作为骨质疏松症潜在外泌体tRNA衍生片段生物标志物的转运RNA衍生片段

Transfer RNA-derived fragments as potential exosome tRNA-derived fragment biomarkers for osteoporosis.

作者信息

Zhang Yan, Cai Feng, Liu Ju, Chang Hongze, Liu Liang, Yang Anli, Liu Xiaodong

机构信息

Department of Orthopedics, Shanghai Yangpu Hospital Affiliated to Tongji University, Shanghai, China.

Department of Orthopedics, Shanghai Zhoupu Hospital, Shanghai, China.

出版信息

Int J Rheum Dis. 2018 Sep;21(9):1659-1669. doi: 10.1111/1756-185X.13346.

DOI:10.1111/1756-185X.13346

PMID:30345646

Abstract

AIM

Osteoporosis is one of the common orthopedic diseases featured in low bone mineral density. Exosomes have been proven to be potential markers for many diseases and health problems. The roles of messenger RNAs and microRNAs in osteoporosis have been comprehensively studied; however, little research has focused on the function of plasma exosomal transfer RNA-derived fragments (tRFs) in osteoporosis.

METHODS

We collected plasma samples from 40 healthy controls and 40 osteoporosis patients, and all exosomes were isolated with combined centrifugation and were characterized by electron microscopy. Small RNA sequence (Yingbio) was performed to detect the plasma exosomal tRFs and tRF markers were validated by real-time quantitative polymerase chain reaction (qPCR). Three exosome diagnostic tRFs were confirmed by receiver operating characteristic analyses.

RESULTS

In this study, 11 upregulated tRFs and 18 downregulated tRFs were identified in osteoporosis compared with normal controls. Higher expression levels of plasma exosomal tRF-25-R9ODMJ6B26 (tRF-25), tRF-38-QB1MK8YUBS68BFD2 (tRF-38), tRF-18-BS68BFD2 (tRF-18) in osteoporosis were confirmed by qPCR. Plasma exosomal tRF-25, tRF-38 and tRF-18 showed better accuracy for osteoporosis diagnosis.

CONCLUSION

Our results suggest that plasma exosomal tRF-25, tRF-38 and tRF-18 might be diagnostic biomarkers for osteoporosis detection.

摘要

目的

骨质疏松症是一种常见的骨科疾病，其特征为骨矿物质密度低。外泌体已被证明是许多疾病和健康问题的潜在标志物。信使核糖核酸（mRNA）和微小核糖核酸（miRNA）在骨质疏松症中的作用已得到全面研究；然而，关于血浆外泌体转运核糖核酸衍生片段（tRF）在骨质疏松症中的功能研究较少。

方法

我们收集了40名健康对照者和40名骨质疏松症患者的血浆样本，通过联合离心分离所有外泌体，并通过电子显微镜进行表征。进行小RNA测序（英潍捷基）以检测血浆外泌体tRF，并通过实时定量聚合酶链反应（qPCR）验证tRF标志物。通过受试者工作特征分析确认了三种外泌体诊断性tRF。

结果

在本研究中，与正常对照相比，在骨质疏松症中鉴定出11种上调的tRF和18种下调的tRF。通过qPCR证实了骨质疏松症患者血浆外泌体tRF-25-R9ODMJ6B26（tRF-25）、tRF-38-QB1MK8YUBS68BFD2（tRF-38）、tRF-18-BS68BFD2（tRF-18）的表达水平更高。血浆外泌体tRF-25、tRF-38和tRF-18对骨质疏松症诊断具有更好的准确性。