Heparan sulfate is required for bone morphogenetic protein-7 signaling

Biochem Biophys Res Commun. 2003 Sep 5;308(4):858-65. doi: 10.1016/s0006-291x(03)01500-6.

Abstract

Although genetic studies have suggested that heparan sulfate (HS) is involved in bone morphogenetic protein (BMP)-mediated embryonic morphogenesis, it is unclear whether HS is directly involved in BMP-mediated signaling. Here, we investigate the involvement of HS in BMP-7 signaling. We show that HS and heparin chains specifically bind to BMP-7. Digestion of cell-surface HS with heparitinase interferes with BMP-7-mediated Smad phosphorylation in ROS 17/2.8 osteoblastic cells. Inhibiting sulfation of cell-surface HS with chlorate also causes interruption of Smad phosphorylation. Addition of exogenous heparin to ROS 17/2.8 cells prevents BMP-7-mediated Smad phosphorylation rather than enhances the BMP-7 signal, suggesting that HS should be anchored on the plasma membrane for BMP signaling. Moreover, BMP-7 binding to ROS 17/2.8 cells is inhibited by chlorate treatment and exogenous application of heparin. These results demonstrate that BMP-7 specifically binds to cell-surface HS and the BMP-7-HS interaction is required for BMP-7 signaling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Morphogenetic Protein 7
  • Bone Morphogenetic Proteins / metabolism*
  • Cell Membrane / enzymology
  • Cell Membrane / metabolism
  • Chlorine / pharmacology
  • Dose-Response Relationship, Drug
  • Enzyme-Linked Immunosorbent Assay
  • Glycosaminoglycans / metabolism
  • Heparin / metabolism
  • Heparitin Sulfate / metabolism*
  • Immunoblotting
  • Models, Chemical
  • Osteoblasts
  • Phosphorylation
  • Polysaccharide-Lyases / metabolism
  • Protein Binding
  • Rats
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sepharose / metabolism
  • Signal Transduction*
  • Transforming Growth Factor beta*
  • Tumor Cells, Cultured

Substances

  • Bmp7 protein, rat
  • Bone Morphogenetic Protein 7
  • Bone Morphogenetic Proteins
  • Glycosaminoglycans
  • Transforming Growth Factor beta
  • Chlorine
  • Heparin
  • Sepharose
  • Heparitin Sulfate
  • Polysaccharide-Lyases
  • heparitinsulfate lyase