Hydrogen peroxide, but not superoxide, stimulates bone resorption in mouse calvariae
Hydrogen peroxide, but not superoxide, stimulates bone resorption in mouse calvariae
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DOI：
10.1016/8756-3282(96)00177-9
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发表时间：
1996-09-01
期刊：
影响因子：
4.1
通讯作者：
Ralston, SH
中科院分区：
文献类型：
--
作者：
Fraser, JHE;Helfrich, MH;Ralston, SH
活性氧物质如超氧化物和过氧化氢已被认为是控制破骨细胞骨吸收的调节因子。虽然超氧化物自由基已被认为是器官培养和体内的主要骨吸收物质，但过氧化氢（H2 O2）最近已被证明在体外激活分离的破骨细胞。我们研究了过氧化氢和超氧化物对小鼠颅骨器官培养物中骨吸收的影响，过氧化氢以浓度依赖的方式刺激颅骨器官培养物中的骨吸收，在1 μ mol/L时作用最大（Ca-45释放;处理/对照= 1.6 +/- 0.07; p < 0.001，对照），过氧化氢酶显著抑制H2 O2诱导的骨吸收至1.2 +/- 0.05; p < 0.02。相反，黄嘌呤和产生超氧阴离子的黄嘌呤氧化酶的组合不能刺激骨吸收，除了在存在超氧化物歧化酶（SOD）的情况下，其导致骨吸收适度增加至1.2 +/-0.05的处理/对照比率; p < 0.02，对暴露于H2 O2的颅骨的分析显示破骨细胞数量显著增加，这表明H2 O2可能能够除了增强成熟破骨细胞的活性外，还刺激破骨细胞的形成。我们的数据与以前的工作是一致的，这表明H2 O2是一种骨吸收因子，既影响破骨细胞的形成，又影响成熟破骨细胞的活性。SOD的实验进一步表明，以前用超氧化物生成系统注意到的骨吸收的增强可能部分是由于H2 O2的产生。
Reactive oxygen species such as superoxide and hydrogen peroxide have been implicated as regulatory factors in the control of osteoclastic bone resorption, While superoxide radicals have been suggested to be the main bone resorbing species in organ culture and in vivo, hydrogen peroxide (H2O2) has recently been shown to activate isolated osteoclasts in vitro, In this study, we investigated the effects of hydrogen peroxide and superoxide on bone resorption in mouse calvarial organ cultures, Hydrogen peroxide stimulated bone resorption in a concentration-dependent manner in calvarial organ cultures with a maximal effect at 1 mu mol/L (Ca-45 release; treated/control = 1.6 +/- 0.07; p < 0.001 from control), Bone resorption induced by H2O2 was significantly inhibited by catalase to 1.2 +/- 0.05; p < 0.02, In contrast, the combination of xanthine and xanthine oxidase, which generates superoxide anions, failed to stimulate bone resorption, except in the presence of superoxide dismutase (SOD), which resulted in a modest increase in bone resorption to a treated/control ratio of 1.2 +/- 0.05; p < 0.02, Analysis of calvarial bones which were exposed to H2O2 showed a significant increase in osteoclast numbers suggesting that H2O2 may be capable of stimulating osteoclast formation in addition to enhancing activity of mature osteoclasts. Our data are consistent with previous work, which has shown that H2O2 is a bone resorbing factor with effects on both osteoclast formation and in activity of mature osteoclasts, The experiments with SOD further suggest that the enhancement of bone resorption previously noted with superoxide generating systems may be due in part to generation of H2O2.