title: Homeobox proteins as signal transduction intermediates in regulation of NCAM expression by recombinant human bone morphogenetic protein-2 in osteoblast-like cells.
abstract: The role of homeobox genes in signaling of recombinant human bone morphogenetic protein-2 (rhBMP-2) was studied in osteoblast-like cells. Expression of several homeobox genes was decreased by rhBMP-2. The finding that this regulation of homeobox gene expression by rhBMP-2 was not dependent on protein synthesis suggests that homeobox proteins can act as direct intermediates in signal transduction of BMPs. Therefore, we studied the regulation of neural cell adhesion molecule (NCAM), which has previously been described as a target gene of both rhBMP-2 and homeobox proteins. We now show that in osteoblast-like cells, rhBMP-2 inhibits NCAM expression, while HOXC6 increases its expression, both acting via the same region of the promoter. As overexpression of HOXC6 could abolish effects of rhBMP-2 on NCAM promoter activity, these data show for the first time that members of the homeobox gene family may form direct functional intermediates in the signaling mechanism of the TGF-beta superfamily.
authors.affiliation: Laboratory for Applied Biology, University of Nijmegen, The Netherlands.
authors.forename: C J
authors.initials: CJ
authors.lastname: Boersma
authors.forename: M
authors.initials: M
authors.lastname: Bloemen
authors.forename: J M
authors.initials: JM
authors.lastname: Hendriks
authors.forename: E A
authors.initials: EA
authors.lastname: van Berkel
authors.forename: W
authors.initials: W
authors.lastname: Olijve
authors.forename: E J
authors.initials: EJ
authors.lastname: van Zoelen
mesh_terms: D000818:Animals; D015139:Blotting, Southern; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002460:Cell Line; D004797:Enzyme-Linked Immunosorbent Assay; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D051379:Mice; D019006:Neural Cell Adhesion Molecules / Q000378:metabolism*; D010006:Osteoblasts; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000032:analysis; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics* / Q000502:physiology; D014162:Transfection; D016212:Transforming Growth Factor beta
chemical_list: C525718:BMP2 protein, human; C525719:Bmp2 protein, mouse; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D018398:Homeodomain Proteins; D019006:Neural Cell Adhesion Molecules; D012333:RNA, Messenger; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C499469:recombinant human bone morphogenetic protein-2