Inhibition of lncRNA MIR31HG Promotes Osteogenic Differentiation of Human Adipose-Derived Stem Cells

Stem Cells. 2016 Nov;34(11):2707-2720. doi: 10.1002/stem.2439. Epub 2016 Jul 5.

Abstract

Osteogenic differentiation and bone formation is suppressed under condition of inflammation induced by proinflammation cytokines. A number of studies indicate miRNAs play a significant role in tumor necrosis factor-α-induced inhibition of bone formation, but whether long non-coding RNAs are also involved in this process remains unknown. In this study, we evaluated the role of MIR31HG in osteogenesis of human adipose-derived stem cells (hASCs) in vitro and in vivo. The results suggested that knockdown of MIR31HG not only significantly promoted osteogenic differentiation, but also dramatically overcame the inflammation-induced inhibition of osteogenesis in hASCs. Mechanistically, we found MIR31HG regulated bone formation and inflammation via interacting with NF-κB. The p65 subunit bound to the MIR31HG promoter and promoted MIR31HG expression. In turn, MIR31HG directly interacted with IκBα and participated in NF-κB activation, which builds a regulatory circuitry with NF-κB. Targeting this MIR31HG-NF-κB regulatory loop may be helpful to improve the osteogenic capacity of hASCs under inflammatory microenvironment in bone tissue engineering. Stem Cells 2016;34:2707-2720.

Keywords: Human adipose-derived stem cells; NF-κB; Osteogenic differentiation; lncRNA MIR31HG.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / cytology
  • Adipose Tissue / drug effects
  • Adipose Tissue / metabolism
  • Animals
  • Cell Differentiation
  • Feedback, Physiological*
  • Gene Expression Regulation
  • Humans
  • Lipopolysaccharides / pharmacology
  • Mice, Inbred BALB C
  • Mice, Nude
  • NF-KappaB Inhibitor alpha / genetics*
  • NF-KappaB Inhibitor alpha / metabolism
  • NF-kappa B p50 Subunit / genetics*
  • NF-kappa B p50 Subunit / metabolism
  • Osteoblasts / cytology
  • Osteoblasts / drug effects
  • Osteoblasts / metabolism*
  • Osteogenesis / drug effects
  • Osteogenesis / genetics
  • Primary Cell Culture
  • Promoter Regions, Genetic
  • Protein Binding
  • RNA, Long Noncoding / antagonists & inhibitors
  • RNA, Long Noncoding / genetics*
  • RNA, Long Noncoding / metabolism
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • Signal Transduction
  • Stem Cell Transplantation
  • Stem Cells / cytology
  • Stem Cells / drug effects
  • Stem Cells / metabolism*
  • Tissue Engineering
  • Transcription Factor RelA / genetics*
  • Transcription Factor RelA / metabolism
  • Transplantation, Heterologous

Substances

  • Lipopolysaccharides
  • NF-kappa B p50 Subunit
  • RELA protein, human
  • RNA, Long Noncoding
  • RNA, Small Interfering
  • Transcription Factor RelA
  • long noncoding RNA MIR31HG, human
  • NF-KappaB Inhibitor alpha