Zhou Xun, Wang Zhengbo, Ni Yihong, Yu Yue, Wang Guantong, Chen Lulu
Department of Basic Medical Sciences, Jiangsu College of Nursing Huai'an 223005, Jiangsu, People's Republic of China.
Department of Anatomy, Histology and Embryology, The Research Center for Bone and Stem Cells, Nanjing Medical University Nanjing 210006, Jiangsu, People's Republic of China.
Am J Transl Res. 2020 Mar 15;12(3):731-742. eCollection 2020.
Oxidative stress can trigger DNA damage response and activation of cellular senescence. Accumulating studies have demonstrated that senescent cells can produce senescence-associated secretory phenotype that leads to increased bone resorption and decreased bone formation. And elimination of senescent cells or inhibition of SASP secretion has been shown to prevent bone loss in mice. N-acetylcysteine (NAC) is a strong antioxidant. However, it is unclear whether reversed estrogen deficiency-induced bone loss by antioxidant NAC was associated with the inhibition of oxidative stress, DNA damage, osteocyte senescence and SASP. In this study, OVX mice were supplemented with/without E2 or NAC, and were compared with each other. Our results showed that oxidative stress, DNA damage, osteocyte senescence and the secretion of senescence-associated inflammatory cytokines were increased in OVX mice compared with sham-operated mice. However, these parameters were obviously rescued in OVX mice supplemented with E2 or NAC. Data from this study suggest that NAC can prevent OVX-induced bone loss by inhibiting oxidative stress, DNA damage, cell senescence and the secretion of the senescence-associated secretory phenotype.
氧化应激可引发DNA损伤反应并激活细胞衰老。越来越多的研究表明，衰老细胞可产生衰老相关分泌表型，导致骨吸收增加和骨形成减少。并且已证明消除衰老细胞或抑制衰老相关分泌表型的分泌可预防小鼠骨质流失。N-乙酰半胱氨酸（NAC）是一种强效抗氧化剂。然而，尚不清楚抗氧化剂NAC逆转雌激素缺乏诱导的骨质流失是否与抑制氧化应激、DNA损伤、骨细胞衰老和衰老相关分泌表型有关。在本研究中，给去卵巢（OVX）小鼠补充或不补充E2或NAC，并将它们相互比较。我们的结果表明，与假手术小鼠相比，OVX小鼠的氧化应激、DNA损伤、骨细胞衰老以及衰老相关炎性细胞因子的分泌增加。然而，在补充E2或NAC的OVX小鼠中，这些参数明显得到改善。本研究数据表明，NAC可通过抑制氧化应激、DNA损伤、细胞衰老以及衰老相关分泌表型的分泌来预防OVX诱导的骨质流失。
