Differential Regulation of circRNA, miRNA, and piRNA during Early Osteogenic and Chondrogenic Differentiation of Human Mesenchymal Stromal Cells

Cells. 2020 Feb 9;9(2):398. doi: 10.3390/cells9020398.


The goal of the present study is to identify the differential expression of circular RNA (circRNA), miRNA, and piwi-interacting RNA (piRNA) after lineage commitment towards osteo- and chondrogenesis of human bone marrow mesenchymal stromal cells (hMSCs). The cells were maintained for 7 days in either osteogenic or chondrogenic medium. RNA sequencing was performed to assess the expression of miRNA and piRNA, while RNA hybridization arrays were used to identify which circRNA were differentially expressed. qPCR validation of a selection of targets for both osteogenic and chondrogenic differentiation was carried out. The differential expression of several circRNA, miRNA, and piRNA was identified and validated. The expression of total and circular isoforms of FKBP5 was upregulated both in osteo- and chondrogenesis and it was influenced by the presence of dexamethasone. ZEB1, FADS2, and SMYD3 were also identified as regulated in differentiation and/or by dexamethasone. In conclusion, we have identified a set of different non-coding RNAs that are differentially regulated in early osteogenic and chondrogenic differentiation, paving the way for further investigation to understand how dexamethasone controls the expression of those genes and what their function is in MSC differentiation.

Keywords: RNA sequencing; circular RNA; dexamethasone; differentiation; human mesenchymal stem cells; miRNA; non-coding RNA; piwi-interacting RNA; transcriptome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Binding Sites / genetics
  • Cell Differentiation / genetics*
  • Chondrogenesis / genetics*
  • Female
  • Gene Expression Regulation*
  • Humans
  • Immunophenotyping
  • Male
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / metabolism
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Middle Aged
  • Osteogenesis / genetics*
  • RNA, Circular / genetics*
  • RNA, Circular / metabolism
  • RNA, Small Interfering / genetics*
  • RNA, Small Interfering / metabolism
  • Reproducibility of Results


  • MicroRNAs
  • RNA, Circular
  • RNA, Small Interfering