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TGFβ-induced factor homeobox 2 blocks osteoblastic differentiation through targeting pSmad3/HDAC4/H4ac/Runx2 axis

Xiang Yu1, Gengyang Shen1, Hui Ren2

  • 1The First Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, China.

Journal of Cellular Physiology
|May 9, 2019
PubMed

Insights

TGFβ-induced factor homeobox 2 (Tgif2) inhibits osteogenic differentiation by targeting the pSmad3/HDAC4/H4ac/Runx2 pathway. Overexpression of Tgif2 in bone marrow-derived mesenchymal stem cells and osteoblasts reduced osteogenic marker expression and mineralization.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • TGFβ-induced factor homeobox 2 (Tgif2) is implicated in cell homeostasis and osteoclastogenesis.
  • Its role in osteogenic differentiation remains largely unexplored.

Purpose of the Study:

  • To investigate the role of Tgif2 in osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) and osteoblasts (OBs).
  • To elucidate the molecular mechanisms underlying Tgif2's effect on osteogenesis.

Main Methods:

  • Assessed Tgif2 expression during osteogenic differentiation of BMSCs and OBs.
  • Utilized lentivirus-mediated gene overexpression (OE) to study Tgif2's effects.
  • Performed alkaline phosphatase (ALP) assay, mineralization assay, and gene expression analysis.
  • Employed co-immunoprecipitation (CoIP) and chromatin immunoprecipitation (ChIP) assays to investigate molecular interactions.

Main Results:

  • Tgif2 expression decreased during osteogenic induction in BMSCs and OBs.
  • Tgif2 overexpression significantly inhibited osteogenic differentiation and reduced osteogenic marker expression (Runx2, Sp7, Alp, Ocn).
  • Tgif2 OE promoted pSmad3/HDAC4 interaction and decreased H4ac at the Runx2-binding site of the Ocn promoter.

Conclusions:

  • Tgif2 plays an inhibitory role in osteoblastic differentiation in vitro.
  • Tgif2 may exert its function by targeting the pSmad3/HDAC4/H4ac/Runx2 signaling axis.
Keywords:
H4acHDAC4Runx2Tgif2osteoblastic differentiationoverexpressionpSmad3

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