Figure 4

Network of upregulated genes in C2C12 cells treated with rhBMP2 and rhBMP7 using the STRING 9.0 pathway analyzer. STRING 9.0 is a database of known and predicted protein interactions. The interactions may be physically direct or indirect (functional). The list of protein names are inserted as input and the organism to be analyzed is selected in a user-friendly web-browser interface. The network, composed of the uploaded proteins, is constructed based on four different sources: genomic context, high-throughput experiments, co-expression and scientific reports (http://string-db.org/). The upregulated genes found in each group (C2C12 cells treated with rhBMP7 or rhBMP2) were matched and classified according to a pre-described interaction (activation, repression, or predicted interaction). The circles represent the genes and the blue edges represent the interaction between them. The edges are based on proteins being co-mentioned in scientific publications as well as their association in curated databases. The edge thickness is directly proportional to the degree of evidence available, with lack of evidence for interactions in the literature being represented as no edges among the genes. Runx2: Runt Related Transcription factor 2; Dlx1/2/5: Distal-less homeobox 1/2 and 5;Id1/2/3: Inhibitor of DNA binding 1/2 and 3; Sp7, an alternative name for Osterix: Transcription factor Sp7; Hoxc8: Homeobox protein Hox-C8; Fkhr1: Forkhead protein FKHR1; Glis1/3: Gli homologous protein 1; Cfdp1: Craniofacial development protein 1; Lrp6: Low-density lipoprotein receptor-related protein 6; Segment polarity protein dishevelled homolog DVL-1; Ecsit: Evolutionarily conserved signaling intermediate in the Toll pathway, mitochondrial; PKCd: Protein kinase C, delta type; Ltbp2: Latent-transforming growth factor beta-binding protein 2; Grn: Granulin; BMP1: Bone Morphogenetic Protein 1; Plod1: Procollagen-lysine,2-oxoglutarate 5-dioxygenase 1; Postn: Periostin; Htra1: Serine protease HTRA1; Kazald1: Kazal-type serine protease inhibitor domain-containing protein 1 (IGFBP-rP10); Wnt3a: Protein Wnt-3a; Dkk1: Dickkopf-related protein 1 and Ctnn1b: Catenin beta-1.