Abstract
Osteogenic protein-1 (OP-1) is a member of the TGF-beta superfamily that is expressed in the nervous system. We recently showed that human recombinant osteogenic protein-1 (hOP-1) strongly promotes the aggregation of dividing neuroblastoma x glioma hybrid NG108-15 cells, in part by inducing the major isoforms of the neural cell adhesion molecule (N-CAM) (Perides, G., Safran, R. M., Rueger, D. C., and Charness, M. E. (1992) Proc. Natl. Acad. Sci. U. S. A. 89, 10326-10330). Here we show that hOP-1 induces L1 expression approximately 6-fold in NG108-15 cells without changing the levels of N-cadherin, neurofilament 200, Thy-1, tau, and G alpha s. OP-1 induction of L1 and N-CAM was unassociated with changes in cell proliferation and was not reproduced by cellular differentiation. The increased adhesiveness of hOP-1-treated NG108-15 cells could be inhibited in part by Fab fragments of an anti-L1 polyclonal antiserum. L1 and N-CAM expression first increased 12-18 h after hOP-1 treatment, reached a maximum after 2-3 days, persisted for up to 5 days, and returned to control levels 3 days after hOP-1 withdrawal. The increases in L1 and N-CAM protein levels were preceded or accompanied by large increases in the abundance of L1 and all detectable N-CAM mRNAs. Actinomycin D prevented the induction by hOP-1 of L1 and N-CAM mRNAs, suggesting that hOP-1 regulates immunoglobulin CAM gene transcription. OP-1 is the first described growth factor that regulates both N-CAM and L1 gene expression.
Highlights
Laboratory, Department of Veterans Affairs Medical Center, West Roxbury, Massachusetts 02132I,ICreative Biomolecules Inc., Hopkinton, Massachusetts01748, the lTDepartment of Neurology and Program in Neuroscience, HarvardMedical School, the lDivision of Neurology, Brigham and Women‘s Hospital, Boston, Massachuset0t2s115, and the Wectwn of Neurology, Department of Veterans AffairsMedical Center, West Roxbury, Massachusetts 02132
We recently showed that human recombinant osteogenic protein-1 stronglypromotes the aggregation of dividing neuroblastoma X glioma hybrid NG108-15 cells, in part by inducing the major isoforms of the neuralcell adhesion molecule (N-CAM()Perides, G., Safran, R
In this report we show that human OP-1 (hOP-1) strongly and selectively induces the expression of L1 andN-CAM in NG108-15 cells by increasing the abundance of L1 andN-CAM mRNA.hOP1 appears toact by atranscriptional mechanism of gene regulation that is independent of cell differentiation
Summary
Increase in L1 Expression-To determine the effects of hOP-1 on L1 expression, NG108-15 cells were cultured for 3 days in the absence and presence of 40 ng/ml hOP-1 and processed for L1 and N-CAM immunofluorescence. The percentage of cells extending neurites was greater after treatment with forskolin or MezSO than with hOP-1; only hOP-1-treated cells showed increased expression of NCAM and L1 (Fig. 5A).
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
