Cortisol inhibits the differentiation and apoptosis of osteoblasts in culture

Glucocorticoids decrease the replication of cells of the osteoblastic linea ge and the function of the osteoblast. However, under certain conditions, t hey enhance the differentiation of osteoblastic cells, an effect that appea rs contradictory to their inhibitory actions on cell function. In this stud y we examine the effects of cortisol on the proliferation, differentiation, and fate of osteoblastic enriched cells from 22-day-old fetal rat calvaria e (osteoblastic cells) in the absence and presence of beta -glycerophosphat e. In the absence of beta -glycerophosphate, there was a progressive accumu lation of DNA and cells, which was impaired by cortisol. In the presence of beta -glycerophosphate, there was an initial accumulation of DNA and cells followed hy a marked decline that was prevented by cortisol, Despite the s ustained number of cells, cortisol did not affect their mineralization, and inhibited Core binding factor al (Cbfa1), but not alkaline phosphatase, os teocalcin, or type I collagen transcripts, The decrease in cell number by c ortisol observed in the absence of beta -glycerophosphate was due to a decr ease in DNA synthesis, whereas the increase in cell number observed in the presence of beta -glycerophosphate was due to a relative increase in DNA sy nthesis and a decrease in apoptosis as determined by DNA fragmentation and acridine orange staining of the cells. This was correlated by a decrease in transcripts of proapoptotic genes and caspase 3 activity, and an increase of antiapoptotic genes. In conclusion, cortisol decreases the replication o f cells of the osteoblastic lineage, but under conditions of differentiatio n/mineralization, cortisol prevents terminal differentiation of the cells a nd maintains an immature cell population. (C) 2001 by Elsevier Science Inc. All rights reserved.