Identification of the key exosomal lncRNAs/mRNAs in the serum during distraction osteogenesis.

Identification of the key exosomal lncRNAs/mRNAs in the serum during distraction osteogenesis.
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牵引成骨过程中血清中关键外泌体 lncRNA/mRNA 的鉴定

DOI:
10.1186/s13018-022-03163-9
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发表时间:
2022-05-28
影响因子:
2.6
通讯作者:
--
中科院分区:
医学3区
文献类型:
--
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牵张成骨(DO)是一种骨再生过程,不仅疗效极高,而且成骨速度远超普通骨折(BF)愈合。外泌体(Exo)被认为在骨再生和愈合中发挥作用,作为细胞与细胞接触的关键参与者。本工作的目的是确定来自DO和BF血清的外泌体是否可以刺激这两个过程中的成骨分化,如果是这样,哪些基因可能参与其中。采用放射学分析和组织学分析评价DO间隙或BF间隙的成骨作用。术后第14天,分离DO-Exos和BF-Exos,与颌骨骨髓间充质干细胞(BMMSCs)共培养。确定JBMMSCs的增殖、迁移和成骨分化,然后进行exosomes RNA-seq以鉴定相关基因。影像学和组织学分析表明,与BF间隙相比,DO间隙中的成骨明显加速。两种类型的Exos都被JBMMSCs摄取,并且它们的迁移和成骨分化也得到改善。但增殖无明显差异。最后,外泌体RNA-seq揭示lncRNA MSTRG. 532277. 1和mRNA F-box和富含亮氨酸的重复蛋白14(FBXL 14)可能在DO中起关键作用。我们的研究结果表明,来自血清的外泌体在DO的快速成骨中发挥关键作用。这种促进作用可能与MSTRG. 532277. 1和FBXL 14的共表达有关。总的来说,这些发现为骨再生提供了新的见解,从而概述了临床干预的可能治疗目标。
Distraction osteogenesis (DO), a kind of bone regenerative process, is not only extremely effective, but the osteogenesis rate is far beyond ordinary bone fracture (BF) healing. Exosomes (Exo) are thought to play a part in bone regeneration and healing as key players in cell-to-cell contact. The object of this work was to determine whether exosomes derived from DO and BF serum could stimulate the Osteogenic Differentiation in these two processes, and if so, which genes could be involved. The osteogenesis in DO-gap or BF-gap was evaluated using radiographic analysis and histological analysis. On the 14th postoperative day, DO-Exos and BF-Exos were isolated and cocultured with the jaw of bone marrow mesenchymal stem cells (JBMMSCs). Proliferation, migration and osteogenic differentiation of JBMMSCs were ascertained, after which exosomes RNA-seq was performed to identify the relevant gene. Radiographic and histological analyses manifested that osteogenesis was remarkably accelerated in DO-gap in comparison with BF-gap. Both of the two types of Exos were taken up by JBMMSCs, and their migration and osteogenic differentiation were also seen to improve. However, the proliferation showed no significant difference. Finally, exosome RNA-seq revealed that the lncRNA MSTRG.532277.1 and the mRNA F-box and leucine-rich repeat protein 14(FBXL14) may play a key role in DO. Our findings suggest that exosomes from serum exert a critical effect on the rapid osteogenesis in DO. This promoting effect might have relevance with the co-expression of MSTRG.532277.1 and FBXL14. On the whole, these findings provide new insights into bone regeneration, thereby outlining possible therapeutic targets for clinical intervention.
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