LncRNA-OG Promotes the Osteogenic Differentiation of Bone Marrow-Derived Mesenchymal Stem Cells Under the Regulation of hnRNPK

Stem Cells. 2019 Feb;37(2):270-283. doi: 10.1002/stem.2937. Epub 2018 Nov 17.

Abstract

Bone marrow-derived mesenchymal stem cells (BM-MSCs) are the main source of osteoblasts in vivo and are widely used in stem cell therapy. Previously, we analyzed long noncoding RNA (lncRNA) expression profiles during BM-MSC osteogenesis, and further investigation is needed to elucidate how lncRNAs regulate BM-MSC osteogenesis. Herein, we used customized microarrays to determine lncRNA expression profiles in BM-MSCs on days 0 and 10 of osteogenic differentiation. In addition, we identified a novel osteogenesis-associated lncRNA (lncRNA-OG) that is upregulated during this process. Functional assays showed that lncRNA-OG significantly promotes BM-MSC osteogenesis. Mechanistically, lncRNA-OG interacts with heterogeneous nuclear ribonucleoprotein K (hnRNPK) protein to regulate bone morphogenetic protein signaling pathway activation. Surprisingly, hnRNPK positively regulates lncRNA-OG transcriptional activity by promoting H3K27 acetylation of the lncRNA-OG promoter. Therefore, our study revealed a novel lncRNA with a positive function on BM-MSC osteogenic differentiation and proposed a new interaction between hnRNPK and lncRNA. Stem Cells 2018 Stem Cells 2019;37:270-283.

Keywords: Heterogeneous nuclear ribonucleoprotein K; Long noncoding RNA; Mesenchymal stem cells; Osteogenic differentiation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Differentiation
  • Heterogeneous-Nuclear Ribonucleoprotein K / genetics*
  • Humans
  • Mesenchymal Stem Cells / metabolism*
  • Osteogenesis
  • RNA, Long Noncoding / genetics*

Substances

  • Heterogeneous-Nuclear Ribonucleoprotein K
  • RNA, Long Noncoding
  • HNRNPK protein, human