MicroRNA-139-3p regulates osteoblast differentiation and apoptosis by targeting ELK1 and interacting with long noncoding RNA ODSM

Cell Death Dis. 2018 Oct 31;9(11):1107. doi: 10.1038/s41419-018-1153-1.

Abstract

Recent studies have confirmed that microRNAs and lncRNAs can affect bone cell differentiation and bone formation. In this study, miR-139-3p was upregulated in the femurs of hindlimb unloading mice and MC3T3-E1 cells under simulated microgravity; this effect was related to osteoblast differentiation and apoptosis. Silencing miR-139-3p attenuated the suppression of differentiation and the promotion of MC3T3-E1 cell apoptosis induced by simulated microgravity. ELK1 is a target of miR-139-3p and is essential for miR-139-3p to regulate osteoblast differentiation and apoptosis. An osteoblast differentiation-related lncRNA that could interact with miR-139-3p (lncRNA ODSM) was identified in MC3T3-E1 cells under simulated microgravity. Further investigations demonstrated that lncRNA ODSM could promote MC3T3-E1 cell differentiation. Therefore, this research was the first to reveal the critical role of the lncRNA ODSM/miR-139-3p/ELK1 pathway in osteoblasts, and these findings suggest the potential value of miR-139-3p in osteoporosis diagnosis and therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / genetics*
  • Base Sequence
  • Caspase 3 / genetics
  • Caspase 3 / metabolism
  • Cell Differentiation
  • Cell Line
  • Femur / metabolism
  • Femur / pathology
  • Gene Expression Regulation
  • Hindlimb Suspension
  • Male
  • Mechanotransduction, Cellular / genetics
  • Mice
  • Mice, Inbred C57BL
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Oligoribonucleotides / genetics
  • Oligoribonucleotides / metabolism
  • Osteoblasts / metabolism*
  • Osteoblasts / pathology
  • Osteogenesis / genetics*
  • Primary Cell Culture
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • RNA, Long Noncoding / genetics*
  • RNA, Long Noncoding / metabolism
  • Weightlessness Simulation
  • bcl-2-Associated X Protein / genetics
  • bcl-2-Associated X Protein / metabolism
  • ets-Domain Protein Elk-1 / genetics*
  • ets-Domain Protein Elk-1 / metabolism

Substances

  • Bax protein, mouse
  • Elk1 protein, mouse
  • MIRN139 microRNA, mouse
  • MicroRNAs
  • Oligoribonucleotides
  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Long Noncoding
  • bcl-2-Associated X Protein
  • ets-Domain Protein Elk-1
  • Bcl2 protein, mouse
  • Casp3 protein, mouse
  • Caspase 3