Activation of non-canonical Wnt/JNK pathway by Wnt3a is associated with differentiation fate determination of human bone marrow stromal (mesenchymal) stem cells

Biochem Biophys Res Commun. 2011 Sep 16;413(1):98-104. doi: 10.1016/j.bbrc.2011.08.061. Epub 2011 Aug 22.

Abstract

The canonical Wnt signaling pathway can determine human bone marrow stromal (mesenchymal) stem cell (hMSC) differentiation fate into osteoblast or adipocyte lineages. However, its downstream targets in MSC are not well characterized. Thus, using DNA microarrays, we compared global gene expression patterns induced by Wnt3a treatment in two hMSC lines: hMSC-LRP5(T253) and hMSC-LRP5(T244) cells carrying known mutations of Wnt co-receptor LRP5 (T253I or T244M) that either enhances or represses canonical Wnt signaling, respectively. Wnt3a treatment of hMSC activated not only canonical Wnt signaling, but also the non-canonical Wnt/JNK pathway through upregulation of several non-canonical Wnt components e.g. naked cuticle 1 homolog (NKD1) and WNT11. Activation of the non-canonical Wnt/JNK pathway by anisomycin enhanced osteoblast differentiation whereas its inhibition by SP600125 enhanced adipocyte differentiation of hMSC. In conclusion, canonical and non-canonical Wnt signaling cooperate in determining MSC differentiation fate.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Adipocytes / cytology
  • Adipocytes / metabolism
  • Anthracenes / pharmacology
  • Bone Marrow Cells / cytology
  • Bone Marrow Cells / drug effects
  • Bone Marrow Cells / metabolism
  • Calcium-Binding Proteins
  • Carrier Proteins / biosynthesis
  • Carrier Proteins / genetics
  • Cell Differentiation*
  • Cell Lineage
  • Cells, Cultured
  • Gene Expression Profiling
  • Humans
  • MAP Kinase Kinase 4 / antagonists & inhibitors
  • MAP Kinase Kinase 4 / metabolism*
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / drug effects
  • Osteoblasts / cytology
  • Osteoblasts / metabolism
  • Protein Kinase Inhibitors / pharmacology
  • Signal Transduction
  • Stromal Cells / cytology
  • Stromal Cells / drug effects
  • Stromal Cells / metabolism
  • Wnt Proteins / biosynthesis
  • Wnt Proteins / genetics
  • Wnt Proteins / metabolism*
  • Wnt Proteins / pharmacology
  • Wnt3 Protein
  • Wnt3A Protein
  • beta Catenin / metabolism

Substances

  • Adaptor Proteins, Signal Transducing
  • Anthracenes
  • Calcium-Binding Proteins
  • Carrier Proteins
  • NKD1 protein, human
  • Protein Kinase Inhibitors
  • WNT3A protein, human
  • Wnt Proteins
  • Wnt11 protein, human
  • Wnt3 Protein
  • Wnt3A Protein
  • beta Catenin
  • pyrazolanthrone
  • MAP Kinase Kinase 4