Nrf2 is required for normal postnatal bone acquisition in mice.
Nrf2 is required for normal postnatal bone acquisition in mice.
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DOI：
10.1038/boneres.2014.33
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发表时间：
2014
期刊：
影响因子：
12.7
通讯作者：
DiGirolamo, Douglas J.
中科院分区：
文献类型：
--
作者：
Kim, Jung-Hyun;Singhal, Vandana;Biswal, Shyam;Thimmulappa, Rajesh K.;DiGirolamo, Douglas J.
大量文献表明，骨代谢易受活性物质的不良影响，这些活性物质在体内积累并导致细胞功能障碍。身体防御这种损害的前线之一是转录因子Nrf 2。这种转录因子调节过多的抗氧化剂和细胞防御途径，以保护细胞免受这种损害。尽管对Nrf 2的功能和活性物质在骨代谢中的作用有广泛的了解，但Nrf 2在骨骼生物学中的直接作用尚未得到彻底的研究。因此，在目前的研究中，我们研究了Nrf 2在小鼠出生后骨代谢中的作用。缺乏Nrf 2（Nrf 2 −/−）的小鼠在出生后骨获取方面表现出明显的缺陷，这在3周龄时最严重，此时成骨细胞数量比对照动物少12倍。虽然Nrf 2 −/−小鼠的原代成骨细胞在体外功能正常，但与对照组相比，这些小鼠的骨髓基质细胞（BMSC）殖民地形成能力显著降低。这种缺陷可以通过用自由基清除剂N-乙酰半胱氨酸（NAC）治疗来挽救，这表明反应性物质应激的增加可能会损害BMSC中的早期成骨细胞生成，并导致在Nrf 2 −/−动物中观察到的骨获取失败。总之，这些研究表明Nrf 2代表了调节骨代谢的关键途径，这可能为治疗骨质疏松症提供未来的治疗靶点。
A large body of literature suggests that bone metabolism is susceptible to the ill effects of reactive species that accumulate in the body and cause cellular dysfunction. One of the body’s front lines in defense against such damage is the transcription factor, Nrf2. This transcription factor regulates a plethora of antioxidant and cellular defense pathways to protect cells from such damage. Despite the breadth of knowledge of both the function of Nrf2 and the effects of reactive species in bone metabolism, the direct role of Nrf2 in skeletal biology has yet to be thoroughly examined. Thus, in the current study, we have examined the role of Nrf2 in postnatal bone metabolism in mice. Mice lacking Nrf2 (Nrf2−/−) exhibited a marked deficit in postnatal bone acquisition, which was most severe at 3 weeks of age when osteoblast numbers were 12-fold less than observed in control animals. While primary osteoblasts from Nrf2−/− mice functioned normally in vitro, the colony forming capacity of bone marrow stromal cells (BMSCs) from these mice was significantly reduced compared to controls. This defect could be rescued through treatment with the radical scavenger N-acetyl cysteine (NAC), suggesting that increased reactive species stress might impair early osteoblastogenesis in BMSCs and lead to the failure of bone acquisition observed in Nrf2−/− animals. Taken together, these studies suggest Nrf2 represents a key pathway in regulating bone metabolism, which may provide future therapeutic targets to treat osteoporosis.
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DOI：
10.1164/rccm.201102-0271oc
发表时间：
2011-10-15
影响因子：
24.7
作者：
Kong, Xiaoni;Thimmulappa, Rajesh;Biswal, Shyam
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DOI：
10.1164/rccm.200804-535oc
发表时间：
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影响因子：
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影响因子：
16.6
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DOI：
10.1006/bbrc.2001.5747
发表时间：
2001-10-19
影响因子：
3.1
作者：
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通讯作者：
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影响因子：
6
作者：
Hubbs, Ann F.;Benkovic, Stanley A.;Ma, Qiang
通讯作者：
Ma, Qiang