Huang Dan, Wu Shuang, Hou Xiaohong, Jia Lixia, Meng Qinghe, Chu Hongqian, Jiang Jianjun, Shang Lanqin, Hao Weidong
Department of Toxicology, School of Public Health, Peking University, Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety, Beijing, 100191, PR China.
Department of Toxicology, School of Public Health, Peking University, Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety, Beijing, 100191, PR China.
Toxicology. 2017 Apr 15;381:1-9. doi: 10.1016/j.tox.2017.02.003. Epub 2017 Feb 16.
Chlormequat Chloride (CCC), a widely used plant growth regulator, could decrease body weight in animals; however, the mechanism has not been well studied. This study was designed to evaluate the skeletal development toxicity of CCC on pubertal male Sprague-Dawley (SD) rats and to investigate whether CCC impacts the development of chondrocyte, osteoblast and osteoclast through growth hormone (GH) and insulin like growth factor 1 (IGF-I). Rats from 23 to 70 on postnatal days were exposed to CCC daily by gavage at doses of 0, 75, 150, and 300mg/kg bw/d. The results showed that the size of femurs and tibias, bone mineral density and biomechanical parameters were significantly decreased in the 300mg/kg bw/d group compared with the control group. The concentration of osteocalcin (OCN) and C-terminal telopeptide of type I collagen (CTX-I) in blood in the 150mg/kg bw/d group was also changed. The mRNA expression ratio of the receptor activator of NF-κB ligand (RANKL) and osteoprotegerin (OPG) in 150 and 300mg/kg bw/d group was increased. Histological analysis of proximal and distal epiphyseal plates of the right femurs showed that both the proliferative zone and hypertrophic zone narrowed in CCC-treated groups. The concentration of IGF-I in blood was reduced with an increase in exposure doses of CCC. The mRNA expression of growth hormone receptor (GHR) in tibia was decreased in the CCC-treated group. The results indicated that CCC might indirectly impact the formation and activation of chondrocytes, osteoblasts and osteoclasts because of the decline of GHR and IGF-I, leading to skeletal development damage.
矮壮素（CCC）是一种广泛使用的植物生长调节剂，可降低动物体重；然而，其作用机制尚未得到充分研究。本研究旨在评估CCC对青春期雄性Sprague-Dawley（SD）大鼠骨骼发育的毒性，并探讨CCC是否通过生长激素（GH）和胰岛素样生长因子1（IGF-I）影响软骨细胞、成骨细胞和破骨细胞的发育。将出生后23至70天的大鼠每天经口灌胃给予0、75、150和300mg/kg bw/d剂量的CCC。结果表明，与对照组相比，300mg/kg bw/d组的股骨和胫骨尺寸、骨密度和生物力学参数显著降低。150mg/kg bw/d组血液中骨钙素（OCN）和I型胶原C端肽（CTX-I）的浓度也发生了变化。150和300mg/kg bw/d组中核因子κB受体活化因子配体（RANKL）与骨保护素（OPG）的mRNA表达比值升高。对右侧股骨近端和远端骨骺板的组织学分析表明，CCC处理组的增殖区和肥大区均变窄。血液中IGF-I的浓度随着CCC暴露剂量的增加而降低。CCC处理组胫骨中生长激素受体（GHR）的mRNA表达降低。结果表明，由于GHR和IGF-I的下降，CCC可能间接影响软骨细胞、成骨细胞和破骨细胞的形成和活化，导致骨骼发育受损。
