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  • Van Zoelen, Everardus J. J.  (3)
  • 1
    In: Journal of Bone and Mineral Research, Wiley, Vol. 14, No. 8 ( 1999-08), p. 1432-1441
    Kurzfassung: Bone morphogenetic protein‐4 (BMP‐4) is a member of the BMP family, which consists of important regulators of bone formation and embryonic development. We have previously isolated the human BMP‐4 encoding gene, which is associated with the heritable disorder Fibrodysplasia Ossificans Progressiva. In this study, we describe the molecular cloning and functional characterization of two promoters involved in the transcriptional regulation of the human BMP‐4 gene, one upstream of exon 1, the second located in intron 1, upstream of exon 2. These two promoters give rise to different transcripts in a cell type– and differentiation‐dependent manner. Mutational analysis showed cell type–specific regulation of both promoter activities. Gel mobility shift assays indicated the presence of cell type–specific transcription factor binding sites in promoter 1. In addition, evidence was found for a novel BMP‐4 transcript. Since various human diseases can be linked directly to aberrant expression of BMP genes, the present findings are of great importance in attempts to develop strategies for therapeutic interference with such diseases.
    Materialart: Online-Ressource
    ISSN: 0884-0431 , 1523-4681
    RVK:
    Sprache: Englisch
    Verlag: Wiley
    Publikationsdatum: 1999
    ZDB Id: 2008867-X
    Standort Signatur Einschränkungen Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 2
    In: Journal of Bone and Mineral Research, Wiley, Vol. 17, No. 12 ( 2002-12), p. 2106-2118
    Kurzfassung: Osteoblasts are cells responsible for matrix deposition during bone development and although temporal expression of many genes has been related to osteoblast differentiation, a complete description of osteoblast‐specific gene regulation will lead to a better understanding of osteoblast function. In this study, microarray technology was used to analyze gene expression on a broad scale during osteoblast differentiation. Expression analysis of 9596 sequences revealed 342 genes and expressed sequence tags (ESTs) to be modulated differentially during a time course experiment in which murine C2C12 mesenchymal progenitor cells were induced to differentiate into mature osteoblasts by treatment with bone morphogenetic protein 2 (BMP‐2). By means of hierarchical clustering, these genes were grouped by similarities in their expression profiles, resulting in subsets of early, intermediate, and late response genes, which are representative of the distinct stages of osteoblast differentiation. To identify new bone markers, the bone specificity of the late response genes was determined by comparing BMP‐induced expression in C2C12 and MC3T3 osteoblasts with that in NIH3T3 fibroblasts. This resulted in the identification of nine novel genes and ESTs that were induced specifically in osteoblasts, in addition to the well‐known markers ALP and osteocalcin. For at least one of these novel genes, Wnt inhibitory factor 1, and two of the ESTs, expression in developing bone was verified in vivo by in situ hybridization of E16.5 mouse embryos. In conclusion, by a combination of in vitro and in vivo screening approaches, a set of new genes related to osteoblast differentiation and skeletal development has been identified.
    Materialart: Online-Ressource
    ISSN: 0884-0431 , 1523-4681
    RVK:
    Sprache: Englisch
    Verlag: Wiley
    Publikationsdatum: 2002
    ZDB Id: 2008867-X
    Standort Signatur Einschränkungen Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 3
    In: Journal of Bone and Mineral Research, Wiley, Vol. 17, No. 12 ( 2002-12), p. 2119-2129
    Kurzfassung: Bone morphogenetic protein (BMP) 2, a member of the transforming growth factor (TGF) β family, is a potent regulator of osteoblast differentiation. In addition, both TGF‐β and activin A can either induce bone formation or inhibit bone formation depending on cell type and differentiation status. Although much is known about the receptors and intracellular second messengers involved in the action of TGF‐β family members, little is known about how selectivity in the biological response of individual family members is controlled. In this study, we have investigated selective gene induction by BMP‐2, TGF‐β1 and activin A in relation to their ability to control differentiation of mouse mesenchymal precursor cells C2C12 into osteoblastic cells. TGF‐β1 can inhibit BMP‐2‐induced differentiation of these cells, whereas activin A was found to be without morphogenetic effect. Using a gene expression microarray approach covering 8636 sequences, we have identified a total of 57 established genes and expressed sequence tags (ESTs) that were either up‐regulated or down‐regulated 2 h after treatment with at least one of these three stimuli. With respect to the established genes, 15 new target genes for TGF‐β family members thus were identified. Furthermore, a set of transcripts was identified, which was oppositely regulated by TGF‐β1 and BMP‐2. Based on the inverse biological effects of TGF‐β1 and BMP‐2 on C2C12 cells, these genes are important candidates for controlling the process of growth factor‐induced osteoblast differentiation.
    Materialart: Online-Ressource
    ISSN: 0884-0431 , 1523-4681
    RVK:
    Sprache: Englisch
    Verlag: Wiley
    Publikationsdatum: 2002
    ZDB Id: 2008867-X
    Standort Signatur Einschränkungen Verfügbarkeit
    BibTip Andere fanden auch interessant ...
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