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PMID: 1438217 Published · ppublish English Journal Article Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

Induction of the neural cell adhesion molecule and neuronal aggregation by osteogenic protein 1.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 89 ·No. 21 ·1992-11-01 ·Pages 10326-30

Perides G, Safran RM, Rueger DC, Charness ME

Abstract

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.

MeSH Terms
Animals Antibodies, Monoclonal/pharmacology Blotting, Western Bone Morphogenetic Protein 7 Bone Morphogenetic Proteins Cell Adhesion/drug effects Cell Adhesion Molecules, Neuronal/analysis,biosynthesis,isolation & purification Cell Aggregation/drug effects Dose-Response Relationship, Drug Fluorescent Antibody Technique Glioma Kinetics Molecular Weight Neuroblastoma Proteins/pharmacology Recombinant Proteins/pharmacology Transforming Growth Factor beta Tumor Cells, Cultured
Chemicals
Antibodies, Monoclonal BMP7 protein, human Bone Morphogenetic Protein 7 Bone Morphogenetic Proteins Cell Adhesion Molecules, Neuronal Proteins Recombinant Proteins Transforming Growth Factor beta
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Perides G
Department of Pathology, Harvard Medical School, West Roxbury, MA.
Safran R M
Rueger D C
Charness M E
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36 references, click to expand
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.89.21.10326
Published
1992-11-01
Pages
10326-30
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC50331
Subset
IM
Grants
NIAAA NIH HHS · AA06662 · United States
NINDS NIH HHS · NS13034 · United States
External Links
PubMed source DOI: 10.1073/pnas.89.21.10326 PMC Full Text View journal details
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