Bone metabolism and oxidative stress in postmenopausal rats with iron overload
Bone metabolism and oxidative stress in postmenopausal rats with iron overload
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DOI：
10.1016/j.tox.2003.12.006
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发表时间：
2004-04-15
期刊：
影响因子：
4.5
通讯作者：
Sakamoto, W
中科院分区：
文献类型：
--
作者：
Isomura, H;Fujie, K;Sakamoto, W
骨质疏松症与营养、细胞因子、激素和衰老等多种病因有关。近年来，活性氧（ROS）被认为是衰老过程和骨质疏松症的原因。本研究采用膳食铁超载和骨代谢指标、氧化应激和抗氧化指标以及细胞因子等指标，研究了青年雌性和绝经后大鼠体内活性氧与骨代谢的关系。与年轻雌性大鼠相比，绝经后大鼠的血清碱性磷酸酶活性和骨形成标志物骨钙素水平显着下降;然而，骨吸收标志物脱氧吡啶啉的尿液排泄量没有变化。另一方面，在绝经后大鼠中，持续4周的5%乳酸铁饮食导致尿脱氧吡啶啉和8-羟基-2 '-脱氧鸟苷（8-OHdG）的排泄显著增加，但不导致血清碱性磷酸酶活性增加。有趣的是，饮食诱导血清骨桥蛋白和TGF-β 1显著增加，通过RANK/RANKL途径增强破骨细胞介导的骨吸收[J. Clin. Invest. 112（2003）181]。TGF-β 1与血清谷胱甘肽过氧化物酶（GPx）活性呈负相关（r =-0.674，P < 0.003），与血清铁水平呈正相关（r = 0.836，P < 0.0001）。两者合计，这些结果表明，第一次，氧化应激可能参与代谢性骨疾病，如骨质疏松症的发病机制，骨代谢和氧化应激之间的关系的分析表明。(C)2004爱思唯尔爱尔兰有限公司保留所有权利。
Osteoporosis is associated with many etiological causes such as nutrition, cytokines, hormones, and aging. Recently, reactive oxygen species (ROS) are considered to be responsible for the aging process and osteoporosis. We investigated the relationship between ROS and bone metabolism in young female and postmenopausal rats, by using dietary iron overload and several indices including bone metabolic markers, oxidative stress and antioxidant markers, and cytokines. Postmenopausal rats exhibited significant decreases in serum alkaline phosphatase activity and the level of osteocalcin as bone formation markers compared with young female rats; however, urinary excretion of deoxypyridinoline, a bone resorption marker, did not change. On the other hand, a 5% iron lactate diet for 4 weeks in postmenopausal rats led to significantly increased excretion of urinary deoxypyridinoline,and 8-hydroxy-2'-deoxyguanosine (8-OHdG) but not serum alkaline phosphatase activity. Interestingly, the diet induced significant increases of serum osteopontin and TGF-beta1, augumenting osteoclast-mediated bone resorption through the RANK/RANKL pathway [J. Clin. Invest. 112 (2003) 181]. TGF-beta1 showed a negative correlation with serum glutathione peroxidase (GPx) activity (r = -0.674, P < 0.003), but a positive correlation with the serum iron level (r = 0.836, P < 0.0001). Taken together, these results suggest for the first time that oxidative stress could be involved in the pathogenesis of metabolic bone diseases such as osteoporosis as demonstrated by analysis of the relationship between bone metabolism and oxidative stress. (C) 2004 Elsevier Ireland Ltd. All rights reserved.