Mocetti P, Silvestrini G, Ballanti P, Patacchioli F R, Di Grezia R, Angelucci L, Bonucci E
Department of Experimental Medicine and Pathology, La Sapienza University Rome, Italy.
Tissue Cell. 2001 Feb;33(1):1-7. doi: 10.1054/tice.2000.0144.
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 of the growth plate have been examined, as well as osteoblasts (Obs), osteocytes (Ots) and osteoclasts (Ocs) of the metaphyseal secondary spongiosa. For each cell type, the Bcl-2 and Bax immunopositive cells were expressed as a percentage of the total number of cells. Bcl-2 and Bax expression was considered to be enhanced when the percentage of positive cells rose. Bcl-2 and Bax were expressed in all cell types, and two main kinds of labeling distribution, both suggestive of association with intracellular organelles, were observed in the cytoplasm: scarce and spotty labeling (type 1) or abundant, 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 labeling 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 cells, 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 immunopositive Obs rose, and their labeling distribution shifted from type 1- to type 2-labeled cells. Ocs showed the highest immunopositivity for both Bcl-2 and Bax, which did not change after CORT administration. These data suggest that CORT treatment, by lowering Bcl-2, and raising Bax expression, may promote the apoptotic process in PCs, MaHCs and Ots. Obs, however, do not undergo the same variations. This finding, together with the results of a previous study showing that CORT administration raises the frequency of apoptotic Obs, does not support a direct relationship between apoptosis and Bax overexpression, 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 not only the machinery of cell death, but also cell proliferation and differentiation.
通过免疫组织化学方法评估了正常大鼠以及高剂量皮质酮(CORT)处理后的大鼠中Bcl-2和Bax的表达。研究了生长板中的增殖性(PC)和成熟/肥大性(MaHC)软骨细胞,以及干骺端次级海绵骨中的成骨细胞(Obs)、骨细胞(Ots)和破骨细胞(Ocs)。对于每种细胞类型,Bcl-2和Bax免疫阳性细胞表示为细胞总数的百分比。当阳性细胞百分比升高时,认为Bcl-2和Bax表达增强。Bcl-2和Bax在所有细胞类型中均有表达,在细胞质中观察到两种主要的标记分布,均提示与细胞内细胞器相关:稀少且点状标记(1型)或丰富、颗粒状且弥漫性标记(2型)。在某些情况下,也可见核膜呈阳性。阳性的PC和Obs通常显示为1型标记,MaHC和Ocs为2型标记,而Ots则为1型或2型标记。给予CORT后,PC和Ots中Bcl-2免疫阳性细胞的百分比下降,Bax免疫阳性细胞的百分比上升。MaHC中也观察到相同趋势,尽管Bcl-2的下降不显著。Bcl-2和Bax免疫阳性Obs的百分比上升,其标记分布从1型标记细胞转变为2型标记细胞。Ocs对Bcl-2和Bax均显示出最高的免疫阳性,给予CORT后未发生变化。这些数据表明,CORT处理通过降低Bcl-2和提高Bax表达,可能促进PC、MaHC和Ots中的凋亡过程。然而,Obs并未发生相同的变化。这一发现与先前一项研究的结果一致,该研究表明给予CORT会增加凋亡Obs的频率,至少在Obs中不支持凋亡与Bax过表达之间的直接关系。CORT的作用可能与细胞类型及其分化状态有关,因此Bcl-2和Bax可能不仅调节细胞死亡机制,还调节细胞增殖和分化。