Yu Du1, Haiyang Tang2, Xia Gu3, Yixin Shi1, Ping Gong1, Yang Yao1. 1. 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. 2. Chengdu Second People's Hospital, Department of Stomatology, China. 3. Stomatological Hospital of Chongqing Medical University, China.
Abstract
OBJECTIVES: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. Clinical Relevance. 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.
OBJECTIVES: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. Clinical Relevance. 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.
Authors: Yu Du; Shufang Du; Liu Liu; Feihong Gan; Xiaoge Jiang; Kaijuan Wangrao; Ping Lyu; Ping Gong; Yang Yao Journal: Radiat Res Date: 2020-07-08 Impact factor: 2.841
Authors: A Moorthi; S Vimalraj; C Avani; Zhiming He; Nicola C Partridge; N Selvamurugan Journal: Int J Biol Macromol Date: 2013-03-01 Impact factor: 6.953