Liu Ting, Hu Wenyun, Zou Xue, Xu Jingchen, He Shushu, Chang Le, Li Xinyi, Yin Yuanyuan, Tian Mi, Li Ziyu, Zhou Jialiang, Jiang Xiaoge, Chen Song
State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, China.
Department of Medical Technology, Gannan Healthcare Vocational College, Ganzhou 341000, China.
Stem Cells Int. 2020 Nov 17;2020:8852307. doi: 10.1155/2020/8852307. eCollection 2020.
The role and underlying mechanism of exosomes derived from human periodontal ligament stem cells (PDLSC) in osteogenesis are unclear. In the present study, we identified the exosomes derived from PDLSCs and found that osteogenic induction can enhance the osteogenic ability of PDLSC-derived exosomes in promoting the osteogenic differentiation of rat bone marrow stem cells (BMSCs). To investigate the underlying mechanism, we analyzed the exosomal miRNA expression profiles of undifferentiated and osteogenic differentiated PDLSCs by RNA sequencing. The results showed that seventy-two miRNAs were upregulated and thirty-five miRNAs were downregulated after osteogenic induction. The results of Gene Ontology analysis and pathway analysis demonstrated that the target genes of differentially expressed exosomal miRNAs participate in the regulation of a variety of biological processes, such as catalytic activity, protein binding, metabolic processes, cell development, and differentiation, and are enriched in osteogenic differentiation-related pathways, such as MAPK signaling, AMPK signaling, and insulin signaling pathways. Our results reveal for the first time that the exosomal miRNAs derived from osteogenic differentiated PDLSCs may promote the osteogenic differentiation of BMSCs, which provides a basis for further research on the regulatory function of exosomal miRNA of PDLSCs during osteogenesis.
人牙周膜干细胞(PDLSC)来源的外泌体在成骨过程中的作用及潜在机制尚不清楚。在本研究中,我们鉴定了PDLSCs来源的外泌体,并发现成骨诱导可增强PDLSC来源的外泌体促进大鼠骨髓干细胞(BMSC)成骨分化的能力。为了探究其潜在机制,我们通过RNA测序分析了未分化和经成骨分化的PDLSCs的外泌体miRNA表达谱。结果显示,成骨诱导后72个miRNA上调,35个miRNA下调。基因本体分析和通路分析结果表明,差异表达的外泌体miRNA的靶基因参与多种生物学过程的调控,如催化活性、蛋白质结合、代谢过程、细胞发育和分化,并富集于成骨分化相关通路,如MAPK信号通路、AMPK信号通路和胰岛素信号通路。我们的结果首次揭示,成骨分化的PDLSCs来源的外泌体miRNA可能促进BMSCs的成骨分化,这为进一步研究PDLSCs外泌体miRNA在成骨过程中的调控功能提供了依据。