激活转录因子4对射频辐射诱导的成骨细胞铁下垂的调控。

IF 1.5 4区 生物学 Q3 BIOLOGY
Haiying Wang, Weijin Zou, Caihua Ding, Yi Cao
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引用次数: 0

摘要

鉴于射频(RF)辐射源在现代环境中无处不在,人们对其对成骨细胞的细胞毒性作用和对骨骼健康的潜在影响感到担忧。本研究调查了这些影响的分子机制,重点关注铁下垂,一种与骨病理相关的调节细胞死亡形式,以及激活转录因子4 (ATF4)的作用。通过对公共基因表达数据库的全面生物信息学分析,我们发现差异表达基因与脂质代谢和铁下垂相关的生物过程之间存在显著相关性。在四种不同的实验条件下对MC3T3-E1成骨细胞进行系统评估:假暴露对照组和三个治疗组暴露于校准的射频辐射强度-低(LRF, 50μW/cm2),中等(MRF, 150μW/cm2)和高(HRF,450μW/cm2)。为了阐明rf诱导铁下垂的分子机制,我们进行了ATF4敲除和过表达实验。结果表明,150μW/cm2的射频辐射引起最明显的影响,其特征是成骨细胞活力降低,脂质过氧化升高,氧化还原平衡被破坏,线粒体功能受损,铁稳态紊乱。值得注意的是,Atf4敲低加剧了这些有害影响,而其过表达则对射频辐射诱导的细胞损伤具有保护作用。这项研究证明了ATF4调节在射频辐射诱导的成骨细胞铁下垂中的关键作用,这一过程可能导致骨质疏松症和骨折愈合受损等骨疾病。这些发现表明,靶向ATF4可能是一种有希望的治疗方法,可以减轻射频辐射对骨骼健康的影响,从而为干预受环境影响的骨骼疾病开辟新的途径。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Activating Transcription Factor 4 regulation of radiofrequency radiation-induced ferroptosis in osteoblasts.

Given the ubiquitous presence of radiofrequency (RF) radiation sources in modern environments, concerns have been raised regarding their cytotoxic effects on osteoblasts and potential implications for skeletal health. This study investigated the molecular mechanisms underlying these effects, focusing on ferroptosis, a form of regulated cell death implicated in bone pathologies, and the role of Activating Transcription Factor 4 (ATF4). Through comprehensive bioinformatic analyses of public gene expression databases, we identified significant correlations between differentially expressed genes and biological processes associated with lipid metabolism and ferroptosis. MC3T3-E1 osteoblasts were subjected to systematic evaluation under four distinct experimental conditions: a sham-exposed control group and three treatment groups exposed to calibrated RF radiation intensities - low (LRF, 50μW/cm2), moderate (MRF, 150μW/cm2), and high (HRF,450μW/cm2). To elucidate the molecular mechanisms underlying RF-induced ferroptosis, both ATF4 knockdown and overexpression experiments were performed. The findings indicated that RF radiation at 150μW/cm2 elicited the most pronounced effects, characterized by reduced osteoblast viability, elevated lipid peroxidation, disrupted redox balance, impaired mitochondrial function, and disturbances in iron homeostasis. Notably, Atf4 knockdown exacerbated these deleterious effects, while its overexpression conferred protection against RF radiation-induced cellular damage. This study demonstrates the crucial role of ATF4 modulation in RF radiation-induced ferroptosis in osteoblasts, a process potentially contributing to bone disorders such as osteoporosis and impaired fracture healing. These findings suggest that targeting ATF4 may represent a promising therapeutic approach to mitigate the effects of RF radiation on bone health, thereby opening new avenues for intervention in environmentally influenced skeletal disorders.

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来源期刊
CiteScore
3.60
自引率
11.80%
发文量
33
审稿时长
>12 weeks
期刊介绍: Aims & Scope: Electromagnetic Biology and Medicine, publishes peer-reviewed research articles on the biological effects and medical applications of non-ionizing electromagnetic fields (from extremely-low frequency to radiofrequency). Topic examples include in vitro and in vivo studies, epidemiological investigation, mechanism and mode of interaction between non-ionizing electromagnetic fields and biological systems. In addition to publishing original articles, the journal also publishes meeting summaries and reports, and reviews on selected topics.
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