{"title":"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。","authors":"Haiying Wang, Weijin Zou, Caihua Ding, Yi Cao","doi":"10.1080/15368378.2025.2547799","DOIUrl":null,"url":null,"abstract":"<p><p>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/cm<sup>2</sup>), moderate (MRF, 150μW/cm<sup>2</sup>), and high (HRF,450μW/cm<sup>2</sup>). 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/cm<sup>2</sup> 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, <i>Atf4</i> 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.</p>","PeriodicalId":50544,"journal":{"name":"Electromagnetic Biology and Medicine","volume":" ","pages":"1-15"},"PeriodicalIF":1.5000,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Activating Transcription Factor 4 regulation of radiofrequency radiation-induced ferroptosis in osteoblasts.\",\"authors\":\"Haiying Wang, Weijin Zou, Caihua Ding, Yi Cao\",\"doi\":\"10.1080/15368378.2025.2547799\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>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/cm<sup>2</sup>), moderate (MRF, 150μW/cm<sup>2</sup>), and high (HRF,450μW/cm<sup>2</sup>). 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/cm<sup>2</sup> 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, <i>Atf4</i> 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.</p>\",\"PeriodicalId\":50544,\"journal\":{\"name\":\"Electromagnetic Biology and Medicine\",\"volume\":\" \",\"pages\":\"1-15\"},\"PeriodicalIF\":1.5000,\"publicationDate\":\"2025-08-19\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Electromagnetic Biology and Medicine\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1080/15368378.2025.2547799\",\"RegionNum\":4,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Electromagnetic Biology and Medicine","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1080/15368378.2025.2547799","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"BIOLOGY","Score":null,"Total":0}
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.
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.