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

Biochem Biophys Res Commun. 2004 Mar 5;315(2):272-80. doi: 10.1016/j.bbrc.2004.01.048.

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

  • 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
  • RNA, Messenger / metabolism
  • Recombinant Proteins / chemistry
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction
  • Tissue Distribution
  • Transforming Growth Factor beta*

Substances

  • BMP2 protein, human
  • BMP4 protein, human
  • Bmp2 protein, mouse
  • Bmp4 protein, mouse
  • Bone Morphogenetic Protein 2
  • Bone Morphogenetic Protein 4
  • Bone Morphogenetic Proteins
  • DNA, Complementary
  • Drosophila Proteins
  • Glycoproteins
  • Intercellular Signaling Peptides and Proteins
  • RNA, Messenger
  • Recombinant Proteins
  • Transforming Growth Factor beta
  • cv-2 protein, Drosophila
  • recombinant human bone morphogenetic protein-2
  • sog protein, Drosophila
  • chordin
  • Alkaline Phosphatase
  • Cysteine