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

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

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.

Keywords: diagnostic biomarker; exosome; osteoporosis; plasma; receiver operating characteristic; transfer RNA-derived fragment.

MeSH terms

  • Case-Control Studies
  • Exosomes / genetics*
  • Exosomes / pathology
  • Genetic Markers
  • Humans
  • Osteoporosis / blood
  • Osteoporosis / diagnosis
  • Osteoporosis / genetics*
  • Predictive Value of Tests
  • RNA, Transfer / blood
  • RNA, Transfer / genetics*
  • Real-Time Polymerase Chain Reaction
  • Reproducibility of Results
  • Sequence Analysis, RNA

Substances

  • Genetic Markers
  • RNA, Transfer