Interaction of LEF1 with TAZ is necessary for the osteoblastogenic activity of Wnt3a

Sci Rep. 2018 Jul 10;8(1):10375. doi: 10.1038/s41598-018-28711-4.

Abstract

Canonical Wnt signalling plays an important role in osteoblast differentiation and bone formation. However, the molecular mechanisms by which canonical Wnt signalling exerts its osteoblastogenic effect remain elusive. Here, we investigated the relationship between lymphoid enhancer-binding factor 1 (LEF1) and transcriptional co-activator with PDZ-binding motif (TAZ), both of which are transcriptional regulators that mediate canonical Wnt signalling during osteoblast differentiation. Reporter assay and co-immunoprecipitation experiments revealed functional and physical interaction between LEF1 and TAZ. Overexpression of dominant-negative forms of either LEF1 or TAZ markedly inhibited Wnt3a-dependent osteoblast differentiation. Moreover, we found that LEF1 and TAZ formed a transcriptional complex with runt-related transcription factor 2 (Runx2) and that inhibition of LEF1 or TAZ by their dominant-negative forms dramatically suppressed the osteoblastogenic activity of Ruxn2. Additionally, Wnt3a enhanced osteoblast differentiation induced by bone morphogenetic protein 2 (BMP2), which stimulates osteoblast differentiation by regulating Runx2. Collectively, these findings suggest that interaction between LEF1 and TAZ is crucial for the osteoblastogenic activity of Wnt3a and that LEF1 and TAZ contribute to the cooperative effect of Wnt3a and BMP2 on osteoblast differentiation through association with Runx2.

MeSH terms

  • Bone Morphogenetic Protein 2 / metabolism
  • Cell Differentiation
  • Cell Line
  • Core Binding Factor Alpha 1 Subunit / metabolism
  • Humans
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Lymphoid Enhancer-Binding Factor 1 / metabolism*
  • Osteoblasts / cytology*
  • Protein Binding
  • Trans-Activators
  • Transcription Factors
  • Transcriptional Coactivator with PDZ-Binding Motif Proteins
  • Transfection
  • Wnt Signaling Pathway
  • Wnt3A Protein / physiology*

Substances

  • BMP2 protein, human
  • Bone Morphogenetic Protein 2
  • Core Binding Factor Alpha 1 Subunit
  • Intracellular Signaling Peptides and Proteins
  • Lymphoid Enhancer-Binding Factor 1
  • RUNX2 protein, human
  • Trans-Activators
  • Transcription Factors
  • Transcriptional Coactivator with PDZ-Binding Motif Proteins
  • WNT3A protein, human
  • WWTR1 protein, human
  • Wnt3A Protein