Induction of the neural cell adhesion molecule and neuronal aggregation by osteogenic protein 1.
The neural cell adhesion molecule (N-CAM) plays a fundamental role in nervous system development and regeneration, yet the regulation of the expression of N-CAM in different brain regions has remained poorly understood. Osteogenic protein 1 (OP-1) is a member of the transforming growth factor beta superfamily that is expressed in the nervous system. Treatment of the neuroblastoma-glioma hybrid cell line NG108-15 for 1-4 days with recombinant human OP-1 (hOP-1) induced alterations in cell shape, formation of epithelioid sheets, and aggregation of cells into multilayered clusters. Immunofluorescence studies and Western blots demonstrated a striking differential induction of the three N-CAM isoforms in hOP-1-treated cells. hOP-1 caused a 6-fold up-regulation of the 140-kDa N-CAM, the isoform showing the highest constitutive expression, and a 29-fold up-regulation of the 180-kDa isoform. The 120-kDa isoform was not detected in control NG108-15 cells but was readily identified in hOP-1-treated cells. Incubation of NG108-15 cells with an antisense N-CAM oligonucleotide reduced the induction of N-CAM by hOP-1 and decreased the formation of multilayered cell aggregates. Anti-N-CAM monoclonal antibodies also diminished the formation of multilayered cell aggregates by hOP-1 and decreased cell-cell adhesion when hOP-1-treated NG108-15 cells were dispersed and replated. Thus, hOP-1 produces morphologic changes in NG108-15 cells, at least in part, by inducing N-CAM. These observations suggest that OP-1 or a homologue may participate in the regulation of N-CAM during nervous system development and regeneration.
Perides
G
G
Department of Pathology, Harvard Medical School, West Roxbury, MA.
Safran
R M
RM
Rueger
D C
DC
Charness
M E
ME
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015153:Blotting, Western; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D002448:Cell Adhesion / Q000187:drug effects*; D015816:Cell Adhesion Molecules, Neuronal / Q000032:analysis / Q000096:biosynthesis* / Q000302:isolation & purification; D002449:Cell Aggregation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005455:Fluorescent Antibody Technique; D005910:Glioma; D007700:Kinetics; D008970:Molecular Weight; D009447:Neuroblastoma; D011506:Proteins / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000494:pharmacology; D016212:Transforming Growth Factor beta; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; C525819:BMP7 protein, human; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D015816:Cell Adhesion Molecules, Neuronal; D011506:Proteins; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta