Du Yu, Tang Haiyang, Gu Xia, Shi Yixin, Gong Ping, Yao Yang
State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Oral Implantology, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
Chengdu Second People's Hospital, Department of Stomatology, China.
Oxid Med Cell Longev. 2021 Feb 15;2021:6646323. doi: 10.1155/2021/6646323. eCollection 2021.
Radiotherapy is a common therapy in head and neck tumors, which may cause a side effect radiation bone injury (RBI). Furthermore, it has been investigated that microRNA (miRNA) expression levels were altered after radiotherapy. Exosomes play a role in bone formation as miRNA containers, while radiation affects exosomes composition, secretion, and function. So, our objective is to explore changes in miRNA levels during bone formation after radiotherapy and identify the differentially expressed miRNAs (DE-miRs) in plasma exosomes during the process of osteogenesis related to irradiation.
In this study, we analyzed nine samples from three rabbits exposed twice to radiation (15 Gy each) and detected DE-miRs from irradiated plasma exosomes during the process of osteogenesis by RNA sequencing. Further, we identified DE-miRs with significant differences and predicted their target genes via the bioinformatics analysis tools Targetscan v7.2 and miRPathDB v2.0. Finally, we identified radiation-responsive miRNAs and predicted their target genes during osteogenesis.
Taken together, we have identified some DE-miRs in irradiated plasma exosomes, which were involved in several vital signaling pathways related to bone physiology, such as the Wnt pathway, MAPK cascade, and calcium modulating pathway.
We have found that plasma exosomes are one of the ways by which radiation can affect bone metabolism and regeneration. However, the specific mechanisms of how these plasma exosomal miRNAs mediate the osteogenesis pathways must be further investigated. . Radiotherapy may cause radiation bone injury, and miRNA expression levels in rabbit plasma exosomes are altered after radiotherapy. High-throughput RNA sequencing can identify the differentially expressed miRNAs in irradiated plasma exosomes during the process of osteogenesis. These findings make sense to develop novel therapeutic strategies for treating radiation-induced bone injury disorders.
放射治疗是头颈部肿瘤的常见治疗方法，可能会导致放射骨损伤（RBI）这一侧效应。此外，已有研究表明放疗后微小RNA（miRNA）表达水平会发生改变。外泌体作为miRNA的载体在骨形成中发挥作用，而辐射会影响外泌体的组成、分泌和功能。因此，我们的目的是探讨放疗后骨形成过程中miRNA水平的变化，并确定与辐射相关的成骨过程中血浆外泌体中差异表达的miRNA（DE-miRs）。
在本研究中，我们分析了3只兔子的9个样本，每只兔子接受两次辐射（每次15 Gy），并通过RNA测序检测成骨过程中辐照血浆外泌体中的DE-miRs。此外，我们通过生物信息学分析工具Targetscan v7.2和miRPathDB v2.0鉴定出具有显著差异的DE-miRs，并预测其靶基因。最后，我们确定了成骨过程中辐射反应性miRNA并预测了其靶基因。
综上所述，我们在辐照血浆外泌体中鉴定出了一些DE-miRs，它们参与了与骨生理学相关的几个重要信号通路，如Wnt通路、丝裂原活化蛋白激酶（MAPK）级联反应和钙调节通路。
我们发现血浆外泌体是辐射影响骨代谢和再生的途径之一。然而，这些血浆外泌体miRNA介导成骨途径的具体机制仍需进一步研究。放疗可能会导致放射骨损伤，放疗后兔血浆外泌体中的miRNA表达水平会发生改变。高通量RNA测序可以鉴定成骨过程中辐照血浆外泌体中差异表达的miRNA。这些发现对于开发治疗辐射诱导的骨损伤疾病的新治疗策略具有重要意义。
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