Pro-protein Cleavage using 9DR Peptides." Thesis, 2008. http://hdl.handle.net/1807/11175.
Full textAbstract:
Introduction: Mammalian cell recombinant bone morphogenetic protein (rBMP) synthesis is reported to be poor. The BMP pro-domain may be involved in folding, stability and secretion. Objectives: Investigate the effect of inhibition of pro-domain cleavage on rhBMP-2 production. Methods: CHO cells transfected with human BMP-2 (hBMP-2) were cultured in the presence of the proprotein convertase inhibitor 9DR in short (multi-well) and long-term (bioreactor) cultures. Mature and proBMP secretion was measured by ELISA and characterized by Western blot. BMP activity was determined by C2C12 bioassay. Results: 9DR significantly enhanced the yields of both pro- and mature hBMP-2 in short and long-term cultures, without any negative effects on cell growth or viability. The rhBMP-2 was biologically active. ProBMP-2 could be converted by exogenous furin treatment into mature BMP-2 as shown by Western blot. Conclusions: 9DR increases rhBMP-2 production and is a simple, but effective way to enhance the yield of active, mature BMP-2 in CHO cells.
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Yetimoglu, Cem [Verfasser]. "Expression von Bone-Morphogenetic-Protein-2 (BMP-2) während der Knochenentwicklung, der physiologischen Knochenheilung und der durch Wachstumshormon (GH) stimulierten Knochenheilung / Cem Yetimoglu." 2007. http://d-nb.info/989176649/34.
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Chatzinikolaidou, Maria [Verfasser]. "Untersuchungen zur Immobilisierung und Freisetzung von rekombinantem humanem bone morphogenetic Protein 2 (BMP-2) in biologisch aktiver Form auf metallischen Implantatoberflächen / Maria Chatzinikolaidou." 2004. http://d-nb.info/975072633/34.
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Simon, Michaela [Verfasser]. "Der Einfluss von Bone-morphogenetic-Protein (BMP-)2, BMP-4 und BMP-7 auf die Regulation der Proliferation und Differenzierung von hämatopoetischen Vorläuferzellen aus dem peripheren Blut / vorgelegt von Michaela Simon." 2009. http://d-nb.info/997897295/34.
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Chen, Chao. "Effects of macrophages and noggin suppression on the BMP-2-induced osteogenesis of human bone marrow mesenchymal stem cells." Master's thesis, 2011. http://hdl.handle.net/10048/1684.
Full textAbstract:
The osteogenic effects of bone morphogenetic protein-2 (BMP-2) on human mesenchymal stem cells (MSCs) are less profound than expected as compared with rodent cells, and supraphysiological dose of BMP-2 is required to achieve desired clinical outcome. The mechanism for this phenomenon is unclear. In this study, we examined the effects of macrophages and noggin suppression on the BMP-2-induced osteogenesis of human bone marrow MSCs in vitro.
Our data show that macrophage conditioned medium significantly decreased the migration capacity, metabolic activity and BMP-2-induced osteogenesis of MSCs. In addition, knocking down noggin by small interfering RNA (siRNA) also significantly decreased BMP-2-induced osteogenesis and proliferation of MSCs.
In summary, our studies demonstrated that macrophages and knocking down the expression of noggin decreased BMP-2-induced osteogenesis of human MSCs in vitro. In the future, manipulation on macrophage activation and noggin expression may allow us to achieve higher BMP-2-induced osteogenesis that leads to better bone healing.<br>Experimental Surgery
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Tampe, Björn. "Die Rolle der Bone Morphogenetic Proteins (BMP)-5 und -7 in der humanen Normalniere und bei der hypertensiven Nephropathie." Doctoral thesis, 2012. http://hdl.handle.net/11858/00-1735-0000-000D-EFB5-7.
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Hildebrandt, Kristin [Verfasser]. "Implantation von Tricalciumphosphat (TCP) und humanen Knochenmarkstammzellen (hBMSC) mit exogenem und endogenem rekombinanten Bone-morphogenetic-Protein-2 (BMP-2) in ein Femur-Defektmodell der Ratte zur Beschleunigung der interkonnektiven Knochenheilung / vorgelegt von Kristin Hildebrandt." 2004. http://d-nb.info/973950218/34.
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Engels, Stefanie [Verfasser]. "Haben programmable cells of monocytic origin (PCMOs) als Stammzellen des peripheren Blutes das Potential, durch Stimulation mit bone morphogenetic protein (BMP)-7 und -2 zu Kollagen-Typ-II-produzierenden Chondrozyten differenziert zu werden? / vorgelegt von Stefanie Engels, geb. Dressel." 2010. http://d-nb.info/1010696971/34.
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