Department of Bone Metabolism, Institute of Radiation Medicine, Fudan University, Shanghai 200032, China.
Environ Toxicol Pharmacol. 2009 Sep;28(2):232-6. doi: 10.1016/j.etap.2009.04.010. Epub 2009 Apr 24.
Cadmium (Cd) may have direct effects on bone metabolism and the mechanism is not fully understood. To investigate the effects of Cd on bone metabolism, effects of Cd on osteoblasts and osteoclasts in vitro were observed at cellular and molecular levels. Osteoblasts were cultured by sequential enzyme digestion from Sprague-Dawley rats calvarial bone and osteoclasts were isolated from long bones of new-born male and female Sprague-Dawley rats, and then cells were exposed to different concentrations of Cd (0-2.0 μ mol/L for osteoblasts; 0.03 μmol/L for osteoclasts). As for osteoblasts, cell viability, alkaline phosphatase (ALP) activity, and mineralization were determined. Osteoprotegerin (OPG) and receptor activator of NF-kB ligand (RANKL) were studied via reverse transcription-polymerase chain reaction (RT-PCR). For osteoclasts, after exposure to Cd (0.03 μmol/L) for 72 h and 120 h, number of osteoclasts and pits formation was observed. Cd inhibited the viability, ALP activity, mineralization and up-regulated RANKL mRNA expression in osteoblasts. But Cd had no obvious effect on OPG mRNA expression. For osteoclasts, cadmium (0.03 μmol/L) could increase the numbers of osteoclasts (p<0.05) and enhance pits formation (p<0.05). These results suggested that Cd could inhibit bone formation at high concentrations and enhance bone resorption at low level. OPG/RANKL may constitute an important pathway of Cd effects on bone.
镉(Cd)可能对骨骼代谢有直接影响,但作用机制尚不完全清楚。为了研究镉对骨代谢的影响,我们在细胞和分子水平上观察了镉对成骨细胞和破骨细胞的体外作用。从 SD 大鼠颅骨中通过连续酶消化培养成骨细胞,从新生雄性和雌性 SD 大鼠长骨中分离破骨细胞,然后用不同浓度的 Cd(0-2.0 μmol/L 用于成骨细胞;0.03 μmol/L 用于破骨细胞)处理细胞。对于成骨细胞,测定细胞活力、碱性磷酸酶(ALP)活性和矿化。通过逆转录-聚合酶链反应(RT-PCR)研究了护骨素(OPG)和核因子-kB 受体激活剂配体(RANKL)。对于破骨细胞,在暴露于 Cd(0.03 μmol/L)72 h 和 120 h 后,观察破骨细胞的数量和陷窝形成。Cd 抑制成骨细胞的活力、ALP 活性、矿化和上调 RANKL mRNA 表达。但 Cd 对 OPG mRNA 表达无明显影响。对于破骨细胞,镉(0.03 μmol/L)可以增加破骨细胞的数量(p<0.05)并增强陷窝形成(p<0.05)。这些结果表明,高浓度的 Cd 可抑制骨形成,低浓度的 Cd 可增强骨吸收。OPG/RANKL 可能构成了 Cd 影响骨骼的重要途径。