Altered microRNA expression profile in exosomes during osteogenic differentiation of human bone marrow-derived mesenchymal stem cells

PLoS One. 2014 Dec 11;9(12):e114627. doi: 10.1371/journal.pone.0114627. eCollection 2014.

Abstract

The physiological role of microRNAs (miRNAs) in osteoblast differentiation remains elusive. Exosomal miRNAs isolated from human bone marrow-derived mesenchymal stem cells (BMSCs) culture were profiled using miRNA arrays containing probes for 894 human matured miRNAs. Seventy-nine miRNAs (∼8.84%) could be detected in exosomes isolated from BMSC culture supernatants when normalized to endogenous control genes RNU44. Among them, nine exosomal miRNAs were up regulated and 4 miRNAs were under regulated significantly (Relative fold>2, p<0.05) when compared with the values at 0 day with maximum changes at 1 to 7 days. Five miRNAs (miR-199b, miR-218, miR-148a, miR-135b, and miR-221) were further validated and differentially expressed in the individual exosomal samples from hBMSCs cultured at different time points. Bioinformatic analysis by DIANA-mirPath demonstrated that RNA degradation, mRNA surveillance pathway, Wnt signaling pathway, RNA transport were the most prominent pathways enriched in quantiles with differential exosomal miRNA patterns related to osteogenic differentiation. These data demonstrated exosomal miRNA is a regulator of osteoblast differentiation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Bone Morphogenetic Protein 2 / genetics
  • Cell Differentiation / genetics*
  • Exosomes / genetics*
  • Female
  • Humans
  • Male
  • Mesenchymal Stem Cells / cytology*
  • MicroRNAs / genetics*
  • Osteogenesis / genetics*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Reproducibility of Results
  • Transcriptome*

Substances

  • BMP2 protein, human
  • Bone Morphogenetic Protein 2
  • MIRN885 microRNA, human
  • MicroRNAs
  • RNA, Messenger

Grants and funding

This study is supported by Medical Scientific Research Foundation of Zhejiang Province, China (Grant No. 2013KYB031), National Natural Science Foundation of China (Grant No. 81200113), the Fundamental Research Funds for the Central Universities (Grant No. 2014FZA7014). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.