Evaluation of apoptosis and the glucocorticoid receptor in the cartilage growth plate and metaphyseal bone cells of rats after high-dose treatment with corticosterone
G. Silvestrini et al., Evaluation of apoptosis and the glucocorticoid receptor in the cartilage growth plate and metaphyseal bone cells of rats after high-dose treatment with corticosterone, BONE, 26(1), 2000, pp. 33-42
A connection has been suggested between glucocorticoid-induced osteopenia a
nd an increase in the apoptosis of bone cells, and between the dimerization
of the glucocorticoid receptor (GR) and the development of apoptosis, On t
his basis, a study has been carried out on the relationships between the oc
currence of apoptotic cells and their detectable GR content, and between ap
optosis frequency and changes in histomorphometric variables, in the growth
plate and secondary spongiosa of rat long bones after the high-dose (10 mg
/day) administration of corticosterone (CORT) and after recovery, The main
results of the CORT treatment were: a significant increase in apoptotic ost
eoblasts, and a concomitant decrease in the histomorphometric variables of
bone formation, with a reversal of both values during recovery; a nonsignif
icant increase in the apoptosis of osteoclasts, without changes in the hist
omorphometric variables of bone resorption; a significant increase in apopt
otic terminal hypertrophic chondrocytes; the presence of GR in all types of
skeletal cells in control rats, with different (cytoplasmic and/or nuclear
) immunohistochemical detection in the same type of cell; a decrease in GR
detection in proliferative chondrocytes and osteocytes in CORT and recovery
groups, and in the maturative/hypertrophic chondrocytes of the recovery gr
oup; a fall in growth cartilage width, possibly due to the reduced prolifer
ation of proliferative chondrocytes and increased apoptosis in terminal hyp
ertrophic chondrocytes, In conclusion, pharmacological doses of CORT reduce
bone formation by increasing osteoblast apoptosis; they reduce growth cart
ilage width, probably by inhibiting chondrocyte proliferation and increasin
g the apoptosis of terminal hypertrophic chondrocytes, and they reduce oste
ocyte GR. Although these effects appear to be mediated by the presence of G
R in all skeletal cells, no precise correlation between GR immunohistochemi
cal detection and apoptosis induction has been found. (C) 2000 by Elsevier
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