Effect of Oxidative Stress-Induced Apoptosis on Active FGF23 Levels in MLO-Y4 Cells: The Protective Role of 17-β-Estradiol.

Effect of Oxidative Stress-Induced Apoptosis on Active FGF23 Levels in MLO-Y4 Cells: The Protective Role of 17-β-Estradiol.
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氧化应激诱导的细胞凋亡对 MLO-Y4 细胞中活性 FGF23 水平的影响:17-β-雌二醇的保护作用。

DOI:
10.3390/ijms23042103
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发表时间:
2022-02-14
影响因子:
5.6
通讯作者:
Brandi ML
Brandi ML
中科院分区:
生物学2区
文献类型:
--
作者:
Domazetovic V;Falsetti I;Ciuffi S;Iantomasi T;Marcucci G;Vincenzini MT;Brandi ML

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骨细胞分泌磷酸尿性成纤维细胞生长因子23(FGF 23)的发现已经将骨定义为内分泌器官。然而,FGF 23的自分泌和旁分泌功能仍然未知。本研究的重点是复杂的控制FGF 23的生产和局部骨重建功能的细胞和分子机制。在存在或不存在17β-雌二醇的情况下,在饥饿的MLO-Y 4骨细胞中使用ELISA试剂盒测定FGF 23。在这些细胞中,氧化应激诱导的细胞凋亡和由于MAP激酶激活与转录因子(NF-κ B)的参与而导致的活性FGF 23水平的上调之间的关系已经被证明。活性FGF 23的增加可能是由于其表达的上调和转录后修饰。17β-雌二醇通过抑制JNK和NF-kB活化、骨细胞凋亡和通过下调破骨细胞生成因子(如硬化素)来防止FGF 23的增加。牙本质基质蛋白1(一种FGF 23负调节剂)的水平没有改变。这项研究的结果确定了药物和雌激素可能作用于其上的生物靶点,以控制氧化应激相关的骨和非骨炎症性疾病中的活性FGF 23水平。
The discovery that osteocytes secrete phosphaturic fibroblast growth factor 23 (FGF23) has defined bone as an endocrine organ. However, the autocrine and paracrine functions of FGF23 are still unknown. The present study focuses on the cellular and molecular mechanisms involved in the complex control of FGF23 production and local bone remodeling functions. FGF23 was assayed using ELISA kit in the presence or absence of 17β–estradiol in starved MLO-Y4 osteocytes. In these cells, a relationship between oxidative stress-induced apoptosis and up-regulation of active FGF23 levels due to MAP Kinases activation with involvement of the transcriptional factor (NF-kB) has been demonstrated. The active FGF23 increase can be due to up-regulation of its expression and post-transcriptional modifications. 17β–estradiol prevents the increase of FGF23 by inhibiting JNK and NF-kB activation, osteocyte apoptosis and by the down-regulation of osteoclastogenic factors, such as sclerostin. No alteration in the levels of dentin matrix protein 1, a FGF23 negative regulator, has been determined. The results of this study identify biological targets on which drugs and estrogen may act to control active FGF23 levels in oxidative stress-related bone and non-bone inflammatory diseases.
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