Accumulation of oxidative damage from excess reactive oxygen species (ROS) may contribute to skeletal aging and mediate adverse responses to physiological challenges. Wildtype (WT) and transgenic mice (male, 16 weeks of age) with human catalase targeted to the mitochondria (mCAT) were analyzed for skeletal responses to the remodeling stimuli of combined hindlimb unloading and exposure to ionizing radiation (137^Cs, 2 Gy). Treatment for 2wk caused lipid peroxidation in WT bones but not mCAT, showing that transgene expression mitigated oxidative stress. Ex vivo osteoblast colony growth rate was 95% greater in mCAT mice than WT, and correlated with catalase activity levels (P<0.005, r=0.67), although terminal osteoblast and osteoclast differentiation were unaffected. Ambulatory control mCAT animals also displayed reduced cancellous and cortical structural properties compared to control WT. In mCAT but not WT mice, treatment caused an unexpectedly rapid radial expansion (+8% cortical area, +22% moment of inertia), reminiscent of compensatory bone growth during advancing age. In contrast, treatment caused similar structural deficits in cancellous tissue of mCAT and WT mice. In sum, mitochondrial ROS signaling via H₂O₂ was important for the acquisition of adult bone structure and catalase overexpression failed to protect cancellous tissue from treatment. In contrast, catabolic stimuli caused radial expansion in mCAT not WT mice, suggesting mitochondrial ROS in skeletal cells act to suppress tissue turnover in response to remodeling challenges.

中文翻译：

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线粒体中过氧化氢酶过表达的骨骼组织调节。

过量的活性氧（ROS）引起的氧化损伤的积累可能有助于骨骼老化，并介导对生理挑战的不良反应。分析了针对人类过氧化氢酶靶向线粒体（mCAT）的野生型（WT）和转基因小鼠（雄性，年龄16周），分析了其对后肢卸载和电离辐射（137 ^Cs）联合重塑刺激的骨骼反应，2 Gy）。2wk的处理导致野生型骨骼中的脂质过氧化，但不引起mCAT，这表明转基因表达减轻了氧化应激。尽管最终的成骨细胞和破骨细胞分化不受影响，但mCAT小鼠的离体成骨细胞集落生长速率比野生型高95％，并与过氧化氢酶活性水平相关（P <0.005，r = 0.67）。与对照野生型相比，非卧床对照mCAT动物也显示出降低的松质和皮质结构特性。在mCAT但不是WT小鼠中，治疗引起了意外的快速径向扩张（皮质区域增加8％，惯性矩增加22％），使人联想到年龄增长时的代偿性骨生长。相反，治疗在mCAT和WT小鼠的松质组织中引起了类似的结构缺陷。总之，通过H ₂ O的线粒体ROS信号传导₂对于获取成人骨骼结构很重要，过氧化氢酶的过表达不能保护松质组织免受治疗。相比之下，分解代谢的刺激在mCAT而非WT小鼠中引起了放射状扩张，这表明骨骼细胞中的线粒体ROS响应重组挑战而抑制组织更新。