4.7 Article

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

Journal

STEM CELLS
Volume 34, Issue 11, Pages 2707-2720

Publisher

WILEY
DOI: 10.1002/stem.2439

Keywords

lncRNA MIR31HG; NF-kappa B; Human adipose-derived stem cells; Osteogenic differentiation

Funding

  1. National Natural Science Foundation of China [81371118, 81402235]
  2. Program for New Century Excellent Talents in University from Ministry of Education of China [NCET-11-0026]
  3. Ph.D. Programs Foundation of Ministry of Education of China [20130001110101]
  4. PKU School of Stomatology for Talented Young Investigators [PKUSS20140104]

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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-alpha-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-kappa B. The p65 subunit bound to the MIR31HG promoter and promoted MIR31HG expression. In turn, MIR31HG directly interacted with I kappa B alpha and participated in NF-kappa B activation, which builds a regulatory circuitry with NF-kappa B. Targeting this MIR31HG-NF-kappa B regulatory loop may be helpful to improve the osteogenic capacity of hASCs under inflammatory microenvironment in bone tissue engineering.

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