The Dual Effects of Reactive Oxygen Species on the Mandibular Alveolar Bone Formation in SOD1 Knockout Mice: Promotion or Inhibition.

The Dual Effects of Reactive Oxygen Species on the Mandibular Alveolar Bone Formation in SOD1 Knockout Mice: Promotion or Inhibition.
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活性氧对 SOD1 敲除小鼠下颌牙槽骨形成的双重影响:促进还是抑制

DOI:
10.1155/2021/8847140
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发表时间:
2021
影响因子:
--
通讯作者:
Guo W
Guo W
中科院分区:
生物学2区
文献类型:
--
作者:
Zhang Y;Yang Y;Xu M;Zheng J;Xu Y;Chen G;Guo Q;Tian W;Guo W

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活性氧(ROS)的状态与口腔颌面部组织的正常发育密切相关。由ROS积累引起的氧化应激不仅影响牙釉质和牙本质的发育,还会引起牙根周围的牙周组织(牙周韧带和牙槽骨)的病理改变。虽然先前的研究表明,ROS的积累在一些口腔颌面组织中起病理作用,但ROS对牙槽骨发育的影响尚不清楚。在这项研究中,我们重点研究了超氧化物歧化酶1 (SOD1)缺乏小鼠的下颌牙槽骨发育。采用显微计算机断层扫描(micro-CT)、TRAP染色、免疫组织化学(IHC)染色和酶联免疫吸附试验(ELISA)进行分析。我们首次发现,SOD1(-/-)小鼠早期(2-4个月)下颌牙槽骨中ROS含量略高,导致骨大小明显增大,骨体积分数(BV/TV)、骨小梁厚度(Tb。Th),碱性磷酸酶(ALP)、runt相关转录因子2 (Runx2)和骨桥蛋白(OPN)的表达。随着ROS积累到氧化应激水平,SOD1(-/-)小鼠在6个月时发现小梁骨分离(tbsp)增加,ALP、Runx2和OPN的表达降低。此外,给予n -乙酰半胱氨酸(NAC)有效减轻骨丢失,并使ALP、Runx2和OPN的表达正常化。这些结果表明,SOD1缺乏引起的氧化还原失衡对下颌牙槽骨发育具有促进或抑制双重作用,其作用与ROS浓度和生长阶段密切相关。我们提出了一个有价值的模型来研究ROS对下颌牙槽骨形成的影响,并强调了ROS在调节组织发育和病理状态中的重要作用,说明了氧化还原信号的复杂性。
The status of reactive oxygen species (ROS) correlates closely with the normal development of the oral and maxillofacial tissues. Oxidative stress caused by ROS accumulation not only affects the development of enamel and dentin but also causes pathological changes in periodontal tissues (periodontal ligament and alveolar bone) that surround the root of the tooth. Although previous studies have shown that ROS accumulation plays a pathologic role in some oral and maxillofacial tissues, the effects of ROS on alveolar bone development remain unclear. In this study, we focused on mandibular alveolar bone development of mice deficient in superoxide dismutase1 (SOD1). Analyses were performed using microcomputerized tomography (micro-CT), TRAP staining, immunohistochemical (IHC) staining, and enzyme-linked immunosorbent assay (ELISA). We found for the first time that slightly higher ROS in mandibular alveolar bone of SOD1(-/-) mice at early ages (2-4 months) caused a distinct enlargement in bone size and increased bone volume fraction (BV/TV), trabecular thickness (Tb.Th), and expression of alkaline phosphatase (ALP), Runt-related transcription factor 2 (Runx2), and osteopontin (OPN). With ROS accumulation to oxidative stress level, increased trabecular bone separation (Tb.Sp) and decreased expression of ALP, Runx2, and OPN were found in SOD1(-/-) mice at 6 months. Additionally, dosing with N-acetylcysteine (NAC) effectively mitigated bone loss and normalized expression of ALP, Runx2, and OPN. These results indicate that redox imbalance caused by SOD1 deficiency has dual effects (promotion or inhibition) on mandibular alveolar bone development, which is closely related to the concentration of ROS and the stage of growth. We present a valuable model here for investigating the effects of ROS on mandibular alveolar bone formation and highlight important roles of ROS in regulating tissue development and pathological states, illustrating the complexity of the redox signal.
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