Cell adhesion to matrix Gla protein and its inhibition by an Arg-Gly-Asp-containing peptide.
Matrix Gla protein (MGP) is a 14-kDa protein found in bone and cartilage which contains the unusual amino acid gamma-carboxyglutamic acid (Gla). The biological function of this protein has not been elucidated. Here we have demonstrated the adherence of chondrocytes, fibroblasts, osteosarcoma cells, and kidney mesangial cells to MGP purified from bovine bone. Maximum adherence occurred at MGP concentrations of 0.5-1.0 micrograms/ml. Removal of the calcium-binding Gla residues by thermal decarboxylation of MGP destroyed the proteins' cell adherence properties. Cell adherence to MGP was not affected by the presence of antibodies directed against the C-terminal (non-Gla) portion of the protein or the presence of cycloheximide during the adherence assay. However, the Arg-Gly-Asp-containing synthetic peptide Gly-Arg-Gly-Asp-Ser-Pro significantly inhibited cell attachment to MGP, whereas the control peptide Gly-Arg-Gly-Glu-Ser-Pro had minimal effect. These data indicate that MGP may function in mediating cell attachment to the extracellular matrix via a receptor that requires intact Gla residues and that can be inhibited by Arg-Gly-Asp-containing peptides.
Loeser
R F
RF
Department of Medicine, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, North Carolina 27157.
Wallin
R
R
D000595:Amino Acid Sequence; D000818:Animals; D001842:Bone and Bones / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000302:isolation & purification / Q000378:metabolism*; D002358:Cartilage, Articular / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D002417:Cattle; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology*; D002460:Cell Line; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D016326:Extracellular Matrix Proteins; D006801:Humans; D007700:Kinetics; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000138:chemical synthesis / Q000494:pharmacology*; D000097568:Matrix Gla Protein
D002135:Calcium-Binding Proteins; D003513:Cycloheximide; D016326:Extracellular Matrix Proteins; D009842:Oligopeptides; D000097568:Matrix Gla Protein; C047981:arginyl-glycyl-aspartic acid