Du Yu, Zhang Yixin, Luo Wenqiong, Gan Feihong, Yang Mao, Gong Ping, Yao Yang
State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, China; Department of Oral Implantology, West China Hospital of Stomatology, Sichuan University, China.
State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, China.
Biochem Biophys Res Commun. 2024 Feb 5;695:149425. doi: 10.1016/j.bbrc.2023.149425. Epub 2023 Dec 22.
Head and neck tumor patients may develop post-radiotherapy diseases after radiotherapy treatment. And radiotherapy can elicit radiation-induced bystander effect, wherein extracellular vesicles (EVs) play a crucial role. For normal parts of the body that have not been directly irradiated, the effect of EVs on them needs to be further explored. This study aims to investigate the functions of plasma-derived EVs in regulating normal osteoblasts during radiation-induced bystander effects.
Rat plasma-derived EVs were isolated and identified firstly, followed by an evaluation of their intracellular biological effects on normal osteoblasts in vitro. Transcriptome sequencing analysis and confirmations were performed to identify potential mechanisms.
Irradiated plasma-derived EVs were found to enhance osteoblast proliferation, migration, and cell cycle progression, concurrently suppressing the expression of osteogenesis-related genes and proteins. Furthermore, these EVs attenuated the expression of osteogenesis and oxidative stress resistance related genes, while upregulating the PI3K-AKT pathway and intracellular reactive oxygen species in osteoblasts.
Irradiated plasma-derived EVs could alter the biological effects in osteoblasts, which is closely associated with the levels of GPX1 and the PI3K-AKT signaling pathway. This suggests that plasma-derived EVs serve as a crucial factor contributing to radiation-induced bystander effect in osteoblasts.
头颈部肿瘤患者在放疗后可能会出现放疗后疾病。放疗可引发辐射诱导的旁观者效应，其中细胞外囊泡（EVs）起着关键作用。对于未直接接受照射的身体正常部位，EVs 对其的影响尚需进一步探究。本研究旨在探讨血浆来源的 EVs 在辐射诱导的旁观者效应中对正常成骨细胞的调节作用。
首先分离并鉴定大鼠血浆来源的 EVs，随后评估其在体外对正常成骨细胞的细胞内生物学效应。进行转录组测序分析及验证以确定潜在机制。
发现受照射的血浆来源的 EVs 可增强成骨细胞增殖、迁移及细胞周期进程，同时抑制成骨相关基因和蛋白的表达。此外，这些 EVs 减弱了成骨及抗氧化应激相关基因的表达，同时上调成骨细胞中的 PI3K-AKT 通路及细胞内活性氧水平。
受照射的血浆来源的 EVs 可改变成骨细胞的生物学效应，这与 GPX1 水平及 PI3K-AKT 信号通路密切相关。这表明血浆来源的 EVs 是促成骨细胞辐射诱导旁观者效应的关键因素。
