Human Crossveinless-2 is a novel inhibitor of bone morphogenetic proteins

• Published in: Biochemical and biophysical research communications Vol. 315; no. 2; pp. 272 - 280
• Main Authors: Binnerts, Minke E, Wen, Xiaohui, Canté-Barrett, Kirsten, Bright, Jessica, Chen, Huang-Tsu, Asundi, Vinod, Sattari, Peter, Tang, Tom, Boyle, Bryan, Funk, Walter, Rupp, Fabio
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 05.03.2004
• Subjects: Alkaline Phosphatase - metabolism; Animals; Bone Morphogenetic Protein 2; Bone Morphogenetic Protein 4; Bone Morphogenetic Proteins - antagonists & inhibitors; Bone Morphogenetic Proteins - metabolism; Cell Differentiation; Cell Division; Cell Line; Cells, Cultured; Cysteine - chemistry; DNA, Complementary - metabolism; Dose-Response Relationship, Drug; Drosophila; Drosophila Proteins - metabolism; Drosophila Proteins - physiology; Glycoproteins - chemistry; Humans; Intercellular Signaling Peptides and Proteins - chemistry; Mice; Osteoblasts - metabolism; Phenotype; Phosphorylation; Protein Structure, Tertiary; Recombinant Proteins - chemistry; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - metabolism; Signal Transduction; Tissue Distribution; Transforming Growth Factor beta
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2004.01.048

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.