The Journal of Bone and Joint Surgery, Vol 77, Issue 3 396-404, Copyright © 1995 by Journal of Bone and Joint Surgery, Inc
The effect of glucocorticoids on osteoblast function. The effect of corticosterone on osteoblast expression of beta 1 integrins
WJ Doherty, ME DeRome, MB McCarthy and GA Gronowicz
Department of Orthopaedics, University of Connecticut School of Medicine, Farmington 06030.
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)