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Transforming Growth Factor Beta (transforming + growth_factor_beta)
Selected AbstractsTGFBI gene mutations in Hungary , polymorphic corneal amyloidosis caused by the novel F547S mutationACTA OPHTHALMOLOGICA, Issue 2009A BERTA Purpose To identify mutations in the Transforming Growth Factor Beta Induced (TGFBI) gene in Hungarian patients with corneal dystrophy and to characterize their histological features. Methods Exons of TGFBI gene were sequenced in 38 members of 15 unrelated families with corneal dystrophy. Exon 12 was sequenced in 100 healthy controls. Immunohistological analysis of corneal buttons excised during penetrating keratoplasty was performed. Results Molecular genetic analysis revealed a heterozygous R124C mutation in 18 patients with lattice type I dystrophy. A R555W heterozygous mutation was detected in five patients with granular Groenouw type I corneal dystrophy and the R555Q heterozygous mutation was found in four patients clinically diagnosed with Reis-Bücklers (one patient) and Thiel-Behnke (three patients) dystrophy. Three patients with "atypical granular" dystrophy later diagnosed as Avellino dystrophy were heterozygous for the R124H mutation. No other than the novel heterozygous T1640C mutation causing the F547S amino acid exchange was detected in a patient with polymorphic corneal amyloidosis. The mutation could not be found in healthy controls. Immunohistochemistry showed the presence of BIGH3 protein deposits in all examined corneal buttons. Electron microscopy confirmed the presence of amyloid fibrils in the case of the novel mutation. Conclusion Our results indicate that molecular genetic analysis is required to confirm the diagnosis of corneal dystrophies. We report the first cases of Avellino dystrophy from Central-Eastern Europe. The novel F547S mutation causes polymorphic corneal amyloidosis. [source] Interleukin-4 antagonizes oncostatin M and transforming growth factor beta-induced responses in articular chondrocytesJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 2 2008Mohammed El Mabrouk Abstract Oncostatin M (OSM) stimulates cartilage degradation in rheumatoid arthritis (RA) by inducing matrix metalloproteinases (MMPs) and aggrecanases (ADAMTS; a disintegrin and metalloproteinase with thrombospondin motif). Transforming growth factor beta (TGF-,1) induces cartilage repair in joints but in excessive amounts, promotes inflammation. OSM and TGF-,1 also induce tissue inhibitor of metalloproteinase-3 (TIMP-3), an important natural inhibitor of MMPs, aggrecanases, and tumor necrosis factor alpha converting enzyme (TACE), the principal proteases involved in arthritic inflammation and cartilage degradation. We studied cartilage protective mechanisms of the antiinflammatory cytokine, interleukin-4 (IL-4). IL-4 strongly (MMP-13 and TIMP-3) or minimally (ADAMTS-4) suppressed OSM-induced gene expression in chondrocytes. IL-4 did not affect OSM-stimulated phosphorylation of extracellular signal-regulated kinases (ERKs), protein 38 (p38), c-Jun N-terminal kinase (JNK) and Stat1. Lack of additional suppression with their inhibitors suggested that MMP-13, ADAMTS-4, and TIMP-3 inhibition was independent of these mediators. IL-4 also downregulated TGF-,1-induced TIMP-3 gene expression, Smad2, and JNK phosphorylation. Additional suppression of TIMP-3 RNA by JNK inhibitor suggests JNK implication. The cartilage protective effects of IL-4 in animal models of arthritis may be due to its inhibition of MMPs and ADAMTS-4 expression. However, suppression of TIMP-3 suggests caution for using IL-4 as a cartilage protective therapy. J. Cell. Biochem. 103: 588,597, 2008. © 2007 Wiley-Liss, Inc. [source] Transforming growth factor-,1 induced alteration of skeletal morphogenesis in vivoJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 4 2004Cristin M. Ferguson Abstract Transforming growth factor beta (TGF-,) is expressed in the growth plate and is an important regulator of chondrocyte maturation. Loss of function results in premature chondrocyte maturation both in vitro and in vivo. While TGF-, inhibits chondrocyte maturation in cell cultures, the effect of increased TGF-, has not been well characterized in an in vivo development model. Addition of Affi-gel agarose beads loaded with TGF-,1 (10 ng/,l) to developing stage 24,25 chick limb buds resulted in limb shortening and altered morphology. In situ hybridization studies showed down regulation of Indian hedgehog (ihh), bone morphogenetic protein 6 (bmp6), and collagen type X (colX) expression, markers of chondrocyte maturation, in TGF-,1 treated limbs. TGF-,1 also decreased chondrocyte proliferation in the developing anlage. The findings confirm a critical role for TGF-, during skeletal development. A more complete understanding of the role of TGF-, and its down-stream signals will lead to improved understanding and treatment of cartilage diseases. © 2004 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved. [source] Latent transforming growth factor binding protein 4 (LTBP-4) is downregulated in human mammary adenocarcinomas in vitro and in vivo,APMIS, Issue 6 2007SUSANNE MAUEL Transforming growth factor beta (TGF-ß) is able to inhibit proliferation of epithelial cells and is involved in the carcinogenesis of human mammary tumours. Three latent transforming growth factor-ß binding proteins (LTBP-1, -3 and -4) are involved in TGF-ß function. The aim of the study was to analyze the expression profiles of TGF-ß 1 and 2 and LTBP-4 in human mammary carcinoma cell lines as well as in human mammary tumours. Expression analysis was performed at the transcription and protein level under in vivo and in vitro conditions. LTBP-4 expression was quantitatively analysed in human carcinomas of the mammary gland and in healthy mammary tissues of the same patients. Downregulation of LTBP-4 in all investigated human mammary tumours compared to normal tissues could be demonstrated. Results also revealed that protein levels of TGF-ß 1 are downregulated and of TGF-ß 2 are upregulated in human mammary carcinoma cell lines compared to primary (normal) human mammary epithelial cells. LTBP-4 reduction in neoplasms leads to a possible decrease of TGF-ß 1 extracellular deposition with reduced TGF-ß 1 bioavailability. TGF-ß 2 was upregulated, which indicates a possible compensatory mechanism. This study demonstrated a possible functional role of LTBP-4 for TGF-ß bioavailability with respect to carcinogenesis of human mammary tumours in vivo and in vitro. [source] Transforming growth factor beta 1 plays an important role in inducing CD4+CD25+forhead box P3+ regulatory T cells by mast cellsCLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 3 2010W. Zhang Summary The role of mast cells (MCs) in the generation of adaptive immune responses especially in the transplant immune responses is far from being resolved. It is reported that mast cells are essential intermediaries in regulatory T cell (Treg) transplant tolerance, but the mechanism has not been clarified. To investigate whether bone marrow-derived mast cells (BMMCs) can induce Tregs by expressing transforming growth factor beta 1 (TGF-,1) in vitro, bone marrow cells obtained from C57BL/6 (H-2b) mice were cultured with interleukin (IL)-3 (10 ng/ml) and stem cell factor (SCF) (10 ng/ml) for 4 weeks. The purity of BMMCs was measured by flow cytometry. The BMMCs were then co-cultured with C57BL/6 T cells at ratios of 1:2, 1:1 and 2:1. Anti-CD3, anti-CD28 and IL-2 were administered into the co-culture system with (experiment groups) or without (control groups) TGF-,1 neutralizing antibody. The percentages of CD4+CD25+forkhead box P3 (FoxP3)+ Tregs in the co-cultured system were analysed by flow cytometry on day 5. The Treg percentages were significantly higher in all the experiment groups compared to the control groups. These changes were deduced by applying TGF-,1 neutralizing antibody into the co-culture system. Our results indicated that the CD4+ T cells can be induced into CD4+CD25+FoxP3+ T cells by BMMCs via TGF-,1. [source] Expression and functional analysis of Tgif during mouse midline developmentDEVELOPMENTAL DYNAMICS, Issue 2 2006Jiu-Zhen Jin Abstract The Tgif gene encodes a homeodomain protein that functions as a transforming growth factor beta (TGF-,) repressor by binding to Smad2. Mutations in the TGIF gene are associated with human holoprosencephaly, a common birth defect caused by the failure of anterior ventral midline formation. However, Smad2-mediated TGF-, signaling in the axial mesendoderm has been demonstrated to be essential for ventral midline formation, and loss of a Smad2 antagonist should in principle promote rather than inhibit ventral midline formation. This suggests a more complex mechanism for the function of TGIF in controlling ventral midline formation. To explore the role of TGIF in ventral forebrain formation and patterning, we investigated Tgif expression and function during mouse development by in situ hybridization and gene targeting. We found that Tgif is highly expressed in the anterior neural plate, consistent with the proposed neural differentiation model in which TGF-, suppression is required for normal neural differentiation. This result suggests a possible role for Tgif in anterior neural differentiation and patterning. However, targeted disruption of the Tgif gene during mouse development does not cause any detectable defects in development and growth. Both histological examination and gene expression analysis showed that Tgif,/, embryos have a normal ventral specification in the central nervous system, including the forebrain region. One interpretation of these results is that the loss of TGIF function is compensated by other TGF-, antagonists such as c-Ski and SnoN during vertebrate anterior neural development. Developmental Dynamics 235:547,553, 2006. © 2005 Wiley-Liss, Inc. [source] Altered subcellular location of phosphorylated Smads in Alzheimer's diseaseEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 8 2006Uwe Ueberham Abstract A number of growth factors and cytokines, such as transforming growth factor beta 1 (TGF-,1), is elevated in Alzheimer's disease (AD), giving rise to activated intracellular mitogenic signaling cascades. Activated mitogenic signaling involving the mitogen-activated protein kinases (MAPKs) and other protein kinases might alter the phosphorylation states of structural proteins such as tau, resulting in hyperphosphorylated deposits. Many intracellular signaling proteins are potential targets of misregulated phosphorylation and dephosphorylation. Recently, a crosstalk between MAPKs and Smad proteins, both involved in mediating TGF-,1 signaling, has been reported. Although TGF-,1 has previously been shown to be involved in the pathogenesis of AD, the role of Smad proteins has not been investigated. In this study we thus analysed the subcellular distribution of phosphorylated Smad2 and Smad3 in the hippocampus of both normal and AD brains. Here we report on strong nuclear detection of phosphorylated Smad2 and Smad3 in neurons of control brains. In AD brains these phosphorylated proteins were additionally found in cytoplasmic granules in hippocampal neurons, within amyloid plaques and attached to neurofibrillary tangles. Our data suggest a critical role of Smad proteins in the pathogenesis of AD. [source] CXC chemokine ligand 4 (Cxcl4) is a platelet-derived mediator of experimental liver fibrosis,HEPATOLOGY, Issue 4 2010Mirko Moreno Zaldivar Liver fibrosis is a major cause of morbidity and mortality worldwide. Platelets are involved in liver damage, but the underlying molecular mechanisms remain elusive. Here, we investigate the platelet-derived chemokine (C-X-C motif) ligand 4 (CXCL4) as a molecular mediator of fibrotic liver damage. Serum concentrations and intrahepatic messenger RNA of CXCL4 were measured in patients with chronic liver diseases and mice after toxic liver injury. Platelet aggregation in early fibrosis was determined by electron microscopy in patients and by immunohistochemistry in mice. Cxcl4,/, and wild-type mice were subjected to two models of chronic liver injury (CCl4 and thioacetamide). The fibrotic phenotype was analyzed by histological, biochemical, and molecular analyses. Intrahepatic infiltration of immune cells was investigated by fluorescence-activated cell sorting, and stellate cells were stimulated with recombinant Cxcl4 in vitro. The results showed that patients with advanced hepatitis C virus,induced fibrosis or nonalcoholic steatohepatitis had increased serum levels and intrahepatic CXCL4 messenger RNA concentrations. Platelets were found directly adjacent to collagen fibrils. The CCl4 and thioacetamide treatment led to an increase of hepatic Cxcl4 levels, platelet activation, and aggregation in early fibrosis in mice. Accordingly, genetic deletion of Cxcl4 in mice significantly reduced histological and biochemical liver damage in vivo, which was accompanied by changes in the expression of fibrosis-related genes (Timp-1 [tissue inhibitor of matrix metalloproteinase 1], Mmp9 [matrix metalloproteinase 9], Tgf -, [transforming growth factor beta], IL10 [interleukin 10]). Functionally, Cxcl4,/, mice showed a strongly decreased infiltration of neutrophils (Ly6G) and CD8+ T cells into the liver. In vitro, recombinant murine Cxcl4 stimulated the proliferation, chemotaxis, and chemokine expression of hepatic stellate cells. Conclusion: The results underscore an important role of platelets in chronic liver damage and imply a new target for antifibrotic therapies. (HEPATOLOGY 2010.) [source] Liver stem cells and hepatocellular carcinoma,HEPATOLOGY, Issue 1 2009Lopa Mishra Although the existence of cancer stem cells (CSCs) was first proposed over 40 years ago, only in the past decade have these cells been identified in hematological malignancies, and more recently in solid tumors that include liver, breast, prostate, brain, and colon. Constant proliferation of stem cells is a vital component in liver tissues. In these renewing tissues, mutations will most likely result in expansion of the altered stem cells, perpetuating and increasing the chances of additional mutations and tumor progression. However, many details about hepatocellular cancer stem cells that are important for early detection remain poorly understood, including the precise cell(s) of origin, molecular genetics, and the mechanisms responsible for the highly aggressive clinical picture of hepatocellular carcinoma (HCC). Exploration of the difference between CSCs from normal stem cells is crucial not only for the understanding of tumor biology but also for the development of specific therapies that effectively target these cells in patients. These ideas have drawn attention to control of stem cell proliferation by the transforming growth factor beta (TGF-,), Notch, Wnt, and Hedgehog pathways. Recent evidence also suggests a key role for the TGF-, signaling pathway in both hepatocellular cancer suppression and endoderm formation, suggesting a dual role for this pathway in tumor suppression as well as progression of differentiation from a stem or progenitor stage. This review provides a rationale for detecting and analyzing tumor stem cells as one of the most effective ways to treat cancers such as HCC. (HEPATOLOGY 2009;49:318,329.) [source] Nicotine inhibits myofibroblast differentiation in human gingival fibroblastsJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 6 2005Yiyu Fang Abstract Cigarette smoking has been suggested as a risk factor for several periodontal diseases. It has also been found that smokers respond less favorably than non-smokers to periodontal therapy. Previous work in our lab has shown that nicotine inhibits human gingival cell migration. Since myofibroblasts play an important role in wound closure, we asked if nicotine affects gingival wound healing process by regulating myofibroblast differentiation. Human gingival fibroblasts (HGFs) from two patients were cultured in 10% fetal bovine serum cell culture medium. Cells were pretreated with different doses of nicotine (0, 0.01, 0.1, and 1 mM) for 2 h, and then incubated with transforming growth factor beta (TGF-,1) (0, 0.25, 0.5, and 1 ng/ml) with or without nicotine for 30 h. The expression level of ,-smooth muscle actin (,-SMA), a specific marker for myofibroblasts, was analyzed by Western blots, immunocytochemistry, and real-time polymerase chain reaction (real-time PCR). Phosphorylated p38 mitogen-activated protein kinase (Phospho-p38 MAPK) activity was analyzed by Western blots. TGF-,1 induced an increase of ,-SMA protein and mRNA expression, while nicotine (1 mM) inhibited the TGF-,1-induced expression of ,-SMA but not ,-actin. Nicotine treatment down-regulated TGF-,1-induced p38 MAPK phosphorylation. Our results demonstrated for the first time that nicotine inhibits myofibroblast differentiation in human gingival fibroblasts in vitro; supporting the hypothesis that delayed wound healing in smokers may be due to decreased wound contraction by myofibroblasts. © 2005 Wiley-Liss, Inc. [source] Ethanol Alters Production and Secretion of Estrogen-Regulated Growth Factors That Control Prolactin-Secreting Tumors in the PituitaryALCOHOLISM, Issue 12 2007Dipak K. Sarkar Background:, Chronic administration of ethanol increases plasma prolactin levels and enhances estradiol's mitogenic action on the lactotropes of the pituitary gland. The present study was conducted to determine whether ethanol's lactotropic cell-proliferating action, like estradiol's, is associated with alteration in the production of 3 peptides that regulate cell growth: transforming growth factor beta 1 (TGF-,1), TGF-,3 and basic fibroblast growth factor (bFGF). Methods:, Using ovariectomized Fischer-344 female rats, we determined ethanol's and estradiol's actions on lactotropic cell proliferation and growth-regulatory peptide production and release in the pituitary gland during tumorigenesis. Results:, Ethanol increased basal and estradiol-enhanced mitosis of lactotropes in the pituitary glands of ovariectomized rats. The level of growth-inhibitory TGF-,1 was reduced in the pituitary following ethanol and/or estradiol treatment for 2 and 4 weeks. In contrast, ethanol and estradiol alone as well as together increased levels of growth-stimulatory TGF-,3 and bFGF in the pituitary at 2 and 4 weeks. In primary cultures of pituitary cells, both ethanol and estradiol reduced TGF-,1 release and increased TGF-,3 and bFGF release at 24 hours. Ethanol's effect on growth factor levels in the pituitary or growth factor release from the pituitary cells was less than that of estradiol. When ethanol and estradiol were applied together, their individual effects on these growth factors were amplified. Conclusions:, These results confirm estradiol's modulation of pituitary growth factor production and release, and provide evidence that ethanol, like estradiol, alters the production and secretion of growth-regulatory peptides controlling lactotropic cell proliferation. [source] Expression of extracellular matrix genes in cultured hepatic oval cells: an origin of hepatic stellate cells through transforming growth factor beta?LIVER INTERNATIONAL, Issue 4 2009Ping Wang Abstract Background: Hepatic oval cells, progenitor cells in the liver, can differentiate into hepatocytes and bile duct cells both in vitro and in vivo. Although hepatic stellate cells are another important cell component in the liver, less attention has been focused on the relationship between hepatic oval cells and hepatic stellate cells. Methods: Hepatic oval cells were isolated from rats fed a choline-deficient diet supplemented with 0.1% ethionine for 6 weeks and characterized by electron microscopy, flow cytometry, reverse transcription polymerase chain reaction, Western blot and bi-direction differentiation. After treatment with transforming growth factor-,1 (TGF-,1), changes in cell viability, morphology, extracellular matrix (ECM) expression and immune phenotype were analysed in these cultured and adherent hepatic oval cells. Results: The primary cultured hepatic oval cells were positive for the oval cell-specific markers OV-6, BD-1/BD-2 and M2PK as well as the hepatocyte markers albumin and ,-foetoprotein. These hepatic oval cells differentiated bipotentially into hepatocytes or bile duct-like cells under appropriate conditions. It is noteworthy that these bipotential hepatic oval cells expressed ECM genes stably, including collagens, matrix metalloproteinases and tissue inhibitor of mellatoproteinase. Furthermore, except for growth inhibition and morphological changes in the hepatic oval cells after exposure to TGF-,1, there was an increased expression of ECM genes, the onset expression of snail and loss expression of E-cadherin. During this process, TGF-,1 treatment induced an upregulation of marker genes for hepatic stellate cells in hepatic oval cells, such as desmin and GFAP. Conclusion: Except for the expression of ECM, the cultured hepatic oval cells could induce an increased expression of hepatic stellate cell markers by TGF-,1 through an epithelial,mesenchymal transition process, which might indicate the contribution of hepatic oval cells to liver fibrosis. [source] Role of transforming growth factor beta in peritoneal fibrosisNEPHROLOGY, Issue 5 2002Reem H AL-JAYYOUSI SUMMARY: Technique survival of peritoneal dialysis is seriously limited by the development of peritoneal fibrosis. the mesothelial cell layer lining the peritoneum is important in the pathogenesis of peritoneal fibrosis. Mesothelial cells are able to produce transforming growth factor beta (TGF-,), and respond to stimulation by this cytokine. In this review, we will detail the evidence available so far for the role of the complex interaction between TGF-, and mesothelial cells in the development of peritoneal fibrosis. [source] Detection of Rare Nonsynonymous Variants in TGFB1 in Otosclerosis PatientsANNALS OF HUMAN GENETICS, Issue 2 2009M. Thys Summary Otosclerosis is one of the most common forms of hearing loss in the European population. We have identified a SNP in the TGFB1 (transforming growth factor beta 1) gene that is associated with susceptibility to otosclerosis. The protective allele of this variant, with isoleucine at position 263 of the protein, is more biologically active than the risk allele, which has a threonine in this position. Because recent studies have shown that not only common, but also rare variants can be involved in complex diseases, we performed DNA sequence analysis of the exons and intron-exon boundaries of TGFB1 in 755 otosclerosis patients and 877 control samples. We found 3 different nonsynonymous variants (E29, A29 and I241) in four otosclerosis patients, but no such changes were found in controls. In silico analysis shows that these variations could influence TGF-,1 function and activity. Taking into account that most rare missense alleles are thought to have a biological effect, the data suggest that multiple rare amino acid changing variants in TGF-,1 may contribute to susceptibility to otosclerosis. [source] Overview of the TGFBI corneal dystrophiesACTA OPHTHALMOLOGICA, Issue 2009GK KLINTWORTH Several phenotypically distinct clinicopathologic entities involving the cornea are caused by mutations in the transforming growth factor beta induced (TGFBI) gene. These disorders include different types of granular corneal dystrophy (GCD): GCD type 1, GCD type 2 (Avellino corneal dystrophy), GCD type 3 (Reis-Bücklers corneal dystrophy) as well variants of lattice corneal dystrophy type 1 and Thiel-Benhke corneal dystrophy. Investigations of these inherited corneal diseases throughout the world strongly suggest that specific mutations in the TGFBI gene account for the specific phenotypes and that the corneal opacities that account for the clinical features of the different phenotypes result from the deposition of all or part of the mutated encoded protein. To date the mutated protein is only known to accumulate in the cornea eventhough the TGFBI is widely expressed throughout the body in experimental animals. This presentation will provide an overview of the TGFBI corneal dystrophies and offer a hypothesis to explain the different phenotypes caused by different mutations in TGFBI. [source] Transforming growth factor beta 1 plays an important role in inducing CD4+CD25+forhead box P3+ regulatory T cells by mast cellsCLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 3 2010W. Zhang Summary The role of mast cells (MCs) in the generation of adaptive immune responses especially in the transplant immune responses is far from being resolved. It is reported that mast cells are essential intermediaries in regulatory T cell (Treg) transplant tolerance, but the mechanism has not been clarified. To investigate whether bone marrow-derived mast cells (BMMCs) can induce Tregs by expressing transforming growth factor beta 1 (TGF-,1) in vitro, bone marrow cells obtained from C57BL/6 (H-2b) mice were cultured with interleukin (IL)-3 (10 ng/ml) and stem cell factor (SCF) (10 ng/ml) for 4 weeks. The purity of BMMCs was measured by flow cytometry. The BMMCs were then co-cultured with C57BL/6 T cells at ratios of 1:2, 1:1 and 2:1. Anti-CD3, anti-CD28 and IL-2 were administered into the co-culture system with (experiment groups) or without (control groups) TGF-,1 neutralizing antibody. The percentages of CD4+CD25+forkhead box P3 (FoxP3)+ Tregs in the co-cultured system were analysed by flow cytometry on day 5. The Treg percentages were significantly higher in all the experiment groups compared to the control groups. These changes were deduced by applying TGF-,1 neutralizing antibody into the co-culture system. Our results indicated that the CD4+ T cells can be induced into CD4+CD25+FoxP3+ T cells by BMMCs via TGF-,1. [source] The use of porous calcium phosphate scaffolds with transforming growth factor beta 1 as an onlay bone graft substituteCLINICAL ORAL IMPLANTS RESEARCH, Issue 6 2004An experimental study in rats Abstract Objectives: Autogeneous bone grafting is regarded to be the golden standard for onlay grafts, but it requires a harvesting procedure and the remodeling pattern over time is unpredictable. New materials are constantly being sought to overcome these problems. An in vivo experiment was carried out to evaluate whether (1) porous calcium phosphate cement is a suitable biomaterial for onlay bone grafting, and (2) the addition of transforming growth factor beta 1 (TGF-,1) accelerates de novo bone formation inside the cement porosity. Material and methods: A carrier of porous calcium phosphate cement (Calcibon®) was designed and 16 rats received one preshaped implant each. In 8 out of 16 implants 0.75 ,g TGF-,1 was applied. The animals were killed after 4 weeks and the characteristics of tissue ingrowth into the onlay graft were evaluated. Results: Histologic and quantitative histomorphometrical measurements demonstrated osteoid-like tissue formation in both experimental groups. The addition of TGF-,1 did not induce significantly more osteoid-like tissue formation. On the other hand, in TGF-,-loaded implants, a higher number of pores contained an inflammatory infiltrate. Conclusion: This study indicated that porous calcium phosphate cement is a promising material for clinical situations where bone formation has to be supported. Résumé La greffe osseuse autogčne est considérée comme la meilleure technique actuelle pour les greffons onlay mais elle requiert un processus de prélevement et le remodelage qui s'en suit est imprévisible. De nouveaux matériaux sont donc constamment recherchés. Cette étude in vitro a essayé d'évaluer si 1) le cément phosphate calcium poreux était un biomatériel favorable pour le greffage osseux onlay, 2) si l'addition de TGF-,1 accélérait la néoformation osseuse ŕ l'intérieur de la porosité du cément. Un porteur de cément phosphate calcium poreux (Calcibon®) a été fabriqué et seize rats ont reçu chacun un implant prédécoupé. Au niveau de huit des seize implants 0,75 ,g de TGF ,1 a été appliqué. Les animaux ont été euthanasiés aprčs quatre semaines et les caractéristiques de la croissance interne tissulaire dans le greffon onlay ont étéévaluées. Les mesures histologiques et histomorphométriques quantitatives ont démontré une formation tissulaire semblable ŕ l'ostéogénie dans les deux groupes expérimentaux. L'addition de TGF-ß1 n'induisait pas plus de formation tissulaire ressemblant ŕ celle d'ostéogénie. D'un autre côté, dans les implants chargés de TGF-,1, un nombre plus important de pores contenaient un infiltrat inflammatoire. Cette étude indique que le cément phosphate calcium poreux est un matériau prometteur pour les situations cliniques dans lesquelles la formation osseuse doit ętre améliorée. Zusammenfassung Ziel: Die Transplantation von autologem Knochen wird heute als Goldstandard für die Onlay-Transplantate betrachtet. Es braucht dazu aber einen zusätzlichen Eingriff für die Entnahme und eine Prognose bezüglich der anschliessenden Remodellationsvorgänge sind kaum möglich. Man sucht ständig nach neuen Produkten, um diese Probleme zu überwinden. Man führte eine in vivo Studie durch und untersucht, ob (1) ein poröser Kalziumphosphatzement ein brauchbares Biomaterial für ein Onlay-Transplantat ist, und (2) der Zusatz von TGF-,1 die Neubildung von Knochen in den Porositäten des Zementes positiv beeinflusst. Material und Methode: Man entwickelte einen Trägerzement aus porösem Kalziumphosphat (Calcibon®) und 16 Ratten erhielten je ein vorgeformtes Implantat eingesetzt. Bei 8 der 16 Implantate fügte man zusätzlich 0.75 ,g TGF-,1 dazu. Vier Wochen später opferte man die Tiere und konnte nun die Charakteristika des in die Implantate einwachsenden Gewebes untersuchen. Resultate: Die histologischen und quantitativen histomorphometrischen Messungen zeigten in beiden experimentellen Gruppen osteoidähnliche Gewebsbildungen. Der Zusatz von TGF-,1 bewirkte keine signifikante Zunahme dieser osteoidähnlichen Gewebsbildungen. Die mit TGF-,1 durchsetzten Implantate enthielten aber mehr mit entzündlichem Infiltrat angefüllte Poren. Zusammenfassung: Diese Arbeit zeigte uns, dass ein poröser Kalziumphosphatzement bei klinischen Situationen, wo die Knochenbildung unterstützt werden muss, ein erfolgsversprechendes Material ist. Resumen Objetivos: El injerto de hueso autógeno está considerado como el estándar de oro para injertos superpuestos, pero requiere un procedimiento de recolección y el patrón de remodelado a lo largo del tiempo es impredecible. Constantemente se están buscando materiales nuevos para superar estos problemas. Se llevó a cabo un experimento in vivo para evaluar si (1) el cemento de fosfato cálcico poroso es un biomaterial apropiado para injerto óseo superpuesto, y (2) la adición de TGF-,1 acelera la formación de hueso de novo dentro de la porosidad del cemento. Material y Métodos: Se diseńó un portador de cemento de fosfato cálcico (Calcibon®) y 16 ratas recibieron un implante preformado cada una. En 8 de 16 implantes se aplicaron 0.75 ,g de TGF-,1. Los animales se sacrificaron tras 4 semanas y se evaluaron las características del tejido crecido hacia adentro del injerto superpuesto. Resultados: Las mediciones histológicas e histomorfométricas cuantitativas demostraron formación de tejido tipo osteoide en ambos grupos experimentales. La adición de TGF-,1 no indujo significativamente más formación de tejido tipo osteoide. Por otro lado, en los implantes cargados con TGF-,1, un mayor número de de poros contenían infiltrado inflamatorio. Conclusión: Este estudio indica que el cemento de fosfato cálcico poroso es un material prometedor para situaciones clínicas donde la formación de hueso ha de ser favorecida. [source] Comparison of three different preparations of platelet concentrates for growth factor enrichmentCLINICAL ORAL IMPLANTS RESEARCH, Issue 5 2002Thorsten R. Appel Abstract: The aim of the present study was to compare three different systems for preparing platelet concentrates: two commercially available bed-side techniques (Curasan system and PCCS) and a procedure used routinely in transfusion medicine. Platelet concentrates were prepared from venous blood of 12 healthy male volunteers using the three different systems. Platelet and leucocyte counts were performed and platelet derived growth factor and transforming growth factor beta were assayed by enzyme linked immunoassay. Handling was also considered. The three systems were able to collect 19.0 ± 16.6% (laboratory system), 41.9 ± 9.7% (Curasan system) and 49.6 ± 21.0% (PCCS) of the absolute number of platelets which were originally in the venous blood volume within the platelet concentrate. Due to the amount of plasma which is left in the platelet concentrate portion, the platelet concentration could be increased between 1.4 ± 1.3 times (laboratory system), 5.0 ± 2.3 times (PCCS) and 11.7 ± 2.4 times (Curasan system) compared to the venous blood. The amount of growth factors correlated with the number of platelets within the platelet concentrates. The two systems for intraoperative use are similar in their effects on the platelets. The absolute gain of platelets seems to be the highest with the PCCS; the highest concentration of platelets per µL is gained with the Curasan system. The laboratory system may offer an alternative if an intraoperative system is not available. 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