miR-342-3p promotes osteogenic differentiation via targeting ATF3

FEBS Lett. 2018 Dec;592(24):4051-4065. doi: 10.1002/1873-3468.13282. Epub 2018 Nov 15.

Abstract

Through their multiple targets, microRNAs (miRNAs) are involved in numerous physiological and pathological processes. In this study, miR-342-3p was found to be deregulated with ossification of ligament or osteoporosis. We demonstrate that silencing miR-342-3p impairs osteoblast activity and matrix mineralization, while over expression of miR-342-3p promotes osteoblast differentiation significantly. Moreover, miR-342-3p directly targets activating transcription factor 3 (ATF3), which inhibits transcription of pro-osteogenic differentiation-associated genes. In addition, there exists a higher frequency of methylation at the CpG island of the Enah/Vasp-Like (EVL) locus in undifferentiated pre-osteoblasts; however, demethylation of the EVL CpG island induces over expression of miR-342-3p during osteogenic differentiation. This study suggests that miR-342-3p may serves as a potential marker for diagnosis and treatment of ossification of ligament and osteoporosis.

Keywords: ATF3; microRNA; ossification; osteogenic differentiation; osteoporosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Activating Transcription Factor 3 / genetics*
  • Activating Transcription Factor 3 / metabolism
  • Animals
  • Cell Differentiation / genetics*
  • Cell Line
  • Cells, Cultured
  • Female
  • Gene Expression Profiling
  • HEK293 Cells
  • HT29 Cells
  • Humans
  • Male
  • Mice, Inbred C57BL
  • MicroRNAs / genetics*
  • Ossification of Posterior Longitudinal Ligament / genetics
  • Ossification of Posterior Longitudinal Ligament / metabolism
  • Osteoblasts / cytology
  • Osteoblasts / metabolism*
  • Osteogenesis / genetics*
  • Osteoporosis / genetics
  • Osteoporosis / metabolism

Substances

  • Activating Transcription Factor 3
  • MIRN342 microRNA, human
  • MicroRNAs

Supplementary concepts

  • Ossification of the posterior longitudinal ligament of the spine

Associated data

  • GENBANK/GSE106253