OSTEOGENIC PROTEIN-1 REGULATES L1 AND NEURAL CELL-ADHESION MOLECULE GENE-EXPRESSION IN NEURAL CELLS

Osteogenic protein-1 (OP-1) is a member of the TGF-beta superfamily th at is expressed in the nervous system. We recently showed that human r ecombinant osteogenic protein-1 (hOP-1) strongly promotes the aggregat ion 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 cell s without changing the levels of N-cadherin, neurofilament 200, Thy-1, tau, and Galpha(s). OP-1 induction of L1 and N-CAM was unassociated w ith changes in cell proliferation and was not reproduced by cellular d ifferentiation. The increased adhesiveness of hOP-1-treated NG108-15 c ells could be inhibited in part by Fab fragments of an anti-L1 polyclo nal antiserum. L1 and N-CAM expression first increased 12-18 h after h OP-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 accompan ied 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 transc ription. OP-1 is the first described growth factor that regulates both N-CAM and L1 gene expression.