Apocynin suppression of NADPH oxidase reverses the aging process in mesenchymal stem cells to promote osteogenesis and increase bone mass.
Apocynin suppression of NADPH oxidase reverses the aging process in mesenchymal stem cells to promote osteogenesis and increase bone mass.
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DOI：
10.1038/srep18572
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发表时间：
2015-12-21
影响因子：
4.6
通讯作者：
Jin Y
中科院分区：
文献类型：
--
作者：
Sun J;Ming L;Shang F;Shen L;Chen J;Jin Y
由于衰老的骨髓基质细胞成骨潜力降低，骨代谢平衡被破坏，导致各种骨疾病。活性氧的增加已被确定为加速骨髓间充质干细胞衰老过程的关键因素之一。在这些细胞中，NADPH氧化酶的表达增加是ROS的主要来源。在目前的研究中，我们使用一种有效的抗氧化剂和自由基清除剂夹竹桃苷抑制NOX的表达，结果表明，老化的BMSCs表现出增强的成骨潜力。使用qRT-PCR评估影响这种逆转的潜在关键靶标的表达，并且显示p53的表达随着NOX的抑制而降低。我们推测，这可能是衰老过程逆转的主要原因之一。我们还检查了夹竹桃素在体内的作用，结果表明，在SAMP 6小鼠中，夹竹桃素治疗3个月后，骨密度和总骨体积增加。总之，我们的研究结果表明，在老化的骨髓间充质干细胞，抑制NADPH氧化酶的夹竹桃苷部分逆转老化过程，提高成骨潜力。
Because of the reduced potential for osteogenesis in aging bone marrow stromal cells, the balance of bone metabolism becomes disrupted, leading to various bone diseases. An increase in reactive oxygen species has been determined to be one of the key factors that accelerates the aging process in BMSCs. In these cells, increased expression of NADPH oxidases is the major source of ROS. In the current study, we suppressed the expression of NOX using apocynin, an effective antioxidant and free radical scavenger, and the results showed that aging BMSCs exhibited an enhanced potential for osteogenesis. The expression of potential key targets influencing this reversal was evaluated using qRT-PCR, and the expression of p53 was shown to be reduced with the suppression of NOX. We speculate that this may be one of the major reasons for the reversal of the aging process. We also examined the effect of apocynin in vivo, and the results showed that in SAMP6 mice, bone mineral density and total bone volume were increased after 3 months of apocynin treatment. In conclusion, our results demonstrate that in aging BMSCs, suppression of NADPH oxidase by apocynin partially reverses the aging process and enhances osteogenic potential.