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鉴定牵张成骨过程中血清外泌体 lncRNAs/mRNAs 的关键特征。

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

机构信息

Department of Oral and Maxillofacial Surgery, Hospital of Stomatology, Guangxi Medical University, Nanning, 530021, People's Republic of China.

Guangxi Key Laboratory of Oral and Maxillofacial Rehabilitation and Reconstruction, Guangxi Key Laboratory of Oral and Maxillofacial Surgery Disease Treatment, Guangxi Clinical Research Center for Craniofacial Deformity, Nanning, 530021, People's Republic of China.

出版信息

J Orthop Surg Res. 2022 May 28;17(1):291. doi: 10.1186/s13018-022-03163-9.

Abstract

BACKGROUND

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.

METHODS

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.

RESULTS

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.

CONCLUSIONS

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.

摘要

背景

牵张成骨术(DO)是一种骨再生过程,不仅效果极佳,而且成骨率远高于普通骨折(BF)愈合。外泌体(Exo)被认为在细胞间通讯中发挥重要作用,是骨再生和愈合的关键因素。本研究旨在确定来自 DO 和 BF 血清的外泌体是否可以刺激这两种过程中的成骨分化,如果可以,哪些基因可能参与其中。

方法

通过影像学分析和组织学分析评估 DO 间隙或 BF 间隙中的成骨情况。在术后第 14 天,分离并共培养 DO-Exos 和 BF-Exos 与颌骨髓间充质干细胞(JBMMSCs)。确定 JBMMSCs 的增殖、迁移和成骨分化情况,然后进行外泌体 RNA-seq 以鉴定相关基因。

结果

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快。两种类型的 Exo 均被 JBMMSCs 摄取,其迁移和成骨分化也得到改善。然而,增殖没有明显差异。最后,外泌体 RNA-seq 显示长链非编码 RNA MSTRG.532277.1 和 F-box 和亮氨酸丰富重复蛋白 14(FBXL14)mRNA 可能在 DO 中起关键作用。

结论

我们的研究结果表明,血清外泌体对 DO 中的快速成骨具有重要作用。这种促进作用可能与 MSTRG.532277.1 和 FBXL14 的共表达有关。总之,这些发现为骨再生提供了新的见解,从而为临床干预提供了潜在的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2edb/9148531/06f7b4e144ec/13018_2022_3163_Fig1_HTML.jpg

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