Prolonged treatment with glucocorticoids is known to produce
osteoporosis, which is characterized by a decrease in bone mass. Therefore,
we studied the effect of glucocorticoids on the formation of bone and on
the expression of beta 1 integrins in a mineralizing organ culture of fetal
rat parietal bone. Integrins are a family of integral membrane
glycoproteins that mediate the adhesion of cells to extracellular matrix
macromolecules and affect the growth and differentiation of cells. In situ
hybridization with a 32P-labeled beta 1 integrin cDNA probe was performed
on parietal bone, treated with or without 100-nanomolar corticosterone for
ninety-six hours, to localize and assess the levels of beta 1 integrin mRNA
quantitatively. Corticosterone decreased beta 1 integrin mRNA in the
osteoblast layer but not in the periosteum. Northern blot analysis
demonstrated a 62 per cent decrease in the levels of beta 1 integrin mRNA
in the osteoblast layer of bone that had been stripped of its periosteum.
Immunofluorescence microscopy confirmed these results, as they demonstrated
a decrease in the levels of beta 1 integrin protein predominantly in the
osteoblast layer. This effect was dependent on the concentration of
corticosterone. During ninety-six hours of culture, the calcium content and
the dry weight of control parietal bone increased 157 per cent and 57 per
cent, respectively. However, treatment of these cultures with 100-nanomolar
corticosterone inhibited calcification by 24 per cent. The administration
of glucocorticoid had no significant effect on the DNA content or dry
weight.(ABSTRACT TRUNCATED AT 250 WORDS)