MiR-137 knockdown promotes the osteogenic differentiation of human adipose-derived stem cells via the LSD1/BMP2/SMAD4 signaling network

J Cell Physiol. 2020 Feb;235(2):909-919. doi: 10.1002/jcp.29006. Epub 2019 Jun 26.

Abstract

MicroRNAs are a group of endogenous regulators that participate in several cellular physiological processes. However, the role of miR-137 in the osteogenic differentiation of human adipose-derived stem cells (hASCs) has not been reported. This study verified a general downward trend in miR-137 expression during the osteogenic differentiation of hASCs. MiR-137 knockdown promoted the osteogenesis of hASCs in vitro and in vivo. Mechanistically, inhibition of miR-137 activated the bone morphogenetic protein 2 (BMP2)-mothers against the decapentaplegic homolog 4 (SMAD4) pathway, whereas repressed lysine-specific histone demethylase 1 (LSD1), which was confirmed as a negative regulator of osteogenesis in our previous studies. Furthermore, LSD1 knockdown enhanced the expression of BMP2 and SMAD4, suggesting the coordination of LSD1 in the osteogenic regulation of miR-137. This study indicated that miR-137 negatively regulated the osteogenic differentiation of hASCs via the LSD1/BMP2/SMAD4 signaling network, revealing a new potential therapeutic target of hASC-based bone tissue engineering.

Keywords: LSD1; human adipose-derived stem cells; microRNA; osteogenic differentiation; signaling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / cytology*
  • Bone Morphogenetic Protein 2 / metabolism
  • Cells, Cultured
  • Gene Knockdown Techniques
  • Histone Demethylases / genetics
  • Histone Demethylases / metabolism
  • Humans
  • Mesenchymal Stem Cells / cytology*
  • MicroRNAs / genetics*
  • Osteogenesis / genetics*
  • Signal Transduction / genetics
  • Smad4 Protein / metabolism
  • Tissue Engineering

Substances

  • BMP2 protein, human
  • Bone Morphogenetic Protein 2
  • MIRN137 microRNA, human
  • MicroRNAs
  • SMAD4 protein, human
  • Smad4 Protein
  • Histone Demethylases
  • KDM1A protein, human