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.
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