Evaluation of apoptosis and the glucocorticoid receptor in the cartilage growth plate and metaphyseal bone cells of rats after high-dose treatment with corticosterone

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 Science Inc. All rights reserved.