LncRNA H19 promotes the committed differentiation of stem cells from apical papilla via miR-141/SPAG9 pathway

Cell Death Dis. 2019 Feb 12;10(2):130. doi: 10.1038/s41419-019-1337-3.

Abstract

Long noncoding RNAs (lncRNAs) exert significant roles at transcriptional and post-transcriptional levels. Stem cells from apical papilla (SCAPs) differentiate into dentin/bone-like tissues under certain conditions. So far, whether lncRNA-H19 can affect the proliferative behaviors and osteo/odontogenesis of SCAPs, as well as its specific mechanism remain to be elucidated. Here, SCAPs were isolated and transfected with the lentiviruses or packaging vectors. Our results showed that lncRNA-H19 had no significant effect on the proliferative behaviors of SCAPs, as presented by CCK-8 assay, EdU assay and flow cytometry (FCM). Furthermore, alkaline phosphatase (ALP) activity, alizarin red staining, Western blot assay (WB), quantitative real-time polymerase chain reaction (qRT-PCR) and in vivo bone formation assay were conducted to verify the biological influences of H19 on SCAPs. Overexpression of H19 led to the enhanced osteo/odontogenesis of SCAPs, whereas knockdown of H19 inhibited these effects. Mechanistically, H19 competitively bound to miR-141 and prevented SPAG9 from miRNA-mediated degradation, thus significantly elevating phosphorylated levels of p38 and JNK and facilitating the committed differentiation of SCAPs. Taken together, the osteo/odontogenesis of SCAPs was upregulated by overexpression of H19 via miR-141/SPAG9 pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism*
  • Adolescent
  • Cell Differentiation*
  • Cell Proliferation / genetics
  • Dental Papilla / cytology*
  • Healthy Volunteers
  • Humans
  • MicroRNAs / metabolism*
  • Odontogenesis / genetics
  • Osteogenesis / genetics
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Stem Cells / metabolism*
  • Transfection
  • Young Adult

Substances

  • Adaptor Proteins, Signal Transducing
  • H19 long non-coding RNA
  • MIRN141 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • SPAG9 protein, human