C-FOS ONCOGENE EXPRESSION IN DEXAMETHASONE STIMULATED OSTEOGENIC CELLS IN CHICK-EMBRYO PERIOSTEAL CULTURES

Although the complex effects of glucocorticoids on bone cells have been studied extensively in vitro, little is known about the molecular mechanisms of glucocorticoid responses in osteogenic cells. As c-fos and its protein product are believed to play a key role in intracellular signal transduction, and since their role in regulation of bone formation is well-recognized, we studied the effect of the glucocorticoid analogue dexamethasone (DEX) on the expression of c-fos oncogene in the chick periosteal osteogenesis (CPO) model. C-fos mRNA expression was determined by in situ hybridization at various time points after 10(-7) M DEX treatment. Prior to DEX treatment, the cultures had been synchronized with 2 mM thymidine. The mean area of positively hybridized cells in experimental (DEX-treated) and control (DEX-free) cultures was quantitated by computer assisted morphometry. In DEX-treated cultures c-fos mRNA could be detected transiently and mainly in the osteogenic layer at 30, 45 and 60 min after treatment whereas no c-fos expression could be detected above background level in the control groups. Differences between experimental and control groups were significant (P < 0.01) as determined by a general linear model (GLM) analysis of variance. These data indicate that in the CPO culture system, DEX (10(-7) M) induces c-fos expression. The findings are compatible with the hypothesis which states that glucocorticoid-induced phenotypic changes in osteogenic cells may be mediated by c-fos.