Bcl-2 and Bax expression in cartilage and bone cells after high-dose corticosterone treatment in rats

The expression of Bcl-2 and Bax has been evaluated by immunohistochemistry in normal rats, and in rats after treatment with high-dose corticosterone ( CORT). Proliferative (PC) and maturative/hypertrophic (MaHC) chondrocytes o f the growth plate have been examined, as well as osteoblasts (Obs), osteoc ytes (Ots) and osteoclasts (Ocs) of the metaphyseal secondary spongiosa. Fo r each cell type, the Bcl-2 and Bax immunopositive cells were expressed as a percentage of the total number of cells. Bcl-2 and Pax expression was con sidered to be enhanced when the percentage of positive cells rose. Bcl-2 an d Bax were expressed in all cell types, and two main kinds of labeling dist ribution, both suggestive of association with intracellular organelles, wer e observed in the cytoplasm: scarce and spotty labeling (type 1) or abundan t, granular and diffuse labeling (type 2). In some cases, nuclear membranes could also be seen to be positive, Positive PCs and Obs generally showed a labeling of type 1, MaHCs and Ocs of type 2, while Ots varied with labelin g of type 1 or type 2. CORT administration induced a fall in the percentage of Bcl-2 immunopositive cells, and a rise in that of Bax immunopositive ce lls, in PCs and Ots, The same trend was observed in MaHCs, although the Bcl -2 decrease was not significant. The percentage of Bcl-2 and Bax immunoposi tive Obs rose, and their labeling distribution shifted from type 1- to type 2-labeled cells. Ocs showed the highest immunopositivity for both Bcl-2 an d Bax, which did not change after CORT administration. These data suggest t hat CORT treatment, by lowering Bcl-2, and raising Bax expression, may prom ote the apoptotic process in PCs, MaHCs and Ots. Obs, however, do not under go the same variations. This finding, together with the results of a previo us study showing that CORT administration raises the frequency of apoptotic Obs, does not support a direct relationship between apoptosis and Bax over expression, at least in Obs. The CORT effect might be related to cell types and their state of differentiation, so that Bcl-2 and Bax might regulate n ot only the machinery of cell death, but also cell proliferation and differ entiation. (C) 2001 Harcourt Publishers Ltd.