Abstract
Drosophila Crossveinless-2 (dCV-2) is required for local activation of Mad phosphorylation in the fruit fly wing and has been postulated to be a positive regulator of BMP-mediated signaling. In contrast, the presence of 5 Chordin-like cysteine-rich domains in the CV-2 protein suggests that CV-2 belongs to a family of well-established inhibitors of BMP function that includes Chordin and Sog [Development 127 (2000) 3947]. We have identified a human homolog of Drosophila CV-2 (hCV-2). Here we show that purified recombinant hCV-2 protein inhibits BMP-2 and BMP-4 dependent osteogenic differentiation of W-20-17 cells, as well as BMP dependent chondrogenic differentiation of ATDC5 cells. Interestingly, hCV-2 messenger RNA is expressed at high levels in human primary chondrocytes, whereas expression in primary human osteoblasts is low. These results suggest that hCV-2 may regulate BMP responsiveness of osteoblasts and chondrocytes in vivo. Taken together we have shown that contrary to the function predicted from the fruit fly, Crossveinless-2 is a novel inhibitor of BMP function.
MeSH terms
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Alkaline Phosphatase / metabolism
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Animals
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Bone Morphogenetic Protein 2
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Bone Morphogenetic Protein 4
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Bone Morphogenetic Proteins / antagonists & inhibitors*
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Bone Morphogenetic Proteins / metabolism
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Cell Differentiation
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Cell Division
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Cell Line
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Cells, Cultured
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Cysteine / chemistry
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DNA, Complementary / metabolism
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Dose-Response Relationship, Drug
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Drosophila
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Drosophila Proteins / metabolism
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Drosophila Proteins / physiology*
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Glycoproteins / chemistry
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Humans
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Intercellular Signaling Peptides and Proteins / chemistry
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Mice
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Osteoblasts / metabolism
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Phenotype
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Phosphorylation
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Protein Structure, Tertiary
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RNA, Messenger / metabolism
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Recombinant Proteins / chemistry
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Reverse Transcriptase Polymerase Chain Reaction
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Signal Transduction
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Tissue Distribution
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Transforming Growth Factor beta*
Substances
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BMP2 protein, human
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BMP4 protein, human
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Bmp2 protein, mouse
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Bmp4 protein, mouse
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Bone Morphogenetic Protein 2
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Bone Morphogenetic Protein 4
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Bone Morphogenetic Proteins
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DNA, Complementary
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Drosophila Proteins
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Glycoproteins
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Intercellular Signaling Peptides and Proteins
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RNA, Messenger
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Recombinant Proteins
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Transforming Growth Factor beta
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cv-2 protein, Drosophila
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recombinant human bone morphogenetic protein-2
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sog protein, Drosophila
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chordin
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Alkaline Phosphatase
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Cysteine