Reactive oxygen species induce chondrocyte hypertrophy in endochondral ossification.
Reactive oxygen species induce chondrocyte hypertrophy in endochondral ossification.
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DOI：
10.1084/jem.20062525
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发表时间：
2007-07-09
期刊：
影响因子：
--
通讯作者：
Suda T
中科院分区：
文献类型：
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作者：
Morita K;Miyamoto T;Fujita N;Kubota Y;Ito K;Takubo K;Miyamoto K;Ninomiya K;Suzuki T;Iwasaki R;Yagi M;Takaishi H;Toyama Y;Suda T
软骨内骨化过程中的软骨细胞肥大是一个良好控制的过程，其中增殖的软骨细胞停止增殖并分化为肥大软骨细胞，然后发生细胞凋亡。软骨细胞肥大诱导血管生成和矿化。这一步骤对于长骨的纵向生长和发育至关重要，但触发该过程的因素尚不清楚。活性氧 (ROS) 与细胞损伤有关；然而，ROS 在软骨形成中的生理作用尚不清楚。我们证明，ROS 水平增加会导致软骨细胞肥大。在肥大软骨细胞中检测到活性氧水平升高。用 N-乙酰半胱氨酸进行体内和体外处理可提高内源性抗氧化剂水平并保护细胞免受氧化应激，从而抑制软骨细胞肥大。在共济失调毛细血管扩张突变（Atm）缺陷（Atm−/−）小鼠中，生长板软骨细胞中的ROS水平升高，并伴有增殖缺陷和软骨细胞肥大的刺激。 Atm−/− 小鼠的增殖减少和过度肥大也可以通过抗氧化治疗得到缓解。这些发现表明，ROS 水平调节增殖抑制并调节软骨细胞肥大变化的启动。
Chondrocyte hypertrophy during endochondral ossification is a well-controlled process in which proliferating chondrocytes stop proliferating and differentiate into hypertrophic chondrocytes, which then undergo apoptosis. Chondrocyte hypertrophy induces angiogenesis and mineralization. This step is crucial for the longitudinal growth and development of long bones, but what triggers the process is unknown. Reactive oxygen species (ROS) have been implicated in cellular damage; however, the physiological role of ROS in chondrogenesis is not well characterized. We demonstrate that increasing ROS levels induce chondrocyte hypertrophy. Elevated ROS levels are detected in hypertrophic chondrocytes. In vivo and in vitro treatment with N-acetyl cysteine, which enhances endogenous antioxidant levels and protects cells from oxidative stress, inhibits chondrocyte hypertrophy. In ataxia telangiectasia mutated (Atm)–deficient (Atm−/−) mice, ROS levels were elevated in chondrocytes of growth plates, accompanied by a proliferation defect and stimulation of chondrocyte hypertrophy. Decreased proliferation and excessive hypertrophy in Atm−/− mice were also rescued by antioxidant treatment. These findings indicate that ROS levels regulate inhibition of proliferation and modulate initiation of the hypertrophic changes in chondrocytes.