INO80 is Required for Osteogenic Differentiation of Human Mesenchymal Stem Cells

Sci Rep. 2016 Nov 2:6:35924. doi: 10.1038/srep35924.

Abstract

Bone marrow derived human mesenchymal stem cells (MSC) are a great source in bone tissue engineering. However, how to improve the efficiency of MSC osteogenesis remains a big challenge in bone regenerative medicine. Here, we characterized the role of INO80 chromatin remodeling complex in osteogenic differentiation of MSC. We showed that silencing of subunits of INO80 reduced the mineral deposition of MSC in osteogenic condition. Moreover, INO80-silencing MSC cultured in osteogenic condition expressed lower mRNA levels of osteoblast-specific genes, including Runx2, Osx, Col1α1 and OCN. INO80 can interact with Wdr5 in MSC and positively regulates the canonical Wnt signaling transduction. Importantly, the mice implanted with INO80-silencing MSC displayed less bone formation. Overall, our study provides a new mechanism regarding osteogenic differentiation of MSC and could potentially be applied in clinical tissue engineering and treatment of osteoporosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATPases Associated with Diverse Cellular Activities
  • Animals
  • Bone Marrow Cells / cytology
  • Cell Differentiation / genetics*
  • Cell Line
  • Collagen Type I / genetics
  • Collagen Type I / metabolism
  • Collagen Type I, alpha 1 Chain
  • Core Binding Factor Alpha 1 Subunit / genetics
  • Core Binding Factor Alpha 1 Subunit / metabolism
  • DNA Helicases / antagonists & inhibitors
  • DNA Helicases / genetics
  • DNA Helicases / metabolism*
  • DNA-Binding Proteins
  • Histone-Lysine N-Methyltransferase / metabolism
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / metabolism
  • Mice
  • Osteogenesis / physiology*
  • Osteopontin / genetics
  • Osteopontin / metabolism
  • RNA Interference
  • RNA, Messenger / metabolism
  • RNA, Small Interfering / metabolism
  • Transplantation, Heterologous
  • Wnt Signaling Pathway

Substances

  • Collagen Type I
  • Collagen Type I, alpha 1 Chain
  • Core Binding Factor Alpha 1 Subunit
  • DNA-Binding Proteins
  • Intracellular Signaling Peptides and Proteins
  • RNA, Messenger
  • RNA, Small Interfering
  • RUNX2 protein, human
  • WDR5 protein, human
  • Osteopontin
  • Histone-Lysine N-Methyltransferase
  • ATPases Associated with Diverse Cellular Activities
  • DNA Helicases
  • INO80 protein, human