Wilson A K, Cerny E A, Smith B D, Wagh A, Bhattacharyya M H
Center for Mechanistic Biology and Biotechnology, Argonne National Laboratory, Illinois 60439-4833, USA.
Toxicol Appl Pharmacol. 1996 Oct;140(2):451-60. doi: 10.1006/taap.1996.0242.
Chronic exposure to cadmium has been linked to bone loss, low bone mass, and increased incidence of fracture. To determine if Cd could directly increase the formation of cells responsible for bone resorption, we cultured normal canine bone marrow cells containing the progenitor cells for osteoclasts. Cultures were evaluated for the number of multinucleate osteoclast-like cells (MNOCs) formed. Exposure to Cd (10-100 nM) increased the number of MNOCs formed over control values when cultured in the presence but not in the absence of a bone wafer. The MNOCs formed were functional, evidenced by pits excavated on the bone wafers included in the cultures. By 12 days, MNOCs formed in the presence of 50 nM Cd excavated significantly more pits and a greater pit area than did untreated MNOCs. By 14 days, the control values were similar to those of the Cd-exposed MNOCs, but pit formation was enhanced by Cd in that the ratio of pit complexes to single pits was increased twofold over that for untreated cultures. Mature osteoclasts, isolated from the long bones of rat neonates and cultured for 1-3 days on bone slices, provided a direct method to assess the effect of Cd on osteoclast activity. Exposure of osteoclast cultures to 100 nM Cd increased the number of osteoclasts present over that for untreated osteoclasts by a factor of 1.7 +/- 0.1, the number of pits excavated by 2.8 +/- 0.6, the area excavated by 3.2 +/- 0.8, and the area excavated per osteoclast by 1.8 +/- 0.4 (mean +/- SE; n = six experiments). These data suggest that Cd accelerates the differentiation of new osteoclasts from their progenitor cells and activates or increases the activity of mature osteoclasts.
长期接触镉与骨质流失、低骨量以及骨折发生率增加有关。为了确定镉是否能直接增加负责骨吸收的细胞的形成，我们培养了含有破骨细胞祖细胞的正常犬骨髓细胞。评估培养物中形成的多核破骨细胞样细胞（MNOCs）的数量。当在有骨片存在而非无骨片存在的情况下培养时，暴露于镉（10 - 100 nM）会使形成的MNOCs数量超过对照值。培养物中包含的骨片上有凹坑，证明形成的MNOCs具有功能。到第12天，在50 nM镉存在下形成的MNOCs挖掘出的凹坑明显多于未处理的MNOCs，且凹坑面积更大。到第14天，对照值与镉暴露的MNOCs相似，但镉增强了凹坑形成，因为凹坑复合体与单个凹坑的比例比未处理培养物增加了两倍。从新生大鼠长骨中分离并在骨切片上培养1 - 3天的成熟破骨细胞，为评估镉对破骨细胞活性的影响提供了一种直接方法。将破骨细胞培养物暴露于100 nM镉，使存在的破骨细胞数量比未处理的破骨细胞增加了1.7 +/- 0.1倍，挖掘的凹坑数量增加了2.8 +/- 0.6倍，挖掘的面积增加了3.2 +/- 0.8倍，每个破骨细胞挖掘的面积增加了1.8 +/- 0.4倍（平均值 +/- 标准误；n = 六个实验）。这些数据表明，镉加速了新破骨细胞从其祖细胞的分化，并激活或增加了成熟破骨细胞的活性。
