Retinoic acid differentially affects platelet-derived growth factor and epidermal growth factor-regulated cell growth...

Retinoic acid (RA) plays an important role in the control of cell growth and differentiation. To elucidate the effects of RA for osteoblasts, we examined here the responsiveness of normal osteoblast-like MC3T3-E1 cells treated with RA for two growth factors, platelet-derived growth factor (PDGF) and epidermal growth factor (EGF). The transcripts of alpha- and gamma-RA receptors were constitutively expressed in MC3T3-E1 cells, and the expression of the beta-RA receptor mRNA was induced by RA. The PDGF-induced mitogenicity of MC3T3-E1 cells was significantly enhanced by 1 microM RA pretreatment, whereas the EGF-induced mitogenicity was suppressed by the same treatment. The expression of both alpha- and beta-PDGF receptor gene products detected by RNA blot and immunoblot analyses was significantly increased by RA. The increased expression of PDGF receptors was accompanied by the augmentation of PDGF-induced receptor autophosphorylation following the enhancement of inositol phosphate hydrolysis. In contrast, EGF-induced receptor autophosphorylation was suppressed in RA-treated cells, whereas the expression level of EGF receptor was not affected. These findings demonstrate that RA could control the cell growth of osteoblast-like MC3T3-E1 cells not only by regulating the gene expression of growth factor receptors, but also by modulating the ligand-induced receptor autophosphorylation.