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Microarray Analysis of Bone Morphogenetic Protein, Transforming Growth Factor β, and Activin Early Response Genes During Osteoblastic Cell Differentiation
Author(s) -
De Jong Diana S.,
Van Zoelen Everardus J. J.,
Bauerschmidt Susanne,
Olijve Wiebe,
Steegenga Wilma T.
Publication year - 2002
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1359/jbmr.2002.17.12.2119
Subject(s) - bone morphogenetic protein , bone morphogenetic protein 2 , biology , osteoblast , transforming growth factor beta , cellular differentiation , activin type 2 receptors , bone morphogenetic protein 7 , bmpr2 , microbiology and biotechnology , transforming growth factor , bone morphogenetic protein 10 , c2c12 , tgf beta signaling pathway , gene , genetics , myocyte , in vitro , myogenesis
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.